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Flashcards in HTN meds: CCB Deck (34)

Next continuing with HTN meds are Calcium Channel Blockers, Verapamil (non-dihydro), Diltiazem (non-dihydro), Nifedipine (dihydropyridine), and Amlodipine (dihydropyrine). What are the clinical applications for these drugs?

Tx: HTN, angina and arrhythmias
--thiazides plus CCB are used as first line in blacks and/or elderly
--the dihydropyrine agents can be combined with beta blockers due to their cardio depressant effects


What is the mechanism of action for CCB?

Block calcium channels located on vascular smooth muscle, cardiac myocytes and cardiac nodal tissue
--reducing calcium entry into these cells
Decreased myocardial force generation
Decreased Heart Rate


CCBs lower blood pressure by decreasing peripheral vascular resistance. Dihydropyridine drugs only act on the vascular smooth muscle not the cardiac, therefore what happens to the heart rate in these patients?

May evoke reflex tachycardia


Calcium channels blockers, the Dihydropyridines, have a very high selectivity for vascular smooth muscle. So they are used to treat what?

---and again you may get reflex tachycardia
--list on page 304 of the dihydropyridines CCBs


The two non-dihydropyridines CCB are verapamil and diltiazem. What is the use for Verapamil?

Effects both myocardium and vascular smooth muscle
--more selective to the myocardium though
--tx of angina and cardiac arrhythmias


What is the use for Diltiazem?

Cardiac Depressant and Vasodilator
--reduces arterial pressure without producing the same degree of reflex tachycardia
--tx of HTN, angina and arrhythmias


What are the adverse effects of the Dihydropyridines?

1. Reflex tachycardia
2. Peripheral Edema
3. Dizziness, flushing, headache, gingival hyperplasia


What are the adverse effects of the Non-dihydropyridines?

Cardiac conduction abnormalities: bradycardia, AV block and heart failure
Anorexia, nausea, peripheral edema and hypotension
Constipation: verapamil


What are the contraindications in using CCB?

Patients with bradycardia, conduction defects or heart failure


The next set of drugs are the alpha 1 adrenoceptor antagonists, Prazosin and Doxazosin. What are the clinical applications of these drugs?

Tx of primary HTN
-needs to be combined with a diuretic though
--there is an increased risk for developing CHF
--so these drugs are saved for patients with BPH or again used in combo with a diuretic


What is the mechanism of action of the alpha 1 adrenoreceptor antagonists?

Block Alpha1
--reduce vasoconstriction and peripheral vascular resistance --- resulting in decreased blood pressure
--again remember there is not reflex tachycardia for these drugs
--again dilate both arteries and veins due to the sympathetic adrenergic innervation


What are adverse side effects of giving a patient an alpha 1 antagonist?

First Dose Phenomenon: orthostatic hypotension, dizziness, and syncope within 1-3h of first dose
Na and H20 reduction: chronic use
Dizziness, drowsiness, headache, lack of energy, nausea and palpitations


Next set of drugs are the Direct Vasodilators, hydralazine and Minoxidil. What is their clinical applications?

HTN (not first line) and HF
--strong reflex tachycardia
--frequent dosing due to short half life
--current use for antihypertensive is limited to tx of hypertensive crisis in pregnant women with eclampsia
--HF: Use Hydralazine: reduces afterload and enhances stroke volume and ejection fraction. Needs to be given with a diuretic
---Severe HTN use Minoxidil


Direct vasodilators cause fluid retention and reflex tachycardia therefore they are most effective when used how?

Most effective in reducing blood pressure when combined with diuretics and beta blockers
--used clinically as 4th line tx for chronic HTN


What is the mechanism of action for direct vasodilators?

Minoxidil: K channel opener that hyperpolarizes vascular smooth muscle cells
Hydralazine: less potent
---Vasodilation --- leads to reflex tachycardia and increase in renin release (leads to Na and H20 retention)


What are the adverse effects of Hydralazine?

Reflex tachycardia and Na/H20 retention: a beta blockers and thiazide diuretic control these side effects


What are the adverse effects of Minoxidil?

Reflex tachycardia, renin release and Na retention effects are much more dramatic then Hydralazine


Next set of cards will discuss cardioinhibitory drugs. First are the Beta Blockers: Propranolol, Metoprolol, Atenolol, Pindolol, and Labetalol. What are the clinical applications for these drugs?

--Tx of HTN, Angina, MI, Arrhythmias, and HF
HTN: first line in patients with CAD, HF or post MI
--second line therapy in combo with first line therapy
--less effective in reducing BP in black patients
HTN Emergencies: Labetalol in patients without second or third degree AV block, bronchospastic disease or bradycardia


By antagonizing beta receptors, B blockers are able to decreased blood pressure by two different mechanisms:

1) decrease myocardial contractility, heart rate and cardiac output (B1 blocked)
2) reduce renin secretion thus decrease circulating angiotensin II levels (B1 blocked)
--no reflex tachycardia due to their negative inotropic/chronotropic actions


List the various B-blockers and their action

1. Propranolol: non selective B blocker
2. Metoprolol and Atenolol: Cardioselective B1 blocker. Most commonly used B blockers for HTN
3. Pindolol: partial agonist: cardioinhibitory effects are less than with other beta blockers. Preferred beta blocker for use in pregnancy
4. Labetalol: blocks both alpha and beta receptors. But a more potent beta blocker. BP is lowered by a reduction in peripheral vascular blockage via alpha and heart rate is not significantly altered due to B receptors blocked


What are the adverse effects of B-blockers?

1. Drug Withdrawal: abrupt withdrawal produces unstable angina, MI or even death in patients with CAD.
--patients without CAD: tachycardia, sweating and increased BP
2. CVS effects: bradycardia, reduced exercise capacity, HF, hypotension
3. Disturb lipid metabolism: increase TAGs and decrease HDL cholesterol levels slightly
4. Hypoglycemia: B2 normally stimulate hepatic glycogen breakdown and pancreatic release of glucagon, which both increase glucose.
5. Bronchoconstriction: effects on B2 receptors
6. CNS effects: reduced sexual function and fatigue


What are the contraindications for a beta blocker?

COPD or asthma
Patients with sinus bradycardia and partial AV blocks


Next set of cards will cover Centrally Acting Sympatholytics, first are the central alpha 2 agonists. Clonidine and Methyldopa. What is their clinical indication?

Tx: chronic HTN and hypertensive crisis
Methyldopa is the drug of choice for tx of pregnancy induced HTN


What is the mechanism of action of clonidine and methyldopa?

alpha 2 receptors decrease sympathetic outflow from the vasomotor center and increases vagal tone
--decrease in heart rate, cardiac output, peripheral resistance and plasma renin activity


What is the mechanism of action for each drug?

Clonidine: partial agonist
Methyldopa: alpha methynorephrinephrine is though to to activate the alpha 2 receptors


What are the adverse effects of clonidine and methyldopa?

1. Rebound HTN: abrupt cessation causes increase in norepinephrine release that follows discontinuation of alpha 2 stimulation
2. Na and H20 retention:
3. Orthostatic Hypotension, dizziness
4. Hemolytic Anemia: coombs positive hemolytic anemia
5. Hepatitis: methyldopa


Moving on to drugs that work for pulmonary HTN. First off what is pulmonary HTN?

Increase in BP in the pulmonary artery, pulmonary vein, or pulmonary capillaries


The first drug used for pulmonary HTN is Bosentan, what is the mechanism of action?

Antagonist at the endothelin receptors located on vascular endothelium and smooth muscle.


Bosentan is a strong inducer of what?



What are the adverse effects of Bosentan?

Cardiovascular: edema
CNS: headache
Endocrine and metabolic: spermatogenesis inhibition


What are the contraindications in Bosentan?

Category X drug: highly teratogenic


The last drug for pulmonary HTN is Epoprostenol, what is the mechanism of action?

Vasodilator of all vascular beds
--potent endogenous inhibitor of platelet aggregation
--decreasing thrombogenesis and platelet clumping in the lungs


What are the adverse effects of Epoprostenol?

CV: tachy, flushing and Hypotension
CNS: headache and anxiety
GI: n/v
Neuromuscular and skeletal: arthralgia and jaw pain


What are the contraindications for Epoprostenol?

--chronic use in patients with heart failure due to severe left ventricular systolic dysfunction