Day 2

Question 1

2 Categories of Calcium Channel Blockers

Answer 1

Dihydropyridines

Non-Dihydropyridines

Question 2

Non- Dihydropyridines (2)

Answer 2

Verapamil (Calan®)

Diltiazem (Cardizem® CD, Cartia® XT, Dilacor® XR, Taztia® XT)

Question 3

Dihydropyridines (4)

Answer 3

Amlodipine (Norvasc®)
Felodipine (Plendil®)
Isradipine (Dynacirc®)
Nifedipine (Adalat® CC, Procardia® XL)

Question 4

Role of Calcium Channels

Answer 4

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)

Question 5

Calcium Channel Blocker MOA

Answer 5

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

Question 6

Calcium Channel Blockers Dihydropyridines

Answer 6

Amlodipine, felodipine, isradipine, nifedipine
Inhibits calcium influx into vascular smooth muscle
Result:
Peripheral vasodilation

Question 7

Calcium Channel Blockers Non-Dihydropyridines

Answer 7

Verapamil and Diltiazem
Inhibits calcium influx into cardiac smooth muscle
Result:
Decrease rate and force of contraction

Question 8

Calcium Channel Blockers Role in Therapy

Answer 8

Place in therapy:
One of the first line options for hypertension

Other uses
Diltiazem and verapamil: supraventricular tachycardia, atrial fibrillation
Verapamil: migraine prophylaxis

Question 9

Adverse reactions of Non-Dihydropyrinde’s

Answer 9

Constipation (Verapamil)
Bradycardia
Exacerbation of CHF
Heart block
Gingival hyperplasia

Question 10

Adverse effects of all CCB

Answer 10

Hypotension

Question 11

Adverse effects of the dihydropyridines

Answer 11

Peripheral edema (worst w/nifedipine)
Amlodipine, felodipine and isradipine OK to use in patients with CHF
Reflex tachycardia
Flushing
Headache

Question 12

Clinical Pearls for CCB

Answer 12

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

Question 13

(3) Alpha 1 Blockers

Answer 13

Prazosin (Minipress®)
Terazosin (Hytrin®)
Doxazosin (Cardura®)

Question 14

Alpha 1 Blocker MOA and place in therapy

Answer 14

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.

Question 15

Uses of Alpha 1 Blocker

Answer 15

Hypertension (generally not monotherapy)
Benign prostatic hypertrophy (BPH)
Tamsulosin (Flomax®) 
Alfuzosin (Uroxatral®) 
Alpha-blockers used ONLY for BPH, minimal systemic effects

Question 16

Adverse Effects of Alpha 1 Blocker

Answer 16

“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

Question 17

Doses of Alpha 1 Blockers

Answer 17

Doxazosin is taken once daily
Terazosin is once to twice daily
Prazosin is two to three times daily

Question 18

Centrally Acting Agents: Alpha 2 Agonists

Answer 18

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

Question 19

Centrally Acting Agents: Alpha 2 Agonists Place in Therapy

Answer 19

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

Question 20

Adverse effects Centrally Acting Agents: Alpha 2 Agonists Place in Therapy

Answer 20

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)

Question 21

Centrally Acting Agents: Alpha 2 Agonists Clinical Pearls

Answer 21

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

Question 22

Vasodilator drugs and MOA

Answer 22

Drug:
Hydralazine
Minoxidil

Mechanism of action:
Direct vasodilator, especially in arteries and arterioles, leading to decreased systemic vascular resistance
Causes peripheral vasodilation

Question 23

Common Adverse effects for Vasodilators

Answer 23

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

Question 24

Common Combo Drugs for HTN

Answer 24

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

Question 25

Drug Induced HTN

Answer 25

Corticosteroids
Excessive alcohol
NSAIDs
ACTH
Amphetamines
Appetite suppressants
Caffeine
Cyclosporine
Estrogen
Pseudoephedrine
Thyroid hormone (in excess)
Duloxetine
Venlafaxine
Bevacizumab
Sorafenib