Alpha blockers and Calcium channel blockers

Question 1

Breakdown of alpha1 and alpha2 receptors

Answer 1

Alpha1:
-a1a: prostate, VSM
-a1b : VSM (increases with age)
Alpha2: inhibit NE and insulin release, a,b,c. (Mostly pre, some on platelets causing aggregation)

Question 2

Alpha blocker examples and effects

Answer 2

-Alpha1 antagonism: Doxazosin, prazosin,terazsin (block all a1 subtypes)+ tamsulosin blocks a1a specifically (prostatism)
Vasodilation
-Alpha2 antagonism: not used clinically
-mixed a1+a2: phenoxybenzamine (used in phaeochromocytoma)

Question 3

Alpha blocker indications

Answer 3

Hypertension: essential hypertension, third line therapy with diuretic, ACEi; very useful with phaeochromocytoma
Prostatism

Question 4

Prostatism

Answer 4

Post micturition dribbling, nocturia, hesitancy

result of enlarged prostate

Question 5

Most commonly used alpha blocker and benefit

Answer 5

Doxazosin
is a reversible a1 blocker and vasodilator
reduces prostate symptoms so two birds one stone.
o.d

Question 6

Alpha blocker adverse effects

Answer 6

• Orthostatic hypotension+dizziness. Can give first dose at night, not standing up much
• lassitude
• nasal stuffiness
• dry mouth
• urinary incontinence in women

Question 7

Rarely used alpha blockers

Answer 7

Phenoxybenzamine: irreversible alpha blockage; phaeo;
marked side effects: tachycardia, stuffy nose, postural decrease in BP + sedation (serotonin receptor block)

Phentolamine: a1=a2 blockage, so ^NE; 5HT block; limited use in phaeo and sympathetic crisis (cocaine?)

Question 8

Combined alpha and beta blocker

Answer 8

Labetalol: (B1=B2>a1>a2), reversible block; hypertension in pregnancy; phaeo
Carvedilol: (B1=B2>a1>a2), Congestive cardiac failure

Question 9

Prostatic symptoms, no BP effects

Answer 9

Tamsulosin

competitive antagonist, a1a and a1d, relaxes bladder and prostate SM, less postural hypotension

Question 10

Calcium channel blockers indications

Answer 10

• Hypertension: vasodilation
• Angina: as they decrease cardiac work + vasodilation
• Arrythmias: (supraventricular tachyarrythmias), atrial fibrillation/flutter, rate control; SVT termination
• Vasospasm- Raynauds, cerebral vasospasm)

Question 11

How do calcium channel blockers work?

then specifically on smooth muscle and cardiac

Answer 11

• Block VOLTAGE gated L type calcium channels, in cardiac and smooth muscle
• some selctivity with drugs: resistance vessels, myocardium, conducting tissue

Smooth muscle: decrease arteriolar tone, decrease PVR, decrease BP. (also biliary, uterine and bowel (constipation)SM)

Cardiac: decrease contractility, and decrease SAN rate and AVN transmission

Question 12

Types of calcium channel blockers. Names. Where do they act? What will they cause

Answer 12

Dihydropyridine:

• Nifedipine, felodipine, amlodipine
• Resitance vessels
• Flushing, headache, oedema (only reduced by dose reduction)

Benzothiapine:

• Diltiazem
• Acts on both resitance vessels and heart

Phenylalkylamine:

• Verapamil
• Cardiac tissue and gut
• Heart block, negative inotrope. Constipation

Question 13

CCB’s pharmacokinetics

Answer 13

• All oral
• IV preps of verapamil and diltiazem for quick resolution of SVT or AF
• p450 metabolism, short half life due to rapid metabolism. Amlodipine long
• due to this have short release or long acting preparations to make o.d possible

Question 14

Nifedipine indications

Answer 14

HT and vasospasm

Question 15

Diltiazem indications

Answer 15

• Angina, tachyarrythmias (AFib), HT
• has various delayed release preps
• side effects range, flushing, bradycardia, oedema, headache
• can be used with beta blockers

Question 16

Verapamil indications

Answer 16

• Tachyarrythmias (SVT, AF- rate control) + HT (negative chronotrope)
• hepatic metabolism + renal excretion
• 7 hour half life
• S/E: bradycardia, -ve inotrope, constipation
• Never use with beta blockers

Question 17

CCB’s interaction

Answer 17

DO not use verapamil with beta blockers

• Inhibits cyp P450
• Care with statins, will stop breakdown so increase risk of rhabdomyolysis
• Inhibit p-glycoproteins, increases digoxin/cyclosporin concs. (these will excrete some drugs, blocking increases amount)

Question 18

Patient with stable angina, asthma and slightly high BP

Answer 18

normally angina first line is BB
Diltiazem, as BB will exacerbate asthma.
Second line anginal drug is CCB

Question 19

Patient with HT and increased lipids. Already on thiazide+ACEi and simvastatin
what els can be used?

Answer 19

• if prostatic symptoms, maybe doxazosin?

- if prostate fine, CCB, such as nifedipine, diltiazem but unlikely verapamil as on statin. So verapamil slow release

Question 20

Final note on alpha blockers and CCB’s

Answer 20

Alpha blockers: 3rd line use for HT; combination with ACEi+diuretic; consider concurrent prostatism

CCB’s: 2nd/3rd line HT, with ACEi+ diuretic; use if concurrent angina; rate control and SVT control