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Drug Categories

Inhibitors of Cell Wall Synthesis Others:

-lactams: Vancomycin and Televancin

Penicillins

Cephalosporins

Carbapenems

Monobactams

Inhibitors of Protein Synthesis Others:

Tetracyclines Clindamycin

Macrolides Quinupristin/ Dalfopristin

Aminoglycosides Linezolid

Daptomycin

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Inhibitors of DNA, RNA and Protein Production

Co-trimoxazole

Fluorquinolones

Metronidazole
Inhibitors of Cell Wall Synthesis

Penicillins- General Info

PCNs are bactericidal

MOA: Work on cell wall, prevent repair or synthesis

PK: Some destroyed by gastric acid, take on empty stomach

Distribution: Wide dist. but poor dist. to eye, prostate, CNS, except inflamed meninges

Usually IV except Benzathine and Procaine which are given IM to delay absorption

Metabolism: Minimal or none by liver

Elimination: t is short, excreted primarily by kidneys except anti-staphylococcal PCNs (Nafcillin and
Dicloxacillin, biliary excretion)

Natural PCNs

Penicillin G (IV) and Penicillin V (PO)

Spec of Activity: Narrow; Penicillinase sensitive

Gram + cocci (non-res. Staph + strep) and mouth anaerobes

Antistaphylococcal PCNs

Nafcillin (IV) and Dicloxacillin (PO)

Spec. of Activity: Narrow; Penicillinase Resistant; Drugs of Choice for MSSA

Hepatically cleared; dose adjust for severe hepatic impairment

Used for skin + soft tissue infections (usually comm. Acquired)

Extended Spectrum PCNs (Aminopenicillins)

Ampicillin (IV+PO) and Amoxicillin (PO)


Amox- 1st Line Tx for Otitis media, sinusitis

Spec. of Activity: Broad; Penicillinase Sensitive (by themselves)

Gram + cocci (non-res. Staph and strep)

Gram

Extended Spectrum Anti-pseudomonas PCNs

Ticarcillin (IV) and Piperacillin (IV) and Mezlocillin (IV)

Spec. of Activity: Broad; Penicillinase Sensitive (by themselves)

Gram and Gram + less effective (use Piperacillin for some Gram + cocci)

Uses: Pseudomonas

- lactam/ - lactamase Inhibitor Combo

Ampicillin/ Sulbactam (IV)

Amoxicillin/ Clavulanic Acid (PO)

Ticarcillin/ Clavulanic Acid (IV)

Piperacillin/ Tazabactam (IV)

These extend Gram + and Gram activity to include - lactamase producing organisms

Adverse Drug Rxns for PCNs

Relatively safe

Hypersensitivity: anaphylaxis vs. allergy? , Desensitization is possible

Diarrhea- especially Augmentin


Cephalosporins

Similar to PCNs but have a broader spectrum

Rapid absorption

CNS Penetration: 1st and 2nd- None, 3rd- Does well

Bacterial resistance: - lactamases

1st Gen. Cephalosporins

Cefazolin (IV, only 1st gen ceph still used parenterally)

Cefadroxil (PO)

Cephalexin (PO)

Spec. of Activity: Gram + primarily, some Gram

No CNS penetration

2nd Gen. Cephalosporins

Cefaclor (PO)

Cefoxitin ** (treats Gram +, Gram and ANAEROBES) - cephamycin

Cefprozil

Cefuroxime

Cefuroxime axetil

Spec. of Activity: Gram + (like 1st Gen.) and Gram (more than 1st Gen.)

No CNS penetration

3rd Gen. Cephalosporins

Cefdinir (PO)

Cefixime (PO)
Cefotaxime* (Parenteral) Gram +

Ceftriaxone* (Parenteral) Gram +

Ceftazidime* (Parenteral) Gram - ; Anti-pseudomonal Agent

* Treats respiratory Bugs

Ceftibuten

Cefditoren

Spec. of Activity: Broad; Good CNS penetration, No anaerobic coverage

If using Ceftazidime, be sure of pseudomonas infection!

4th Gen. Cephalosporins

Cefepime

Spec. of Activity: VERY BROAD, max coverage

5th Gen Cephalosporins

Ceftaroline

Spec. of Activity: MRSA (will be on test!); Multi-drug resistant (MDR) staph and strep

Only use Ceftaroline for MRSA! Very important.

Cephalosporin Side Effects

Hypersensitivity Rxns

Cross rxns with PCN allergic pts (10% cross-reactivity)

MTT side chain can cause prolonged bleeding


Carbapenems

Imipenems/ Cilastatin

Meropenem

Doripenem

Ertapenem (exception, see below)

Spec. of Activity: Most broad single agents

Top 3 drugs: Gram + aerobes, Gram - aerobes, and anaerobes. Has pseudomonas activity.

Ertapenem (exception): No pseudomonas activity. Comm. Acquired infections (not nosocomial)

Side effects of Carbapenems

Hypersensitivity (cross sensitivity with PCN allergic pts), N+V, Seizures

Monobactams

Aztreonam

Spec. of Activity: Gram only (excellent) including Pseudomonas

Good substitute for aminoglycosides

Cross reactivity between PCNs and Carbapenems AND PCNs and Monobactams

Due to common - lactam group, True IgE allergic rxn only (<1%)
The following drugs are also cell wall synthesis inhibitors but have a glycopeptide structure

Vancomycin

Bactericidal; Glycopeptide structure; treats glycopeptide sensitive organisms (GSSA, GISA, GRSA)

IV only (PO absorption is too low)

Spec. of Activity: Gram + aerobes only! Including MRSA.

Blood levels can be measured

Adverse events: Hypersensitivity, Red man Syndrome, ototoxicity +nephrotoxicity (when used with
other nephrotoxic agents)

Elimination: Vancomycin clearance is almost identical to the Glomerular filtration rate so dose it
perfectly! Dose adjust per pharmacokinetics

Televancin

Glycopeptide structure, lipid form of Vancomycin

Teratogen!!!
Protein Synthesis Inhibitors

Target several steps in bacterial protein synthesis so it can damage mammalian tissue

Rapidly dividing cells (GI mucosa, skin, bone marrow) and cells in tissues exposed to high drug levels
(kidney, liver) show greatest toxicities from these protein synthesis inhibitors

Tetracyclines

Doxycycline

Minocycline

Tetracycline

MOA: Inhibits bacterial protein synthesis

Chelation Drug Interactions- when given with any Positively charged item, results in decreased absorp.

Spec. of Activity: Some Gram + aerobes, Some Gram aerobes

Adverse Rxns: Gastric discomfort (take with non-calcium based foods), Phototoxicity

Contraindication** (Test Question!): Pregnant or breast feeding women and children under 8 y/o

Macrolides

Erythromycin (not usually prescribed, too many issues)

Clarithromycin

Azithromycin (exception)

Telithromycin

MOA: Inhibits bacterial protein synthesis

Metabolism: Erythromycin and Clarithromycin are inhibitors of CYP 3A4. Azithromycin is the exception. It
does not metabolize. Has no issues.

Spec. of Activity: Some Gram + aerobes, Some Gram aerobes

Adverse Rxns: Epigastric Distress- Erythtro (worst on stomach)>> Clarithro> Azithro (easiest on stomach)

Inhibitors of the Cytochrome P450 3A4 system, Interact with calcium channel blockers

It can stop the heart

Aminoglycosides
Amikacin

Gentamicin

Tobramycin

MOA: Inhibits bacterial protein synthesis

PK: PO poorly absorbed

Metabolism + Excretion: Close linkage with drug blood level and renal function. Dose adjust!

Distribution: Unique; High conc. only in kidney and endolymph + perilymph of inner ear

Spec. of Activity: Gram aerobes including pseudomonas

Synergistic Combo: Active against MSSA, MRSA, + Enterococcal species when given with cell wall active
agent (PCNs, ampicillin, Vancomycin)

Extended Interval Dosing works better with less ototoxicities and neprotoxicities, Monitoring of peak and
trough high blood levels
The following drugs are also protein synthesis inhibitors:

Clindamycin

Bacteristatic

MOA: Inhibits bacterial protein synthesis

Spec. of Activity: Gram + and anaerobes, May work for comm. Acq. MRSA

Adverse Rxns: Skin rashes + GI intolerance, reversible change in LFT;

AST + ALT are acute markers of drug-induced liver toxicity

Quinupristin/ Dalfopristin

MOA: Protein synthesis inhibitors

IV only

Major inhibitor of P450 3A4 system

Spec. of Activity: Multi drug Resistant Gram + infections, GSSA + GRSA

Adverse Effects: Arthralgia- myalgia syndrome, infusion related

Linezolid

MOA: Protein synthesis inhibitor

IV + PO

Neither inhibitor or inducer of cytochrome P450

Spec. of Activity: Multi drug Resistant Gram + infections

Adverse Rxns: Tyramine restricted diet Italian deli meat diet, Thrombocytopenia

Daptomycin

MOA: Protein synthesis inhibitor

Spec. of Activity: Multi Drug Resistant Gram + infections

Adverse Rxns: Eosinophilic pneumonia


DNA, RNA and Protein Production Inhibitors

Co-trimoxazole

Anti-metabolite-sulfa drugs

MOA: Inhibits DNA, RNA, and Protein production

PK: PO + IV; highly protein bound (>95%); penetrates most body fluids including CSF

Spec. of Activity: enteric Gram bugs; CA- MRSA

Uses: UTIs, travelers diarrhea

Adverse Drug Rxns: Dermatologic (rash + photosensitivity); HIV pts 50% higher chance getting rash

Fluoroquinolones

Ciprofloxacin

Norfloxacin

Ofloxacin

Levofloxacin

Moxifloxacin

Gemifloxacin

Respiratory Fluoroquinolones ** (Test question) Levofloxacin, gemifloxacin, + Moxifloxacin

MOA: Inhibits DNA gyrase, breakage of bacterial DNA

PK: PO and IV; Moxifloxacin not renally eliminated

Spec. of Activity: Gram aerobes, including pseudomonas, some Gram - anaerobes; Some Gram +
aerobes

Uses: STDs, skin infxs

Resistance: development of FQ resistance : age > 65 with Hx of COPD and previous tx with a FQ
Ciprofloxacin: Can take with Food and/ or OJ but never with only a lone glass of OJ; All FQs produce a
photosensitivity

Contraindications** (Test Question): Avoid in pregnancy, in nursing mothers, and in children <18 y/o
due to possibility of arthropathy (Cartilage Damage)

Metronidazole

Bactericidal

MOA: DNA inhibitor

PO + IV

Uses: Anaerobic infxns, STDs

Adverse Drug Rxns: Avoid Alcohol! For more than 72 hours after disc. Of metronidazole

Sulfa List

Co-trimoxazole

Celecoxib

Note whats not hepatotoxic: Ethambutol

NSAID LECTURE 1

**NSAIDs: ibuprofen, naproxen, indomethacin, ketorolac (PARENTERAL)

-anti-inflam

-aspirin prototypical, inc ibuprofen

-DOESNT include COX-2 spec or sel, nor acetaminophen

**MECHANISM - 1971

-Cascade: NSAIDs work on arachidonic prostaglandins (Support renal and platelet func, protect gut,
inflammation & pain)
-Give NSAIDs: cyclooxygenase or prostaglandin inhibitors

-ADRs: vasoconstrict kidney & inhibit platelets

**NEW PARADIGM: Outcome of inhibiting enzymes - 1991

-Just inhibit COX-1 = bad but if just inhibit COX-2 = good bc no fx COX-1

-COX-2 (inducible) induced into prod with injury or genetic autoimm inflam dis

-Outcomes = anti-pyretic, analgesic, anti-inflammatory

-COX-1 = bad, tough on stomach and GI tract, vasoconstrict kidneys, inhibits platelets

- aspirin = irrev platelet inhibition vs NSAIDs = rev (inc CV risks)

-COX-2 = no adverse fx, ONLY dec GI toxicity, no inhibition platelets (problem)

-Celecoxib = COX-2 specific inhibitor, only benefit is slight dec GI toxicity, bad bc expensive

-Meloxicam = COX-2 selective inhibitor, only benefit is slight dec GI toxicity

-Valdecoxib and refecoxib pulled off market bc inc CV thrombotic events

-Favocoxid + zinc = medical food w/COX-2 ppl are divided

-CV risk = Celecoxib and NSAIDs caused inc risk of CV thrombotic EXCEPT aspirin (bc irrev inhibition)

-GI risk = NSAIDs (Celecoxib too) inc risk of GI adverse rxns bleeding, ulcers, perfs of stom and
intestines

**NSAIDs Doses

-Ibuprofen = 200-800 mg q6 prn, max 3,200 mg, anti-inflam dose starts at 1,200 mg

-Ketorolac = parenteral NSAID, q6 max 5 days (longer = inc risk renal fx and bleeding)

-If 1 doesnt work, try another until relief; use lowest dose possible

**ADRs of NSAIDS

**1.) Fx on Platelets
1) aspirin = irrev inhibition of platelets = good bc protective, NSAIDs rev = bad, inc risk CV events
1) Aspirin 81 mg rec dose, 160 mg full pH-agg inh (platelet aggregation inhibition)
2) Prolonged bleeding time, d/c with surgery 3 days before (NSAIDs) or 1 wk (aspirin)
3) Celecoxib and meloxicam are exceptions

**2.) RENAL FX NSAIDs and COX-2 Specific and Selective

-prostaglandin related, needed to maintain vasodilation and blood flow to kidneys

-renal perfusion: NSAIDs inhibit COX in kidney, PGE2 dec, vasoconstrict acute renal failure

-peripheral edema, acute renal insuff, hyperkalemia, renal necrosis long term use

**3.) Hypersensitivity Rxns

-if aspirin allergy, then allergic to other NSAIDs and COX-2 agents. Bronchoconstirction, nasal polyps (bc
inhibition prostaglandin synthesis)

-Celecoxib = sulfa cross-sensitivity

**4.)CNS toxicity bc cross BBB = HA, dizziness, tinnitus, mostly salicylates aspirin prototype

**5. )Reye Syndrome

-unpredictable, sometimes fatal bc hepatitis and cerebral edema

-aspirin specific, only for viral inf in children

-give acetaminophen or ibuprofen instead

-DO NOT give aspirin to kids 14-20

**6.)GI = ~15% treated chronically with NSAIDs major GI event. Most common is epigastric distress,
N/V, microscopic GI bleeding ~universal, maj GI bleed, perforation. Take with food AND enteric coated

-2 drugs with food: NSAIDs and steroids

**Acetaminophen (Tylenol)
-APAP = N-acetyl-p-aminophenol, paracetamol

-lacks GI, renal, and bleeding ADRs like NSAIDs

-pain and fever, NOT an NSAID and NO anti-inflam, dunno how mech works

-FDA changing childrens dose

-APAP = 4,000 mg/day max dose

-ADRs = well tolerated if short time-frame and low-dose, hepatic inj in chronic alcohol users or pts with
pre-existing liver dis, mainy OTC and RX ccontain acetaminophen, hep metabolized to sulfate and
glucuronide conjugates

-sm amt metabolized by CYP450 into a hepatotoxic metabolite (NAPQI). NAPQI normally binds to
glutathione and if these stores are depleted (misuse or OD), then NAPQI is not detoxified so free to bind
to hepatocytes = hepatotoxicity

-Chronic alcohol use = shifting metabolism of acetaminophen, so more NAPQI.

-Antidote N-acetylcysteine (NAC)

**PLATELET INHIBITORS

1.) Aspirin = bottom of chain. Mech of action = weak platelet inhibitor, irr inhibition of platelets,

-Dose/PK = 81 mg, take with lgst meal of day (prev local irritation)

-Men 45-79 = prev AMI

-Women 55-79 bc menopause = prev ischemic stroke

-M & W > 80 yo = rec ONLY if high CV risks and no addl GI bleeding risks

-Benefit = smokers, HTN, hyperlipidemia .. Bleeding risks may not benefit

2.) Thienopyridine Derivatives =

-Ticlopidine causes blood dyscrasia (off) and leukopenia, fatal, so no longer used

-Clopidogrel (Plavix) = safer than ticlopidine so used.

MOA = irrev inhibition of ADP pathway of platelets by blocking ADP rec on platelets w/
no fx on prostaglandins.
PK/Dosing = dose-dep anti-thrombotic.
ADR = thrombocytopenia
Misc = CYP2C19 poor metabolizers dec efficacy of clopidogrel so inc chance CV or
cerebrovascular event
3.) Ticagrelor = sec prev atherothrombotic events in pts with acute cornary syndrome w/ aspiring

MOA = REV (diff than prev!) inhibit ADP receptor


DOSE = dose-dep so take with 81 mg aspirin, > 100 mg will impair MOA
ADR = dyspnea, bradycardia, bleeding
DRUG INTERACTION = substrate CYP3A4
4. ) Prasugrel

MOA = irrev inhibits ADP rec


Dose = take with 81 325 mg aspirin
ADR = bleeding
Drug Interactions = other durgs that inc bleeding risk warfarin, NSAIDs
5.) Glycoprotein IIb/IIIa inhibitors = abciximab, Eptifibatide, Tirofiban indicated in pts with acute
coronary syndrome

MOA = targets platelet IIb/IIIa rec complex (final path for platelet aggregation)
-Anti-platelet capabilities = GP IIb/IIIa inhibitors > Thienopyridine derivatives (plavix) > aspirin

-Ibuprofen 2 hrs prior to aspirin (imp one) = dec anti-platelet fx bc competitive drug interaction

-ASA 30 min before Ibuprofen or 8 hrs after

-fish oil and Vit E also inhibits platelet aggregation

6.) Miscellaneous Anti-Platelet

-Dipyridamole
-Dipyridamole + Aspirin
-MOA = WEAK anti-platelet activity

Antimycobial Agents Lecture

-Antimycobial Agents

INH = isoniazid
RIF = rifampin
Eth = ethambutol
PZA = pyrazinamide
STM = streptomycin

-CDC = lead federal gov agency for TB prev, control, and elim
-1989 = CDC goal of elim TB from US by 2010

-Latent TB immune TB = mycobacterium tuberculosis (thin rod w/ lipid-laden walls, high lipid content so
AFB [or rod] on staining)

-Exposure = us inhale suspended droplets, land in middle or lower lungs (highest air flow),
causes local infiltration neutrophils and macrophages.
-AFB mult and live in macrophages (not destroyed), move thru lymph sys and set-up in distant
sites (short-lived bc cell-med immunity, can be full blown if not intact imm sys)

-Cell-Med Immunity = exposure, immune reaction (AFB present selves to T-helper cells that multiply and
recruit macrophages to kill AFB caseous necrosis caseous granuloma), and granuloma formation
(latent but viable)

-Asymptomatic Primary Inf = addl exposure localized, delayed hypersensitivity rxn. PPD causes localized
skin swelling and redness that becomes red, raised, and hard after 1-2 days (+ test is hardness > 10 mm
after 48 hrs, + > 5 mm immunocomp. + w/o symptoms means latent TB and inf)

-Secondary or Reactivation TB aka active TB pts = bac dormant and weaken imm sys; organs seeded in
prim inf; contagious, 10% lifetime (5 % 1st 2 yrs, 5% lifetime risk), HIV 10%/yr

***1st Line

1.) Isoniazid ADRs

-neurotoxicity = peripheral neuropathy (numb, tingling), prev by Pyridoxine (B6) esp high risk pts

-hepatotoxicity =

overt hepatitis (1% pts isoniazid, 4% pts rifampin and isoniazid (synergistic), us 1 st 1-2
mos therapy, risk inc with concomitant alcohol and age > 35 yo
inc serum transaminases
if symptomatic, then dealbreaker!
2.) Rifamycins ADRs. Rifampin latent, most active against AFB. Also rifabutin, rifapentine

-ADR:

-discoloration of body fluids red/or (think R and R)


-flushing rxn cosmetic, uncomfortable, up to 5%, 2-3 hrs after ingestion
-hepatotoxicity
-Drug Interactions = rifamin induce cytochrome P450, worst, followed by rifapentine then rifabutin
3.) Pyrazinamide (PZA) ADRs

-arthralgia (40% nongouty and polyarthralgias, gouty arthritis rare)

-flushing rxn

-hepatotoxicity

4.) Ethambutol ADRs (think E and E)

-optic neuritis uncommon with low doses and intermittent

-arthralgia (think exception to hepatotoxicity)

5.) Streptomycin most beneficial in TB. ADR = nephrotoxicity, ototoxicity

*Mgt Hepatotoxicity

-asymptomatic pts with inc LFTs from baseline > 3-5x hold INH until returns. < is normal

-symptomatic = hold drugs and get LFTs

*Treatment Latent TB: give INH for 6 (competent imm sys) or 9 mos (immunocompromised)

-DOT (direct observed therapy) for 2x/wk dosing

*TB Phases

-Induction:: Daily INH, RIF, PZA and EMB; 4 drugs for 2 mos

-Continuation:: Daily INH and RIF or 2x/wk INH and RIF; 2 drugs for 4 mos

-total 6 mos of therapy

-bc get AFB results in 2 mos

NSAID LECTURE 2
*Anti-coagulants

1.) Warfarin = initially as rodenticides, Coumadin in 1950

-MOA: inhibits Vitamin K dep coag factors (2, 7, 9, 10, protein C and S incomplete coag factors not
biologically active)

-Pregnancy category D, give heparin instead

-Dosing = 100% PO bioavailable, highly p bound, t1/2 = +/- 40 hrs

-many small doses/strengths, typical dose 5 mg and adjust according to INR for efficacy (PT)

-INR (no units) 2.5-3.5 aim for 3.0 for wiggle room

-us maintenance dose 2-10 mg daily @ same time every day on empty stomach routine is imp

-efficacy = delay warfarin action bc anticoagulant fx balance btwn partially inhibited synthesis and
unaltered degradation of 4 vit K-dep clotting factors

-dosing considerations: watch drug interactions! Look up constantly

-maintain consistent vitK in diet, avoid sporadic ingestion of foods high in vitamin K (beef and pork liver,
green tea, green leafy vegs)

-ADRs: bleeding (skin necrosis/gangrened bc paradoxical thrombosis 1 st few days of therapy, us localized
to limbs, breast, penis. Inc risk if protein C or S def)

-Warnings/Precautions:

dont switch brands after therapeutic res


use with vit K may dec anticoag fx (also used as antidote and/or FFP)
use w/NSAIDs and aspirin
if surgery, then stop warfarin 3 days before and check INR (goal 2.5-3.5)

*Misc PO Anti-Coag

1.) Dabigastran new, 1st PO anticoag approved in US in 50 yrs

-MOA = dir thrombin inhibitor (factor IIa)

-Indications = red risk of stroke and sys embolism in pts w/ a-fib, doesnt req INR monitoring

-ADR = bleeding, GI bleeding, dyspepsia (tartaric acid helps with absorption which causes dyspepsia.
Food or acid-control meds will help heartburn)

-compliance is key! if dose missed, effectiveness wanes w/in 15 mins


-many guidelines available for switching drugs

PHARM GUIDE LAST QUIZ

***NSAID 2 Lecture***

**Rivaroxaban = PO
-MOA = factor 10a inhibitor
-indications = in place of warfarin or LMWH to prev venous thrombosis after hip or knee replacement
surgery
-ADR = bleeding
-no coagulation monitoring req, fast onset of action
-Drug interactions = CYP3A4 substrate
-Misc = avoid in impaired renal function

**Apixaban = out in 2012, factor 10a inhibitor too. More effective and less bleeding than warfarin?!

**Heparin = heterogenous mixture of mucopolysaccharides, very very huge


-traditional heparin therapy = UFH (beef and pork sources)
-drug but also a category; subcategory = LWMH
-prego cat C
-MOA = inhibits thrombin and 10a
-Dosing/PK = SC and IV (loading dose)
-heparin is parenteral only. Warfarin is PO
-t = 1-5 hrs (quick so overshooting not a big deal), aPTT monitoring (unfrac only)
-non-linear PK (little change is big difference in blood level)
-ADR = bleeding, allergic rxns, alopecia, osteoporosis w/ long-term therapy
-HIT = platelets not low but sticking together so N/A, hypercoagulable state in 1-4%, happens bc animal
origin
-rapid and consistent drop in pt is a red flag for HIT
-monitoring = platelets and aPTT
-info baseline, note specific and easy to follow protocols available

**LMWH = enoxaparin/Lovenox (1st out, most common, can get generically now), dalteparin, ardeparin,
tinzaparin
-can substitute for UFH, biggest issue is cost, dont haveta use aPTT
-MOA = inhibit 10a, insufficient length to inhibit thrombin
-Dosing/PK = SC only, daily (benefit)
-t 1/2 = longer than UFH
-predictable responses,
-ADR (sim UFH) = bleeding, thrombocytopenia (note not HIT not animal origin), hypersensitivity,
osteoporosis

**Misc Parenteral Anticoagulants = Fondaparinux

**Direct Thrombin Inhibitors = Desirudin, argatroban, bivalirudin, lepirudin


**Thrombolytic Agents = streptokinase, urokinase, anistreplase, tissue plasminogen activators,
reteplase, tenecteplase
-MOA = lyse clots, use in ischemic strokes
-Dosing/PK = time sensitive, > 3 hrs = contraindication
-Contraindications = worry pt will bleed out, specific protocols at all institutions
-only use thrombolytic in life/death

***URTI, LRTI Lecture***

**Therapeutic Mgmt mech = cough suppression is in part of brainstem that mediates cough reflex
1.) Codeine = opioid analgesic
-dose = prn
-schedule V (higher is less addictive)
-side fx = GI upset, CNS depression, drying fx on mucus
2.) Hydrocodone = opioid analgesic
-dose = prn
-schedule III
-side fx = CNS depression, GI upset (N/V, constipation). Stomach c/o most common, vomiting center
triggered. Pain meds shut down the gut.
-note side fx all different but not rly different
3.) dextromethorphan = d-isomer of opiod agonist levomethorphan, no pain control
-for sleep
-OTC, Rx
-robotripping abuse = 300-1800 mg lg dose, lasts 3-6 hrs, LSD-like fx
4.) Benzonatate
-work locally at lungs not centrally
-some ppl use this in pts allergic to opioids or abuse Hx
-take around the clock NOT prn
5.) local anesthetics = anesthetize stretch receptors in airways and pleura. Includes camphor and
menthol. Be careful in kids (def not in infants)

**Expectorants = red viscosity of tenacious secretions by inc res tract fluid (loosens/thins sputum and
bronchial secretions)
1.) guaifensin
-water is best
-many combo prods w/ cough suppressants, esp Robitussin counter intuitive
-immediate rel Robitussin, best are sustained release (only Mucinex imp in sinusitis, rest off market
now)

**Decongestants = sympathomimetics act on adrenergic receptors in the nasal mucosa, producing


vasoconstriction
A.) Topical (-zoline ending)
-intranasal = naphazoline, phenylephrine, oxymetazoline (Afrin - US most common), xylometazoline
-ophthalmic = naphazoline, oxymetazoline .. Same chemicals. <3 days. Overused > 3 days then rebound
congestion, can be worse off than started (rhinitis medicamentosa)

B.) Systemic
-phenylpropanolamine (PPA) and ephedrine off-market now
-pseudoephedrine (Sudafed) = OTC 30 mg, Rx 120 mg. Allegra D. BTC, more superior
-phenylephrine (Sudafed PE)
-Side FX::
Sympathetic
Topical = local irritation, prolonged vasoconstriction, rebound congestion
Systemic = CV (inc BP and HR, palpitations), CNS (nervousness, irritability, restlessness, insomnia)
-2 yo cutoff
-co-morbid dis states contraindications: glaucoma (specific type), thyroid dis, cardiac dis (HTN
controlled HTN is ok tho, angina, post-MI)

C.) Analgesics/antipyretics = aspirin, acetaminophen, ibuprofen, naproxen

**URTI
A.) Pharyngitis
-Viral (lgst portion) 85% in kids, 90% adults. Bacteria (GABHS) 15% kids, 10% adults
-Clinical presentation::
fever, H/A, chills, sore throat, cough, PND = mult symptoms in multiple places and diverse so
usually means viral inf
fiery red mem, tonsillar exudate; edematous uvula, tender and enlgd l nodes; scarlitiniform rash
(sandpaper feeling) = usually means bac inf
-Treatment
lim ab for ppl likely w/ GABHS
clinically screen all adults for 4 criteria: Hx fever, tonsillar exudates, no cough, and tender
anterior cervical lymphadenopathy (lymphadenitis)
dont test and dont treat pts w/ none or bc GABHS is unlikely
RAT (rapid ag test) valuable, 95% accuracy
DOC = penicillin, amoxicillin (BID, traditional 30-40 mg/kg or high dose 80-90 mg/kg for decent
strep pneumo coverage). Dont use NVK bc QID is annoying and compliance issues
use macrolide if PCN allergy for 10 days to treat symptoms

B.) Sinusitis can be nebulous


-Haemophilus influenza, Streptococcus pneumonia
-Clinical presentation::
Rhinorrhea, persistent daytime cough > 10-14 days bacterial
Severe symptoms = fever > 39C/102.1F w/ purulent nasal discharge, facial pain or tenderness w/
periorbital swelling
-Treatment::
Acute bac rhinosinusitis resolves w/o ab treatment usually
Symptomatic treatment and reassurance is pref intial mgmt strategy for mild symptoms
Ab reserved for ppl with all 4 criteria
Use most narrow-spectrum agent for initial treatment
-DOC = high dose amoxicillin, amoxicillin/calvulanate (bad bc B-lactamase resistance)
-PCN allergic = use azithromycin (length of time downside), clarithromycin, FQ. See improvement in 2-3
days, cont treatment for 7 days after symptoms improve (us 10-14 days)
-Drug interactions:: ETOH/CNS depressants esp w/ 1 st gen

**LRTI
A.) Acute Otitis Media (AOM)
-most common inf in kids for ab
-controversy: treat (US) or not (Euro)
Does the pt have effusion? Look for bulging and swollen eardrum
Signs or symptoms of AOM? Ear pain, fever, and bulging yellow or red TM
NO:: OME (otitis media w/ effusion) = effusion w/o signs/symptoms acute inf. Nonspecific signs
and symp (rhinitis, cough, diarrhea nonspecific so viral) us present.
YES:: AOM = Hx acute onset of signs and symptoms w/ middle ear effusion and signs/symp of
middle-ear inflame. Go to Tx table. <6 mos all get ab therapy; 6 mo 2 yrs (certain dx then ab tx,
if uncertain dx then ab if severe or observation 2- 3 days if nonsevere); >2 yo (certain dx then ab
if severe or observe in nonsevere, uncertain than observe)
mgt should include assessment of pain. If present, recommend ibuprofen or acetaminophen (< 6
mos use only this). Can give steroids and/or numbing eardrops ok but fewer is better so consider
-See drug chart in PPT slide

B.) CAP
-common inf dis, acquire thru inhalation or aspiration
-IDSA = inf dis society of america, give guidelines
-etiology (5) = strep pneumo, H flu; DIFF is location (not all ab can get in high enough conc in lungs).
Atypical mycoplasma* pneumoniae, chlamydophila pneumoniae. Also res viruses
-minor and major criteria, observe for a few days
-outpt tx = prev healthy and no use of antimicrobials within prev 3 mos beware of resistance. Macrolide
(azithro, clarithro), doxycycline (choose if smoker)
-usually from atypical orgs, strep pneumo us sicker
-otherwise, if presence of comorbidities like chronic heart, lung, liver, or renal dis, DM, alcoholism,
malignancies, asplenia, immunosuppresing cond/drugs, or use of antimicrobials last 3 mos = at risk for
drug-res strep pneumo (DRSP).
use respiratory FQ (moxiflox, gemi, levo)
b-lactam + macrolide (high dose amoxicillin; amox/clav preferred, alts ceftriaxone, fepodoxime,
cefuroxime)
-duration of therapy = tx min 5 days (from zpac), should be afebrile 2-3 days and no more than 1 CAP-
assoc sign of clinical instability before discont therapy, longer therapy if initial therapy unactive. 10 days
is typical duration (same w/ sinusitis and AOM)

C.) HAP aka Nosocomial = 48+ hrs after adm. (How to distinguish btwn CAP and HAP)
-early onset = w/in 4 days
-late onset = 5th day or after
-Etiologies: very broad g (-), g (+), atypical Pseudomonas aeruginosa, Klebsiells, E. coli, Acinetobacter,
MRSA, S. pneumo, H. flu

-Tx duration = 14 days

ALLERGIES LECTURE

**Antihistamines
-reacts w/ H1-3
-H1 receptors = inc bv dilation, contraction bronchi and intestines, inc itch and pain perception, dec
autonomic muscarinic and vestibular activity
-H2 receptors = inc secretion gastric HCl and pepsin
-H3 receptors = inhibit rel histamine
-excessive exposure to H1= Type 1 Hypersensitivity (Allergy)
triple histamine response = simultaneous redness (vessel dilation) + flare (vessel dilation due to
nerve stim) + wheal (inc vessel perm/edema)
drugs bind to H1 receptors in Type 1 Hypersensitivity
-pathogens have high affinity for IgE receptors
-drugs target H1-H3, IgE receptors, mast cells and basophils
-H1 receptor agonists = 1st gen penetrates CNS, 2nd does not

**1st gen:: (-amine, -zine)


-diphenhydramine (Benadryl), dimenhydramine (motion sickness too), brompheniramine,
chlorpheniramine, doxylamine, meclizine (#1 for motion sickness), cyclizine, promethazine, hydroxyzine
-drowsiness bc cross CNS why can treat anaphylactic rxns and has many ADRs
-inhibit histamine from binding in sm mus of sm veins, bronchi, and intestines
-Blocking at muscarinic/cholinergic/parasympathetic
-used in Type 1 hypersensitivity rxns (rhinitis, urticaria, conjunctivitis, and anaphylaxis), prophylaxis for
motion sickness and vestibular disease (Menieres Disease)
-Bromopheniramine and Chlorpheniramine = least sedating, Children 2-5 yrs (lowest age 2 bc higher
likelihood of morbidity and mortality)
-Clemastine mod sedation
-Diphenhydramine most sedating

**2nd Gen
-systemic:: cetririzine (Zyrtec) most sedating can penetrate CNS a lil and cause drowsiness and struc
related to Hydroxyzine, levocetirizine, desloratadine (Clarinex), Loratidine (Claritin), Fexofenadine
(allegra)
-Nasal Sprays:: Azelastine just as well as Zyrtec
-Opthalmic antihistamines:: Azelastine, emedastine. Most expensive in pharmacies
-Opthalmic Antihistamines/Decongestant combos:: Antazoline + Naphazoline, Pheniramine +
Naphazoline
-Prevent histamine from binding in smooth muscle of: small veins, bronchi, and intestines, Inhibit IgE-
induced mediator release from mast cells and basophils
-Used in Type 1 hypersensitivity rxns (rhinitis, urticaria, conjunctivitis, NOT anaphylaxis)
-Side Fx: anticholinergic (1st gen only dry eyes/mouth/nose, blurred vision, urinary retention, mental
status change in older pts) and CNS (mostly 1 st gen sedation, impaired motor/mental performance)

DERM LECTURE

-Consider::
Duration
freq (some topical agents use skin as reservoir, need only 1x/day despite short t1/2)
sparingly vs liberally sparingly most of the time. More is not better!
Absorption
o occlusive dressing not breathable/permeable, dangerous bc inc absorption by 5070
fold. can be put over a numbing cream. Ex: disposable diapers (diaper rash)
o Humidity higher then more absorbed
o Temperature higher then more absorbed
o Thickness of skin thicker then less. Ex: More easily at head than palms
-At a glance::
topical most freq prescribed
Effective to reduce inflam sx, doesnt address underlying cause of dis
Topical glucocortoid research aim to optimize potency while min side fx; class # differs (1 is
worst)
New molecules w/ higher anti-inflam, good compliance (1x/day ok), rare cross-sensitivity rxns,
less skin-atrophy (more w/ injected)

**Topical corticosteroids
-indications = Dermatitis, eczema, psoriasis, diaper rash, etc.
-MOA = Vasoconstriction and dec inflammation - local
-Guidelines:
Potency low-medium on thin skin vs med-high on thick skin
Vehicle lotions < cream < ointment < gels; Ex: B-methazone
-ADR = 3 mos high risk for ADRs.
Hypopigmentation bleached skin
Typically no real HPA-axis suppression - aka no real steroid crisis if used appropriately
High potency for prolonged time inc systemic ADRs esp in PEDs
Acne
Atrophy
Tachyphylaxis tolerance to vasoconstriction of topical steroids
Telangiectasia
Delayed wound healing used as immunosuppressants

**Classes::
1) Class 1 super potent
Strongest anti-inflam fx
Alternative to systemic steroids
For short duration and small surfaces
Avoid occlusive dressings
Uses thick chronic lesions
Optimized vehicle aka augmented inc solubility and absorption w/ fewer side fx. ONLY CLASS 1
Inc risk side fx skin atrophy
2) Class 2 potent
Strong
Intermediate duration, or longer periods w/ thickened skin sec to chronic cond
Ok on face and intertriginous areas for short duration
3) Classes 3 (potent, upper mid-strength), 4 (mid), 5 (lower-mid)
Moderate
Face and intertriginous for lim duration
Uses chronic eczematous dermatoses
4) Class 6 (mild) and 7 (least)
Lowest
Safest long term
Safe on face, intertiginous, w/ occlusion on infants and children

**Potency of Selected Topical Gluocorticoids


-1::
Betamethasone dipropionate cream and ointment (both diff, optimized vehicle for better
efficacy)
Clobetasol propionate cream and ointment (Class 1 only)
Diflorasone diacetate - Formulated slighly diff in diff classes
Halobetasol propionate
-2:: lost optimized vehicle
-3:: lost ointment and optimized vehicle
-5:: lotion
-7:: Hydrocortisone O.5 and 1% OTC, higher (2.5%) is prescription only

**Definitions
SSTI skin and soft tissue inf; inf inv any or all layers of skin, SC fat, fascia, and muscle
Cellulitis inflam skin and SC fat, acute
Diabetic foot ulcer open wound on foot of DM pt, may not necessarily be infectious
Osteomyelitis may result from SSTI, inflam of bone marrow and surr bone
Why tx? Bc if untreated septic arthritis, osteomyelitis, or bacteremia
**Most likely orgs:
1.) Non-DB = typically 1 organism
G (+) aerobes = S. Aureus resistant? (MSSA, MRSA, 90% of skin inf and 10-15% of these are
MRSA) and Strep pyogenes
G (-) aerobes = E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae;
-Most skin inf :: non-resistant g (+) organism
2.) DB = may be polymicrobial
G (+) aerobes = S. aureus (MSSA, MRSA), Strep pyogenes, S. epidermis, Enterococcus faecalis
G (-) aerobes = E. coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus spp
Anaerobes
-Best tx complicated cellulitis? Find something w/ g (+), g (-), and anaerobes

**Cellulitis - Correct tx can fix in 1 dose


lesions typ hot, painful, eythematous w/ poor margins, may or may not see entry pt
Us sec to trauma/lesion
Mild no evidence of systemic inf (no fever, no toxic) can respond to local tx (cleaning and
irrigation w/ soap and water)

**Tx:: Empiric therapy in healthy, non-DB pt is typically mono-microbial and strep before staph (unless
abscess or penetrating trauma MRSA worry)
10 days
Use anti staph PCN (PO dicloxacillin in mild ambulatory and IV nafcillin in mod-severe
hospitalized) in healthy pts
o good vs MSSA and strep, well tolerated
Cephalosporin (1st gen PO Cephalexin, IV Cephazolin)
o more broad than what you need
o Some give 1 parental dose of ceph (more $$) then switch to PO
Macrolides, Quinolones
PCN allergic:: use erythromycin and clindamycin (also good in CA-MRSA)

**Resistant Staph Infections


-CA-MRSA (10-15% endemic res), often causes SSTI (>90%) from close contact
-AB Tx?
Bactrim (TMP-SMX)
Doxycycline
Clindamycin (some abcess penetrating ability)
Rifampin NEVER by itself bc can develop resistance
-AB Tx in Serious CA-MRSA in Hospitalized AND Tx HA-MRSA except Clindamycin?
Vancomycin and telavancin
Linezolid
Daptomycin
clindamycin
-Definitive therapy in healthy, non-DB
Strep spp: switch to PCN VK or G
Staph spp: MSSA leave on diclox, MRSA swith to vanco or linezolid
-Empiric Therapy in DB
Typically polymicrobial: g (+), g (-), anaerobes. Tx for 3-4 days after ALL signs of inf are gone
Mild same as non-DB. If anaerobes add clindamycin or metronidazole
mod-severe expand ab coverage. also culture, drainage, and surgical debridement. Ex:
clindamycin IV (G+ and anaerobes) + ciprofloxacin IV (g- aerobes, some g- anaerobes, some g+
aerobes), clindamycin + 3rd gen Ceph (g+ and g-), Beta-lactam/Beta-lactamase inhibitor combo
(extend g+ and g- to include B-lactamase prod organisms), Carbapenem (very broad), Cefoxitin
(treats g+, g-, and anaerobes)
-Definitive therapy in Diabetics
Based on C & S results

***HLD***

PHARM GUIDE 2

***HYPERLIPIDEMIA*** Study the Chart

**CHD and CHD Risk Equivalents


(+) risk factors = >45 M, >55 F, FHx early CHD, smokers, HTN, Low HDL
(-) risk factor = high HDL

**LDL Goals and Tx Chart


CHD or CHD Risk Equivalents: LDL goal < 100 mg/dL (goal <70)
2+ Risk Factors (10-20% risk): <130 (optional goal <100)
2+ (<10%): <130
<2 (<10%): <160

**Bile Acid Sequestrants (chole-) = cholestyramine (granules), colestipol (granules and tablets),
colesevelam (tablets)
MOA = sequester bile acids, target LDLs specifically, NOT systemically absorbed (so GI Fx)
Side Fx: GI (flatulence, constipation, bloating, fullness, nausea), inc TGs
Drug Interactions: binds to many drugs and vitamins (think snowball fx), watch fat-sol vit
absorption (ADEK)
Efficacy: Max fx 6-8 wks. Dec LDL, inc HDL, inc or no change TG

**HMG-CoA Reductase Inhibitors (-statins) = atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin,


rosuvastatin, pitavastatin
MOA: HMG-CoA reductase is enz responsible for conversion of HMG-CoA to mevalonate, the
early rate-lim step in cholesterol synthesis. Fx all 3 lipid components
Potencies: Rosuva > atorva = pitava > simva = prava > lova > fluva
Dosing: Daily HS (chol made at night)
Rule of 6 = Most sig red in LDL at usual starting doses; each 2x daily dose is addl 6% red in LDL
Pts no longer up to 80 mg of Simvastatin bc higher incidence of mus breakdown
Side Fx:
o DM inc blood sugar and HgA1C
o Dose-related (only statins)
o Inc LFTs
o Myopathy (gen for mus complaints)/myalgia (#1 common, mus complaints w/o inc
CK)/myositis (mus complains with inc CK)/rhabdomyolysis (> 10x inc CK, inc Cr, br urine,
and urinary myoglobin)
o Memory Loss

**Deal with Muscle Aches


Drugs Implicated: Niacin, Statins
MOA: ??? Ubiquinone deficiency
RF: adv age, F, renal insuff, liver dysfunction, sm body frame and frailty, mult meds
Rare, so routine CK monitoring NOT rec
Iffy = Consider switching to a different statin: fluva, rosuva, prava, pitava (less lipophilic and no
CYP450 3A4 interference)
Co Q10: not routine rec
Prevention: use lowest poss dose, lower doses est CLcr < 30 ml/min, watch drug interactions
Drug Interaction: Grapefruit juice except the 4 exceptions
Efficacy: 6-8 wks, check LFTs. Dec LDL, inc HDL, dec TG (go-to class!)
DO NOT use in pregos or acute/chronic liver dis, watch drug interactions

**Niacin = nicotinic acid, Vit B3, extended rel Niaspan


MOA: red VLDL in liver so dec LDL, dec TG, inc HDL, prim biotransformation in liver
Dosing/PK: sustained rel
Side Fx: cutaneous flushing (take ASA or ibuprofen 30 min before to avoid), inc uric acid, inc
blood sugar, liver dysfunction, muscle complaints
Drug Interactions: watch hepatotoxic agents, ETOH, agents that induce gout
Avoid in gout, DM, PUD, chronic liver dis
**Fibric Acid Derivative (-fib) = gemfibrozil, fenofibrate, fenofibric acid
Dosing/PK: gemfibrozil BID, fenofibrate daily
Monitoring Side Fx: gallstones and cholecystitis, myositis and myopathy (us with niacin or statin)
Drug Interactions: With statins have inc hepatotoxicity and inc rhabdomyolysis list
Efficacy: dec LDL, inc HDL, dec TG (worry about TG first! < 500 goal bc it thickens blood)

**Cholesterol Absorption Inhibitors


MOA: in sm intestine
Monitoring Side Fx: GI and musculoskeletal
No drug interactions
Efficacy: dec LDL, dec TG, sm inc HDL

**Combo therapy: monitor closely bc inc risk similar side fx. Vytorin (simvstatin + ezetimibe) recent
controversy

**Red Yeast Rice: MOA same as statins

**Omega-3 FA = eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)


2 types: Fish-based (better) and nut-based
Lovaza Rx has both
Bad for prostate CA and pts on anticoag
Must d/c before Sx bc it has anticoag fx
Purity issues = mercury in fish, can have contaminants like PCBs (to deodorize). Look for USP
certified brands
ADR = fishy aftertaste/burping up, doses>3g/day can inc bleeding risk, GI complaints

LDL LIST
Bile Acid Sequestrants

ALL 3 LIST
Statins
Niacin

NOT FOR PREGOS


ACEI/ARBs
Statins
Warfarin

INC URIC ACID/GOUT


Thiazides
Niacin

***CHF AND ANGINA***


**Pharmacologic intervention: reduces load on myocardium; decreases ECF volume; improves cardiac
contractility; slows rate of cardiac remodeling

**Digoxin use last or close to last, dont use 1st anymore bc tells failing heart to work harder
Good for severe L vent systolic dysfunction after ACEI and diuretic given
Cant replace bc they decompensate
MOA: inhibits Na and K transport by binding to Na+K+-ATPase aka (+) inotropic fx
o Inc tissue perfusion, dec edema and symp tone. (-) chronotropic fx
Maintain brand
Eubacterium lentum = can fx how much pt needs
Wide variable absorption btwn pts
Excreted w/ clearance ~GFR
ADR = narrow TI, CV (arrhythmia atrial or vent; AV block), CNS (vision changes, fatigue, stupor),
GI (N/V, anorexia) note all anti-arrhythmic can create or fix (pro-arrhythmics)
o Blurred or yellow vision, halos can be 1st Sx
Drug Interactions: drugs causing hypokalemia like diuretics can predispose to dig toxicity. Also
quinidine, verapamil, amiodarone (inc dig levels)

**ACE/ARBS = -pril/-artan
in chronic CHF or pts w/ L ventricular dysfunction and no edema (pts lowest EF with greatest
benefit)
MOA: dec preload and afterload to slow vent dilation
ARBs if intolerant to ACEI (us cough)

**Diuretics = relieve pulmonary congestion and peripheral edema


Prn in mild HF, scheduled in more severe
Thiazide = mild HF
Loops = more severe edema Watch K levels! Esp if on digoxin too
Aldosterone = HF high aldosterone bc AG 2 stim and dec liver clearance of aldosterone
Spironolactone (aldosterone antagonist)= dec morbidity and mortality in mod-sev HF
o ADRs = gynecomastia, dec libido, impotence
Eplerenone = new drug aldosterone antagonist, use to avoid hormonal ADRs

**Beta-Blockers (-lol) = metoprolol and carveldilol


Random salts in HF (metoproplol (XL) sussinate used, other one is too short-acting we want
long-acting)
Red in ppl with stable severe CHF
MOA: dec high catecholamines, dec HR, renin, and remodeling

***Misc Agents***

**Bipyridine Derivatives: Inamrinone and Milrinone (-rinone)


IV
Added to digoxin therapy when CHF persists despite digoxin
MOA: phosphodiesterase inhibitors inc SV, contractility, EF, and sinus rate. Dec vascular res
ADR: GI, hepatotoxicity, fever, thrombocytopenia, H/A, long-term use causes inc mortality
**Dobutamine
Inc CO in CHF
B1-rec adrenergic agonist that inc contractibility w/o inc HR or BP; min fx bv
Very short t1/2

**Direct Vasodilators: Hydralazine + Isosorbide dinitrate


Nitrate = Dilate venous bv dec cardiac preload
Hydralazine = Arteriolar dilators so dec systemic res and afterload
Use in CHF pts intolerant to ACEIs or BB, combo used

**Tx of Chronic HF Chart


1) Stage A = High risk w/ no sx aka asymp HF. Tx w/ risk-factor red and pt edu
2) Tx HTN, DB, dyslipidemia, ACEI or ARBs in some pts
3) Stage B = Structural heart dis no sx. Tx w/ ACEI or ARBS
4) Stage C = Structural heart dis, prev or current sx. Tx w/ ACEI and BB in all pts
5) Dietary Na restriction, diuretics, and digoxin
BB ONLY in stable HF

***ANGINA***

**Nitrates
Commonly used anti-anginal agent, can treat all forms angina
Can use immed before exercise or stress to prevent ischemia
Improves exercise tolerance and t to onset in exertional angina
Dilates lg myocardial arteries = inc blood to heart. Pooling blood in veins reduced preload (VR)
Basically, inc blood supply to heart mus = dec O2 consumption bc dec workload
Red angina sx but no data that they dec mortality or AMI rate
PK/PD = all effective but differ in onset of action and elim rate
o SL peak 1-2 mins; duration 30-60 mins
o IV onset 2 mins; duration 3-5 mins
o Transdermal peak 30-60 mins; duration 1 day
o Topical paste onset 1 hour; duration 2-12 hours
o SL, transdermal, and Isosorbide dinitrate are exceptions that avoid liver
biotransformation
Tolerance = dev rapidly and occurs w/ cont exposure bc bv desensitized to vasodilation
o Daily nitrate free period to restore sensitivity ~1/2day

ADRS:
o Hypotension
o Facial flushing
o Rebound tachycardia
o Cerebral ischemia aka H/A most common
o Contact dermatitis with transdermal preps
o Peripheral edema aggravated
Drug Interactions:
o ETOH, antihypertensives, vasodilators (ex viagra) = inc risk orthostatic hypotension
o Pts w/ angina sx despite nitrate therapy may need an addl agent
***Misc drugs for Angina***

**Cardioselective Beta-Blockers = atenolol, metoprolol


o Dec HR and BP to red ischemia
o Dec Mis by 10-20%
o More popular than CCBs bc better long-term outcomes
o Side Fx: depression, dizziness, bradycarida, impaired exercise tolerance, insomnia, ED

**CCBs
Dihydropyrine = amlodipine, isradipine, nicardipine (hazardous)
o Amlodipine better for vasospastic angina
Non-dihydropridine
o Verapamil and Diltiazem

**Ranolazine (new can gen energy, ~ 1 less angina attack/wk) = metabolic inhibitor is ADR

**Aspirin = 81 mg

***Anti-Arrhythymics***

** Types
Type I = Na channel blockers, subtypes based on fx and AP (Ia, Ib, Ic)
Type II = B-Blockers = sympatholytics that red B-adrenergic heart activity
Type III = block outward flow of K+ and prolong AP
Type IV = CCBs

**CAST 1991 = Cardiac Arrhythmia Suppression Trial = many anti-arrhythmic agents have inc mortality,
risk must not outweigh benefit! Also amiodarone and B-Blockers are safer and more beneficial

**Quinidine = Type Ia
MOA: Na channel blocker
ADRs = cardiac (excessive QT prolongation and torsade de pointes, syncope, and anticholinergic)
and extracardiac (GI 50%, CNS at toxic levels, idiosyncratic rxns)
**Procainamide = Type Ia
MOA: NA channel blocker
PK: hepatically metabolized w/ active metabolites (NAPA elim via kidneys, watch renal failure)
ADRs: cardiac (hypotension, arrhythmia) and extracardiac (Lupus-like arthralgias and arthritis,
maybe pleuritis, pericarditis, pul dis, GI, agranulocytosis)

**B-Blockers = Type II = acebutolol, esmolol, propranolol, sotalol


MOA: block cardiac beta-receptors

**Amiodarone = Type III MAJOR AGENT USED


MOA: K channel blocker = prolong AP, also blocks Na, weak adrenergic and Ca blocking, effective
in atrial and ventricular aryrhthmias
PK: poor GI absorption, IV exists too
T1/2 = 56-83 days
Age issues
ADRs: cardiac (bradycardia, heart block) and extracardiac (maj lim, must monitor LFTs, PFTs, TFTs,
ocular exam bc accumulate in lung, liver, skin, and tears)
o Pul toxicity
o Abnormal LFTs and hepatitis
o Corneal microdeposits
o Optic neuritis
o Blocks conversion T4 to T3
Dronedarone = similar struc to amiodarone
Bretylium, Dofetilide, Ibutilide

**Type 4 = CCBs
Verapamil, diltiazem
PHARM GUIDE QUIZ 1

***PARASYP AND SYMP NERVOUS SYSTEM***


-ANS divided to cholinergic (parasymp acetylcholine released) and noradrenergic (sympathetic
norepi/epi released; fight or flight or fright)
-mimetic = mimic
-lytic = cut/stop
-agonist = stimulate nervous sys
-antagonist = inhibit nervous sys
-ANS regulates cardiac mus, smooth mus, and glands. Div to symp and parasymp
-Anticholinesterase is an enzyme and an agonist (parasympathomimetic cholinergic, promotes
acetylcholine to hang around)
-symp is E division (exercise, excite, emergency, embarassment) and parasymp is D division (digestion,
defecate, diuresis)

**CHART**
-red sympathomimetic (adrenergic); blue parasympathomimetic (cholinergic)
-Eye = dilation (mydriasis) of pupil; constriction (miosis)
-Trachea and Bronchioles = dilation (asthmatics); constriction and secretions
-Kidney = symp only. Secrete renin (B1 [mostly heart] inc, A1 dec)
-Ureters and Bladder = relax detrusor and contract trigone and sphincter (shutdown urinary sys);
contract detrusor and relax trigone and sphincter
-Male Genitalia = ejaculation. Beta-blockers are sympatholytic and cause ED; erection
-Lacrimal glands = parasymp only. Tears
-Salivary glands = thick viscous secretion; copious watery secretion
-Gut = shut down so no pee or poop; diarrhea
-sweat glands exception to parasymp, have combo innervation
-Heart = inc rate/CO/contract; dec these
-Blood vessels = sympathetic dilate skeletal muscle and constrict skin/mucous mem/splanchics

-Epinephrine is TOC for anaphylatic shock bc its the only drug that addresses the most serious
manifestations. B1 inc CO, B2 relaxes constricted bronchioles, A1 constricts capillaries
-catecholamines and noncatecholamines
-HTN = propanolol, metoprolol, and other B-Blockers reduce CO and renin secretion
-Glaucoma = high intraocular pressure, timolol and other B-blockers reduce secretion of aqueous humor
-Migraines = propanolol provides prophylactic effect
-Thyrotoxicosis = propanolol reduces cardiac rate and potential for arrhythmias

-parasympathetic (DUMBELS and SLUDGE)


-anticholinergic side fx = dry eyes and mouth, urinary retention, constipation, blurred vision sometimes,
change in mental status sometimes esp elderly aka cant see, pee, shit, spit

***HYPERTENSION*** KNOW CHART

-Target End Organ Damage/Clinical CVD = heart dis (LVH, angina, prior MIs, heart failure), stroke or TIA,
nephropathy, PAD/PVD, retinopathy
Loc: brain (stroke, TIA), eye (blind), heart (angina, heart attack or failure), kidney (failure), legs
(PAD)
HTN is a silent killer
-DASH (dietary approaches to stop hypertension) eating plan healthy lifestyle mod

**JNC VII
Always see if pts can use Thiazide-type diuretics. DB compelling indication that can lead to a diff
drug path aka compelling indications or comorbidities
Most patients with hypertension will require two or more antihypertensive medications to
achieve goal blood pressure (<140/90 mmHg, or <130/80 mmHg for patients with diabetes or
chronic kidney disease).
Thiazides are TOC, should be considered in all pts. Can start w/ this alone but if has compelling
indications and/or needa lower BP >20/10 lower then need 1+ drug
130/80 is new target, 125/75 for DB or kidney dis

***Diuretics
MOA = renal excretion of excess Na and H2O by inhibition of Na and Cl re-absorption in distal tubules.
Vol depletion dec CO

**Thiazides = Hydrochlorothiazide (HCTZ), indapamide (lozol), metolazone


Dec Na and H2O retention Dec blood vol (bc pee out) Dec CO (bc less vol) and peripheral
res (slowly dec size)
Major site of action is DCT to inhibit NaCl absorption. Dec Ca excretion (preserve, Only 1 that
does this, aka baby Fosamax, Tx osteoporosis and nephrolithiasis)
Magnitude of diuresis is lim bc only < 15% glomerular filtrate reaches DCT
Inc Mg2+ excretion (hypomagnesemia), dec urate excretion (hyperuricemia and exacerbates
gout)
Thiazides ineff if GFR <30 mL/min (impaired renal func - use loop)
Sulfonamide derivatives
Lim ability to sig lower BP alone, 1-3 wks to see stable BP reduction
Typical dose = 12.5 25 mg 1x/day
Aka ceiling diuretic
Dec urinary excretion = inc blood levels of uric acid (bad) and Ca (good)
Inc urinary excretion = dec blood levels of Na, K, and urine vol
**Loops = Ethacrynic acid (exception to sulfa allergy); bumetanide, furosemide (Lasix - prototype),
torsemide
Fast-acting (quick inc diameter), short t1/2 of 2-4 hrs
Na, K, and ATPase inhibitors (ototoxicity, inner ear pump to shift fluids)
Inhibit NaCl reabsorption to bloodstream
Inc Ca excretion in urine
Loops for dec renal func and/or CHF
DOC red acute pulmonary edema in CHF (thiazides cant. pull fluids out of 3rd spacing =
outside vascular in ankles), Tx hypercalcemia and hyperkalemia
Dec urinary excretion of uric acid (inc in bloodstream), inc Na, K, Ca, and urine vol (they compete
vs uric acid and it loses)

**K Sparing = amiloride, spironolactone (aldactone), triamterene, amiloride/HCTZ, triamterene/HCTZ


(caps-Dyazide; tabs-Maxzide)
Act at CT and interfere w/ Na resabsorption and K secretion
Weak diuretic bc fractional Na reabsorption in CT is <3% of filtered load
Combo w/ thiazides or loops to restrict K loss/augment diuretic action
Spironolactone = aldosterone analog that binds to mineralocorticoid receptors in kidney to
inhibit aldosterone (Tx acne). Also for CHF
Summary: dec K excretion, inc Na and urine vol excretion

**ADRs
Thiazides = hypokalemia, hyponatremia, hyperuricemia, hypercalcemia, hypersensitivity sulfa,
photosensitivity
Loops = acute hypovolemia; hypokalemia, hyponatremia; hypomagnesemia, hyperuricemia,
hearing loss
K-sparing = hyperkalemia (spironolactone), note hormonal ADRs

**Drug Interactions
NSAIDs dec effectiveness cause Na and H2O retention
Watch loops w/ ototoxic drugs (AG and vancomycin)

**Special Considerations
Thiazides ineffective if GFR <30 mL/min (use loops!) bc small amt of GF left by then (4)
Loops for decreased renal function and/ or CHF
Use in combowith vasodilators to dec Na+ and H20 retention
K+ sparing diuretics in combo with thiazides (watch Klevels and ACE Inhibitor use)

**B-Blockers (Beta-adrenergic antagonists) are sympatholytic target B-receptors.


1.) Non-Selective (equal affinity B1 and B2 can cause bronchoconstriction) = propranolol
(Inderal)
2.) B-Blockers w/ ISA (sympatholytic w/ ISA to rel catecholamines and maintain HR so partial
agonist [doesnt inc TG or dec HDL]) = acebutolol (Sectral)
3.) Cardioselective b-Blockers (B1, inhibit B2; dose-dep and unreliable, best for HTN) = atenolol
and metoprolol
4.) a/B-Blockers (balances dilation and constriction in peripheral vessels) = carvedilol
MOA::
o CV: dec CO (-chronotrope and inotrope), bradycardia, dec O2 consumption (helps w/
angina!)
o Renal: dec renin and dec peripheral res
o Peripheral vasoconstriction: block Brec prev B-2 vasodilation. TPR to normal or dec w/
long-term use
o Bronchoconstriction: contraindication in COPD and asthmatics bc B2 in lungs blocked
and bronchiolar sm mus contracted. But still use in Post-MI even though contraindicated
Study picture
ADRs
o Fatigue
o Depression
o Sleep disturbances (nightmares)
o Sexual dysfunction (BB #1 cause)
o B-blockade (Loss of glycemic control mask hypoglycemia)
o Bradycardia (Dont give addl if HR <60bpm)
o Bronchospasm
o Cold extremities top complaint
o Lipid abnormalities (inc TG, dec HDL) - ACEI ONLY doesnt alter lipids
o
Drug Interactions - NSAIDs dec effectiveness, combo w/ other HR lowering drugs can cause symp
bradycardia or heart block (deadly)
2 classes HTN meds have direct cardiac depressive fx = BB and some CCBs
Key pts:
o Dec morbidity and mortality
o Rel cheap
o Dose dep so not 100% safe in bronchospastic pts
o Taper over 14 days bc cardiac fx angina, MI, rebound HTN
o Impotence and dec libido in red pt compliance

**ACEI (-pril) = Benazepril (prototype, not used, short t), captopril, enalapril, fosinopril, lisinopril (most
common), quinapril, ramipril
MOA: Block ACE from converting AG1 to AG2 so dec vas res w/o inc CO, rate, or contraction. Also
inact bradykinin breakdown. NO reflex in symp action (tachycardia) like vasodilators
Net Result: dec BP
Key Pts
o ACEI and ARBs slow diabetic nephropathy progression and dec albuminuria
o Very effective in microalbuminuria, DM, CHF, CKD, postMI
o Less effective in AA unless comboed w/ diuretic
o ACEI are renoprotective
ADRs
o ACE cough nonprod dry and annoying, consider ARBs instead
o Angioedema
o Hyperkalemia
o Severe hypotn in hypovolemic pts
o Renal insufficiency - CONTRAINDICATED in B/L renal artery stenosis
Drug Interactions

o May ppt hyperkalemia when used w/ K sparing diuretics

o Efficacy can be dec when used w/ NSAIDs

**CHART
Renin (kidney) converts angiotensinogen to AG1. ACE converts AG1 to AG2. Dec aldosterone
causes retention Na and H2O. Also dec symp, vasodilate vas sm mus
ACEI dec conversion AG1 to AG2 (potent vasoconstrictor) to make vasodilating fx and also inhibit
degradation of bradykinin so it inc
ARBs similar to ACEI DO NOT inhibit breakdown of bradykinin (vasodilator) so no cough

**ARBs (-artan)
No bradykinin associated cough (why use over ACEI)
Goes to receptor instead of enz (prev ACE-escape)
ADR and drug interactions same as ACEI

**Direct Renin Inhibitor (aliskiren, -kiren) = doesnt dec morbidity so not imp

**CCB
Non-dihydropyridine = verapimil and diltiazem
Dihydropyridine = nifedipine (old 1st gen); amlodipine (2nd gen)
MOA: cardiac depressant bc dec IC Ca, peripheral dilator bc relaxed sm muscle
Us used w/ thiazides but not nec
Good vasodilators dont need diuretics bc sm and slow transition (no rapid drop BP and
compensatory symp res)
Verapamil = constipation (common in elderly F), gingival hyperplasia, anti-seizure, worsens CHF
bc dir cardiac depressant
Diltiazem = diarrhea
NO BB w/ verapamil and diltiazem
1st Gen DHPs
o vasodilators dec PR
o initial reflex tachycardia can occur
o Side fx = dizziness, flushing, palpitations, peripheral edema

**Peripheral a1-adrenergic blockers (-zosin) = Doxazosin (Cardura), prazosin (Minipress), terazosin


(Hytrin)
MOA: inhibit a1-vasoconstrict properties
Relieve BPH
No reflex tachycardia
ADRs: First dose syncope, postural hypotn, dizziness

**Tx Algorithm for HTN


Compelling indication managed in parallel with BP CHF, post MI, high coronary dis risk,
chronic kidney dis, recurrent stroke prev
Thyroid Lecture

***Hyperthyroidism***

**PTU go to drug and Methimazole


MOA = Thionamides (both have Th in them), inhibit organification and peripheral conversion of
T4 T3
Onset of Effect T1/2 = Follow up in 6 wks, 1 month is ideal
Dose = PTU 6-8 hrs TID, Meth more potent so BID or QD
ADR = pruritic rash, arthralgia, fever, transient leukopenia, agranulocytosis (toxic effect not
hypersensitivity), hepatitis (new black box warning, liver toxicity w/ PTU), lupus-like syndrome
Black box so F/U do baseline LFTs
Adv = non-invasive, low risk permanent hypothyroidism
Disadv = low cure rate (30-80%), adverse drug rxns, drug compliance

**RAI Sodium Iodine 131


Colorless, tasteless liquid, well-absorbed and concentrates in thyroid
Over wks, follicles that take up RAI destruction gland bc breakdown and destroy sm vessels
Contraindicated in pregnancy and BF
Adv = cure hyperthyroidism, cost
Disadv = perm hypothyroidism, postpone prego up to 1 yr

***Adjunctive Tx Measures***

**Iodides (Potassium Iodide, Lugols Soln)


Blocks thyroid hormone rel, inhibits biosynthesis, and dec vascularity so less bleeding in Sx. ALSO
blocks RAI accumulation = dec risk thyroid CA from exposure
Give 10-14 days prior to Sx
Sometimes RAI adjunct but given AFTER RAI so it can concentrate
ADRs = hypersensitivity, salivary gland swelling, iodism (metallic taste, burning mouth and
throat, sore teeth and gums, sxof head cold, stomach upset)

*BB = atenolol, metoprolol, etc


MOA = suppress sympathetic sx, some direct antithyroid fx bc inhibit T4 to T3 conversion but
NOT antithyroid (amiodarone is)
Just adjunctive to control clinical sx
Sometimes 7-10 days prior to Sx to keep HR < 90

***Hypothyroidism***

**Levothyroxine (Synthroid/Levoxyl/Levothroid/Levoxine) 1 st 2 most common


Synthetic T4
Adv = low allergic potential, stable predictable potency, generics bioequivalent so DOC for all
forms of thyroid issues
Disadv = variable absorption btwn products, synthroid takes time to breakdown
Take these 1st thing in AM w/ empty stomach bc many things dec levothyroxine absorption
Sm changes in thyroid dose = big changes in TSH, NOT a linear relationship!!
Common doses = 100, 112, 125 mcg
Drug interactions = CYP 450 3A4
Monitor sx hypo or hyperthryroidism
Dessicated Thyroid = T4 + T3 + Iodine. Clinical Pearl: No evidence that desiccated thyroid works
better than synthetics (Synthroid, Levoxyl). Desiccated thyroid is natural ground up pork thyroid
gland so ppl want but hard to get and standardize so discouraged
Liothyronine = T3 (liothyronine) is a little faster acting some patients think it gives them a lift
Liotrix = T3 + T4
Active form = T3

UTI Lecture

**What microorganisms commonly cause CA-UTIs?


85% uncomplicated from E. coli; 15% primarily Proteus and Klebsiella, sometimes Staph
saprophyticus
Complicated moreso g (-) orgs and E. faecalis

**Cystitis
1) Trimethoprim-Sulfamethoxazole (TMP/SMX) = Bactrim adult tablets (#1 Tx for uncomplicated
UTI), Septra suspended
Spectrum = g (-) (E. coli), Proteus can be R
Resistance up to 22%, even if R can cure UTI bc high [urinary]
ADRs = photosensitivity, GI complaints
Avoid in sulfa allergies and pregos
Uncomplicated = no pyelonephritis, congenital and structural abnormalities, stents,
indwelling catheters, other hardware
2) Fluoroquinolones (-floxacin) = ofloxacin, ciprofloxacin (best), norfloxacin, levofloxacin
For pyelonephritis, prostatitis, or R infections
3) Nitrofurantoin (macro-) = Macrobid, Macrodantin
Good as tx and prophylaxis, no real R despite long therapy course
ADRs: may limit use: GI intolerance, neuropathies, pul rxns
4) Cephalosporins
5) PCNs
6) Single-Dose Therapy = Fosfomycin tromethamine

**Cystitis Drug Regimens


3-day regimen for uncomplicated cystitis, clean slate UTI only/childbearing age
Conventional Therapy = 7-10 days for pregos, 1 st time UTIs, males, failed 3-day regimen
Exam ?: Cipro 7 day regimen good for uncomplicated UTI in F? NO! use 3 day

**Non-pharmacologic Therapy
Aggressive hydration = increase voiding and washing out of bacteria
Acidification of urine = cranberry juice (not good bc sugar, esp in obesity/DM) but fructose and
tannins interfere w/ pathogen adherence
Lactobacillus = help prev F UTIs
Urinary tract analgesics = phenazopyridine
OTC or Rx
Considerations: mask sx UTIs and numbs from kidney urethra, also stains anything it
touches
Problem: Use only for a few days bc wont know if ab is working

**Pyelonephritis Guidelines:
Factors to consider are inpt, outpt, IV, PO, etc. Pt ranges

Antimicrobial Agents x 14 days


1) TMP/SMX
2) FQ
3) 2nd and 3rd Gen Cephalosporins
If pt admitted for pyelo, start IV and tx until fever is gone for 12-24 hrs then switch to PO
to complete 14 days

**Prego = Tx 7 days, avoid Bactrim (TMP/SMX - hyperbilirubinemia), FQ (cart), and tetracyclines


(teratogen)
Complications = pyelonephritis, labor
Asymptomatic Bacteriuria = Tx regardless
Cystitis same bugs basically; consider amox/clav, cephalosporin, maybe tmp/smx
Pyelonephritis usually tx aggressively

GI Part 1

**Antacids
MOA = neutralize gastric acid by inc intragastric pH and therefore reduce intragastric acidity
Al + Mg most popular bc dont produce gas/CO2 byproduct
Sodium bicarbonate (baking soda, alka seltzer) reacts with HCL = CO2 and NaCl
Calcium carbonate (tums, Os-Cal) reacts with HCl = CO2 and CaCl2
Magnesium or aluminum hydroxide react with HCL = Al-chloride or Mg-chloride
Adjunctive therapy primarily for pain relief related to DU or GU healing, tx dyspepsia (not GERD)
Side Fx:
o Al and Ca containing agents: constipation
o Mg containing agents: NVD
o Metabolic alkalosis
o CO2 causes GI distention and belching
Drug Interactions: Either bind drug or inc gastric pH

**H2 Antagonists aka H2 Blockers (-tidine) = cimetidine, famotidine, nizatidine, and ranitidine
Cimetidine = serious ADRs like antialdosterone, gynecomastia, impotence, endocrine. Used for
warts
Drug Interactions: Cimetidine interferes with CYP450 = prolong t1/2 for agents metabolized by
these enzymes
MOA: inhibit histamine receptors on parietal cells in gastric mucosa dec cAMP dec p+
pump activation dec H+ dec gastric acid
Acid neutralizing capabilities in Rx strength inhibit 60-70% of 24-hr acid secretion .. Still need
some acid to digest food!
Especially effective in nocturnal acid prod (due to histamine) rather than meal-stimulated acid
producion (due to gastrin, Ach, histamine)
PKs/PDs: rapidly absorbed from GI tract
RX acid suppression is 10-24 hours (daily vs 2x daily)
Monitoring Parameters: diarrhea, H/A, fatigue, myalgias, constipation, CNS changes
Therapy Use: Tx DU and GU and maintain remission, GERD, stress ulcer prophylaxis

**PPI (-prazole) = lansoprazole, omeprazole, esomeprazole (most $$) , rabeprazole, pantoprazole,


dexlansoprazole
MOA = irrev inhibits/inactivates H+/K+ATPas pump dec H+/K+ exchange dec gastric acid
PKs/PDs = food dec absorption by so give on empty stomach, exceptions are rabeprazole,
pantoprazole, and dexlansoprazole
Short t1/2 but acid suppression lasts 24 hrs
Inhibit both fasting and meal-stimulated acid secretion (90-98% 24 hr acid prod)
Monitoring parameters/ADRs: diarrhea, H/A, ab pain
With prolonged use: dec B12 levels, inc risk enteric inf and pneumonia, fx
Drug Interactions: rabeprazole and pantoprazole = few interactions; omeprazole = most. All
metabolized by CYP450 (2C19)
Recent concern that PPIs dec clopidogrel (Plavix) efficacy, maybe taking PPI + clopidogrel can inc
CV fx
Therapy Use: Tx DU and GU, maintain remission, NSAID-induced ulcers, erosive esophagitis,
GERD

***Mucosal Protective Agents


A) Sucralfate
MOA = forms viscous gel at pH < 4 which binds to damaged/ulcerated tissue barrier vs gastric
acid

B) Misoprostol
MOA = prostaglandin E1 analog
Place in therapy = prev NSAID-indulced ulcers in pt w/ other RF
ADRs = diarrhea, cramping, spontaneous abortions
Contraindications = women of child-bearing age not on BC

C) Bismuth subsalicylate (think aspirin) = pepto bismol


Coats ulcers and erosions and forms protective layer, use with multi-drug regiments to manage
H. pylori inf
Therapy Use: adjunctive tx w/ clarithromycin for H. pylori eradication
ADRs: H/A, diarrhea, dark stools and tongue, taste disturbance, anemia, Reye Syndrome (dont
give to ppl < 14), black hairy tongue

**Prokinetic agent = metoclopramide


Selectively stim gut motor function
MOA: cholinergic stimulation enhances gastric emptying

**Simethicone = GasX, rolaids anti-gas


Anti-foaming agent dec surface tension of gas bubbles so combine to lgr ones thats easier to
dispose
Doesnt dec amt of gas, just exits faster
Not systemically absorbed

GI Part 2
**H. Pylori
Regimen w/ PPI and 2 ab for min 14 days is ok

**Laxatives
Drugs causing constipation: analgesics (opiates, some NSAIDs) and anticholinergics
(antihistamines, antiparkinson agents, phenothiazines, tricyclic anti-dep)
Agents that soften feces in 1-3 days, soft/semi-fluid stool 6-12 hrs, watery evacuation 1-6 hrs

**Bulk-Forming Laxatives = psyllium, methylcellulose, polycarbophil


MOA: binds to intestinal fluid forming emollient gels that faciliate passage thru intestines
and stimulate peristalsis
ADRs: esophageal/intestinal obsruction, flatulence
Pt Info: Must take w/ 8 oz fluid
If take w/ Lipitor, snowball fx will poop out so avoid

**Stool Softeners = Docusate sodium (colace very common), docusate calcium, docusate sodium + senna
Place in therapy: relieve chronic constipation? (yes only in senna!!)
Prevention NOT tx constipation, Not effective in prev if causative factors are not concurrently
addressed (opiate use, uncorrected pathology, inadequate dietary fiber)
Use where straining must be avoided
Takes 1-3 days to work
MOA = stool softener by mixing water, fat, and stool
ADRs = safe

**Lubricants = mineral oil


Takes 2-3 days to work
MOA = oil slick coat for stool for easier passage
ADRs = routine use discouraged bc ADRs, can be absorbed sys and cause rxn in lymphoid tissue;
can be aspirated in debilitated/recumbent = lipoid pneumonia; Dec absorption of fat-sol
vitamins; can leak from anal sphincter causing pruritis and soiled clothes

**Glycerin suppository = safe in children, osmotic action in rectum, onset < 30 min

**Osmotics = lactulose, sorbitol


Place in therapy = acute evacuation of bowel (poisonings, long-standing constipation)
ADRs = flatulence, cramps, diarrhea, electrolyte imbalances

**Stimulants = Senna (better), Bisacodyl


MOA = irritate GI mucosa and inc peristalsis
ADRs = lax-dep, ab cramps, fluid and electrolyte imbalances with chronic use
Pt info = lg inter-pt variability in dose
Some pts on chronic pain meds us senna + docusate daily

**Saline = magnesium citrate, magnesium hydroxide, sodium phosphate, polyethylene glycol solutions

**Sodium Phosphate Preps = fleets phosphosoda, visicol, osmoprep


ADRs: acute phosphate nephropathy acute kidney injury with deposits of Ca-P crystals in renal
tubules = pot permanent renal impairment

**Polyethylene Glycol Preps


Miralax is safe bc no electrolytes added = GoLytely Lavage Solution Colyte
Sulfate-free PEG electrolyte lavage solution = NuLytely, TriLyte
Low-volume PEG/PEG 3350 electrolyte lavage soln (HalfLytely)
Precautions/contraindications: ileus, gastric retention, perforated bowel, GIobstruction, toxic
colitis, toxic megacolon, or severe colitis. Caution in impaired gag reflex, prone to regurgitation
or aspiration, or un/semiconscious
ADRs: dec SBP up to 20 mmHg, pulmonary aspiration, cardiac dysrhythmia, pancreatitis, colitis
Test ?:: Which med is not rec in vol lim? PEG

**Methylnaltrexone
Tx constipation in pts using opiods, opiod antagonist like naltrexone
Only for palliative care/hospice pts who arent relieved from laxatives

Antidiarrheal agents

**Antiperistaltics (opiod agonists) = loperamide (Imodium), diphenoxylate + atropine, opium tincture


Place in therapy = mild to mod acute diiarrhea, travelers diarrhea
MOA = inhibits GI peristalis inc H2O and nutrient absorption (loperamide works only
peripherally, opiates work centrally and peripherally)

Limitations = addiction pot and worsening diarrhea in inf cases

Contraindications = bacterial enteritis from E. coli, shigella, salmonella, pseudomembraneous


colitis, acute IBD

Travelers diarrhea fever maybe, blood and mucus in stool are dealbreakers for Imodium bc
toxin/gas produced can perforate gut

**Antisecretory = bismuth subsalicylate


Darkening tongue and stools, Reye syndrome in kids

**Adsorbents = methjylcellulose, psyllium

**Antiemetic Agents = phenothiazines = prochlorperzine (go-to), promethazine (Phenergan),


perphenazine, chlorpromazine, thiethperazine
MOA = dopamine antagonist primarity in CTZ (chemoreceptor trigger zone)
ADRs = sedation, dry mouth, ur retention, blurred vision, extrapyramidal sx
**Serotonin Antagonist (-setron) = ondansetron (Zofran), granisetron, dolasetron
MOA = inhibits serotonin receptors in vomiting center
Side Fx = H/A, malaise, constipation (blackbox), hypotension, extrapyramidal sx, anorexia

**Butyrophenones = haloperidol, droperidol, domperidone


**Cannabinoids = dronabino, nabilone
**Benzodiazepines = lorazepam (ativan), diazepam (valium), alprazolam (xanax)
**Corticosteroids = dexamethasone, methylprednisolone
**Antihistamines/Anticholinergics = diphenhydramine, dimenhydrinate, meclizine, buclizine, cyclizine,
scopolamine

Serum Sickness Syndrome

After 7-10 days exogenous ag or passive immunity (Ig, murine monoclonal ab)
Get formation of immune complexes (act complement, gen anaphylatoxins, and chemoattraction
of PMN leukocytes)
Presentation = sustained high fever > 101, maculopapular or urticarial pruritic rash, angioedema,
polyarthralgias, polyarthritis, LAN, nephritis (mild or ARF)
Lab findings = elev ESR and LFTs, leukocytosis. If nephritis then proteinuria and hematuria
Tx = discontinue agent, NSAIDs, antihistamines, systemic steroids in severe and topical steroids in
mild

***ASTHMA***

Asthma control req < 2 days/wk (< or = for rescue inhalers)


MDIs (metered dose inhalers) no longer contain CFC (chloroflurocarbons), now use HFA
(hydrofluoroalkane) as an alternative
Newer DPIs (dry powder inhalers)

***LONG TERM***

**Corticosteroids = Fluticasone propionate, Flunisolide, Budesonide


Most potent and effective, long-term prev, suppress dis, and REVERSAL of inflam. Systemic forms
used for prompt control only
MOA = anti-inflam activity of aerosolized drug in lung is unknown
ADR: Oral candidiasis

**Mast Cell Stabilizers (-crom) = cromolyn, nedrocromil


MOA = stabilizes mast cell mem and inhibits act and rel of mediators from eosinophils and
epithelial cells
This and ICS only for long-term control NOT emergencies

**Immunomodulator = omalizumab, anti-IgE


SC powder Injectable (trio of Is Immunomodulator, IgE, injectable)
Used in adults w/ allergic asthma who failed everything else
**Long-acting B-2 agonists (LABA) salmeterol and formoterol are FDA approved, arformoterol and
formoterol not and used in COPD
For long-term prev sx, added to ICS
Blackbox warning Increase risk sev asthma attacks and death if LABA monotherapy bc it
controls sx but NOT underlying inflam
Also available in combo w/ ICS
MOA = antagonism of bronchospasm
Inhaled
Contraindications = arrhythmias assoc w/ tachycardia or heart block; narrow angle glaucoma
ADRs: sympathomimetic: tachycardia, skel mus tremor, hypokalemia, prolong QT interval in
overdose, dizziness, N/V, pharyngitis. Potential risk fatal exacerbation
Drug interactions: BB decrease fx

**Combos
Fluticasone propionate + salmeterol xiafoate ( Advair Diskus, Advair HFA )
budesonide + formoterol (Symbicort)
mometasone + formoterol (Dulera)

**Asthma Daily Meds


Step 1: SABA prn (everyone gets rescue inhaler w/asthma)
Step 2: Low-dose ICS
Step 3: Low-dose ICS + LABA or Med-Dose ICS
Exam ?:: reasonable regimen for step 3 pt? needs SABA, low does ICS + LABA OR move from low
dose to med dose ICS + SABA

**Methylxanthime = theophylline
MOA bronchodilator, increase diaphragm contractility and mucociliary clearance
ADR = dose-rel acute toxicities. Tachycardia, restlessness, convulsions, insomnia

**Leukotriene Modifiers montelukast sodium (singulair)


MOA: LTRA
ADR: Suicide (think sodium and suicide)

**SABA albuterol and levalbuterol


TOC for quick-relief, asthma and COPD acute sx, rescue inhalers, prev EIB before exercise
MOA = binds to B-2 adrenergic rec
Adm: MDI, PO, aerosol
Contraindications: cardiac arrhthymias w/ tachycardia or heart block; narrow angle glaucoma
ARDs: tachycardia, skel mus tremor, dizziness, N/V, hypokalemia, increase lactic acid, H/A,
hyperglycemia, [? arrhthymia], palpitations. In gen, inhaled well-tolerated
Drug Interactions: MAO inhibitors, can increase BP HTN crisis; decrease BB fx
Therapeutic issues: DOC for acute bronchospasm; inhaled route faster onset, fewer ADRs, >
systemic

**Anticholinergics = Ipratropium TOC


Maybe added benefit to inhaled B2 agonists in severe exacerbations
Sympathomimetic/anticholinergic fight or flight rescue meds = bronchodilation (LABA and SABA).
Opp is parasympathathetic agonist =bronchoconstriction
COPD more cholinergic mediated bronchospasm
ADRs = dry mouth, dry eyes, ur retention, constipation, pot change mental status, tremor
Therapeutic issues = If added to SABA in ED can give additive fx, TOC bronchospasm bc BB meds
What do we use for asthma? ICS!!

**Spacers
Anyone can benefit, esp <5-6 yo, children, elderly, and hand or coordination problems
Decrease amt that sticks to back throat and oral thrush

**Pharm therapy for COPD


Anticholinergics = 1st line COPD
Combo (Combivent inhaler, Duoneb nebulizer) = anticholinergic + sympathomimetic

**Corticosteroids
Lil controversy

***Infective Endocarditis***

**Patho = inf of endocardial heart sur, us heart valves


Multi-layer bacteria, fibrin, protected vegetation
Must check MIC of bacteria to see how strong ab is needed, Want 3 blood draws sep by 1 hr
before starting ab
Vegetations = avascular so untouched by normal host def, so need high doses bactericidal and
long term parenteral ab
NVE = native valve endocarditis
PVE = prosthetic valve endocarditis
Bacteriology = strep and staph 80-90%
o Strep viridans = children and young F w/ mitral valve inv
o Staph aureus = HC related (sx, med devices), IVDU (IV drug users g (-) orgs, fungi, and
anaerobes)
o Staph epidermis = prosthetic valve
Goals Therapy: eradicate inf agent from thrombus and address valvular inf

**Change in endocardial surface of heart valve Deposition of sterile thrombi Microbial


Colonization of valve due to bacteremia Growth of protected vegetation If no intervention =
death

**Therapy of Native Valve Endocarditis (NVE) Caused by Highly PCN-Sensitive Strep viridans
Aq crystalline PCN G OR Ceftriaxone x 4 wks +/- Gentamicin x 2 wks
PCN-Allergic = Vancomycin x 4 wks
Clinical Pearl: Gentamicin makes a synergistic combo. Is q 8hr NOT qD bc synergy peaks needed
in IE

**Therapy for NVE Caused by Penicillin-Resistant Strains of Streptococcus viridans = Not as highly
sensitive
Only diff is lower dose aq crystalline PCN and DEFINITELY use gentamycin here
Aq crystalline PCN G OR Ceftriaxone x 4 wks + Gentamicin x 2 wks
PCN-Allergic = Vancomycin x 4 wks

**Therapy for Endocarditis in Prosthetic Valves or Other Prosthetic Material Caused by Streptococcus
viridans
Increase Tx time
PCN-S = Aq crystalline PCN G OR Ceftriaxone x 6 wks +/- Gentamycin x 2 wks OR vancomycin x 6
wks
PCN-R = Aq crystalline PCN G OR Ceftriaxone x 6 wks + Gentamycin for 6 wks (no vancomycin
here)
PCN allergic = vancomycin x 6 wks

**Tx Staph Endocarditis


Gentamycin ? benefit, only in NVE from staph
NVE Oxacillin/methicillin-S Staph
o Non-PCN Allergic= Nafcillin (4-6 wks) w/ optional gentamycin (3-5 days)
o PCN-Allergic = Cefazolin (4-6 wks) w/ optional gentamycin (3-5 days) or Vancomycin x 4-6
wks
NVE Methicillin-R Staph
o Use Vancomycin (4-6 wks ?), consider linezolid or daptomycin
Only place ? Benefit vancomycin in MRSA is in MRSA bacteremia

**Prosthetic Valve Endocarditis (PVE)


Methicillin-S Staphylococci = Nafcillin + Rifampin x > 6 wks + Gentamicin x 2 wks
Methicillin-R Staphylococci = Vancomycin + Rifampin x > 6 wks + Gentamicin x 2 wks
Clinical Pearl: Use Rifampin bc anti-staph benefit but NEVER use by self bc builds up resistance

**Prev IE/Ab Prophylaxis


Tends to be overtx
Maintaining good oral hygiene prob > effective in prev IE; gingivitis is #1 source of spontaneous
bacteremias

**Prophylaxis in: artificial heart valve, hx heart inf, certain serious heart conditions since increase birth,
and heart transplant that develops a heart valve problem

**Endocarditis Prophylaxis Regimen Indicated for Patients with Cardiac Conditions


1 dose 30-60 min before dental or URT procedure
PO: Amoxicillin
PCN-allergic: Clindamycin OR Cephalexin OR Azithromycin or Clarithromycin
Unable to take PO:
o Ampicillin IM or IV
o PCN-allergic: Clindamycin IV OR Cefazolin IM or IV

***DB***
Type 1 = pancreatic Beta cells destroyed so severe or lack insulin
Type 2 = insulin res in tissue
Metabolic Syndrome = prediabetes. RF are abdominal obesity, atherogenic dyslipidemia, elev BP,
insulin res or glucose tolerance, prothrombotic state, and proinflam state

**HgA1C = glycosylated Hgb measured at 3 months bc ~ blood turnover rate


Measures most heavily/accurately 1-2 wks before blood draw
Tight control decrease or delays DM complications in eyes, kidney, and nerves (DCCT Trial). The
younger the pt, the tighter the control

Goal < 6.5% - < increase in CV complications


To convert HgA1c to eAG: eAG = 28.7 x A1c - 46.7

Hypoglycemia: sweating, trembling, dizziness, mood changes, hunger, headaches, blurred


vision, extreme tiredness and paleness
Hyperglycemia: dry mouth, extreme thirst, frequent urge to urinate, drowsiness, stomach pain,
extreme hunger

**Oral (Type 2 Only)


None rec in children, prego, or breast-feeding F (insulin only)
TZD and metformin = exceptions

**Sulfonylureas = 1st gen not used, 2nd gen (-gl and -ride) glyburide, glipizide, glimepiride
Sulfa allergy Worry most about Celebrex crossreactivity, then sulfonylurea, then diuretics
MOA = stim rel of insulin from pancreatic beta cells
Precautions = hypoglycemia (higher incidence with glyburide), loss of control of blood glucose,
sulfa allergy, GI, and CV dis
PK Issues: work quickly, fastest of all PO agents
Considerations: cheap, wt gain, hypoglycemia

**Biguanides = Metformin go-to drug


MOA: decrease hepatic glucose prod and intestinal absorption of glucose. Improves insulin
sensitivity (increase peripheral glucose uptake and utilizaiton) in liver, gut, and peripheral tissue
Take with food
Precautions:
o Renal impairment (not in Scr >1.5 mg/dl M, 1.4 F) or in est ClCr < 60 ml/min, concern is
lactic acidosis blackbox warning
o Watch other meds that may fx renal func and radiologic studies (d/c metformin 48 hrs
before)
o Hypoxic states
o ETOH intake
Can cause DNV, dlatulence, ab discomfort. Hypoglycemia lim in monotherapy
Clinical tip: GI complaints first stating and when increase dose so start on low dose and titrate
Considerations: Take w/food, max dose 2,000 mg daily, weight neutral
**Thiazolidinediones (TZDs, -glitazone) rosiglitazone, pioglitazone hydrochloride
MOA: improves insulin sensitivity in mus and adipose tissue. Sites are muscle, fat, and liver

Inhibits hepatic gluconeogenesis

PK Issues: extensively metabolized


Precautions: OK in renal dysfunction
DO NOT use in liver dysfunction (must check LFTs often) or CHF
Black box warning CHF and MI: TZDs make worse or can cause (excessive and rapid wt gain,
dyspnea, and/or edema)
Rosaglitazone: Meta-analysis showed AVANDIA assoc w/ increase risk of myocardial ischemic
events such as angina or MI. However 3 other studies didnt entirely confirmed so data is
inconclusive
Other ADRs: increase risk of Fx (esp F in forearm, hand, wrist, foot, ankle, fibula, tibia), can
cause ovulation, GI complaints, CV ADRs rosiglitazone, increase risk bladder CA pioglitazone
Considerations: take w/o regard to meals, do not use in ppl taking insulin (increase risk
edema) or nitrates (increase risk MI), pioglitazone can improve lipid profile and protect
against MI, wt gain, expensive

**Meglitinides (-glinide) = Repaglinide, Nateglinide


MOA: Stim insulin rel from pancreas
Indications and Usage: Adjunctive therapy for post-prandial hyperglycemia
Precautions: hypoglycemia

**Alpha Glucosidase Inhibitor = Acarbose and Miglitol


MOA: Delays digestion of CHOs
Indications: adjunctive therapy, pp hyperglycemia
Precautions: GI adverse effects, not sys absorbed

**Incretin Mimetics: GLP-1 Agonists = exenatide (BID SQ), liraglutide


Byduren = long=acting 1/wk version of exenatide
MOA: Stim GLP-1 receptor wich enhances glucose-dep insulin secretion by pancreatic beta-cell,
suppresses glucagon secreiton after meals, slows gastric emptying, some appetite suppression
and weight loss
Indications: adjunctive therapy to improve glycemic control in Type 2 DM adults taking other PO
antidiabetic agents
Precautions: can dev ab, exenetide contraindicated in renal impairment, liraglutide cautioned in
renal dis
ADR: GI (NVD, constipation, hypoglycemia. Animal studies shows liraglutide is dose-dep and tx
duration dep thyroid C-cell tumors,pancreatitis
Considerations: Weight loss, sig ADRs, $$

**DDP4 Inhibitors aka Gliptins (-agliptin) = sitagliptin phosphate, saxagliptin


MOA: incretin sys lowers blood glucose, stim this mech by INHIBITING DPP-4 (enz that breaks
down endogenous incretin). Inhibits breakdown of GLP-1 (incretin); incretin stimulates insulin
release from beta cells in response to food and inhibits livers production of glucose = promotes
insulin activity and inhibits gluconeogenesis by preventing incretin inactivation
Indications and Usage: adjunctive therapy to improve glycemic control in Type 2 DM adults
taking other PO antidiabetic agents
ADRs:
o low incidence of hypoglycemia if used as monotherapy
o occasional diarrhea and stomach discomfort
o URTI
o Headache
o Stuffy nose
o Sore throat
o Acute pancreatitis with sitagliptin
o Hypersensitivity reactions
Emergency administered if: Swelling of throat, tongue, lips, face, Allergic reaction, Difficulty
breathing and hives

Considerations: weight neutral; some CYP450 interactions


**Amylin Analogs = Pramlintide (Symlin)
MOA: modulates pp glucose, slows gastric emptying leading to early satiety, decrease pp glucon
secretion
Can use in Type 1 and 2 preprandial
ADRs: hypoglycemia (so lower doses at mealtimes), GI (N/V, anorexia)

**Misc: Bromocriptine
Trad tx hyperprolactinemia, acromegaly, and Parkinsons. This newly FDA-approved to adjunct
diet and exercise to control Type 2 DM

**Insulin Preps
DOC all Type 1 DM and for Type 2 who cant control cond w/ diet, ex, and OADs
MOA: reg glucose metabolism in mus and other tisues
Semisynthetic = identical AA to endogenous human insulin
Dosing: no ceiling dose, but less at higher doses. Concentrate on reducing insulin resistance thru
exercise, less carbs, and metformin
Categories:
o Rapid onset (SQ, IV, insulin pump, need Rx) = insulin lipro, insulin aspart, insulin glulisine.
Onset <1/4 hr, peak 1 hr, lasts 3.5-4.5 hrs

o Short-acting (SQ, IV, insulin pump, dont need Rx): Human (Humulin R, Novolin R. Onset
hr, peak 2-4 hrs, lasts 6-8 hrs. Velosulin BR w/ buffer to prevent accumulation of tubing
of insulin pump
o Intermediate-acting (SQ) aka NPH = human (Humulin N, Novolin N). Onset 1-2 hrs, peak
6-12 hrs, lasts 18-24 hrs
o Long acting: Insulin detemir (Levemir), insulin glargine (Lantis). Onset 4-6 hrs, peak 8-20
hrs, lasts 24-48 hrs
Do not mix with other insulins bc altered PK/PD
o Dosing: 0.5 U/kg/day -0.6 U/kg/day

**Aspirin = Prev 2nd heart attacks, may prev 1st heart attack

**Tx Type 2 DM:


1) Dx Type 2 DM: Counsel lifestyle mods (wt loss and exercise) and initiate metformin 500 mg 1x or
2x daily, titrate to 850-1,000 mg 2x daily
2) 1 med A1C 7% or greater 3 mos later: Add sulfonylurea, basal insulin (bedtime intermediate or
morning long-acting), pioglitazone, or exenatide
3) Combo A1C 7% or greater 3 mos later:
o In those receiving metformin and basal insulin or sulfonylurea, change to metformin +
intensive or basal insulin, respectively
o In patients not yet receiving metformin plus insulin, change to metformin + basal insulin
o In those receiving metformin plus basal insulin, intensify insulin and continue to adjust

WOMENS HEALTH

Estrogen content = dose dec over yrs from 100 to 20 mcg/day (10 is Lo Loestrin)
Typical use and Perfect use (low prego rate but can happen)
Mono-phasic = fixed doses estrogen and progestin in cycles
Also bi (alter 2x), tri, and 4-phasic

**Progestins = vary in potency and activity


Drosperinone (worst K-sparing capability so benefit), dienogest = progestogenic, anti-
androgenic, anti-mineralocorticoid. Also an antialdosterone (mimics spironolactone adv acne
and HF, disadv hyperkalemia and thromboembolism);)

**Starting OCs
Day 1 = 1st pill on Day 1 of period; rapid contraceptive fx (M dont needa use backup
contraception)
Sunday start = 1st pill on 1st Sun after period. Benefit is period-free wknds
Quick start = 1st pill any day, competition btwn hormones
Test ?: Fastest contraception? Day 1

**Monophasic
Ocella (Yasmin) w/ drosperinone
High-Dose = 50 mcgs

**Extended and Cont Regimens


84 days active pill with 7 days pill-free interval (Seasonale) or 7-day low-dose estrogen interval
(Seasonique think technique is better so ppl wont forget)
Lybrel = 1st cont use OC
Can also stack and eliminate 7 placebos for 2-3 cycles
Loestrin-24 FE, Yaz, Beyaz = 24/4-day cycle pills
Lo Loestrin Fe = 26/2
o Candidates: F w/ N, V, bloating, dec libido, breast tenderness with 20 mcg OC
o May also be used in nonsmoking perimenopausal F (benefit smooth out hormonal
fluctuations) = can still get prego so precaution
Yaz and Beyaz (B vit also) w/ drosperinone
Natazia = 4-phasic, contains EV (estradiol valerate) and dienogest

**Progestin-Only Pills = Micronor


Mini-pills = blood-clotting contraindications

**ADRs
Too much estrogen (nausea, breast tenderness, inc BP, melasma aka prego mask, H/A) try OCPs
3 mos to R/O not working
Too much progestin (mood swings)
Drospirenone and dienogest = hyperkalemia

**Thromboembolism
Low risk 1/10,000 per yr
35 < incidence than 50 mcg/day why we say 35 or less is low-dose estrogen
No data that 20 < incidence than 35 mcg/ day
Controversy: Drospirenone may inc risk DVT
Patch may have higher risk
Contraindication = heavy smoking (>15 cigs) and over 35 yo inc chance thromboembolism

**Drug Interactions
Ethinyl estradiol = broad-spectrum ab can dec circ estrogen levels by dec intestinal bac (wipe out
normal flora), so can dec OC efficacy = bleeding and prego. Also CYP450 3A4 substrate

PAIN MEDS

2 types of pain
o Nociceptive = normal processing
o Neuropathic = abnormal processing
Physiologic Effects = Inc catabolic demands, dec limb movement, respiratory effects, tachycardia,
and elev BP
Acute Pain Goal = pt comfort and min ADRs
Chronic Pain Goal= pt comfort (poss not pain free) and min ADRs + integrate normal life and
ADLs
Drug options = non-opiods (acetaminophen and NSAIDs), opiods ( agonists & mixed agonist-
antagonists), adjuvants (multipurpose & specific)

**Controlled Substance Schedules


I = cant prescribe, research only
II = more likely to abuse
III = safer, less likely to abuse
IV = as effective as acetaminophen
V = may help with cough

**Opiods (narcotics) = meperidine and morphine w/ active/toxic metabolites


No max dose
Acute and chronic pain
If morphine and derivative allergy (codeine) then use meperidine, fentanyl, or methadone
MOA = opium derived from poppies, relieves pain and induces euphoria by binding to opiod
receptors (mu, delta, kappa), mimics actions of endogenous opiod compounds (enkephalins,
dynorphins, endorphins)

1.) Morphine = MS Contin, MSIR (immediate rel), Avinza, Kadian (long-acting)


Severe pain, use IR to establish dose needed then switch to CR formulations
Avinza and Kadian 24 hr SR fewer fluctuations and less freq dosing
Altering drug deliver sys daily drug supply rel immed = pot OD and death
SR should not be crushed/chewed
Active metabolites may accumulate in renal dysfunction

2.) Hydromorphone (Dilaudid)


Mod-severe pain
? < sedating than morphine
3.) Oxycodone Products
? > addictive than heroin
1.) OxyCONtin
Tampering for IV abuse = gel-coded so cant draw into syringe, now you cant crumble it
Test ?: NOT for acute pain mgmt
2.) OxyIR and Roxicodone = only readily available oxycodone only immed-rel products
3.) With APAP:
a. Percocet = oxycodone + APAP, beware of combos w/ acetaminophen
b. Roxicet (soln, +APAP)
c. Percodan (+ ASA)
4.) Fentanyl very short acting
Fentanyl Patch (Duragesic) = mcg dosage, us change q3 days, crappy adhesive
a. Pt may want brand-name only
b. Well absorbed topically (avoid sun exposure, heat)
c. 6-12 hrs until significant systemic levels, 14+ before plateau
d. Blackbox for acute pain
e. Test ?: Never use in an opiod-nave pt
Fentanyl lozenge on a stick (ACTIQ)
f. Breakthru pain or if have trouble swallowing
g. NOT for opiod-nave!
h. Good in hospice ppl who have trouble swallowing
5.) Codeine - weak
a. + APAP/aspirin = III
b. + expectorant = V
6.) Hydrocodone + APAP (Norco, Vicodin, Lortab), Hydrocodone + IBU (Vicoprofen)
a. If pt was on oxycodone + APAP, this will be inadequate pain control

**APAP and opiod analgesic combos


Synergistic pain control
1.) Meperidine
a. Euphoric, stimulates drug seeking
b. No longer pref for acute or chronic pain
c. M for metabolites CNS stimulant, seizures, visual disturbances, twitching, anxiety
d. May only be appropriate in morphine allergic pt
2.) Methadone
a. Biphasic alpha (analgesic) and beta phase (prev withdrawal, pain control)
b. For mgmt opiod abuse and chr pain
c. Equianalgesic dose of methadone will dec progressively as morphine equivalents inc

***Other Opiod Agonists***


1.) Tramadol (Ultram) and Tramadol + APAP (Ultracet)
o Dual action = mu receptors & inhibits neuronal uptake of serotonin and norepinephrine
o PO mod pain, also used for chronic pain
o Lowers seizure threshold, inc serotonin levels (2 ss)
o Not controlled
o Test ?: DOES NOT tx 7-10
2.) Tapentadol
**Opioid Equivalency
Morphine IV 3x > morphine PO. So 10 mg IV = 30 mg PO
Oxycodone PO 1.5x > morphine PO. So 20 mg oxy = 30 mg morphine
o Example ?: 60 mg morphine PO = 40 mg oxycodone PO
Hydrocodone 1.5x > morphine PO. So 20-30 mg = 30 mg morphine
Methadone PO 3-5mg = 30 mg morphine PO. Higher doses of morphine means less linear
transition of methadone to morphine
Hydromorphone PO 7-7.5 mg = 30 mg morphine PO
Fentanyl is super strong. If on high-dose 50 mg morphine PO then can switch to lowest dose
fentanyl

**Pain Scales
Numerical: 0 10
o Mild 1-3: APAP, Ibuprofen
o Moderate 4-6: APAP/codeine, APAP/oxycodone, tramadol
o Severe 7-10: morphine, hydromorphone, morphine controlled release
o Example ?: Tramadol least effective for which type of pain? Severe. It is best for a 3 or 4
(mild or mod)
Faces: children and elderly
Colors: blue/white red (10)

**Considerations of Dosing Formulations


Long vs. short-acting: basal rate w/ breakthru = CR (or long-acting) + something for breakthru
pain
Approx 10% of daily-dose long-acting is given as breakthru
Example: 60 mg oxycontin BID so 120 mg total, look for 6-9 mg oxycodone for breakthru pain,
could do 1-2 5 mg tablets or 2 mg hydromorphone tablets

***Pt Controlled Analgesia = PCA


IV or SC cont infusion narc w/ breakthru doses pt can control
Locked button that delivers dose
For acute pain
May use less total narc than traditional PRN dosing (morphine, fentanyl, hydromorphone)

**Opioid Effects/ADRs
Constipation (give stool softener + stimulant combo live docusate + senna)
Pruritis - . IV more likely to cause
N/V triggers CTZ
Sedation
Respiratory depression deadly
Inhibition of cough reflex
Confusion
Dysphoria/euphoria
Hallucinations
Prolongation of labor
Urinary retention
miosis

**Opioid Drug Interactions


Other CNS depressants
Methadone has CYP450 3A4 drug interactions
ETOH + opiod = respiratory depression

**Withdrawal from Opioids


Time of onset, intensity, and duration of abstinence sx depends on drug prev used (t1/2)
Muscular aches and yawning
Administration of opiod at time of withdrawal sx = suppression of abstinence s/sx almost
immediately

**Opioid Antagonists = naloxone and naltrexone


Quickly reverses fx morphine and other opioid agonists, tx opioid overdose
Antagonist-precipitated withdrawal w/in 3 min after injection withdrawal sx appears, peaks 10-
20 mins, subsides 1 hr
ADRs = insomnia, HA, nervous, low energy

**Mixed Opioid Agonist-Antagonist = buprenorphine, butorphanol, nalbuphine, pentazocine


Partial agonist or antagonist activity at mu receptors, agonist or antagonist activity at kappa
receptors
Buprenorphine/Naloxone (Suboxone) = Tx opioid abuse .. But can eventually abuse this too!
ADRs: less respiratory depression and abuse potential?
Precipitiate withdrawal in an opioid-dependent pt

**Adjuvant Analgesics and Co-Analgesics


Enhance analgesic efficacy, work on specific pain types, relieve concurrent sx that exacerbate
pain
NSAIDs, antidep/convulsants, corticosteroids, benzos, muscle relaxers

**Dependence (formerly physical dep) = Occurs in all pts on chronic opioids


**True addiction (formerly psychological dep) = Compulsive use despite harm
**Pseudoaddiction = end result of under-tx pain, drug-seeking behavior (demanding doses before
scheduled time, hoarding), go to 1+ pharmacy/Dr., cured by inc daily dose and monitoring pt
**Tolerance = escalation of dose to maintain effect (analgesia or euphoria may be life threatening bc
res dep doesnt show much tolerance)
**If opioid intolerance, use meperidine, methadone, or morphine

WOMENS HEALTH

**Other Hormonal Contraceptives


1) Depo-provera
o progesterone-only IM q3 mos
o most common and widely used
o weight gain after 5 yrs of chronic use (gain 3-5 lbs/yr)
2) Implanon
o implantable subdermal rod, up to 3 yrs
o progestin only
o ? Efficacy in morbid obesity
3) NuvaRing
o in for 3 wks, out for 1
o can be stacked
4) Mirena
o umbrella-like IUS
o very effective
5) ParaGard IUD (Copper-T)
o IUD up to 10 yrs
o non-hormonal
o Issue for Mirena and ParaGard is nonparity bc more likely to have chronic pain from
products
6) Ortho Evra
o transdermal patch q1 wk x 3 wks, week 4 is patch free
o Issues: overweight, thromboembolism, lousy adhesive in some (us bc lotion)

**Menopause
Intact uterus must get most estrogen and progesterone [unopposed estrogen can lead to
endometrial CA]
Good candidates = osteoporosis [worry about cardiac issues]

**Major sx of estrogen withdrawal


2 most common sx = vasomotor instability (hot flushes, sweating) and vaginal atrophy
(discomfort)
Other sx are loss of concentration and libido, wt gain, depression, thinning hair, joint discomfort,
disrupted sleep

**HRT = CV risk!!!
**Soy products = phytoestrogens. Can eat enough to be in HRT state. Bad bc high pesticides

OSTEOPOROSIS

**Institute of Medicine
F 50-70: 1200 mg Ca, 600 IU Vit D, 800-1000 IU Vit D rec daily intake (National Osteoporosis
Foundation)
F > 70: 1200 mg Ca, 800 IU Vit D
M 50-70: 1000 mg Ca, 600 IU Vit D (note diff here)
M > 70: 1200 mg Ca, 800 IU Vit D

**Commonly Used Ca Salts


Take sm amts throughout days, NOT with high fiber meals, consider TUMS
Recommended 3-5 tablets/day
1.) Calcium Carbonate (40% elemental Ca) Tums, Caltrate, Oscal
Needs acid to absorb (take w/ food)
Not good for ppl on PPIs (or those who take antacids regularly) and elderly (lack of acid)
#1 complaint is gas and bloating in F
2.) Calcium Citrate (21%) Citracal
Does NOT need acid to absorb

**Vit D deficiency tx = 50,000 IU PO 1x/wk x 6-8 wks, re-level in 8 wks, weight-bearing exercise (walking,
weight training)

**Drug Therapy: 2 Major Categories


1.) Antiresorptive Meds (bisphosphonates, calcitonin, estrogen, and SERMs) slow bone loss
2.) Anabolic Drugs (teriparatide/Forteo) only one that inc rate of bone formation

**HRT - premarin, estrace, prempro, femhrt


For post-menopausal F, works too just not used. Inhibit bone resorption

**SERMS Raloxifene (Evista)


Prevention and tx osteoporosis in postmenopausal women only, also for breast CA
Benefits of estrogen w/o ADRs
MOA estrogen agonist in bone, none in breast and uterus, anti-resorptive
Other: reduces risk breast CA by 65% over 8 yrs

**Bisphosphonates
Prev and tx in post-menopausal women and in M, steroid-induced in both (Fosamax)
MOA inhibit osteoclast activity and dec bone resorption. Dec bone loss and risk fx, inc bone
density, anti-resorptive
Oral:
o 1.) Alendronate (Fosamax) prev is tx
o 2.) Ibandronate (Boniva)
o 3.) Risedronate (Actonel)
o 4.) Risedronate (Atelvia) H sensitive coating so can travel thru stomach and rel in sm
intestine, has EDTA to pick-up stray cations, can be taken after breakfast instead of 30
min before, Needleless injection
Parenteral:
o 1.) Ibandronate (Boniva)
o 2.) Zoledronic Acid (Reclast)
Side Fx: GI upset in PO agents (N, diff swallow, heartburn, irritate esophagus, gastric ulcer,
esophageal CA)
ALL FORMS: musculoskeletal pain, uveitis, femur fx
ONJ: bisphosphonates inhibit bone turnover to heal these injuries, some ppl more at risk
(improper fitting dentures can form ulcers), use chlorhexidine gluconate rinse (Peridex) qd and
before dental sx to help
Contraindications: hypocalcemia, hx esophageal dis, gastritis, PUD, renal impairment (SCr > 2.5
mg/dl), inability to sit/stand uprt for > 30 min
Other Considerations: take first thing in the morning with 8 oz H2O, sit/stand 30 min, do not
eat/drink anything else for 30 min, do not take in a fasting state (inc risk ab pain and GI issues)
Clinical Pearls: take for 5 yrs and d/c. Then check DEXA scan in 2 yrs (if stable then d/c 1-2 more
yrs and recheck DEXA)
**Calcitonin - Calcimar SC/IM, Miacalcin intranasally
Tx osteoporosis in postmenopausal F who are at least 5 yrs beyond menopause
Nat occuring hormone for Ca regulation and bone metabolism = slow bone loss, inc bone density
in spine and red risk spine fx, least effective of all
Target: post-menopausal F, M, bone pain
Contraindications: hypersensitivity to salmon protein
Side Fx: N, H/A, nasal dryness, nasal and skin irritation, allergy, flushing of face and hands,
urinary freq, N, bloody nose

**Miscellaneous
1.) Denosumab (Prolia) psotmenopausal F at hi risk for rx or those who failed/intolerant to
other meds like bisphosphonates
MOA: human IgG2 monoclonal ab which inhibits RANKL (cytokine member of TNF family)
Dose SQ 2x/yr

**Bone Forming (Anabolic) Meds


1.) Teriparatide (Forteo)
Parathyroid hormone, take max 2 yrs
Postmenopausal F and men hi risk fx
Rebuilds bone (only one!) and sig inc bone mineral density (esp spine)
ADRs leg cramps and dizziness

DEPRESSION MEDS

**Background
Dunno the exact causes
All meds with diff MOA but all can inc monoaminergic neurotransmission in the brain inc
activity of neuropathways utilizing serotonin (5-HT), NE, sometimes DA

1.) TCA (-triptyline) = amitriptyline (Elavil), nortriptyline (Pamelor)


Block reuptake of NE and/or 5-HT into noradrenergic or serotonergic nerve terminals so inc and
prolonged stimulation in both
Problem: ALSO block dirty receptors = muscarinic cholinergic, a1 adrenergic, and histamine H1
receptors (cause many side fx)
Amitriptyline active metabolites (a and a)
Varying degrees of selectivity for reuptake pumps for NE and 5-HT, much < SSRIs
Most commonly used in chronic pain syndromes to help pt sleep

2.) SSRIs = citalopram (Celexa), Escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), sertraline
(Zoloft)
Highest affinity for 5-HT transporter
Fluoxetine (Prozac) active metabolites for so long that 1x/wk dosing is ok, thought to increase
suicide ideas (disproven but watch), can help tx bulimia and anorexia, 1x/wk for depression
Citalopram
Escitalopram = GAD
Fluoxetine = bulimia, anorexia, premenstrual dysphoric d/o, peds (depression, OCD)
Fluvoxamine = OCD
Paroxetine = social anxiety d/o, GAD
Sertraline = social anxiety d/o
Sexual dysfunction in Citalopram, Fluoxetine, Paroxetine, and Sertraline

3.) Atypical = SNRIs, NDRIs, SARIs, NaSSA, SRI/5-HT1A


Good for sleep = TCAs, trazadone (t for tiredness), mirtazapine
Venlafaxine/desvenlafaxine acts as SSRI at lower doses but once you reach higher dose
threshold, become more norepi driven
Mirtazapine = weight gain a problem (think m for metabolic)
Mirtazipine and nefazodone = lowest incidence of sexual dysfunction
Bupropion = smoking cesation
Duloxetine = peripheral neuropathy (fibromyalgia)
Mirtazapine = sedative
Trazodone = insomnia
Venlaxafine =neuropathic pain, hot flashes, sexual dysfunction
Vilazodone

4.) MAOI
1 of the enz responsible for breaking down NE and dopamine
Pooly tolerated so must be restrictive dietary wise bc turn off 1 of the pathways to breakdown
norepi
Inhibition of MAO persists even after d/c meds
Blocking MAO causes significant accumulation of tyramine
Tyramine restriction with MAOI bc increase stores of catecholamines so sensitizes pt to indirect
sympathomimetics (like tyramine) in some fermented foods, beverages, and decongestants =
potentially fatal hypertensive crisis

**ADRs with Anti-depressant Agents


Tricyclics
o T (tiredness)
o C (cardiac) = orthostatic hypotension, conduction defects, arrhthymias
o A (antimuscuranic) = blurred vision, constipation, urinary hesitancy, confusion
o s (seizures)
o Also weight gain, sexual disturbances
MAOI = postural hypotension, tyramine containing foods
Mirtazapine = somnolence, inc appetite, wt gain
Trazadone = drowsiness
Venlafaxine/Desvenlafaxine = sexual disturbances, HTN
Duloxefine/Simbalta (l in both) = liver problems
Bupropion = seizures, dec appetite
Fluoxetine/Other SSRIs = anxiety, dec libido, sexual dysfunction, teratogenic potential
Duloxetine and bupropion are weight neutral

**Serotonin Syndrome
May occur when SSRI given w/ another agent that results in a relative inc in 5-HT (MAOIs,
triptans, tramadol)
May be fatal so best plan is prevention. Watch drug interactions

**Choosing an Agent
Dosing is empiric depending on pts acceptance of ADRs, tolerance may occur
Most agents are equivalent in efficacy, type of depression determines class/agent (best are SSRIs
and SNRIs [atypicals])
Most valuable guide = FHx success/failure with class/agent
Deciding upon agents is often influenced by insurance

**Tx Algorithm
1) Acute tx phase (Wks 1-12)
2) Continuation phase (Mos 4-9)
3) Maintenance phase (Mo 9) = good time to re-eval tx plan or tapering off meds. Most pts have
longer than this

**Tapering Down Anti-Depressants


SSRIs and SNRIs can cause flu-like sx, anxiety, tremor, and other sx when stopping them cold
turkey
Should taper most anti-depressants over 4 wks, more time needed for paroxetine and
venlafaxine (TCA)
You'll see more emphasis on tx depression in pts with CAD or post-MI. Pts often get clinically
depressed after an MI, which inc risk of recurrent cardiac events
**Medication Guide
Federal law to give every time anti-depressant is dispensed

SEDATIVES

**Agents Used to Induce Sleep


1.) Antihistamines = diphenhydramine (Benadryl), doxylamine (Unisom)
Not #1 choice may cause hangover effect or idiosyncratic hyperactivity, sig anticholinergic ADRs
after cont use, many prods available instead like Tylenol or Advil PM
2.) Benzodiazepines (BZDPs, -zepam or -zolam) = Long-acting are flurazepam (Dalmane), quazepam
(Doral); Intermediate-acting 10-20 hrs = estazolam (Prosom), temazepam (Restoril); Short-acting 3 8
hrs = triazolam (Halcion)
Marketed for sleep
Also alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium),
clorazepate (Tranxene), lorazepam (Ativan), oxazepam (Serax)
CIV
MOA: interact with gamma-aminobutyric acid (GABA) receptor, act as an agonist to an inhibitory
sys
Sedative, hypnotic, mus relaxant, amnesia, anxiolytic properties, ETOH withdrawal
Work well as sedatives but tolerance develops rapidly to sedative fx (days wks), must balance
need to fall asleep with hangover fx of agents in the AM
Also effective in tx autonomic and somatic sx of anxiety d/o (internal sx)
DO NOT use in elderly inc falls
Duration of action varies in benzos, formation of active metabolites plays a major role in fx
ALA = alprazolam, lorazepam, oxazepam = shorter t1/2 and min drug accumulation (few/no
active metabolites)
CYP450
Onset of Action: Rapid 15-30 min, Intermediate 30-45 min, Slow 45-90 min
T1/2: Short <10 hrs, Inter 10-36 hrs, Long > 48 hrs
1) Alprazolam = intermediate onset, intermed t1/2
2) Flurazepam = rapid onset, long t1/2
3) Lorazepam = inter onset, inter t1/2
4) Oxazepam = slow onset, short t1/2
5) Triazolam = rapid onset, short t1/2
ADRs = CNS depression most common (sedation, psychomotor impairment, ataxia), anterograde
amnesia (cant create new memories after event)
Midazolam (Versed) = amnesia, used as anesthetic
Tolerance/Dependence = high dose, chronic therapy (GAD, panic d/o)
Benzo withdrawal shorter t1/2 with chronic use leads to worse withdrawal and a rapid onset.
Consider switching to longer acting benzo then tapering
Sedative hypnotics
1) Flurazepam = shortens time to fall asleep, lengthens sleep time, dec awakenings. No
rebound insomnia, sig AM hangover sedation, active metabolites can last 80+ hrs
2) Temazepam = pts who cant stay asleep, take 1-2 hrs before bed, less hangover fx bc
intermediate acting
3) Triazolam = short-acting, pts who cant fall asleep, tolerance to sedative fx dev rapidly
(days), rebound insomnia is the worst here

3.) Z-Hypnotics =Zolpidem (Ambien), Zaleplon (Sonata), Eszopiclone (Lunesta)


CIV controlled
MOA: act on subset of benzo receptor family BZ1
No anticonvulsant, mus relaxant, withdrawal, little/no tolerance
PK differences:
1) Zolpidem has rapid GI absorption, available IR or CR, dont use longer than 2 wks
2) Zaleplon = fast t1/2 (<1 hr), for night-time awakening lasts 4 hrs. if wakes up at 3 AM
can still take it and wake up in the AM whereas lunesta and ambien needs 8 hr sleep
3) Eszoplicone: rapidly absorbed, effective up to 6 mos
All have some addiction pot?
Little/no tolerance after prolonged use
Can produce some rebound insomnia
Side Fx = nightmares, sleep eating, sleep walking, agitation, HA, GI upset, dizziness, daytime
drowsiness, anxiety, chest pain, migraine, unpleasant taste

4.) TCA (-triptylline) = amitriptylline (Elavil), nortriptylline (Pamelor)


Good candidates = pain syndromes to help w/ sleep d/o can help with neuropathic pain
Marked sedation with hangover so take 3 hrs before bed ... So should take at 5 PM
Lower seizure threshold, cardiac fx

5.) Ramelteon (Rozerem)


MOA: works on melatonin rec as agonist at MT1 and MT2 receptors

6.) Melatonin
Nat occurring hormone, prod in nocturnal circadian cycle and only in darkness
Safe in children

7.) Barbiturates DONT use

ANXIOLYTIC GUIDE

**Anxiety Background
Crossover with depression sx
Many diff types of anxiety disorders
Imp to distinguish btwn situational (temp, normal to stress) vs chronic anxiety d/o
Long term goals = remission with minimal or no anxiety sx with no functional impairment

**Drugs Associated w/ Anxiety sx


CNS depressant withdrawal in anxiolytics/sedatives, barbiturates, ethanol, narcotics
CNS stimulants = albuterol, amphetamines, cocaine, caffeine, ephedrine, phenylephrine,
phenylpropanolamine, pseudoephedrine

**Specific Meds
1.) Benzos = Lorazepam (Ativan) and Alprazolam (Xanax)
o Most effective, safe, and commonly rx drugs for rapid relief of acute anxiety sx and prn
meds for breakthrough anxiety
o All equally effective choose based on kinetics and pt
o Most effective in tx autonomic and somatic sx (internal sx/noise, restlessness)
o High dose = hypnosis and stupor
o Tolerance/Dependence: abuse rare
2.) Buspirone (Busbar) = unrelated to benzos, as effective w/o anticonvulsant, mus relaxant, motor
impairment, and sedative fx
For pts w/o comorbid depressive sx/anxiety d/o that benefit from antidepressant
Not prn, ATC
Basically no abuse potential use in ppl w/ abuse hx

**DOC
Gen Anxiety = 1st line use venlafaxine, paraoxetine, excitalopram, duloxetine, sertraline
Social Anxiety = venlafaxine, paroxetine, duloxetine, sertraline
Basically 1st line anti-depressants, 2nd line benzos
Test ?: Best drug for depression w/ anxiety component? Ans: 1 of the 5 drugs
Test ?: Pt w/ anxiety, depression, and wants weight neutral drug? Ans: Duloxetine
Test ?: Worst choice for above pt? Paroxetine
Test ?: Best for no weight gain? Prozac
3.) Propranolol (Inderal) =mgmt anxiety sx, esp stage-fright
4.) Antidepressants = 1st line tx for long-term mgmt chronic anxiety

**Antipsychotic Agents and Mood Stabilizers Background


Antipsychotic and neuroleptic used interchangeably to tx schizophrenia (mainly) and other
psychoses/agitated states
Tx schizophrenia, Tourettes syndrome, behavioral issues in Alzheimers disease, psychotic
depression, ADD/ADHD, refractory depression, and autism

**Agents = dopamine antagonist


1.) Typical (older, conventional) antipsychotics [zine, loxapine, Haldol, thiothixene] = chlorpromazine
(Thorazine), fluphenzine (Prolixin), haloperidol (Haldol), thioridazine (Mellaril), thiothixene (Navane),
loxapine (Loxitane)
Use for psychotic agitation
2.) Atypical (newer) [-pine and done, abilify]= aripiprazole (Abilify), clozapine (Clozaril), olanzapine
(Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon), paliperidone (Invega),
asenapine (Saphris), Iloperidone (Fanapt), lurasidone (Latuda)
Low potency agents (high dose) = chlorpromazine (Thorazine), thioridazine (Mellaril)
High potency agents (low dose) = haloperidol (Haldol)
o More potent, more bang for buck
Can all cause EPS (extra-pyramidal sx)
o Clozapine = agranulocytosis (must check WBC and calc absolute neutrophil count), HIGH
wt gain, DM, dyslipidemia. Lim to pts who failed to respond to conventional agents or
atypical drugs
o Risperidone = EPS
o Olanapine = HIGH wt gain, DM, dyslipidemia
o Quetiapine = sedation (quiet)
o Ziprasidone, Aripiprazole, asenapine, paliperidone = QT prolongation
o Asenapine, paliperidone = QT prolongation
o Aripipraole = A for augmentation therapy, Alzheimers, autism, ADD/ADHD sometimes,
less wt gain, long t1/2, novel mech, ? novel toxicities
PK = IM injections (typical older agents)

**EPS = side fx of typical older agents and Risperadone (only newer one)
Dystonia = side fx tx initiation within 24-48 hrs, bizarre muscle spasms usually involving the head
and neck
Akathisia = us within 1st few mos, desire to be in constant motion caused by dopamine
Akinesia = us within 1st few mos, diminished spontaneity see this in Parkinsons
Drug-Induced Parkinsonism = maybe indistinguishable from idiopathic parkinsonism, mus rigidity
and bradykinesia are common, us controlled by anticholinergic agents or amantadine
Tardive dyskinesia = major side effect that responds poorly to therapy, invol and repetitive
movements of limbs, trunk, and facial struc - tongue protrusion, licking lips, chewing, eye
blinking); best tx is prevention
Neuroleptic Malignant Syndrome = life-threatening, pts sensitive to EP fx of these meds

**Choice of Agents = New agents tx both pos and neg sx (clozapine), older only tx positive sx
**Lithium = For bipolar d/o, used to be standard but now less used
MOA: None
ADRs = wt gain, hand tremor, GI (NVD, dyspepsia)
Dehydration, Na restriction, V, D, drug interactions that dec lithium clearance = inc risk of lithium
toxicity

MGMT GOUT AND HYPERURICEMIA

**Intro
ETOH (beer is the worst), diuretics (thiazides and loops), high fat diets
Metabolic disease

**Therapeutic Agents

1.) NSAIDs all except aspirin


1st line mgmt acute gout attacks w/ normal renal function and no PUD
MOA = inhibit prostaglandin synthesis and urate crystal phagocytosis
Ex of indomethacin dosing = 50 mg tid until a response is seen, then dec dose to 25 mg tid x 5
7 days

2.) Systemic Steroids


Unable to take NSAIDs or colchicine (bc renal insufficiency)
2 drugs that irritate stomach the most are NSAIDs and steroids (microbleeds, so take with food)

3.) Colchicine = Relieves pain and inflammation with no effect on metabolism or excretion of urates
Indications = prev of recurrent episodes of gout in pts unable to take NSAIDs or steroids (peptic
ulcer risk), no longer TOC to manage acute attacks (bc ADRs, esp D)
MOA = Inhibits neutrophil engulfment of UA crystals by binding to intracellular protein tubulin =
inhibition of leukocyte migration and phagocytosis, antimitotic fx (arrest cell division in G1),
inhibits leukotriene B4
PO Dosing:
o Prophylaxis 0.6mg
o Acute attack Trad: 0.6-1.2 mg asap then 0.6 mg q2 hrs until pain relieved or diarrhea aka
beginning of toxicity
o Acute attack New: 1.2mg stat, then 0.6 mg * 1
o IV: dont do anymore bc inc bone-marrow toxicity
ADRs = GI = (NVD, abdominal pain; diarrhea most common), bone marrow depression

4.)

GOUT CONTINUED

**Uricosurics = Probenecid, Sulfinpyrazone


Indications = uric acid under-excreters, use 2-3 wks after acute attack
MOA = inhibits re-absorption of UA in renal tubules
Test ? = Which drug needs to be delayed several wks after gout attack to avoid kidney stones or
need to be started with another drug? Uricosurics
ADRs = kidney stones, prev by 2L/day lg urine vol
Drug Interactions with Probenecid = ASA (retains uric acid) and PCN

**Allopurinol (Zyloprim)
Indications: standard btwn acute gouty episodes to dec total uric acid levels in body, for over-
producers
MOA: xanthine oxidase inhibitor
Dose: should use colchicine or NSAID until uric acid levels are 6 mg/dL to prevent gout attack
Renal impairment dose adjustment exists
ADRs: GI (NVD), peripheral neuritis, necrotizing vasculitis, BM suppression, allergic rxn (skin
lesions/rash is #1 common), hepatic toxicity, interstitial nephritis
Drug Interactions: azathioprine or mercaptopurine, allopurinol inhibits metabolism of
probenecid and warfarin

**Febuxostat (Uloric) = new xanthine oxidase inhibitor (non-purine) similar to allopurinol


Indications = tx chronic gout in over-producers or under-excreters
Dosing: no dose adjustment needed in renal impairment (vs allopurinol)
ADRs: use colchicine or NSAID at the beginning of tx until urate levels dec, LFT abnormalities,
N/D, H/A

**Corticosteroids = intra-articular injections

GENITOURINARY MEDS

**BPH
1.) 5a-Reductase Inhibitors (-eride) = finasteride, dutasteride
Good if enlgd prostate (can shrink, if dont want sx); if cant tolerate CV SEs of a-antagonists; pts
w/ arrhythmias, angina, anti-hypertensives
MOA = convert testosterone and androtestosterone to dihydrotestosterone aka inhibit
testosterone and interfere with stimulatory fx on prostate (no libido), works on epithelial tissue
in prostate which is under androgen control
Only shrinks size 25% bc stromal tissue containing alpha-1a rec is lg amt
These agents can: shrink prostate over time, improve long-term urinary sx, dec risk of acute
urinary retention, dec need for prostate sx
Monitoring Efficacy: slow onset bc takes 6 mos to shrink max enlgd prostate, should dec PSA
50%, size and sx go back to baseline, in PSA if doesnt dec by 50% by then then recheck for CA
Monitoring Toxicity: inc sexual dysfunction so dry/delayed ejaculation, ED, and gynecomastia

2.) A-adrenorec antagonists (alpha blockers; -zosin) = prazosin, doxazosin, terazosin


Not as good as monotherapy in BPH and HTN, NOT DOC ANYMORE!
They relax bladder mus to quickly improve urinary flow and dec uncomfortable sx of enlgd
prostate but dont shrink size
3.) Alpha-1a Adrenoreceptor Antagonist(-osin) = tamsulosin (Flomax), alfuzosin, silodosin
Uroselective (1A) enz, pts who cant tolerate hypotn of prev agents, CAD, arrhythmias,
orthostasis, liver failure, mult BP meds
1st line if need QUICK RELIEF!
MOA: relax prostatic stromal smooth mus (majority prostate tissue), dont shrink size
Monitoring: do not dec PSA, works quickly
Toxicity: dec CV side fx due to specificity

4.) Saw palmetto = bad, dont use bc better options

**ED = Drugs DO NOT tx libido, ejaculatory, or infertility d/o

1.) Phosphodiesterase Type 5 Inhibition (PDE5) (-afil) = sildenafil (Viagra), vardenafil (Levitra), tadalafil
(Cialis)
MOA: Inhibition of PDE5 prev degradation of cGMP in penis, all sinister causes should be
RO/identified
Vasodilates globally
Viagra
o Dosing: M > 65, hepatic or renal insufficiency should start w/ a lower dose
o Half-life of Levitra is 3-4 hrs, Cialis 17 hrs, Efficacy up to 36 hrs aka weekender (higher
dose Cialis)
o Use approx 1 hr before sexual activity, take Viagra 30 min-4 hrs before sex
o Viagra and Levitra must be taken a certain amt of time before sex, only work if there is
sexual stimulation
Levitra max is once per day
ADRs: H/A, flushing, rhinitis (1st 3 vasodilator ADRs), indigestion, auditory issues (loss of hearing,
tinnitus, Cialis back pain bc PDE11 isoform inhibition, visual disturbances (blue tinge, blurry
vision, blue and gr confusion, loss of vision 1 or both eyes), transient global amnesia (< 6 hrs)
Precautions: prolonged erection > 4 hrs, priapism is a painful erection > 6 hrs seek help ASAP bc
penile tissue damage and permanent loss potency are ADRs
Cause systemic vasodilation (PDE5 also in peripheral vas tissue) = transient dec BP; eval
appropriateness of use in pts with cardiac issues (MI, arrythmias, obstruction issues (aortic
stenosis), hypo tn, extreme drops in BP, stroke)
Drug Interactions: Absolute contraindication with nitrates (fatally low BP bc PDE5 in peri vas
tissue)
Also see daily use of these agents to tx BPH 2-for-1 b/c many men have ED and BPH

2.) MUSE = 1-time use, med TU sys to deliver alprostadil to M urethra


MOA: dose-dependent smooth muscle relaxation and vasodilation in penile tissue
Dosing: Duration of fx ~30-60 min, each pt should be instructed by med professional on proper
tech for administering MUSE prior to self-administration
ADR: Local mechanism of action so reactions with other medications is unlikely

3.) Caverject impulse = injectable alprostadil dual chamber sys


Prefilled syringe if dont respond or cant use pills
Local mechanism of action so reactions with other medications is unlikely
4.) Dietary supplements = Zimaxx, Libidus, Neophase, Nasutra, Vigor-25, Actra-Rx, 4EVERON
Not rec

Rheumatoid Arthritis

**Introduction
Systemic autoimmune disease = shortened life span traditionally, joint disease = reduced
mobility and QOL
Higher rates of morbidity and mortality death from inf and CV causes
Inflammation of joints is hallmark = swelling, tenderness, restricted ROM. Deformity may result
as dis progresses
Other organs can be affected (extra-articular manifestations) - eyes, lungs, heart and bv, liver,
hematologic system
Traditional therapy centered around dec pain and inflammation bc inflammatory dis not
immunologic

1.) NSAIDs= Ibuprofen, naproxen sodium


Test ?! :: Symptomatic relief, dont tx dis itself
Dec inflammation and pain = better movement and ADL with little/no effect on progression of
bone and cartilage destruction
Currently used to tx sx but thats it. Tx now centered around controlling the immunologic
mechanisms for the dsease (DMARDs and biologics)

2.) Systemic steroids


For severe flares inv multiple jts, extra-articular manifestations (pericarditis, eye)
Detrimental to someone with autoimm dis bc suppress further with steroids

3.) Intra-articular injections (-one) = methylprednisolone, betamethasone, triamcinolone


Systemic steroid bc drug stays in the joint space
Local anesthetic added = quick relief but wears off in a few hrs so joint may feel worse for 1-few
days
Steroid irritates tissue in some patients = severe pain for a few days so ice ASAP after injection
on and off for 24 hrs, may take up to 10 days to see full benefit
ADRs: inc pain or swelling of injected joint for 1 st 24 hours; swelling, redness, or inc pain after 24
hours may signal inf and needs to be evaluated; tendon rupture, damage to bone

**DMARDs
1.) Methotrexate
MOA= inhibits dihydrofolate reductase and leukotriene synthesis
1st choice DMARD
Low folic acid in these pts so must take supplement
Dec rate of appearance of new erosions
Test ?! :: Only one that dec death from CV dis
Some data: May dec death due to other causes in RA pts further eval needed
Monotherapy; Also in pts on biologics (esp infliximab Remicade) bc boost efficacy and dec
ability of body forming ab vs drug
PO only 2.5 mg tablets, some use smaller doses if taken with other DMARDs or due to ADRs
ADRs: N and stomatitis most common; BMS, liver toxicity, pulmonary toxicity, alopecia
Prescription 1 mg Folic acid or folinic acid helps limit GI and liver toxicity, take 6 days/wk NOT on
methotrexate day

2.) Leflunomide
L for liver toxicity

3.) Hydroxychloroquine (Plaquenil)


Anti-malarial
Can cause ophthalmic problems bc very tissue-bound in melanin-containing tissues
Methotrexate-sparing = boosts efficacy so same efficacy at lower dose so fewer mtx ADRs
ADR: ocular toxicity, dyspepsia, NV, ab pain, rashes (psuedo-psoriasis us on face), nightmares
Safe in pregos

4.) Gold (Au-) = IM aurothiomalate and aurothioglucose; PO auranofin


ADR: Metallic taste

5.) Sulfasalazine
Effective in RA dec radiologic dis progression
Inc in use esp if cant take methotrexate
ADRs: N, V, HA, rash, hemolytic anemia, neutropenia, thrombocytopenia, pul toxicity, infertility
rev in M
Safe in pregos Plaquenil and this are the only ones

**Biologics = also a DMARD


Cytokines lg role in imm res and RA
TNF and TNA-a trouble makers
Do not administer live vax
Not allowed to have dose if any active signs or sx of inf or if patient was on ab, must have
regimen for 7 days prior to next dose

TNF
1.) Etanercept (Enbrel)
Indications: RA, juvenile RA, psoriasis, psoriatic arthritis, ankylosing spondylitis
Dec rate of formation of new erosions = to mtx alone
MOA: Inactivates TNF-a = down-reg macrophages and T-cell func
Injectable ADRs: rejection site irritation and discomfort, mild URT sx, rare aplastic
anemia/pancytopenia/death from sepsis, activation latent TB, macrophage-dep inf, lymphoma?

2.) Infliximab (Remicade)


Boost efficacy and prev formation of anti-infliximab ab = inact efficacy

3.) Adalimumab (Humira)

4.) Certolizumab (Cimzia)


PEGylated medication = forms protective barrier around compound so it stays in body longer
5.) Golimumab (Simponi)

T Cell
1.) Abatacept (Orencia)
MOA: unique mech, selectively modulate co-stim signal req for full T-cella ct, works upstream
from TNF-a agents
Indications: reduce signs and sx and slows progression of struc dam in adults with mod-severe
active RA who had inadequate response to TNF inhibitors or other DMARDs

IL-6
1.) Anakinra (Kineret)
MOA: IL-1 receptor antagonist

2.) Tocilizumab (Actemra)


MOA: inhibits IL-6
Maybe only biologic ok for monotherapy, pts who failed TNFI therapy
ADR: inc LDL

B-Cell
1.) Rituximab (Rituxan)
PML scares ppl
MOA: B-cells aka WBC of immune sys has role in immune system attacking bodys joints. This
med targets specific B-cells and sel reduces them in blood, this lim immune sys attack and pain
and sx

**Bascially:
1st line too much TNF = etanercept, infliximab, adalimumab, certolizumab, golimumab
Then IL-6 = anakinra, Tocilizumab
Or T cell activity same level as above = abatacept
Last choice too much B cell activity = rituximab

**Tx decisions: Traditionally NSAIDs 1st then DMARDs added Currently DMARDs sooner, do not use
after 3 months of RA dx
1.) Methotrexate gold standard 1st line, Sulfasalazine/Hydroxychloroquine 2nd choice
Along with NSAIDs prn but toxic though
Consider short burst systemic steroids at dx and intra-articular injections
Try at least 3 TNFI before moving onto the next dot (Rutuximab)
Active dis = monitor q3 months, adjust if no improvement or target not reached in 6 mos
2.) If 3-6 mos later if not improved enough then add another DMARD same choices
3.) If fail then go to a biologic use all with methotrexate except tocilizumab

OA
Mild Mod pain = APAP, COX2, NSAIDs, tramadol (only one safe long term)
1.) Intra-articular Injections (hyaluronic acid derivatives) = hyalgan, synvisc
Theory = supplements knee jts endogenous synovial fluid = relief from pain and imp in knee use;
inhibit inflam mediators; stim cartilage matrix synthesis
Tx = 3 or 5 shots into knee jt over 3-5 wks
ADRs = pain and swelling of jt, ? long-term
2.) Corticosteroids = inj up to 3-4x/yr in 4-6 mo intervals
3.) Chondroprotective agents = adjunctive = glucosamine and chondroitin
Typically rec combo product but efficacy alone or in combo is debated
Research possibility may modify OA
Can take 4++ wks to see benefits
4.) Topical Analgesics = adjunctive
a.) Capsaicin cream = red pepper, must use consistently (NOT PRN) to get max benefit
b.) Diclofenac Sodium Gel 1% (Voltaren)
o 1st RX topical NSAID for pain
o Dosing = dosing card to show how much gel/gram
c.) Diclofenac epolamine patch (Flector patch)
o 1st transdermal NSAID patch in US
o For topical tx acute pain from minor strains, sprains, and contusions
d.) Lidoderm patch = for mod-sev chronic pain in OA, numbing patches that stay in patch areas,
most common ADR is skin rxn

HEADACHES

**Non-Specific Agents = mild to mod attacks, 1 st line!


1.) NSAIDs = 1st line are ibu, naproxen sodium
a. Problem is hi dose and feq use, so problematic ADRS
2.) APAP = 1st line too!
a. Short duration of action so must take mult doses bc H/A longer t than dose
3.) Analgesic combo = freq use as 1st line, caffeine inc drug absorption
a. butalbital (barbituate)/APAP/caffeine (Fioricet)
b. butalbital/ASA/caffeine (Florinal)

**Specific agents = work on neurovas mech


1) Ergotamine prods
MOA = constrict peripheral (problematic) and cranial vessels
Test ?: Avoid this drug in who? Pts w/ PVD, CV dis, cerebrovas dis, hep or renal disease
2) Triptans = sel 5-HT1B/1D rec agonists (inc serotonin so DO NOT use with them or else serotonin
syndrome); agonists at these receptors that are loc on sm peripheral nerves that innervate
intracranial vas
a. Sumatriptan = needleless inj
i. Ex: Sumatriptan (imitrex) instructions = take 1 tablet at onset, may repeat in 2
hrs * 1, DO NOT EXCEED max 200mg/day dose!
ii. Aura = take dose at onset
b. Naratriptan = Test? :: 1-2.5 mg at onset, rep in 4 hrs prn, max 5
c. Rizatriptan = 5 mg if on propranolol, #1 drug for migraine prophylaxis
i. 5-10 mg onset, rep 2 hrs prn too, max 30

ii. Use SQ > PO bc speedier, some pts think it works better


iii. If 1 doesnt work try another
d. Teximet (sumatriptan + naproxen) = migraines, 1st triptan/NSAID combo
e. Triptan ADRs = CNS like paresthesia, dizziness (1 central, 1 peripheral)
i. CV = causes coronary vasospasm
ii. DO NOT use in CV dis, uncontrolled HTN, cerebrovas dis, PVD bc 5-HT is a
vasoconstricter so problems appear when cardiac endothelium is damaged and
vasoconstriction occurs
f. Triptan Drug interactions = serotonin syndrome (SSRIs and tramadol), hypertensive crisis
(MAOI), and ergots (sep by up to 2 wks)
Rebound H/A = overuse of agents (any) or abrupt withdrawal (triptans) can ppt sev rebound H/A
that can inc in severity and freq; limit meds to 2 days/wk max
Prev therapy = if migraines occur 2x+/mo or if refractory to drugs or if predictable attack pattern
= BB (esp propranolol), topiramate
o BB cant be used in bradycardia, asthma and COPD (bronchospastic dis), depression w/
sev anxiety
o #1 ADR of topiramate is kidney stones

SEIZURES

1.) Phenytoin = Dilantin, Parke-Davis aka diphenylhydantoin (DPH)


Good in focal seizures
Absorption = highly p bound (90% mostly to albumin)
Elimination = dose dep elim, very low blood levels = metabolism follows 1 st order kinetics
ADRs = ny for nystagmus, gingival hyperplasia, Stevens Johnson Syndrome (necrotizing skin rxn)
2.) Carbamazepine (Tegretol)
Also for bipolar d/o bc related to older anti-dep
Good in focal seizures
Elim = >95% hep metabolism; active metabolite
Autoinduction (chew self up) = stim own metabolism by day 3 and is max after 1 month, occurs
everytime dose is altered t1/2 hrs (36 hrs initiation therapy 8-12 on cont therapy)
3.) Valproic acid = depakene, depakote, enteric coated tablets
Good in Tonic-clonic, Absence, Focal, and Atypical Absence/Myoclonic, and Atonic seizures
Food delays rate but not absorption
P binding
Hepatic elimination
Hepatic necrosis ADR
4.) Phenobarbital = sedating
5.) Ethosuximide - nv
6.) Gabapentin (Neurontin)
#1 use is neuropathic pain, paresthesis from DM
Tonic clonic seizures
ADR = sedation, confusion, wt gain
7.) Pregabalin (lyrica) = neuropathic pain too, replaces gabapentin
a. ADRs = weight gain, dizziness, somnolence, ataxia, speech disorder, confusion
8.) Lamotrigine (lamictal) = neuropathic pain too
a. Tonic-clonic, atyp absence/myoclonic/atonic
b. In psychosis (bipolar, schizophrenia)
c. ADRs = Stevens Johnson dis (also phenytoin!)
9.) Topiramate (topamax)
a. Neuropathic pain, migraine H/A prophylaxis
b. ADR = weak carbonic anhydrase inhibitors so can inc kidney stone risk (alkalinize urine)

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