Hypertension Drugs

Question 1

Candesartan
Irbesartan
Losartan
Valsartan

Answer 1

AT1 antagonists (ARBs)

• Non-peptide competitive agonists of AT1 receptors (inhibits vasoconstriction, Na retention, and renin feedback), reduce plasma volume, decrease cellular hypertrophy, residual AT2 stimulation (promote vasodilation and natriuresis), increase Ang-(1-7)
• Fewer side effects than ACEIs – hypotension, hyperkalemia, acute renal failure, not for pregnancy or nursing moms
• Hypertension, heart failure, diabetes, chronic kidney disease, prevent secondary MI

Question 2

Catopril
Enalapril
Lisinopril
Fosinopril
Quinapril

Answer 2

ACE Inhibitors

• More potent arterial than venous dilators (reduce afterload and increase SV and CO)
• Block conversion of AI to AII and AIII (classical RAS pathway), elevate bradykinin levels, decrease peripheral resistance, decrease aldosterone, increase plasma renin, increase Ang-(1-7)
• DRY COUGH, angioedema, hypotension, hyperkalemia, acute renal failure, rash, not for pregnancy or nursing moms

Question 3

Conivaptan

Answer 3

Vasopressin Receptor Antagonists

• V1/V2 receptor antagonist
• Hyponatremia caused by SIADH (IV to hospitalized patients

Question 4

Tolvaptan

Answer 4

Vasopressin Receptor Antagonists

• Selective V2 receptor antagonist - oral
• Hypervolemic and euvolemic hyponatremia resistant to fluid restriction (heart failure, cirrhosis, SIADH)

Question 5

Aliskiren

Answer 5

Renin Inhibitor

• Direct, competitive inhibitor of renin – increase plasma renin but not renin activity
• GI/allergic symptoms, hypotension, hyperkalemia, acute renal failure, not for pregnancy or nursing moms
• Essential Hypertension

Question 6

Atenolol  (oral/IV)
Metoprolol (oral/IV)
Acebutolol
Esmolol (IV only)
Bisoprolol

Answer 6

Sympatholytics

• B1 Receptor Antagonists
• Decrease CO, renin secretion, central sympathetic outflow, resetting of baroreceptors, decrease HR and contractility, improve LV structure and function, improved abnormal Ca handling
• Nausea, vomiting, confusion, fatigue, sleep disorders, avoid in asthmatics or PVD, increase in type 2 diabetes, hypoglycemia, hyperlipidemia, bradycardia, impotence, hypotension
• Alone or in combo for hypertension, coronary heart disease w/o signs of acute heart failure (combo with nitrates), heart failure due to LVEF, atrial arrhythmias, slow AV node conduction, prevent sudden cardiac death post MI

Question 7

Propranolol (oral/IV)
Nadolol
Pindolol
Timolol
Carvedilol (also a1

Answer 7

Sympatholytics

• Nonselective beta antagonists
• Decrease CO, renin secretion, central sympathetic outflow, resetting of baroreceptors, decrease HR and contractility, vasoconstriction, bronchoconstriction, impaired glycogenolysis, improve LV structure and function, improved abnormal Ca handling
• Nausea, vomiting, confusion, fatigue, sleep disorders, avoid in asthmatics or PVD, increase type 2 diabetes, hypoglycemia, hyperlipidemia, bradycardia, impotence, hypotention
• Alone or in combo for hypertension, coronary heart disease w/o signs of acute heart failure (combination with nitrates), heart failure due to LVEF, atrial arrhythmias, slow AV node conduction

Question 8

Doxazosin
Prazosin
Terazosin

Answer 8

Sympatholytics

• A receptor antagonists. Blockade of a1 receptors on VSM – dilation of arterioles and capacitance veins
• Reflex tachycardia, orthostatic hypotension, fluid retention, GI upset, palpitation, tinnitus, headache, dizziness, urinary incontinence
• Alone or in combination of hypertension, pheochromocytoma

Question 9

Carvedilol

Answer 9

Sympatholytics

• Mixed a/b antagonists
• Non-selective B and a1 receptor antagonist
• Antioxidant and antiprolifeartive – hypertension and heart failure

Question 10

Labetalol

Answer 10

Sympatholytics

• Mixed a/b antagonists
• Non-selective B and a1 receptor antagonist
• Chronic hypertension and hypertensive emergencies

Question 11

Reserpine

Answer 11

Inhibitor of Peripheral Transmission

• Deplete NE from adrenergic nerve endings, inhibits reuptake of NE into storage terminal, decrease peripheral resistance and CO
• Postural hypotension, sedation, dry mouth, nightmares, sodium and water retention
• Mild to moderate hypertension - can use low dose in combination with thiazide diuretic

Question 12

a-methyldopa
Clonidine
Guanabenz

Answer 12

Central-Mediated Agents

• Stimulate brainstem a2 adrenergic receptors (decrease sympathetic outflow), vagal activity to heart increased, decreased PVR and CO
• Withdrawal/rebound, sedation, dry mouth, depression, drowsiness, sodium and water retention, postural hypotension
• Resistant hypertension (clonidine), pregnancy induced hypertension (methyldopa)

Question 13

Epoprostenol

Answer 13

Vasodilators

• Prostacyclin – direct vasodilator via cAMP, counteracts thromboxane A2
• Potent antihypertensive (continuously administered), primary pulmonary hypertension

Question 14

Hydralazine

Answer 14

Vasodilators

• Arterial vasodilator. Mechanism unclear – reduced intracellular Ca, preferential effect on arterioles, decrease PVR/MAP, reflex increase in HR, contractility, CO, increase renal blood flow.
• Headache, anorexia, nausea, dizziness, sweating, angina or ischemic arrhythmias, incrased renin and fluid retention, Lupus
• Mild to moderate hypertension in combination with diuretic and B-blocker, advanced heart failure

Question 15

Minoxidil

Answer 15

Vasodilators

• Preferential effect on arterioles, decrease PVR, activates K channels and VSM relaxation, reflex increase in HR, contractility, CO, renin secretion, fluid retetntion
• Fluid retention, decreased PVR, activates K channels/VSM relaxation, reflex increase in HR
• Resistant hypertension in combination with diuretic and B-blocker

Question 16

Nitroglycerin

Answer 16

Nitrovasodilators

• Short duration of action, tolerance, give sublingual
• Effects mostly veins (decrease preload) and large arteries (relieve vasospam), generates nitric oxide through mtALDH which activates guanyyl cyclase, increase in cGMP, inhibits platelet aggregation
• Headache (really bad), orthostatic hypotension, dizziness, flushing, syncope, reflex tachy, GI distress, don’t use with PDE5 inhibitors
• Produce hypotension in surgery and hypertensive emergencies, CHD, angina, L sided heart failure due to acute MI

Question 17

Nitroprusside

Answer 17

Nitrovasodilators

• IV only. Direct vasodilator, generates nitric oxide which activates guanylyl cyclease, increase in cGMP, effects on veins (decrease preload) and arteries (relieve vasospasm), inhibits platelet aggregation
• Rapid decrease in MAP, cyanide accumulation, headache (really bad), orthostatic hypotension, dizziness, flushing, syncope, reflex tachy, GI distress, don’t use with PDE5 inhibitors
• Produce hypotension in surgery and hypertensive emergencies, CHD, angina, decompensated heart failure

Question 18

Riociguat

Answer 18

Vasodilators

• Directly stimulates guanylyl cyclase – increase cGMP
• Headache, nausea, dizziness, diarrhea, hypotension, birth defects
• Priamry pulmonary hypertension, thromboembolic pulmonary hypertension, combined with ET receptor blockers

Question 19

Diltiazem

Verapamil

Answer 19

Ca channel blockers

• Cardioselective – negative chronotropic. Block voltage sensitive L-type Ca channels, decrease contractility of cardiac myocytes, decrease MAP, slow conduction.
• Contraindicated in heart failure (edema), depresses AV conduction and contractility, headache, dizziness, nausea, gingival inflammation, arrhythmias, constipation
• Best for African Americans with hypertension, chronic CHD, cerebral hemorrhage or vasospasm, re-entry SVTs involving AV node

Question 20

Amlodipine
Nicardipine
Nifedipine
Nimodipine (SAH only – lipophilic)

Answer 20

Ca channel blockers

• Vasoselective. Block voltage sensitive L-type Ca channels, relax and dilate arteries (minimal effect on veins), prevent vasospasm, decrease MAP
• Contraindicated in heart failure (edema), depresses AV conduction and contractility, headache, dizziness, nausea, gingival inflammation, arrhythmias, constipation
• Best for African Americans with hypertension, chronic CHD, supraventricular arrhythmias, cerebral hemorrhage or vasospasm

Question 21

Chlorothiazide
Chlorthalidone
Hydrochlorothiazide

Answer 21

Diuretic - thiazide

• Block Na-Cl symporter in DCT – moderate diuresis (reduced by NSAIDs)
• Hypokalemia, decrease uric acid excretion, sulfa cross-reactivity
• Hypertension (1st line) and heart failure

Question 22

Ethacrynic acid
Bumetanide
Furosemide
Torsemide

Answer 22

Diuretic – loop agents

• Block Na-K-2Cl cotransporter in thick ascending limb of Loop of Henle
• Hypokalemia, decrease uric acid excretion, deafness, allergic reaction
• Hypertension and heart failure, use with edema (most effective)

Question 23

Amiloride

Triamterene

Answer 23

Diuretic – K+ sparing agents

• Late distal tubule and collecting duct – Na channel blockers
• Hyperkalemia
• Hypertension and heart failure (use with thiazides)

Question 24

Eplerenone

Spironolactone

Answer 24

Aldosterone Receptor Antagonist

• Collecting duct – block Na and H2O reabsorption, K sparing – inhibits aldosterone adverse effects on structure/function of heart
• Hyperkalemia – don’t use without diuretics
• Mild diuresis – resistant hypertension and CHF with hypertension, moderately sever heart failure or LV dysfunction after MI

Question 25

Avanafil
Sildenafil
Tadalafil
Vardenafil

Answer 25

PDE5 inhibitor

• Increase levels of cGMP, modest drop in blood pressure
• Hypotension when combined with nitrates or a blockers (excess cGMP), headache, rhinitis, flushing, back pain, loss of hearing/vision
• ED and primary pulmonary hypertension (sildenafil)