Day 2 Flashcards
2 Categories of Calcium Channel Blockers
Dihydropyridines
Non-Dihydropyridines
Non- Dihydropyridines (2)
Verapamil (Calan®)
Diltiazem (Cardizem® CD, Cartia® XT, Dilacor® XR, Taztia® XT)
Dihydropyridines (4)
Amlodipine (Norvasc®)
Felodipine (Plendil®)
Isradipine (Dynacirc®)
Nifedipine (Adalat® CC, Procardia® XL)
Role of Calcium Channels
When channels are opened: causes calcium influx into smooth muscle. Specifically,
Cardiac smooth muscle
Vascular smooth muscle
Results in activation of intracellular calcium with ultimately leads to muscle contraction (activates myosin and actin)
Calcium Channel Blocker MOA
Inhibits calcium influx into cells to prevent muscle contraction
Inhibition at cardiac smooth muscle
Decreases inotropy (force of contraction)
Decreases chronotropy (rate of contraction)
Inhibition at vascular smooth muscle
Vasodilation
Calcium Channel Blockers Dihydropyridines
Amlodipine, felodipine, isradipine, nifedipine
Inhibits calcium influx into vascular smooth muscle
Result:
Peripheral vasodilation
Calcium Channel Blockers Non-Dihydropyridines
Verapamil and Diltiazem
Inhibits calcium influx into cardiac smooth muscle
Result:
Decrease rate and force of contraction
Calcium Channel Blockers Role in Therapy
Place in therapy:
One of the first line options for hypertension
Other uses
Diltiazem and verapamil: supraventricular tachycardia, atrial fibrillation
Verapamil: migraine prophylaxis
Adverse reactions of Non-Dihydropyrinde’s
Constipation (Verapamil) Bradycardia Exacerbation of CHF Heart block Gingival hyperplasia
Adverse effects of all CCB
Hypotension
Adverse effects of the dihydropyridines
Peripheral edema (worst w/nifedipine) Amlodipine, felodipine and isradipine OK to use in patients with CHF Reflex tachycardia Flushing Headache
Clinical Pearls for CCB
Dihydropyridines are useful for patients with isolated systolic hypertension (esp. elderly)
Clevidipine I (IV only) is contraindicated in soy or egg allergy
Drug interactions with verapamil:
Metabolized by cytochrome P450 3A4
Also an inhibitor of this enzyme
(3) Alpha 1 Blockers
Prazosin (Minipress®)
Terazosin (Hytrin®)
Doxazosin (Cardura®)
Alpha 1 Blocker MOA and place in therapy
Mechanism of action:
Competitively inhibits alpha-1 receptors in the periphery which causes vasodilatation
Place in Therapy: Only as an add on especially in males. Not to be used often.
Uses of Alpha 1 Blocker
Hypertension (generally not monotherapy) Benign prostatic hypertrophy (BPH) Tamsulosin (Flomax®) Alfuzosin (Uroxatral®) Alpha-blockers used ONLY for BPH, minimal systemic effects
Adverse Effects of Alpha 1 Blocker
“First dose effect” – significant orthostatic hypotension with first dose and any subsequent dose titrations
Orthostatic hypotension, dizziness, vertigo
Reflex tachycardia, especially early in therapy (not seen if also on beta-blocker, but may worsen orthostatic effects)
Need to slowly titrate dose upward
Fatigue, vivid dreams, depression, dry mouth
Doses of Alpha 1 Blockers
Doxazosin is taken once daily
Terazosin is once to twice daily
Prazosin is two to three times daily
Centrally Acting Agents: Alpha 2 Agonists
Drugs:
Methyldopa (Aldomet®)
Clonidine (Catapres®, Catapres TTS®)
Mechanism of action:
Stimulates alpha2 receptors in brain, reduces sympathetic outflow from brain, which produces a decrease in BP and peripheral vascular resistance
Centrally Acting Agents: Alpha 2 Agonists Place in Therapy
Methyldopa has limited use
Good in pregnancy (category B)
Clonidine is often used for resistant hypertension. Other uses:
Substance abuse treatment (opiate withdrawal and avoidance)
Adjunct in pain management
Adverse effects Centrally Acting Agents: Alpha 2 Agonists Place in Therapy
Orthostatic hypotension , dizziness
Fatigue, depression, sedation
Sodium and water retention
Rebound tachycardia and hypertension if stopped abruptly
Methyldopa: liver toxicities, hemolytic anemia
Clonidine: rash with patch, “anticholinergic-like” side effects (dry mouth, sedation, constipation, urinary retention)
Centrally Acting Agents: Alpha 2 Agonists Clinical Pearls
Clonidine is available at a patch (Catapres TTS)
Applied every 7 days
Effects begin within 12-24 hours and last up to 3 days after patch removal
Vasodilator drugs and MOA
Drug:
Hydralazine
Minoxidil
Mechanism of action:
Direct vasodilator, especially in arteries and arterioles, leading to decreased systemic vascular resistance
Causes peripheral vasodilation
Common Adverse effects for Vasodilators
Reflex tachycardia, consider coadministration of beta blocker
Increase in renin as response to vasodilation, consider co-administration with diuretic
Headache is common
Hydralazine: Lupus–like syndrome, dermatitis, drug fever, peripheral neuropathy, hepatitis
Minoxidil: Hirsutism
Common Combo Drugs for HTN
Preferred Combos:
ACE-I/ARB + Thiazide
ACE-I/ARB + Dihydropyridine CCB
Acceptable Combos:
CCB + Thiazide
Thiazide + potassium-sparing diuretic
Beta-blocker + diuretic or dihyropyridine CCB
Drug Induced HTN
Corticosteroids Excessive alcohol NSAIDs ACTH Amphetamines Appetite suppressants Caffeine Cyclosporine Estrogen Pseudoephedrine Thyroid hormone (in excess) Duloxetine Venlafaxine Bevacizumab Sorafenib
