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Penicillins
Cephalosporins
Carbapenems
Monobactams
Tetracyclines Clindamycin
Aminoglycosides Linezolid
Daptomycin
1
Inhibitors of DNA, RNA and Protein Production
Co-trimoxazole
Fluorquinolones
Metronidazole
Inhibitors of Cell Wall Synthesis
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
Elimination: t is short, excreted primarily by kidneys except anti-staphylococcal PCNs (Nafcillin and
Dicloxacillin, biliary excretion)
Natural PCNs
Antistaphylococcal PCNs
Gram
Gram and Gram + less effective (use Piperacillin for some Gram + cocci)
Uses: Pseudomonas
These extend Gram + and Gram activity to include - lactamase producing organisms
Relatively safe
Rapid absorption
Cefadroxil (PO)
Cephalexin (PO)
No CNS penetration
Cefaclor (PO)
Cefprozil
Cefuroxime
Cefuroxime axetil
Spec. of Activity: Gram + (like 1st Gen.) and Gram (more than 1st Gen.)
No CNS penetration
Cefdinir (PO)
Cefixime (PO)
Cefotaxime* (Parenteral) Gram +
Ceftibuten
Cefditoren
Cefepime
Ceftaroline
Spec. of Activity: MRSA (will be on test!); Multi-drug resistant (MDR) staph and strep
Hypersensitivity Rxns
Imipenems/ Cilastatin
Meropenem
Doripenem
Top 3 drugs: Gram + aerobes, Gram - aerobes, and anaerobes. Has pseudomonas activity.
Monobactams
Aztreonam
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)
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
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
Chelation Drug Interactions- when given with any Positively charged item, results in decreased absorp.
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
Clarithromycin
Azithromycin (exception)
Telithromycin
Metabolism: Erythromycin and Clarithromycin are inhibitors of CYP 3A4. Azithromycin is the exception. It
does not metabolize. Has no issues.
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
Aminoglycosides
Amikacin
Gentamicin
Tobramycin
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
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
Spec. of Activity: Gram + and anaerobes, May work for comm. Acq. MRSA
Quinupristin/ Dalfopristin
IV only
Linezolid
IV + PO
Adverse Rxns: Tyramine restricted diet Italian deli meat diet, Thrombocytopenia
Daptomycin
Co-trimoxazole
Anti-metabolite-sulfa drugs
PK: PO + IV; highly protein bound (>95%); penetrates most body fluids including CSF
Adverse Drug Rxns: Dermatologic (rash + photosensitivity); HIV pts 50% higher chance getting rash
Fluoroquinolones
Ciprofloxacin
Norfloxacin
Ofloxacin
Levofloxacin
Moxifloxacin
Gemifloxacin
Spec. of Activity: Gram aerobes, including pseudomonas, some Gram - anaerobes; Some Gram +
aerobes
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
PO + IV
Adverse Drug Rxns: Avoid Alcohol! For more than 72 hours after disc. Of metronidazole
Sulfa List
Co-trimoxazole
Celecoxib
NSAID LECTURE 1
-anti-inflam
**MECHANISM - 1971
-Cascade: NSAIDs work on arachidonic prostaglandins (Support renal and platelet func, protect gut,
inflammation & pain)
-Give NSAIDs: cyclooxygenase or prostaglandin inhibitors
-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
-COX-1 = bad, tough on stomach and GI tract, vasoconstrict kidneys, inhibits platelets
-Celecoxib = COX-2 specific inhibitor, only benefit is slight dec GI toxicity, bad bc expensive
-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
-renal perfusion: NSAIDs inhibit COX in kidney, PGE2 dec, vasoconstrict acute renal failure
-peripheral edema, acute renal insuff, hyperkalemia, renal necrosis long term use
-if aspirin allergy, then allergic to other NSAIDs and COX-2 agents. Bronchoconstirction, nasal polyps (bc
inhibition prostaglandin synthesis)
**4.)CNS toxicity bc cross BBB = HA, dizziness, tinnitus, mostly salicylates aspirin prototype
**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
**Acetaminophen (Tylenol)
-APAP = N-acetyl-p-aminophenol, paracetamol
-pain and fever, NOT an NSAID and NO anti-inflam, dunno how mech works
-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
**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)
-M & W > 80 yo = rec ONLY if high CV risks and no addl GI bleeding risks
-Ticlopidine causes blood dyscrasia (off) and leukopenia, fatal, so no longer 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 = 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
-Dipyridamole
-Dipyridamole + Aspirin
-MOA = WEAK anti-platelet activity
-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
-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:
-flushing rxn
-hepatotoxicity
*Mgt Hepatotoxicity
-asymptomatic pts with inc LFTs from baseline > 3-5x hold INH until returns. < is normal
*Treatment Latent TB: give INH for 6 (competent imm sys) or 9 mos (immunocompromised)
*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
NSAID LECTURE 2
*Anti-coagulants
-MOA: inhibits Vitamin K dep coag factors (2, 7, 9, 10, protein C and S incomplete coag factors not
biologically active)
-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
-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:
*Misc PO Anti-Coag
-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)
***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?!
**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
**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)
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)
**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
**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
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
**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
**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
**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)
***HLD***
PHARM GUIDE 2
**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
**Combo therapy: monitor closely bc inc risk similar side fx. Vytorin (simvstatin + ezetimibe) recent
controversy
LDL LIST
Bile Acid Sequestrants
ALL 3 LIST
Statins
Niacin
**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)
***Misc Agents***
***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***
**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)
**Type 4 = CCBs
Verapamil, diltiazem
PHARM GUIDE QUIZ 1
**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
-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
**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)
**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
**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
***Hyperthyroidism***
***Adjunctive Tx Measures***
***Hypothyroidism***
UTI Lecture
**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
**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
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
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
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
**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
**Glycerin suppository = safe in children, osmotic action in rectum, onset < 30 min
**Saline = magnesium citrate, magnesium hydroxide, sodium phosphate, polyethylene glycol solutions
**Methylnaltrexone
Tx constipation in pts using opiods, opiod antagonist like naltrexone
Only for palliative care/hospice pts who arent relieved from laxatives
Antidiarrheal agents
Travelers diarrhea fever maybe, blood and mucus in stool are dealbreakers for Imodium bc
toxin/gas produced can perforate gut
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***
***LONG TERM***
**Combos
Fluticasone propionate + salmeterol xiafoate ( Advair Diskus, Advair HFA )
budesonide + formoterol (Symbicort)
mometasone + formoterol (Dulera)
**Methylxanthime = theophylline
MOA bronchodilator, increase diaphragm contractility and mucociliary clearance
ADR = dose-rel acute toxicities. Tachycardia, restlessness, convulsions, insomnia
**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
**Corticosteroids
Lil controversy
***Infective Endocarditis***
**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
**Prophylaxis in: artificial heart valve, hx heart inf, certain serious heart conditions since increase birth,
and heart transplant that develops a heart valve problem
***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
**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
**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
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
**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
**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)
**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)
**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
WOMENS HEALTH
**Menopause
Intact uterus must get most estrogen and progesterone [unopposed estrogen can lead to
endometrial CA]
Good candidates = osteoporosis [worry about cardiac issues]
**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
**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)
**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
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
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
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
**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
SEDATIVES
6.) Melatonin
Nat occurring hormone, prod in nocturnal circadian cycle and only in darkness
Safe in children
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
**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
**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
**Intro
ETOH (beer is the worst), diuretics (thiazides and loops), high fat diets
Metabolic disease
**Therapeutic Agents
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
**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
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
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
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
**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
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
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?
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
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
SEIZURES