• block L-type Ca2+ channels
• arterial dilation: dihydropyridine derivatives such as nifedipine or amlodipine are the most potent vasodilators
• short-acting dihydropyridines produce a rapid drop in BP and reflex sympathetic nervous system activation leads to tachycardia
• coronary artery dilation: prevention of relief of coronary vasospasms improves myocardial blood flow
• negative chronotropic effect: verapamil and diltiazem slow the rate of firing of the SA node and slow conduction of the impulse through the AV node
• reduce cardiac contractility: particularly verapamil has a negative inotropic effect

1. arterial dilation: headache, flushing, dizziness, ankle edema -> these are most common with dihydropyridines
2. reduced cardiac contractility: can precipitate heart failure in patients with pre-existing poor left ventricular function (verapamil)
3. tachycardia and palpitations with dihydropyridines
4. bradycardia and heartblock with verapamil or diltiazem
5. altered gut motility; constipation (verapamil)
6. nausea and heartburn (nifedipine)

• all Ca2+ channel blockers are equally effective when used alone for the treatment of mild to moderate hypertension
• Ca2+ channel blockers are as effective as beta blockers or diuretics
• these agents are not the first choice of drug therapy for patients who have left ventricular hypertrophy, or patients who had a myocardial infarction
• the efficacy of Ca2+ channel blockers is enhanced by the concomitant use of an ACEI, methyldopa, or beta blocker
• have little effect on most venous beds and hence do not affect cardiac preload significantyl

1. hypertension (all)
2. angina (all)
3. diabetic nephropathy (verapamil, diltiazem)
4. atrial flutter (verapamil, diltiazem)
5. atrial fibrillation (verapamil, diltiazem)
6. migraine prophylaxis (verapamil, diltiazem)

• causes direct relaxation of arteriolar smooth muscle (does not effect venous side that much)
• molecular mechanism is not clear
• does not dilate epicardial coronary arteries or relax venous smooth muscle
• hydralazine-induced vasodilation is associated with powerful stimulation of the sympathetic nervous system
• because of preferential dilation of arterioles over veins, postural hypotension is not a common problem

• the parent drug minoxidil is inactive
• minoxidil sulfate (metabolite) activates K_ATP channel
• by opening K channels in smooth muscle, it allows K efflux and causes hyperpolarization and relaxation of smooth muscle
• produces arteriolar vasodilation with essentially no effect on capacitance vessels
• associated with a reflex increase in myocardial contractility and in cardiac output
• salt and water retention due to increased proximal renal tubular reabsorption, which is in turn secondary to reduced renal perfusion pressure

• a nitrovasodilator that release NO
• NO activates Guanylyl Cyclase
• mimics the production of NO by vascular endothelial cells
• tolerance develops to nitroglycerin but not to nitroprusside
• dilates both arterioles and venules
• must be given by continuous intravenous infusion to be effective (in emergency situations)
• can also be used in many situations when short-term reduction of cardiac preload and/or afterload is desired

1. headache, dizziness, flushing (all)
2. tachycardia (all)
3. fluid retention (all)
4. a systemic lupus erythematosis-like syndrome (hydralazine)
5. thiocyanate accumulation; causes tachycardia, sweating, hyperventilation, metaboli acidosis (nitroprusside)

• hydralazine is no longer a first-line drug to treat hypertension due to its adverse effects
• minoxidil is best reserved for the treatment of severe hypertension that responds poorly to antihypertensive medications
• minoxidil should never be given alone; should be given along with a diuretic to avoid fluid retention or a beta blocker to control reflex tachycardia
• nitroprusside is used primarily to treat hypertensive emergencies

hypertension

hypertensive emergency (hydralazine, nitroprusside)

Non-Dihydropyridine Ca2+ Channel Blocker

Adverse Effects:

1. Reduced cardiac contractiliy: can precipitate heart failure in patients with pre-existing poor left ventricular function
2. bradycardia and heart block
3. Constipation

Indications

1. hypertension
2. angina
3. diabetic nephropathy
4. atrial flutter
5. atrial fibrillation
6. migraine prophylaxis

Non-Dihydropyridine Ca2+ Channel Blocker

Adverse Effects:

bradycardia and heart block

Indications:

1. hypertension
2. angina
3. diabetic nephropathy
4. atrial flutter
5. atrial fibrillation
6. migraine prophylaxis

Dihydropyridine Ca2+ Channel Blocker

Adverse Effects:

1. atrial dilation: headache, flushing, dizziness, ankle edema
2. tachycardia and palpitations
3. nausea and heartburn

Dihydropyridine Ca2+ Channel Blocker

Adverse Effects:

1. atrial dilation: headache, flushing, dizziness, ankle edema
2. tachycardia and palpitations

Dihydropyridine Ca2+ Channel Blocker

Adverse Effects:

1. atrial dilation: headache, flushing, dizziness, ankle edema
2. tachycardia and palpitations

Indications:

1. hypertension
2. angina