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Antihypertensive Agents

I. Classes - All act on 1 or more of the four anatomic control sites


a. Diuretics: deplete sodium
b. Sympathoplegics: decrease PVR, reduce CO
c. Direct Vasodilators: relax vascular smooth muscle
d. Anti-angiotensins: block activity or production
II. Sympathoplegics
a. Centrally Acting Sympathoplegic Drugs - 2 > 1
i. Methyldopa - Agonist at CNS adrenoceptors
1. Not recommended for first line therapy
2. Treatment fallback for unresponsive hypertension
3. Pregnancy induced hypertension
ii. Clonidine - Agonist at CNS adrenoceptors
1. Brief rise (peripheral alpha agonism), followed by
prolonged hypotension
2. Partial agonist
3. Back-up antihypertensive
4. ADHD, Tourettes, Withdrawl symptoms, Anxiety, PTSD
5. Sedative prolong anesthesia
b. Ganglion Blocking Agents - Block Sympathetic and Parasympathetic
Hexamethonium
c. Adrenergic Neuron Blocking Agents - Block NE release from adrenergic
neurons
i. Guanethidine - no CNS effects
1. Toxicities - Orthostatic Hypotension, Diarrhea, Ejaculation
impairment
2. Local anesthetic properties
ii. Reserpine - Also rarely used due to toxicity
d. Adrenoceptor Antagonist an blockers
i. Prazosin (1)
1. Retention of salt and water
2. Most effective when used with a blocker or a diuretic
ii. Propanolol () - prevents reflex tachycardia
1. Lacks cardioselectivity
2. Replaced by Metoprolol and Atenolol (selective for cardiac
1)
III. Vasodilators Elicits compensatory responses - given in conjunction with other
hypertensives
a. Hydralazine oral - K+ channel activation, hyperpolarization of smooth
muscle
b. Minoxidil - oral - K+ channel activation, hyperpolarization of smooth
muscle
c. Nitroprusside parenteral - HT emergencies, Cardiac failure - CN
accumulation
i. Breaks down in blood to release NO - cGMP
d. Fenoldopam - parenteral - Agonist of D1 receptors (Renal
vasodilation)
e. Calcium channel blockers bind alpha subunit and block L-Type
calcium channels
i. Also Antianginal, Antiarrhytmic

ii. Verapamil (more cardiac), Diltiazem, Dihydropyridines


f. Nitrates
IV. Angiotensin Inhibitors
a. ACE inhibitors - Captopril
b. Angiotensin receptor blockers Losartan, Valsartan

Angina Pectoris

All decrease myocardial oxygen demand - HR, ventricular volume, BP, or


contractility
I. Nitrates & Nitrites - Large veins best response ( venous capacitance,
ventricular preload
a. Nitroglycerin - NO release in vascular smooth muscle - SL
i. Mononitro forms (isosorbide dinitrate)
ii. Amyl Nitrite
b. Onset : 1-3 minutes, Duration: 20-30 minutes
II. Calcium Channel Blockers - contractility, SA node pacemaker rate, AV node
conduction
a. Most effective treatment for variant form of angina pectoris
b. Not for heart failure - Calcium channel blockers make worse
III. Beta Blockers - oxygen demand, HR, BP, Contractility

Congestive Heart Failure

I. Calcium (Ca-Chloride, Ca-gluconate)


II. Cardiac Glycosides - Positive inotropic, narrow therapeutic index
a. Digoxin - Inhibits Na+/K+ ATPase - oral
i. Na gradient, AP duration
ii. Pro-arrythmogenic
III. PDE Inhibitors - prolong cAMP and cGMP I.V.
a. Bipyridines positive inotrope, PVR
IV. Catecholamines Dopamine, Dobutamine positive inotrope
V. Diuretics
VI. ACE Inhibitors, ARBs
VII. Calcium sensitizers (Levosimendan) positive inotrope, not available in US
VIII. Vasodilators
IX. Beta-Blockers

Cardiac Arrhythmias

Reduce ectopic pacemaker activity, modify conduction (disable reentry)


Vaughn-Williams Classification
I. Class I sodium channel blockade
a. Class IA prolong APD, Intermediate dissociation
i. Quinidine oral, declining
ii. Procainimide
b. Class IB shorten APD, Fast dissociation
i. Lidocaine low tox
ii. Phenytoin anti-convulsant
c. Class IC No effect on APD, slow dissociation - Flecainide
II. Class II sympatholytic (beta-blockers) propranolol, esmolol, satolol (Class III)

III. Class III prolong action potential duration (other mechanisms besides sodium
channels K+)
a. Amiodarone (all 4 classes) toxicity, long half-life
IV. Class IV block cardiac calcium channel currents Verapamil
V. Miscellaneous Agents - do not fit into conventional classes I-IV
a. Digitalis pro-arrythmogenic
b. Adenosine enhanced K+ conductance - brief
c. Magnesium ionic gradients
d. Potassium - Increasing serum K+ when disrupted

Diuretic Agents

I. Carbonic Anhydrase Inhibitors - Rarely used now (K+ depletion, toxicity)


a. Acetazolamide - 85% supression of HCO3- reabsorption in PCT
i. Glaucoma, Alkalinization of urine, Metabolic alkalosis, Acute
Mountain Sickness
ii. Toxicity - Depletion of buffering capacity of blood, Kidney stones
II. Loop Diuretics - inhibit NaCl reabsorption in TAL - Inhibit Na/K/2Cl (NKCC2)
a. Furosemide (sulfonamide) - allergies
b. Ethacrynic acid
III. Thiazides - Inhibit NaCl transport in DCT - sulfonamides
a. Hydrochlorothiazide
IV. Potassium Sparing Diuretics aldosterone receptor antagonists
a. Spironolactone - Block aldosterone receptors
b. Amiloride - Inhibition of sodium flux through ion channels in luminal
membrane
V. Agents that Alter Water Excretion - Osmotic Diuretics
a. Mannitol - ICP
b. Conivaptan ADH antagonist