Alpha blockers and Calcium channel blockers Flashcards
Breakdown of alpha1 and alpha2 receptors
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)
Alpha blocker examples and effects
-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)
Alpha blocker indications
Hypertension: essential hypertension, third line therapy with diuretic, ACEi; very useful with phaeochromocytoma
Prostatism
Prostatism
Post micturition dribbling, nocturia, hesitancy
result of enlarged prostate
Most commonly used alpha blocker and benefit
Doxazosin
is a reversible a1 blocker and vasodilator
reduces prostate symptoms so two birds one stone.
o.d
Alpha blocker adverse effects
- Orthostatic hypotension+dizziness. Can give first dose at night, not standing up much
- lassitude
- nasal stuffiness
- dry mouth
- urinary incontinence in women
Rarely used alpha blockers
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?)
Combined alpha and beta blocker
Labetalol: (B1=B2>a1>a2), reversible block; hypertension in pregnancy; phaeo
Carvedilol: (B1=B2>a1>a2), Congestive cardiac failure
Prostatic symptoms, no BP effects
Tamsulosin
competitive antagonist, a1a and a1d, relaxes bladder and prostate SM, less postural hypotension
Calcium channel blockers indications
- Hypertension: vasodilation
- Angina: as they decrease cardiac work + vasodilation
- Arrythmias: (supraventricular tachyarrythmias), atrial fibrillation/flutter, rate control; SVT termination
- Vasospasm- Raynauds, cerebral vasospasm)
How do calcium channel blockers work?
then specifically on smooth muscle and cardiac
- 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
Types of calcium channel blockers. Names. Where do they act? What will they cause
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
CCB’s pharmacokinetics
- 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
Nifedipine indications
HT and vasospasm
Diltiazem indications
- Angina, tachyarrythmias (AFib), HT
- has various delayed release preps
- side effects range, flushing, bradycardia, oedema, headache
- can be used with beta blockers
Verapamil indications
- 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
CCB’s interaction
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)
Patient with stable angina, asthma and slightly high BP
normally angina first line is BB
Diltiazem, as BB will exacerbate asthma.
Second line anginal drug is CCB
Patient with HT and increased lipids. Already on thiazide+ACEi and simvastatin
what els can be used?
- if prostatic symptoms, maybe doxazosin?
- if prostate fine, CCB, such as nifedipine, diltiazem but unlikely verapamil as on statin. So verapamil slow release
Final note on alpha blockers and CCB’s
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
