Vasodilators & Angiotensin System Inhibitors

Question 1

Calcium Channel Blockers

Answer 1

Dihydropyridines: Amlodipine

Non-Dihydropyridines: Verapamil, Diltiazem

Question 2

K-Channel Activators

Answer 2

Minoxidil

Question 3

Guanylate Cyclase Activators

Answer 3

Nitroprusside, Nitroglycerin, Isosorbide Denitrate, Nitric Oxide, Hyralazine

Question 4

Dopamine D1 Receptor Agonists

Answer 4

Fenoldopam

Question 5

Phosphodiesterase Inhibitors

Answer 5

Sildenafil, Tadalafil

Question 6

ACE Inhibitors

Answer 6

Lisinopril, Enalapril

Question 7

ATII Receptor Antagonists

Answer 7

Losartan, Valsartan

Question 8

Renin Inhibitors

Answer 8

Aliskiren

Question 9

Arterial dilation

Answer 9

decrease TPR

compensatory increased HR and fluid retention

Question 10

Venous dilation

Answer 10

decrease venous return leads to decrease CO

compensatory increased HR and fluid retention

Question 11

Ca-Channel Blockers

Answer 11

Amlodipine, Diltiazem, and Verapamil
Direct Effects:
Blood Vessels - decrease influx of Ca through L-type Ca-channels, vasodilation (arterial > venous), decrease TPR
Heart - L type Ca-channels inhibited by Verapamil > Diltiazem&raquo_space; DHPs, inhibit phase 2 (plateau) of AP in A&V muscle to cause decreased Ca entry, decreasing SR Ca release, causing a decrease contractility, inhibits phase 0 depolarization in SA and AV nodes to decrease firing rate of SA node leading to a decrease in HR, a decrease in conduction velocity in AV node causing an AV block

Undergoes Hepatic Metabolism

Question 12

Uses of Ca-Channel Blockers

Answer 12

Chronic Stable and Variant Angina: to cause coronary vasodilation to increase myocardial O2 supply, causes systemic vasodilation decreasing afterload and decreasing O2 demand (Verapamil and Diltiazem are decrease HR and contractility leading to decrease O2 demand)
Supraventricular Tachyarrhythmia: Verapamil can decrease AV nodal conduction leading to a control of V rate in A flutter and Afib as well as terminating paroxysmal supraventricular tachycardia
Hypertension: decreases TPR and CO (amlopdipine is good for this)

Question 13

Adverse Effects of Ca-Channel Blockers

Answer 13

Hypotension (DHPs>Verapamil>Diltiazem)
CHF (Verapamil>Diltiazem>DHPs)
AV Block (Verapamil>Diltiazem>DHPs)
Edema (DHPs>Diltiazem>Verapamil)
Headache (DHPs>Verapamil>Diltiazem)
Constipation (Verapamil>Diltiazem>DHPs)

Question 14

Contraindications and Precautions using Ca-Channel Blockers

Potential Drug Interactions

Answer 14

CHF (verapamil & diltiazem)
Hypotension (all)
AV Block (verapamil & diltiazem)
Severe hepatic disease (all)
Sick sinus syndrome (verapamil & diltiazem)

Drug Interactions:
CYP3A4 inhibitors/inducers, concurrent Beta-Blockers, digoxin, and antiarrhythmic drugs

Question 15

K-Channel Openers - Minoxidil

Answer 15

cause an increase in efflux of K+ leading to hyperpolarization and decreasing the TPR

Effects: potent vasodilator causing decreased TPR leading to a compensatory increase in HR, CO, and fluid retention

Uses: refractory hypertension, promote hair growth to treat baldness

Adverse Effects & Toxicities: marked fluid retention when used with diuretic, tachycardia with a Beta-blocker, hypertrichosis, pericardial effusion/cardiac tamponade

Question 16

Guanylate Cyclase Activators

Answer 16

lead to an increase in guanylate cyclase increasing cGMP leading to vascular smooth muscle relaxation and vasodilation

Question 17

Sodium Nitroprusside

Answer 17

Effects: arteriodilation = venodilation, arteriodilation decreases TPR, decreasing BP, leading to an increase in HR
venodilation decreases LVEDV decreasing the CO then the BP causing an increase in HR
Overall effects - decrease TPR, decrease BP, decrease CO, increase HR

Only given IV

Uses: hypertensive crisis, acute CHF, and MI

Adverse Effects:
acute - excessive hypertension
chronic - thiocyanate and/or cyanide toxicity
(If sufficient thiosulfate –> thiocyanate toxicity)
(if insufficient thiosulfate –> CN- toxicity)

Question 18

Organic Nitrates

Answer 18

Nitroglycerin & Isosorbide Dinitrate

Effects: ventilation&raquo_space; arteriodilation
Low dose: venodilation (decrease LVEDV, decrease SV, decrease CO) overall - decrease CO, +/- BP
High dose: venodilation decreasing CO and BP, arteriodilation decreasing TPR and BP, have a reflex increase in HR, overall - decrease CO, TPR, BP, and increase HR

Kinetics: hepatic metabolism with extensive first pass elimination, given IV, sublingual, and transdermal

Uses: angina, CHF, acute MI

Adverse Effects: excessive hypotension and tolerance

Question 19

Nitric Oxide

Answer 19

Kinetics: inhalational, very short half life, excreted in urine

Uses: hypoxic respiratory failure in term/near-term neonates with associated pulmonary hypertension

Adverse Effects: pulmonary edema, hypoxemia upon sudden withdrawal

Question 20

Hydralazine

Answer 20

Effects: arterial vasodilation causing decreased TPR and BP

Uses: CHF and Hypertension

Adverse Effects & Toxicities: fluid retention, tachycardia, +ANA leading to lupus-like syndrome presenting with myalgia, butterfly rash, but no renal effect

Question 21

Fenoldopam

Answer 21

D1 Receptor agonist causing peripheral vasodilation decreasing TPR and BP

Given IV, rapid acting, moderate duration

Uses: hypertensive emergency

Adverse Effects: hypersensitivity (because sodium metabisulfite in formulation), tachycardia, and hypotension

Question 22

Phosphodiesterase Inhibitors

Answer 22

Sildenafil and Tadalafil
inhibits PDE Type 5 leading to an increase in NO-induced increase in cGMP causing a smooth muscle relaxation

Effects: relaxation of smooth muscle in corpus cavernosum leading to an erection and relaxation of lower urinary tract smooth muscle facilitating urination

Uses: erectile dysfunction and BPH (tadalafil)

Kinetics: mainly hepatic metabolism
Adverse Effects: hypotension

Contraindications, precautions, and interactions: concurrent organic nitrates, concurrent alpha-blockers, CYP3A4 interacting drugs

Question 23

Angiotensin Converting Enzyme Inhibitors (ACEIs)

Answer 23

Drugs: Lisinopril and Enalapril
Mechanism: decreasing angiotensin II, decreasing aldosterone secretion causing Na+ and H2O retention, decreases ATII mediated vasoconstriction, decreases ATII mediated adrenergic mediated vasoconstriction, decreases ATII mediated CV remodeling

Effects: decrease TPR, decrease Na+ and fluid retention, decrease BP

Kinetics: all but captopril lisinopril are prodrugs, renal excretion

Uses: hypertension, CHF, post MI, and prevention of diabetic nephropathy

Adverse Effects: fetopathic, cough (because of inhibiting metabolism of bradykinin), hyperkalemia, hypotension, hypersensitivity (rashes, pruritus, angioedema)

Contraindications: pregnancy, K+ supplements, K+ sparing diuretics, hypersensitivity

Question 24

Angiotensin II Receptor Blockers (ARBs)

Answer 24

Losartan and Valsartan
competitive antagonist at AT1 receptors
Effects: similar to ACEIs, less cough, less angioedema

Uses: hypertension, CHF, post MI, and prevention of diabetic nephropathy

Adverse Effects & Toxicities: fetopathic, hyperkalemia, hypotension, and hypersensitivity

Contraindications: pregnancy, bilateral renal vascular stenosis, K supplements, K-sparing diuretics, hypersensitivity

Question 25

Renin Inhibitors

Answer 25

Aliskiren

inhibits renin –> decrease ATI

Effects: similar to ACEIs, less cough
Uses: Hypertension
Adverse Effects & Toxicities: fetopathic, hyperkalemia, hypotension, hypersensitivity reactions

Contraindications, precautions, and interactions: pregnancy, bilateral renal vascular stenosis, K supplements, K-sparing diuretics, hypersensitivity