COMPREHENSIVE TABLE OF DRUGS

1st Shifting Period NOTE: Should there be any discrepancies between this table and whats written in the transes, please consult KATZUNG for confirmation and go instead with whats indicated in the textbook. Thank you!

Monique Wine Jamie Juria Lenard

Section 2D Batch 2014

PHARMACOLOGY: COMPREHENSIVE TABLE OF DRUGS (1st Shifting Period) | Page 1 of 29

CHOLINERGIC ANTAGONISTS (PARASYMPATHOLYTICS) CHOLINERGIC AGONISTS (PARASYMPATHOMIMETICS)

A. ANTI MUSACRINIC DRUGS CHOLINORECEPTOR-ACTIVATING Mechanism of Action
Atropine Acetylcholine Reversible blockade of actions of Binds cholinomimetics to and activates at muscarinic or nicotinic muscarinic receptors receptors. (competitive binding and inhibition). 2 Major mechanisms: How do acetylcholine and anti-muscarinic 1) Ach release drugs bind to activates muscarinic muscarinic receptors? Aspartate receptors on in the third effector cells & transmembrane alters organ segment of the function directly. muscarinic receptors forms a nitrogen bond 2) Ach Release with the nitrogen ion interacts with the of acetylcholine and muscarinic the anti-muscarinic receptors on nerve drugs, which explains terminals to inhibit their competitive release of binding. neurotransmitter. When atropine binds to the muscarinic receptor, it prevents two mechanisms: the release of IP3 and the inhibition of adenylyl cyclase.

Organ System Effects Organ System Effects

Central Nervous System Eyes Miosis Atropine has minimal stimulant effects on the Accommodation for near CNS the vision (especially parasympathetic Contraction of both the medullary centers) and a smooth muscles of the slow, long-lasting iris and the ciliary sedative effect on the muscles facilitate brain. aqueous humor outflow into the canal more Scopolamine has of marked central effects: Schlemm, draining the drowsiness anterior chamber and amnesia; can also thus helping in cause the excitement, agitation, treatment of hallucinations, and coma glaucoma. in toxic doses. Cardiovascular System Reduction of inotropic, tremors (-) in Parkinsons disease. chronotropic, Parkinsonian tremors dromotropic effects are caused in peripheral Reduction by a relative excess of cholinergic vascular resistance activity because of a Vasodilation deficiency of Decreased BP activity in dopaminergic reflex increase in heart gangliarate the basal striatum system. Direct cardiac actions of muscarinic Motion sickness appears stimulants to involve muscarinic are mediated by M2 cholinergic receptors transmission. while Best alleviated by vasodilation arises from scopolamine. of activation M3 Eyes receptors. Respiratory System The pupillary constrictor Bronchoconstriction on muscle depends Stimulation ofcholinergic bronchial muscarinic gland secretions activation. This Gastrointestinalis blocked by activation System anti-muscarinic Increased motility drugs and results in mydriasis Relaxation of sphincters (pupillary dilation).gastric Stimulation of secretions, but less Cyclopegia stimulation in pancreatic weakening the and intestinal secretions contraction of the ciliary muscle, The M3resulting in the receptor is loss of the ability to required for direct accommodate and thus activation of smooth cannot focus on near muscle contraction while vision.2 receptor reduces the M cAMP Decreased lacrimal formation and secretion relaxation caused by Cardiovascular System adrenergic agonists.

Adverse Effects Adverse Effects

Mydriasis Cycloplegia Atropine poisoning: dry mouth, mydriasis, hot and flushed skin, agitation, delirium for as long as one week. Remember: Dry as a bone, blind as a bat, red as a beet, mad as a hatter. Hyperthermia, especially in children

Indications Indications
anti-diarrheal, antisialogogic, antidote to muscarinic poisoning for bradycardia in acute myocardial infarction for routine preoperative medications to counter the increase in airway secretions and laryngospasms induced by anesthetics anti-spasmodic, anti-motion sickness for reduced amnesia associated with surgical or obstetric delivery for routine preoperative medications to counter the increase in airway secretions and laryngospasms induced by anesthetics anti-spasmodic Anti - parkinsonism mydriatic, cycloplegic for synechia (adhesion in uveitis and iritis)

Contraindications Contraindications
Angle-closure glaucoma Benign Prostatic Hyperplasia Gastric ulcer (because of slowing of gastric emptying time, causing increased gastric secretions and possible aggravation of gastric ulcer)

Other Notes Other Notes

very rapidly hydrolyzes, therefore needing a large amount given in IV to take effect (but only lasts 5-20 seconds)

Methacoline

more resistant to hydrolysis

Scopolamine

rapidly and widely distributed in the CNS, where it has a greater effect there than other antimuscarinic drugs.

Carbachol

Dicyclomine Benzropine Homatropine

Since the blockade produced by these drugs is reversible, their effects can be overcome by increased concentrations of acetylcholine or other muscarinic agonists.

Monique Wine Jamie Lenard

Ipratropium Tiotropium

Because they do not block nicotinic receptors, these drugs have little to no action at skeletal neuromuscular junctions or autonomic ganglia. Muscarinic receptors are constitutively active, and drugs that block the actions of due to acetylcholine are Section Tachycardia Juria 2D Batch 2014 the Genitourinary System sensitivity of inverse agonists that to sinoatrial of detrusor Stimulation node shift the equilibrium of muscarinic receptor muscle and relaxation of the receptor to its blockade and (particularly trigone bladder inactive state. the prejunctional M1 muscles increased Most sensitive in

Also used for complete ophthalmologic examination through induction of temporary ciliary PHARMACOLOGY: COMPREHENSIVE Page 2 of 29 paralysis post-op ileus, reflux esopahagitis,

TABLE OF DRUGS (1st Shifting Period) |

more resistant to hydrolysis and

ADRENERGIC AGONISTS
Mechanism of Action
Phenylephrine Milodrine Clonidine Methyldopa Norepinephrine Phenylephrine Methoxamine Epinephrine Isoproterenol Albuterol Metaproterenol Terbutaline Isoproterenol Epinephrine Phenylephrine Apraclonidine Brimonidine Ritodrine Terbutaline Ephedrine Psuedoephrine Amphetamine Methylphenidate Dexmedetomidine Modafinil Mitodrine Ephedrine Eyes mydriasis, cyclopegia, decrease aqueous humor production Cardiovascular System vasoconstriction, (+) inotropy and chronotropy Respiratory System bronchodilation Gastrointestinal Tract decrease motility and secretion GUT slow voiding and urinary retention Glands decrease sweat, lacrimal, nasopharyngeal constriction CNS - stimulant Endocrine Beta - increase lipolysis, glycogenolysis, insulin Alpha - inhibit or opposite alpha

Organ System Effect

Adverse Effects

Indications
Nasal congestion Chronic orthostatic hypotension Hypotension Hypertension Hypertension Acute hypotension Acute hypotension Acute hypotension Cardiac arrest and complete heart block Cardiac arrest and complete heart block Bronchial asthma Bronchial asthma Bronchial asthma Bronchial asthma Anaphylactic Mydriatic Glaucoma Glaucoma Suppressing premature labor Suppressing premature labor Stress incontinence Stress incontinence Euphoriant ADHD For sedation under intensive care situations and during anaesthesia narcolepsy Chronic orthostatic hypotension Chronic orthostatic hypotension

Contraindications

Other notes
Alpha agonist Alpha 1 agonist Alpha 2 agonist Also found effective in treatment of diarrhea in diabetics with autonomic neuropathy Alpha 2 agonist

Direct Agonist directly bind and activate receptors Indirect Agonists displace stored NE from nerve endings (eg. Tyramine) or inhibit reuptake of release NE (ex. Cocaine and tricyclic antidepressants) 1 increases DAG, IP3 thus activates protein kinases 2 inhibits adenylcyclase thus decreases CAMP 1,2,3 stimulates adenylyl cyclase, increases ATP to CAMP conversion, increases Ca influx inside myocardial cells, promotes relaxation of smooth muscle D1 stimulates adenylcyclase, vasodilation D2 inhibits adenylyl cyclase, opens K channels, decreases Cainfux

Beta 2 selective Beta 2 selective Beta 2 selective Beta selective

ADRENERGIC ANTAGONISTS
Mechanism of Action Alpha receptor Antagonists
Phentolamine Blockade of peripheral dopamine receptors minor clinical importance at present

Organ System Effect

Eyes - contraction of iris sphincter, ciliary muscle Cardiovascular System

Adverse Effects
antagonist drugs as stated in mechanism of action may cause orthostatic hypertension,

Indications
Pheochromocytoma, erectile dysfunction

Contraindications

Other notes
Reversible antagonist

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Section 2D Batch 2014

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Prazosin Labetalol Phenoxybenzamine Terazosin Doxazosin Indoramin Urapidil Chlorpromazine Haloperidol Tamsulosin Alfuzosin Urapidil

Blockade of CNS dopamine receptors clinically significant 1 receptor antagonist drugs vasodilation and tachycardia 1 receptor antagonist drugs acts on receptors on vascular smooth muscle decreased arteriolar and venous tone decreased peripheral vascular resistance and blood pressure vasodilation increased venous pooling in the periphery cannot maintain BP in the upright position orthostatic hypotension 1 receptor antagonist drugs prevent pressor effects of usual doses of agonists 1 selective antagonist drugs convert a pressor to a depressor, response of agonists with both and effects (eg. epinephrine) B receptor antagonist drugs HPN, ischemic heart disease, arrhythmias, endocrinologic and neurologic disorders, glaucoma

vasodilation, (-) inotropy and chronotrophy Respiratory System bronchoconstriction, increase T-B secretion Gastrointestinal Tract increase motility and secretion GUT increase voiding Glands increase sweat, lacrimal and nasopharyngeal secretion CNS decrease migraine and tremors Endocrine inhibit lipolysis glycogenolysis, T4-T3 and increase VLDL

vasodilation leading to tachycardia Eyes blockade of receptors in other tissues leading to miosis Gut blockade of 1 receptors in base of bladder and prostate leading to resistance to urine flow and urinary retention

Chronic hypertension, peripheral vascular disease, urinary obstruction Hypertensive emergencies Pheochromocytoma, peripheral vascular disease Chronic hypertension, urinary obstruction Chronic hypertension, urinary obstruction Chronic hypertension Chronic hypertension, urinary obstruction Chronic hypertension Chronic hypertension Urinary obstruction Urinary obstruction Urinary obstruction

Reversible antagonist Reversible antagonist Irreversible antagonist

Beta Receptor Antagonists

Propranolol Metoprolol Atenolol Bisoprolol Pindolol Metoprolol Bisoprolol Carvediol Timolol Betaxolol Labetalolol Timolol Propranolol Metoprolol Sotalol Bisoprolol Carvediol Betaxolol Carteolol Levobunolol Metipranolol

Hypertension Hypertension Hypertension Hypertension Hypertension CHF CHF CHF Glaucoma Glaucoma Hypertension Ischemic heart disease, glaucoma, neurologic disorders Ischemic heart disease, hyperthyroidism, neurologic disorders Ischemic heart disease, heart failure, neurologic disorders Cardiac arrythmia Heart failure Heart failure Glaucoma Glaucoma Glaucoma Glaucoma

Non-selective Selective, non partial agonist Selective, non partial agonist Selective, non partial agonist Selective, partial agonist

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Section 2D Batch 2014

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Atenolol Nadol

Neurologic disorders Neurologic disorders

INOTROPIC CARDIOTONICS
A. SS ADRENOCEPTOR & DOPAMINE RECEPTOR AGONISTS Mechanism of Action Organ System Effect Adverse Effects Indications Contraindications Other notes

Dopamine

Stimulation of cardiac 1 adrenoceptorinotrophy >chronotrophy Peripheral vasodilation myocardial demand CO ventricular filling Stimulation of peripheral postjunctional D1 and prejunctional D2 receptors Splanchnic vasodilation and renal Tachycardia, arrhythmia, peripheral vasoconstriction oxygen CVS: hypotension due to receptor stimulation Tachycardia, Arrhythmia, Angina Acute Heart failure Synthetic analog of Dopamine

Dobutamine

Acute heart failure

B. - NON-SELECTIVE
Epinephrine Norephinephrine

Sympathetic agonist Physiologic antagonist of Histamine-1 receptors Stimulates heart and blood vessels

Drug of choice in anaphylactic shock Does not act on 2 receptors (cannot be used in asthma)

C. BYPIRIDINES (PHOSPHODIESTERASE INHIBITORS)

MILRINONE (drug of choice) Levosimendan Inamrinone Inhibits phosphodiesterase III (PDEIII)cAMP vasodilation inotropic effect Less toxic than Inamrinone Ventricular Arrhythmia Toxic for bone marrow and liver Half-life: 3-6 hours Excretion: 10-40% urine

D. CARDIAC GLYCOSIDES (DIGITALIS)

Digoxin

Inhibits Na-K (channel antagonist)

ATPase receptor

Digitalis-induced arrhythmia (V Arrhythmia) Acute Congestive Heart Failure

Digitoxin

Works in tandem with the Na-Ca exchange channel: inhibition of Na-K ATPase increase in intracellular Na (sodium retention)

Less mortality than digitoxin Former primary drug Very narrow PI FAB ANTIBODY- Antidote to adv effect Half-life:36-40 hours Longer-acting

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Section 2D Batch 2014

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increase in intracellular Ca (calcium retention) binding of Ca (sequestered from SR) with troponin C excitation-contraction

NON-INOTROPIC CARDIOTONICS
A. VASODILATORS Mechanism of Action
Isosorbide Dinitrate (ISDN) Isosorbide Mononitrate (ISMN)

Organ System Effect

Adverse Effects
Severe headache due to vasodilation (Monday Disease)

Indications

Contraindications

Other notes
Venodilator

Venodilation
preload

reduction in

Releases nitric oxide Activates guanylylcyclase Reduces

output blood and afterload

Arteriolar dilatation reduction in afterload Hydralazine pressure

Results in increased cardiac

Sodium Nitroprusside

SLE (sue to acetylating property in Phase II metabolism either fast or slow) Cyanide Poisoning

Arteriodilator

B. ANGIOTENSIN-CONVERTING ENZYMES INHIBITORS (ACE INHIBITORS) Reduce aldosterone

secretion reducing salt and water retention reducing preload Reduce resitance afterload peripheral reducing Dry Cough Angioedema Heart Failure (with diuretics) Pregnant women (fetal nephrotoxicity)

Releases NO spontaneously Activates guanylylcyclase

CAPTOPRIL ENALAPRIL LISINOPRIL PERINDOPRIL QUINAPRIL RAMIPRIL

Reduction in tissue angiotensin levels reduce sympathetic activity (diminution of angiotensins presynaptic effects) Reduces long term remodeling of the heart and vessels reduction mortality and morbidity in

C. ANGIOTENSIN II BLOCKERS Monique Wine Jamie Juria Lenard Section 2D Batch 2014 PHARMACOLOGY: COMPREHENSIVE TABLE OF DRUGS (1st Shifting Period) | Page 6 of 29

LOSARTAN VALSARTAN EPROSARTAN OLMESARTAN CANDESARTAN

Same CI as that of ACE inhibitors

EPROSARTAN longacting; given once a day

LOOP DIURETICS

D. DIURETICS (See page 15 for more comprehensive information on diuretics)

Reduction of facilitation of sympathetic nervous system Preload reduction: reduction of excess plasma volume and edema fluid Afterload reduction: lowered blood pressure

Furosemide

POTASSIUM-SPARING DIURETICS
Spironolactone Eplerenone Ethacrynic acid Act on the collecting tubule blocks the release of aldosterone Genitourinary: antiandrogenic No antiandrogenic effect Lowering of electrolyte Hyperuricemia Autotoxicity leading to deafness

E. ADRENOCEPTOR BLOCKERS
Bisoprolol Carvedilol Metropolol Propanolol (PO/IM) Esmolol (IO) Reduction in damaging the sympathetic influences in the heart (Tachycardia, arrhythmias) Inhibition of renin release

Carvedilol:

Peripheral vasodilation via adrenoceptor blockade

Bradycardia, precipitate decompensation of cardiac function

Chronic Heart Failure

ANTI-ARRHYTHMICS
A. CLASS 1 Sodium-Channel Blocking Mechanism of Action Subgroup 1A
Procainamide

Organ System Effect

Adverse Effects
Torsade de pointes arrhythmia, syncope, SLElike syndrome Torsade de pointes, Syncope, Cinchonism (headache, dizziness and tinnitus), Nausea, Vomiting Same as quinidine, may precipitate heart failure, atropine-like activity,

Indications

Contraindications

Other notes

Slows

down upstroke of action potential and conduction QRS duration and action potential peripheral resistance Blocker: vascular

Quinidine Disopyramide

Prolongs

Atrial and Ventricular Arrhythmias

Ganglion

Rarely used because of cardiac and extracardiac adverse effects Heart failure, glaucoma Cardiac antimuscarininc effects even more marked than those of quinidine

Supraventricular Arrhythmias

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Section 2D Batch 2014

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worsening of pre-existing glaucoma

Subgroup 1B
Lidocaine Blocks activated and inactivated sodium channels with rapid kinetics Alters Na, K, Ca conductance, membrane potentials and the concentration of amino acids and nuerotransmitters: (NE, Ach, GABA) Similar to lidocaine Hypotension, Asystole, malignant HPN (rare), CNS manifestations Nystagmus, ataxia, drowsiness, Gingival hyperplasia, Peripheral neuropathy Hypotension and CNS symptoms Ventricular tachycardia Ventricular fibrillation Digitalis Induced Arrhythmias Ventricular Arrhythmia Ventricular Arrhythmias Local anesthetic

Phenytoin

Antiseizure Orally administered Increased metabolism: phenytoin, phenobarbital, rifampin Decreased: cimetidine

Mexiletine

Subgroup 1C
Potent blocker of Na and K channels with slow unblocking kinetics (-) chronotrophic effect Similar to quinidine but does not prolong AP (-) chronotrophic effect Potent sodium channel blocker that does not prolong AP Inhibit catecholamine binding at beta-receptors Direct membrane stabilizing property May cause severe exacerbation of arrhythmia, Brugada Syndrome Metallic taste, constipation,arrhythmia exacerbation Ventricular Arrhythmia Supraventricular Arrhythmia, SV Tachycardia, VT, WolffParkinsons-White Arrhythmias Increased metabolism: propranolol, quinidine. amiodarone Increased metabolism: Warfarin, digoxin, metropolol Withdrawn from market Phenothiazine derivative

Flecainide

Propafenone Moricizine

B.

CLASS 2 -ADRENOCEPTOR-BLOCKING DRUGS

Hypotension, bradycardia, CHF, Wheezes, Raynauds, Depression, Hypoglycemia, Insomnia, Decreased libido

Propranolol (nonselective) Timolol Metropolol Esmolol (Intraoperative Arrhythmia, IV) Acetabulol (oral)

(-) inotropic, chronotrophic effects

C. CLASS 3 K-Channel Blockers

Amiodarone Bradycardia, Hypo/Hyperthyroidism, asymptomatic corneal deposits, dose-related pulmonary toxicity (pulmonary fibrosis) Bioavailability: 35-65% Ventricular Arrhythmia Supraventricular Arrhythmia (low doses) Ventricular Tachycardia

Multiple actions:

Dronedarone

Class IVAV nodal conduction Class I- depresses Vmax Class II- noncompetitively blocks and

Similar with amiodarone without the thyroid and pulmonary toxicity Dysgeusia (disturbance of taste), sneezing, paresthesia, cough, Atrial Fibrillation

Vernakalant

Multi-channel blocker Prolongs atrial effective

Structural analog of amiodarone Lacks iodine atoms 1st antiarrhythmic drug to demonstrate a reduction in mortality/hospitalization in patients with AF New Class III drug

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Section 2D Batch 2014

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Sotalol

refractory period Slows conduction over AV node Does not change QT interval Non-specific -adrenergic receptor-blocker (class 2) Action potential (repolarization) prolonging (class 3) Ibutilide: activate slow inward sodium current Reduces the plateau height of the action potential, slightly shortens action potential, and slightly prolongs total Purkinje fiber AP

hypotension

Dose-related incidence of Torsade de pointes

Ventricular Arrhythmias

100% bioavailability excretion: kidneys IV for Ibutilide Dofetilide: PO, 100% bioavailability

Ibutilide Dofetilide

QT Prolongation

SVT

D. CLASS 4 Calcium Channel Blocking Drugs

Dose-related cardiotoxic effects, can induce AV block in large dosages, constipation, lassitude, nervousness, peripheral edema

Verapamil

Adenosine

Digoxin

Peripheral vasodilationtransient hypotension (-) inotropic effects Inhibits the AV node by acting with 1 receptors that opens the adenosine sensitive K channel to hyperpolarize and inhibit AV node and indirectly inhibit calcium channel opening Slowing sinus node discharge rate, shortening atrial refractoriness, prolonging AV nodal refractoriness

SVT Reduction of ventricular rate in AF and flutter

Prototype Bioavailability: 20% PO dosage>IV dosage because of 1st pass effect

Flushing, dyspnea, chest pressure

Drug of choice for prompt conversion of paroxysmal SVT to sinus rhythm

Contraindicated in the presence of Methylxanthines due to inhibition of action

Naturally occurs in the body T : 1 to 6 secs

See cardiotonics

ANTIHYPERLIPIDEMICS
A. COMPETITIVE INHIBITORS OF HMG-COA REDUCTASE (REDUCTASE INHIBITORS) STATINS Organ System Mechanism of Action Adverse Effects Effects
Pravastatin Inhibits HMG-CoA Reductasepreventing the formation of mevalonate (rate limiting step of sterol synthesis) Induces an increase in high affinity LDL receptors on hepatocytes

Indications

Contraindications

Other Notes
Most effective in reducing LDL together Decrease oxidative stress Decrease vascular inflammation

Increases stability of atherosclerotic lesion

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Section 2D Batch 2014

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Lovastatin

Has an open active lactone ring Inactive lactone prodrug

Simvastatin

Fluvastatin

Increases both fractional catabolic rate of LDL and livers extraction of LDL precursors (VLDL remnants) from the blood LDL Interfere with the synthesis of lipid intermediates with important biological effects May HDL cholesterol by preventing the geranylation of Rho A and phosphorylation of peroxisome proliferatoractivated receptor (PPARa)- factor that regulates APO A1 transcription

Myopathy cessation upon removal of therapy Hepatic toxicity Cataract Pancreatitis Headache Dizziness Insomnia Blurred vision Dysgeusia Skin rashes

Hydrolyzed in the GIT hydroxyl derivatives Same as Lovastatin More potent than lovastatin Most effective in reducing LDL together Decrease oxidative stress Decrease vascular inflammation Increases stability of atherosclerotic lesion Fluorine containing Almost completely absorbed

Pregnant and lactating women and those likely to become pregnant, hepatic and renal impairment, porphyria, untreated hypothyroidism

Drugs used to lower lipid levels in the body (e.g. cholesterol, LDL)

Rosuvastatin

Fluorine containing 19 hours (long lasting) Same as rosuvastatin but only lasts for 14 hours

Atorvastatin

B. FIBRIC ACID DERIVATIVES (FIBRATES) LIPOPROTEIN LIPASE STIMULANTS

Fenofibrate Gemfibrozil Bezafibrate Ciprofibrate Increases peripheral clearance of lipoproteins Peroxisome proliferatoractivated receptor agonist Effects on plasma levels of Lipoprotein:

VLDL and chylomicron or LDL Mosly only modest in LDL Others, especially with combined hyperlipidemia, LDL often Moderate in HDL Effects on plasma levels of lipids: TG Cholesterol

Cholesterol gallstonesreflecting in cholesterol content of bile Hepatotoxicity aminotransferases or alkaline phosphatases Myositis, myopathy, rhabdomyolysis, myoglobinuria, renal failure GIT anorexia, nausea, GI discomfort Skin rashes, urticarial, hair loss Fatigue, headache, impotence Anemia, leucopenia

Hypertriglyceridemia with VLDL or chylomicrons Hypertriglyceridemia- Type I, IV, V Familial combined hyperlipidemi (Type IIb), VLDL is Familial dysbetalipoproteinemia (Type III) Hypertriglyceridemia d/t treatment with viral protease inhibitors

General: Absorption: >90% with meal Plasma protein binding: >95% Excretion: Predominantly as glucoronide conjugates Conjugates: 80-90% in urine; smaller amounts in feces; (Katzung) 60% in urine as glucoronide conjugates; 25% in feces

Monitor: Serum levels of creatine kinase, aminotransferases, and plasma proteins Renal function tests

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Hypokalemia, arrhythmias WBC or Hct

Thyroid status T : Fenofibrate- 20 hrs Gemfibrozil- 1.5 hrs Clofibrate- 15 hrs.

C. STEROL ABSORPTION INHIBITOR

Blocks sterol transporter NPC1L1 in intestine brush border inhibits reabsorption of cholesterol excreted in bile: LDL and phytosterols Selective inhibitor of intestinal absorption of cholesterol & phytosterols Inhibit absorption of cholesterol both in diet and in bile Actions: LDL, minimal in HDL cholesterol Synergistic with statin Effect on plasma levels of lipoproteins:

Ezetimibe

Familial combined hyperlipidemia when LDL is increased Familial hypercholesterolemia (heterozygous, homozygous)

Readily absorbed Conjugated in intestine to an active glucoronide Enterohepatic circulation T of active metabolite: 22 hrs 80% excreted in the feces Drug interactions: - with fibrates - with cholestyramine

NIACIN VLDL SECRETION INHIBITORS

Nicotinic Acid (Vit. B3) and derivatives

Decreases catabolism of apoA1; reduces VLDL secretion from liver HDL, LDL and TG

VLDL, IDL, LDL, Lp(a), HDL Most effective agent for increasing levels of HDL Only antihyperlipidemic drug that decreases Lp(a) significantly Estrogen and Neomycin also decreases Lp(a) significantly

Skin and mucous membrane: o Harmless cutaneous vasodilator (flush), uncomfortable sensation of wamth and pruritus o Rashes, dry skin, dry mucous membranes o Acanthosisnigricans GIT o Hepatotoxicity o Myopathy o Metabolic: Hyperglycemia, Hyperuricemia CVS: Arrhythmia, hypotension Ocular toxicity: Amblyopia (reversible)reduced vision in an eye not correctable by a manifest refraction; Maculopathy

Effect on plasma levels of lipids:

Acanthosisnigricans Peptic ulcer/severe pepric disease Hepatic disease Diabetes mellitus Gout Pregnancy Patients on hypertensive therapy

Monitor serum levels of: glucose, aminotransferase, uric acid, albumin, CK Pharmacokinetics: Absorption almost complete Metabolism extensive Excretion urine mostly as metabolites; Doses daily vitamin requirement as antihyperlipideic T - 60 mins.

BILE ACID BINDING RESINS

TG Cholesterol

Other effects: Fibrinogen Tissue plasminogen activator

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Colestipol Cholestyramine Colesevelan

Binds bile acids in gut preventing reabsorption, increases cholesterol catabolism, up regulates receptors LDL Enhanced conversion of cholesterol to bile acid

absorption of - Folic acid - Drugs - Fat soluble vitamins GI: constipation, sensation of fullness, discomfort Hypoprothrombonemia Increase bleeding tendency Increase effects of anticoagulants Hypertriglyceridemia Hypertriglyceridemia Diverticulitis Hemorrhoids Biliary obstruction Large polymeric cationic exchange resins and insoluble in water

ANTI-HYPERTENSIVES
DRUGS THAT ALTER SNS FUNCTION A. Centrally acting Sympathoplegic drugs
rarely used - Methyldopa - Clonidine -Reduce sympathetic outflow from vasomotor center in brain -increase sensitivity to baroreceptor center Central adrenoceptor stimulation -Decrease TPR, HR, CO -Decrease renal vascular resistance - Block nicotinic receptors on postganglionic neurons of SNS and PNS -Inhibit release of NE from sympathetic nerves transported by NET -interferes with VMAT >depletes NE, dopamine, 5HT in central and peripheral nerve endings -only used pregnancy for HPN in -Dry mouth -sedation -depression -Lactation > prolactin secretion (Methyldopa) -HPN crisis > inc SNS activity (Clonidine withdrawal)

B. Ganglion- Blocking drugs

Trimetaphan - Not used Severe hypotension Sexual dysfunction Constipation Urinary retention Glaucoma Postural hypotension Sedation Depression Extrapyramidal s/sx GI sx

C. Adrenergic Neuron Blocking Drugs

- Guanethidine - Guanadrel >do not enter CNS Reserpine

D. Adrenoceptor Antagonists
1. Beta Blockers - Decrease CO, TPR, HR - Propranolol Cardioselective: - Metoprolol Atenolol - Nadolol - Betaxolol - Bisoprolol Partial Agonists: - Pindolol - Acebutolol With blocker: Labetalol - Carvedilol - depress RAAS by blocking the intrarenal & extrarenal Breceptors involved in renin secretion - same as propranolol in B1 blockade but less potent B2 - less CO & HR depression than other B blockers - most widely used - long half lives > OD administration useful in pt with bradycardia & Peripheral Vasc Disease - tx of HPN in pt with pheochromocytoma and HPN crisis - tx ofpt with HF & HPN Bradycardia DM Peripheral vascular insufficiency

2. 1 Blockers Selective: - Prazosin - Terazosin - Doxazosin Nonselective: - Phentolamine Phenoxybenzamine

-Blocks 1 receptors in arterioles, venules -Vasodilation

- tx of BPH & HPN - dx & tx of pheochromocytoma

1st dose effect > occurs in salt & H2O depleted pt > reduce 1st dose & administer at h.s. Dizziness Headache Lassitude

II. DIRECT VASODILATORS

A. Arteriolar - Hydralazine - Minoxidil - Diazoxide - Fenoldopam - HPN emergencies Tachycardia flushing Hypertrichosis HA

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B. Arteriovenous Sodium Nitroprusside Calcium Channel Blockers Dihydropyridine: - Nifedipine - Amlodipine Nicardipine - Nisoldipine > More selective vasodilator > Less cardiac depressant than Verapamil & - Diltiazem - Nimodipine: cerebral blood vessels

Activates guanylyl cyclase > inc intracellular cGMP > relaxed smooth muscle -bind to L-type Ca++ channel (heart smooth muscle) -decrease trans-membrane Ca++ current -smooth muscle relaxation -Decrease myocardial contractile force - decrease myocardial O2 requirement decrease HR (Verapamil, Diltiazem) -relief vasospasm in coronary artery RX: Angina pectoris -Decrease AV node conduction RX: Supraventricular tachycardia - AF Peripheral vasodilator RX: HPN - Raynauds phenomenon Nicardipine RX: Severe HPN thru IV

Cyanide Accumulation

Cardiac depression peripheral edema flushing dizziness

III. ANGIOTENSIN INHIBITORS

1. ACE inhibitors Excreted in kidneys except Fosinopril - Enalapril Lisinopril - Benazepril - Perindopril - Quinapril Ramipril - Trandolapril 2. Angiotensin Receptor Blocker - Valsartan - Candesartan - Eprosartan - Irbesartan - Telmisartan - Olmesartan 3. Renin blockers Clonidine (central extrarenal) Aliskiren SNS) blockers (renal, - Inhibits peptidyl transferase and inactivates bradykinin ---- Reduced SNS stimulation - Low Na+ delivery - Low Na+ distal renal tubule - Low renal arterial Pressure - Tx in pt with chronic kidney disease and DM - Tx of HF reduced incidence of DM in pt with MI - pt with HF and chronic kidney disease - can be given to DM nephropathy Acute renal failure Hyperkalemia Dry cough Angioedema CI for pregnant pt

- No effect on bradykinin Metabolism > more selective blocker of angiotensin effects than ACE inh Reduces plasma renin activity, aldosterone Greater anti HPN effect angiotensin I, II,

Same with ACE inh except for the cough and angioedema

ANTI-HYPERTENSIVES: DIURETICS
A. CARBONIC ANHYDRASE INHIBITORS Mechanism of Action
Acetazolamide

Organ System Effect

Inhibition of bicarbonate reabsorption in the proximal convoluted tubule depletion of bicarbonate increased NaCl reabsorption in the rest of the renal tubules

Adverse Effects
Hyperchloremic metabolic acidosis

Indications

Contraindications
Hepatic encephalopathy/hepatic coma/impaired liver function alkaline pH decreases urinary NH4 excretion

Other notes
Prototype drug Well-absorbed after oral administration

Acts on the proximal convoluted tubules where reabsorption of sodium bicarbonate occurs Sodium bicarbonate will be absorbed through the sodium-hydrogen

Glaucoma

Renal stones: decreased citrate excretion, Ca++ salt precipitation d/t presence of alkaline pH Renal potassium wasting Drowsiness

(Dorsolamide, Brinzolamide topical or eyedrop forms for organ selectivity) decreased formation of aqueous humor

Excretion of the drug is by secretion in the proximal tubule S2 segment Onset of action: 30 minutes to 2 hours

Metabolic alkalosis

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exchanger Na ions will be reabsorbed into the interstitium of the kidneys while H will be secreted to the tubular lumen H ions will combine with bicarbonate to form carbonic acid Carbonic acid will dissociate to H2O and CO2 by the enzyme carbonic anhydrase Acetazolamide inhibits this enzyme No sodium ion will be reabsorbed due to the decreased ability to exchange Na with H ions Blocks sodium bicarbonate rabsorption Acts on the Loop of Henle, particularly in the thick ascending limb Inhibits Na-K-2Cl transporter in the thick ascending limb decreased NaCl, Mg, Ca reabsorption Increases renal blood flow useful for patients with decreased urine output Also shown to induce expression of COX-2 increased synthesis of prostaglandins (PGE2) from arachidonic acid inhibits salt transport in the thick ascending limb (this can be blocked by NSAIDs) Blocks NaCl transporter in the distal convoluted tubule inhibits NaCl reabsorption, but

decreased bicarbonate reabsorption

Acute mountain

sickness decreased production of CSF

Urinary alkalinization:
Paresthesias Nervous system toxicity (seen in patients with renal failure) Allergic reactions

decreased bicarbonate reabsorption increased urinary pH enhanced excretion of weak acids Adjuvants in treatment of epilepsy, hypokalemic periodic paralysis, and in increasing urinary phosphate excretion during severe hypophosphatemia.

Duration: 12 hours 85% of the bicarbonate reabsorptive capacity of the proximal convoluted tubule is inhibited. Diuretic efficacy of acetazolamide decreases significantly with use over several days.

B. LOOP DIURETICS

Furosemide 20/40 mg tab; 20mg amp prototype drug Butenamide (Lasix) 1mg tab; 0.5mg amp Torsemide (not available locally) Ethacrynic Acid (not available locally)

Hypokalemia/Hypokalemi c Metabolic Acidosis Hypomagnesemia Ototoxicity (reversible) Hyperuricemia, gout (d/t increased reabsorption of uric acid in renal tubules secondary to hypervolemia) Allergic reaction diuretics sulfonamides) (loop are

Pulmonary edema (inhibits Ca++ reabsorption)

Acute hypercalcemia Hyperkalemia (inhibits

K+ reabsorption) Allergic reaction Liver cirrhosis Borderline renal failure

Most effective type of diuretics because of the large sodium chloride absorptive capacity of the thick ascending limb effect is not diminuted by acidosis, unlike other types of diuretics Onset: 2-3 (furosemide); 1 (torsemide) hours hour

Acute renal failure

Severe dehydration (d/t excessive urine output)

(increase rate of urine flow by increasing renal blood flow; increased K+ excretion)

Duration: 2-3 hours (furosemide); 4-6 hours (torsemide) Rapidly absorbed Eliminated by the kidney by glomerular filtration and tubular secretion Diuretic activity of loop diuretics correlates with their secretion by the proximal tubule.

C. THIAZIDES
Chlorothiazide Hydrochlorothiazide (12.5/25 mg tab) Indapamide (1.5mg tab)

Metabolic alkalosis Hyperuricemia Hyperglycemia (d/t impaired insulin release

Hypertension Congestive Failure Hypercalciuria

Heart

Hydrocholorthiazide: prototype drug All thiazides can be

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increases Ca reabsorption Increase in calcium reabsorption is postulated to result from effects in both the proximal and distal convoluted tubules:

PCT:

thiazideinduced volume depletion enhanced Na+ and passive Ca++ reabsorption thiazideinduced blockade of Na entry decreased intracellular Na enhances Na-Ca exchange in the basolateral membrane increased Ca reabsorption

administered orally but there are differences in their metabolism: Chlorothiazide is not very lipid soluble and must be given in large doses; this is the only thiazide available for parenteral administration.

and decreased glucose utilization) Hyperlipidemia Dilutional hyponatremia (d/t ADH production secondary to hypovolemia) Allergy

DCT:

Nephrogenic
insipidus

diabetes

All thiazides are secreted by the organic acid secretory system in the proximal convoluted tubule and compete with the secretion of uric acid by that system thiazides may blunt uric acid secretion and elevate serum uric acid level. Usually combined with other drugs, such as beta blockers, ARBs, and ACE inhibitors to potentiate the effects of controlling blood pressure. There are drugs available that already have combined beta blocker/ARB/ACE inhibitor and diuretic effects. However, if diuretics are to be given with calcium channel-blockers, they should be given separately. Acute Renal Failure Hyperkalemia Liver disease Direct Antagonists of Aldosterone Receptors Spironolactone Synthetic steroid that acts as a competitive antagonist to aldosterone Substantial inactivation of spironolactone occurs in the liver Rather slow onset of action, requiring several days before full

D. POTASSIUM-SPARING DIURETICS
Spironolactone Eplerenone Amiloride Triamterene

K-sparing diuretics

prevent K+ secretion by antagonizing the effects of aldosterone at the late distal and cortical collecting tubules. direct pharmacologic antagonism of mineralocorticoid receptors (spironolactone, eplerenone) or by inhibition of Na+ influx through ion channels in the luminal membrane (amiloride, triamterene)

Hyperkalemia Metabolic acidosis Spirinolactone Indomethacin Triamterene

Gynecomastia, impotence ARF Triamterene + Renal stones

Inhibition may occur by

Hyperaldosteronism Primary Conns syndrome Secondary CHF, liver cirrhosis, nephrotic syndrome

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 Spironolactone and

eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. Amiloride and triamterene do not block aldosterone, but instead directly interfere with Na+ entry through the epithelial Na+ channels (ENaC) in the apical membrane of the collecting tubule. Since K+ secretion is coupled with Na+ entry in this segment, these agents are also effective potassium-sparing diuretics

therapeutic effect is achieved Eplerenone More selective: less active on androgen, progesterone receptors Spironolactone analog with much greater selectivity for the mineralocorticoid receptor Several hundredfold less active on androgen and progesterone receptors than spironolactone Fewer adverse effects Inhibitors of Na+ influx through ion channels in luminal membrane Amiloride Triamterene Metabolized in the liver, but renal excretion is a major route of elimination for the active form and the metabolites Because triamterene is extensively metabolized, it has a shorter half-life and must be given more frequently than amiloride (which is not metabolized)

Amiloride
E. OSMOTIC DIURETICS

and triamterene are direct inhibitors of Na+ influx in the CCT (cortical collecting tubule).

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 Osmotic diuretics have

Mannitol

their major effect in the proximal tubule and the descending limb of Henle's loop. Through osmotic effects, they also oppose the action of ADH in the collecting tubule. Prevents the normal absorption of water by interposing a countervailing osmotic force resulting to increased urine volume.

Mannitol
Decreases intracranial pressure Decreases intraocular pressure Congestive heart failure Increased ECF volume Hyponatremia Dehydration

prototypic drug; the only osmotic diuretic available is poorly absorbed by the GI tract, and when administered orally it causes osmotic diarrhea. For systemic effect, mannitol must be given parenterally.

Mannitol

Increase in urine flow

rate decreases the contact time between fluid and the tubular epithelium, thus reducing Na+ as well as water reabsorption.

F. ADH AGONISTS
Vasopresin Desmopresin Renal action appears to be mediated primarily via V2 receptors although V1a receptors may also be involved. ADH antagonists inhibit the effects of ADH in the collecting tubule Both lithium and demeclocycline appear to reduce the formation of cyclic adenosine monophosphate (cAMP) in response to ADH Central Diabetes Insipidus

G. ADH RECEPTOR ANTAGONISTS

Conivaptan (only drug approved for use) Lixivaptan Tolvaptan Syndrome of Inappropriate Diuretic Hormone (SIADH) Congestive Heart Failure

Nephrogenic Diabetes Insipidus

ANTI-ANGINA
A. NITRATES Mechanism of Action
Nitroglycerin Isosorbide Dinitrate (ISDN) Nitrates will be removed of its nitrate group by Gluthatione S-Transferase

Organ System Effect

Adverse Effects
Hypotension because it is not only the coronary vessels that are dilated

Indications
Angina

Contraindications
Increased intracranial pressure

Other notes
Nitroglycerin considered as the prototype of the

dilation of veins decreased preload (venous return)

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Isosorbide Mononitrate (ISMN)

which will release the free nitrate. The free nitrate will then be converted to nitric oxide. The nitric oxide causes activation of guanylylcyclase and an increase in cGMP which, in turn, would cause smooth muscle relaxation as stated in the previous mode of action.

dilation of arteries decreased LV volume and wall tension (decrease afterload)

but also the other blood vessels (peripheral blood vessels) Tachycardia Severe headache (due to vasodilation of cerebral vessels)

group not sensitive to sunlight but may lose its potency due to volatilization and adsorption to plastic surfaces, therefore it should be kept in a tightly closed glass containers Isosorbide dinitrate/mononitrate sublingual administration to prevent first pass effect in the liver

can also be given transdermally by placing a patch on any part of the chest or even in the abdomen; will be absorbed in the skin mucous membrane and will produce the therapeutic effect

Onset: 1-3 minutes Duration: 15-30 minutes Types of Administration: SL, Transdermal, SR 1-3 minutes of administration would provide immediate relief of the chest pain. If the chest pain is not relieved, wait for another 15 minutes then administer again (duration of action: 15-30 minutes). If the chest pain is not yet relieved by this, the patient must have a probable MI and should be admitted immediately to an ICU. Slow Release tablets: used as

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maintenance given once a day

B. SILDENAFIL, TADANAFIL, VARDENAFIL

Sildenafil is a drug used for the treatment of impotence or erectile dysfunction which blocks the action of phosphodiesterase. By blocking PDE, there will be an increase in cGMP which will result to relaxation. This mode of action can also aggravate the hypotensive effects of the nitrates. Activate cardiac potassium channels thereby hyperpolarizing the smooth muscle membrane therefore decreasing heart rate (myocardial protection) Can also release nitric oxide in the endothelium thereby dilating the coronary vessels Inhibit oxidation of fatty acids in the myocardium thereby improving the metabolic status of ischemic tissues Blocks the late Na current also blocking the calcium causing decrease myocardial contractility Inhibits hyperpolarization by the activated Na channels in the SA node thereby decreasing heart rate

Sildenafil Tadanafil Vardenafil

Sexual impotence Erectile dysfunction

Patients taking nitrates

C. NEW DRUGS FOR ANGINA

Decreased HR Dilation of coronary vessels Better than the nitrates Available in 5, 10, 20 mg doses and is given twice a day every 12 hours A nicotinamide nitrate ester

Nicorandil

Trimetazidine

20 mg (given 3x a day) 35 mg (every 12 hrs)

Ranolizine

Decreased myocardial contractility Decreased HR Other effects similar to calcium channel blockers

Ivabradine

MUCOKINETICS (EXPECTORANTS)
A. DIRECTLY-ACTING Mechanism of Action
Guaiphenesin/Guaifenesin Decrease sputum viscosity and increase sputum volume thereby decreasing

Organ System Effect

Adverse Effects
Nausea, gastric disturbances, drowsiness

Indications
Productive cough

Contraindications
Hypersensitivity

Other notes

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Na+, K+ citrate/acetate

difficulty in expectoration Increase bronchial secretion by salt action

and rash Productive cough

Na content H2O
content Cause irritative action on bronchial mucosa resulting to production of excess respiratory tract fluid w/c is easier to cough

B. REFLEXLY-ACTING
Nausea and vomiting Productive cough Irritant to gastric mucosa

Ammonium chloride

Potassium Iodide

Productive cough Depolymerizes polysaccharide directly as well as by liberating lysosomal enzymes w/c breaks down the fiber network in the tenacious sputum Makes the phlegm in the airway thinner and less sticky by increasing the bodys natural production of surfactant (anti-glue) Splits disulphide bonds linking proteins in the mucus thereby reducing mucus viscosity Liquefies viscid sputum

C. MUCOLYTIC
Rhinorrhea, lacrimation, gastric irritation Productive cough Hypersensitivity

Bromhexine

Ambroxol

Mild GI effects and allergic reaction

Productive cough

Hypersensitivity, epileptic patients

Metabolite of Bromhexine

Acetylcysteine

Productive cough

Hypersensitivity Hypersensitivity, Active peptic ulcer, children under 2 years old

Also used in management of paracetamol poisoning

Carbocisteine

Nausea, gastric discomfort, GI bleeding, skin rash

Productive cough

ANTITUSSIVES
A. NARCOTIC ANTITUSSIVE Mechanism of Action
Codeine Directly suppresses cough center by binding to distinct receptors in medulla

Organ System Effect

Adverse Effects
(TD)Sedations, nausea, constipation Higher dose: respiratory depression, drowsiness Stupor, ataxia, respiratory depression, convulsion in children

Indications

Contraindications
Asthmatic px, px with diminished respiratory reserves

Other notes
Pholcodeine- has similar efficacy as codeine with longer duration (12hrs) with no analgesic or addictive property

Dry cough

B. NON-NARCOTIC ANTITUSSIVES
Dextromethorpan Depress cough center in medulla and increasing the threshold for cough Spasmodic cough children below 6 yrs., px taking MOA inhibitors A synthetic compound

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Noscapine

Depress cough

Headache and Nausea

Spasmodic cough

*Asthmatic patients

Equally antitussive as codeine No narcotic, analgesic or dependance properties

C. ANTI-HISTAMINICS
Chlorpheniramine Diphenhydramine Promethazine Sedative and anticholinergic action Urinary retention Blurred vision Drowsiness Nausea Vomiting Constipation Headache Lack selectivity for cough centers No efficacy in asthma

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ANTI-ASTHMA
(ANTI-INFLAMMATORY CONTROLLERS) A. CORTICOSTEROIDS
ORAL: A. Reduce airway reactivity Mechanism of Organ System Prednisone , Methyprednisolone (dose Increase airway Action diameter depend on severity) INHALED: Terbutaline Inhibit lymphocytic, Budesonide, Fluticasone (Long Acting q 12 Albuterol eosinophilic airway hrs) Salbutamol mucosal Promotes bronchodilation inflammation Fenoterol Reduce frequency of Activate G protein asthma cAMP intracellular Ca attacks Formoterol Potentiate effects of Salmeterol 2 agonists

Mechanism of Organ System Adverse Indications ANTI-ASTHMA Effects Action (BRONCHODILATOR RELIEVERS AND CONTROLLERS) Effects

Contraindication s

Other Notes
effective in improving all indices of asthma Other notes controlseverity of symptoms, tests of R isomer activate beta airway caliber and bronchial receptorreactivity, frequency causes S isomer of exacerbations, inflammation and quality of life Long acting Corticosteroid + LABA No anti-inflammatory (Long Acting 2 property Agonist) ( inhaled)

2 AGONISTS

Effect Adverse

Oropharyngeal candidiasis Effects inhaled give spacer devices

Indications

Contraindications

B. SYMPATHOMIMETIC
Epinephrine Bronchodilation CV: vasoconstriction

C. MUSCARINIC ANTAGONISTS
Atropine

Hoarseness advise to drink Throbbing headache, gurgle H20 or Tremors, tachycardia, Asthma after inhaler palpitation Adrenal insufficiency best time 8am to mimic diurnal Tachycardia, arryhtmia, variation worsening of angina Status asthmaticus pectoris Slow growth rate children

Budesonide + Formeterol mins. Onset- 15 Duration- 60-90 mins. + Fluticasone Salmeterol (Seretide) Prototype drug Only have partial reversible property for COPD Inhibits M3 receptors prevent Leukotriene synthesis Approved as treatment for Prevent LT action COPD Bronchoconstriction, bronchial reactivity, mucosal edema, mucus hypersecretion Narrow therapeutic window Less potent and shorter Cromolyn poorly absorbed from acting than theophylline the gastrointestinal tract and must be inhaled as a microfine powder or aerosolized solution. Nedocromil also has a very low bioavailability and is available only in metered-dose aerosol form.

Inhibit the effect of

5 lipoxygenase inhibitor ( not available ) receptors Zileuton Tiotropium LTD4 receptor Antagonist Montelukast, Zafirlukast (available in D. market) METHYLXANTHINES Uncertain: Res: bronchodilation phosphodiesterase CV: cardiac stimulation inhibition, adenosine Musculoskeletal: increased C. Theophylline STABILIZERS MAST CELL receptor antagonist skeletal INHALED: inhibits degranulationmuscle strength (Katzung) (diaphragm) Na Cromoglycate of mast cell (inhibits Competitive nonselective & serotonin) histamine PDE inhibitor Res: bronchodilation Cromolyn, Nedocromil Inhibit antigen, Aminophylline IV Non selective adenosine exerciseinduced receptor antagonist asthma, slightly bronchial reactivity Inhibit mast cell degranulation Produces an alteration in the function of delayed chloride channels in the cell membrane, inhibiting cell activation. This action on airway nerves is thought to be responsible for nedocromil's inhibition of cough; on mast cells, for inhibition of the early response to antigen challenge; and on eosinophils, 2D Section for inhibition of the inflammatory response to inhalation of allergens

B. Ipratropium ANTI-LEUKOTRIENES acetylcholine at muscarinic

Osteoperosis cataract Treatment of asthma liver toxicity

Dizziness, intraocular pressure, tachycardia Anorexia, nausea, vomiting, abdominal discomfort, anxiety, headache, seizures, arrhythmias, insomnia

Asthma, COPD Aspirin-induced asthma Bronchial asthma allergic rhinoconjunctiv itis Applying the solution by nasal spray or eye drops several times a day is effective in about 75% of patient

are minor and are localized to the sites of deposition. throat irritation cough mouth dryness rarely, chest tightness, and wheezing

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can be prevented by inhaling a 2adrenoceptor agonist before cromolyn or nedocromil treatment Serious PHARMACOLOGY: adverse Page 22 of 29 effects are rare Reversible dermatitis,

COMPREHENSIVE TABLE OF DRUGS (1st Shifting Period) |

AUTACOIDS Role Found in skin, GI mucosa, lungs, liver, placenta, brain Mediator of immediate allergic & inflammatory reactions Gastric acid secretion MOA Binds with membrane receptors: H1 *smooth muscle *endothelium H2 *gastric mucosa *cardiac muscle *brain *immune cells H3 *pre-synaptic brain *myenteric plexus H4 *eosinophils *neutrophils *CD4T cells Organ System Effects 1. HISTAMINE CNS *stimulate sensory nerve endings (pain, itch) CVS *vasodilatation * (+) inotropy * (-) chronotropy *fluid transudation RS *bronchoconstriction (H1) GIT *increased intestinal motility * increased gastric acid * increased pepsin *Intrinsic Factor secretion Antagonists I. Physiologic Antagonist Epinephrine II. Inhibitors of Histamine Release Cromolyn, Nedocromil, 2 agonists inhibits degranulation of mast cells III. Histamine Receptor Antagonist A. H1 Receptor Antagonists (1st Generation) for hypersensitivity reactions 1. Sedation (1st generation, side Highly sedative effect) Diphenhydramineq6-8 Dimhenhydrinateq8 Promethazine (parenteral) Hydroxyzine (itarax) LA Moderately Sedative Buclizine (appetite stimulant) Cinnarizine (vertigo/motion sickness) Meclizine Pheniramine Cyproheptadine Mild Sedative Chlorpheniramine Clemastine LA Dimethidine Methdilazine NA Mepyramine NA Triprolidine NA Cyclizine NA Rx: Scopolamine (not available) Promethazine (IM) Dimenhydrinate Cyclizine Meclizine (Bonamine) Betahistine Cenarizine Rx: Diphenhydramine High anti-cholinergic action Promethazine Diphenhydramine (Benadryl) Dimenhydrinate Pheniramine Cyproheptadine Low anti-cholinergic action Chlorpheniramine Hydroxyzine Cyclizine Meclizine

2.Anti-emetic, anti-nausea (Menieres syndrome)

3.Anti-Parkinsonism suppress extrapyramidal symptoms 4.Anti-cholinergic urinary retention, blurred vision (side effects)

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5.Adrenoceptor-blocking () orthostatic hypotension 6. Serotonin blocking

Minimal/ absent anti-cholinergic action Clemastine Terfenadine (arrhythmia effect) Astemizole Loratidine (Alerta) Ebastine Cetirizine Rx: Promethazine (should be in supine postion) Cyproheptadine (appetite stimulant)

7.Allergy Urticaria, Allergic rhinitis Side Effects/Toxicity Sedation, decreased alertness & concentration, motor incoordination, light-headedness, dryness of mouth, urinary hesitancy, blurring of vision Cyclizine, Meclizine teratogenic B. H1 Blockers (2nd generation) Loratadine Higher H1 selectivity Desloratadine No anti-cholinergic side Cetirizine inhibits H release & cytotoxic mediators from platelets & effects eosinophil chemotaxis no CNS depressant property Azelastine (Do not potentiate alcohol, Ebastine benzodiazepine) Terfenadine blocks cardiac K+ channels (overdose); Torsades de Inhibit late phase allergic pointes reaction by acting on LT, antiFexofenadine no arrhthymogenic potential platelet activating effect Poor anti-pruritic, antiemetic, anti-tussive properties Used for: Allergic rhinitis, conjunctivitis, hay fever, urticaria, atopic eczema, acute allergic reactions C. H1 Blockers (3rd generation) Levocetirizine D. H2 Blockers Anti-ulcer Cimetidine Cytochrome P450 inhibitor, anti-androgen effects Ranitidine Famotidine Nizatidine

Major source in intestines (90%) Platelets Brainstem (mood, sleep, appetite, pain perception,

CNS *Vomiting *Pain *Itch *Bezold-Jarisch reflex (5HT3) *chemoreceptor reflex marked outflow of vagal stimulation to the heart bradycardia

SEROTONIN I. Serotonin (5-HT) Agonists A. 5HT1A Receptor Buspirone (anxiolytic) B. 5HT1D Receptor Amlotriptan NA Sumatriptan Zolmitriptan (constrict cerebral vessel)(migraine headache) C. 5HT4-Cisapride(toxic) Tegaserod (partial agonist) irritable bowel syndrome

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temperature & BP regulation, vomiting)

CVS *vasoconstriction (5HT2) except skeletal muscle, heart *platelet aggregation RS *bronchoconstriction (5HT2) GIT *increases motility thru ACh (5HT4) Skeletal muscles *serotonin syndrome (5HT2) *hyperthermia

II. Serotonin (5-HT) Antagonists 1. 5HT1-5HT2 2. 5HT2 3. 5HT2, H1 4. 5HT3 Therapeutic Uses 1. controls S/S carcinoid, post-gastrectomy dumping syndrome 2. Raynauds disease 3. Anti-emetic (anti-cancer, radiotherapy) 4. Migraine prophylaxis, Carcinoid, post-gastrectomy dumping syndrome 5. Migraine (better tolerated) 6. Schizophrenia

Synthesized

from tryptophan

Methysergide Ketanserin blocks platelet aggregation for stroke Ritanserindecreases thromboxane formation for stroke Cyproheptadin for cold-induced urticaria for carcinoid syndrome Ondansetron chemotherapy-induced nausea & vomiting Cyproheptadine sedative, stimulates appetite, good anti-pruritic Ketanserin blocks platelet aggregation for stroke Ritanserindecreases thromboxane formation for stroke Ondansetron Methysergide Sumatriptan Zolmitriptan Risperidine Clozapine

Degraded by

MAO 5HT1,2,3,4,5,6 ,7 receptors

ERGOT ALKALOIDS
Mechanism of Action Organ System Effect Adverse Effects Indications Contraindications Other notes

Amine Alkaloids Ergometrine Ergonomine Amino Acid/Peptide Alkaloids Ergotamine Regotoxine Semi-Synthetic Alkaloids Ergometrine Ergonomine

agonist, partial agonist, antagonist at receptors, serotonin receptors, CNS dopamine receptors

CNS powerful hallucinogen (Lysergic Acid Diethylamide or LSD) Bromocriptine inhibits prolactin CVS vasoconstriction d/t partial agonist effects at adrenoceptors

Nausea, vomiting (high dose) Prolonged vasospasm gangrene, bowel infarction Drowsiness, hallucinations

Ergotamine, Ergonovine, Methysergide migraine headache (partial agonist & 5HT2) Uterus postpartum hemorrhage, induces labor Ergonovine, Oxytocin (parenteral), Methylergometrine (Methergine) parenteral or oral

EICOSANOIDS
Mechanism of Action
Arachidonic Acid Arachidonic Acid Oxygenated by 4

Organ System Effect

CVS

Adverse Effects

Indications

Contraindicati ons

Other notes
Lipid-derived autacoids Oxygenation products of polyunsaturated long chain

TXA2, PGF2

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Prostaglandins

routes:

Lipoxygenase: HETEs, leukotrienes, lipoxins Cytochrome P450 (epoxygenase) EETs, vasodilator Icoeicosanoid: Isoprostane, vasoconstrictor Cyclooxygena se: PG, prostacyclin, thromboxane

vasoconstriction, bronchoconstriction, contraction of uterus

fatty acids Plant & fish oil precursors

GIT

PGI2/prostacyclin, PGE1 vasodilatation, bronchodila, relaxes uterus Epoprostenol (PGI2) pulmonary HPN Alprostadil (PGE1) patency of DA COX inhibitor (Indomethacin) closes ductus arteriosus Misoprostol/cytotec (PGE1) for peptic ulcer (NSAID- induced), for abortion

Arachidonic Acid most important precursor

Eicosanoid Inhibitors

Corticosteroids: Non-Steroidal

inhibits all pathways by stimulating synthesis of inhibitory protein, inhibit phospholipase A prevent arachidonic acid release Anti-Inflammatory Drugs (NSAIDs): blocks prostaglandin & thromboxane formation by inhibiting cyclooxygenase activity Aspirin (Acetylsalicylic Acid) irreversible acetylation of platelet cyclooxygenase (other drugs not irreversible); inhibits TXA2 synthesis

PGH synthase-1 (COX1): gastric epithelial protection PGH synthase-2 (COX2): source in inflammation

Mechanism of action: irreversibly inhibits platelet COX1 (8-10 days)

Prostaglandin Bind to receptors on cell surface

Enprostil NA (PGE) inhibit HCl secretion Respiratory System PGE2, PGI2 bronchodilatation PGD2, TXA2 bronchoconstriction

Indications: transient ischemic attack (TIA), CAD (coronary artery disease) Adverse Effects: Gastric/duodenal ulcer Hepatotoxic Allergy (most common)

Non-selective COX inhibitors blocks prostaglandin, TXA2 synthesis

PGF2, LT bronchoconstriction Platelet aggregation PGD2, PGE2, PGI2 inhibit TXA2 stimulate

Pyrazone Oxybutazone

Phenylbutazone,

Indole Indomethacin, Sulindac Propionic acid Ibuprofen, Naproxen, ketoprofen Anthranilic acid Mefenamic acid Aryl-acetic acid Diclofenac Oxicam Piroxicam, Tenoxicam

Aspirin inhibits platelet COX1 Kidney PGE2, PGI2 vasodilatation

Pyrolopyrole Ketorolac COX-2 Selective Inhibitors Mechanism of action: bind to and block active site of COX2 enzyme (reversible) Less GI effects, no platelet effect Adverse Effects: Fluid retention Hypertension Hepatotoxic Nephrotoxic Rashes

TXA2 vasoconstriction Reproductive system

PGF2, PGE2- uterine contraction, soften cervix Dinoprostone, Misoprostol, Carboprost PGE2, PGF2 SE dysmenorrhea (take NSAIDs)

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Alprostadil (PGE1) relax smooth muscle of corpora cavernosa for erectile dysfunction lipooxygenase, P450

Effects of cytochrome metabolites: CVS

GIT

12Hydroxyeicosatetrae noic (HETE) chemoattractant for smooth muscles LTC4, LTD4 myocardial depressant, constriction of coronary arteries

LTB4 chemoattractant for PMNs Respiratory LTC4, LTD4 bronchoconstriction, mucus secretion, plasma exudation Blood LTB4 chemoattractant for T cell, eosinophils, monocytes, mast cells Renal System

20 HETE vasoconstriction

EET vasodilatation, natriuresis

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VASOACTIVE PEPTIDES
ANGIOTENSIN RECEPTOR ANTAGONISTS Mechanism of Action Valsartan
Selective antagonist of AT1 receptors competitive angiotensin

Organ System Effects

Arteriolar dilation decreased aldosterone secretion increased sodium and water excretion

Adverse Effects

Indications
Hypertension

Contraindications

Other Notes
Eprosartan, irbesartan, candesartan, olmesartan, telmisarta - similar to valsartan

CONVERTING ENZYME INHIBITORS Mechanism Action Enalapril RENIN INHIBITORS Mechanism Action Aliskiren KININ ANTAGONISTS Mechanism Action Icatibant

of

Organ System Effects

Arteriolar dilation decreased aldosterone secretion increased sodium and water excretion

Adverse Effects

Indications
Hypertension heart failure

Contraindications

Other Notes
Captopril and many others -similar to enalapril

Inhibits conversion of angiotensin I to angiotensin II

of

Organ System Effects

Arteriolar dilation decreased aldosterone secretion increased sodium and water excretion

Adverse Effects

Indications
Hypertension

Contraindications

Other Notes

Inhibits catalytic activity of renin

of

Organ System Effects

Blocks effects of kinins on pain, hyperalgesia, and inflammation

Adverse Effects

Indications
Potential use for inflammatory pain and inflammation

Contraindications

Other Notes

Selective antagonist of kinin B2 receptors

VASOPRESSIN AGONISTS Mechanism Action Arginine vasopressin

of

Organ System Effects

Vasoconstriction

Adverse Effects

Indications
Vasodilatory shock

Contraindications

Other Notes
Terlipressin - more selective for V1 receptor

Agonist of vasopressin V1 (and V2) receptors

VASOPRESSIN ANTAGONISTS Mechanism Action Conivaptan

of

Organ System Effects

Vasodilation

Adverse Effects

Indications
Potential use in hypertension and heart failure hyponatremia

Contraindications

Other Notes
Relcovaptan increased selectivity for V1 receptor

Antagonist of vasopressin V1 (and V2) receptors

NATRIURETIC PEPTIDES Mechanism Action Nesiritide

of

Organ System Effects

Increased sodium excretion vasodilation and water

Adverse Effects

Indications
Heart failure

Contraindications

Other Notes

Agonist of natriuretic peptide receptors

Monique Wine Jamie Juria VASOPEPTIDASE INHIBITORS Lenard Mechanism Action

Decreases metabolism

Section 2D Batch 2014 of

of

Organ System Effects

PHARMACOLOGY: COMPREHENSIVE TABLE OF DRUGS (1st Shifting Period) | Page 28 of 29 Adverse Effects Indications Contraindications Other Notes

NITRIC OXIDE
Mechanism of Action Organ System Effects
1.

Adverse Effects

Indications

Contraindications

Other Notes

Nitric Oxide

Monique Wine Lenard

blood vessels vasodilator inhibits PMN adhesion to endothelium 2. respiratory system relax smooth muscles NO activates soluble for pulmonary hypertension guanylyl cyclase to elevate and ARDS cGMP levels in vascular 3. platelets smooth muscle inhibits platelet adhesion, Jamie Juria Section 2D Batch 2014 aggregation, enhance fibrinolysis 4. CNS modifies NT release, learning & brain development

Methemoglobinemia

Hypoxic respiratory failure and pulmonary hypertension

Inhaled gas

PHARMACOLOGY: COMPREHENSIVE TABLE OF DRUGS (1st Shifting Period) | Page 29 of 29