Alpha blockers and calcium channel blockers Flashcards
the two classes of adrenergic receptors and their affinites
alpha and beta
alpha: NE > epinephrine»_space; isoprotenol
Beta: Isoprotenol > epinephrine > NE
Alpha 1 receptors
postsynaptic, vasoconstriction, (veins and arterioles) inc BP
alpha 1 a = prostate, VSM
alpha 1 b = VSM
alpha 1 d
alpha 2 receptors
pre and post synaptic inhibit norepinephrine and insulin release alpha 2 a alpha 2 b alpha 2 c
alpha 1 antagonists
Doxazosin, prazosin, terazoin (block all alpha 1 subtypes)
vasodilatation, hypotension
Tamsulosin (alpha 1 a specific), so helpful in reducing prostate size when increased whereas doxazosin will also have an effect on BP
alpha 2 antagonism
not used clinically
combined alpha 1 and 2 antagonists
phenoxybenzamine
alpha blockers indications
hypertension
- essential hypertension
useful in combination therapy (e.g. diuretic, ACEi and alpha blocker)
- pheochromocytoma –> alpha blockers useful here, this is also a tumor of the SNS usually in the adrenal gland, where too much adrenaline and noradrenaline produced treatment is surgery but perioperativly use alpha-blockers
Doxazosin
reversible alpha blockade alpha1»_space;» alpha2
- vasodilator: blocks tonic sympathetic activity on resistance vessels
- reduce prostatic symptoms
start low dose an titrate
od
oral
first pass hepatic metabolism
Why aren’t prazosin and terazosin as good as doxazosin?
prazosin has very short half life and so needs to be taken twice to 3x daily, and terazosin has slightly more side effects than D
alpha blockers adverse effects
hypotension - give first dose at night Dizziness Lassitude (tiredness) Nasal stuffiness Dry mouth Urinary incontinence in women
rarely used alpha blockers: phenoxybenzamine
oral irreversible alpha blocker antagonist alpha1 > alpha2 blocks serotonin receptors used in pheochromocytoma used preoperatively marked side effects - postural dec BP, tachycardia - nasal stuffiness - CNS
Rarely used alpha blockers: phentolamine
poorly absorbed, give in IV
competitive antagonist alpha 1 = alpha 2
increase NE release
5HT antagonist
- limited use, hypertensive crisis e.g. phaeco and cocaine OD
combined alpha and beta blocker: labetalol
reversible antagonist
hypertension in pregnancy
phaecochromocytoma
combined alpha and beta blocker: carvedilol
also antioxidant properties
specific alpha blockers: tamsulosin
oral competitive antagonist alpha1a and d Relax bladder and prostate smooth muscle less postural hypotension long t1/2, given once daily
Calcium channel blockers - indications
hypertension (vasodilation)
angina (decreased cardiac work, vasodilatation)
arrhythmias (SVT tachcyarythmias)
- atrial fibrillation / flutter rate control
- SVT termination
Vasospasm
e.g. raynauds phenomenon, cerebral vasospasm
Calcium channel blocker mechanism and selectivity
block voltage gated L type Ca2+ channels - cardiac and smooth muscle (decrease arteriolar smooth muscle tone, decrease peripheral vascular resistance, decrease BP)
cardiac cells –? decrease sinus node rate and AVN transmission
some selectivity
- resistance vessels
- Myocardium
- conducting tissue
The dihydropyridines
e.g. Nifedipine –> are pure vasodilators, useful in lowering BP and in angina as they also dilate coronary arteries. resistance vessels (flushing, headaches, oedema)
e.g. of a benzothiazepine
diltiazem = in between effects
phenylalkylamine example
verapamil
very little effect on calcium channels in resistance vessels, its mechanism on calcium channels in conducting tissues
- cardiac tissue = heart block, negative inotrope
constipation because peristalsis in bowel inhibited
Ca2+ blocker pharmacokinetics
oral = all
IV preparations = diltiazem and verapamil
Significant first pass hepatic metabolism: cytochrome P450 system
Variable half life:
nifedipine/ diltazem few hours so do slow release capsule
amoldipine = long in days
Nifedipine
hypertension vasospasm e.g. raynauds Oral, do not use sublingual = too intense SR tablets hepatic metabolism protein bound renal excretion oedema, flushing, headache * no effect on conducting system of the heart therefore no use in slowing e.g. atrial fib
Diltiazem
effects on conducting tissue therefore can slow HR and vasodilator activity Angina, hypertension, tachyarrythmias Oral and IV hepatic metabolised, fecal excreted Various delayed release preparations oedema, flushing, headache, bradycardia
verapamil
tachyarrythmias (SVT, AF rate control) hypertension Oral and IV hepatic metabolism + renal excretion decreased bioavailability S/E - bradycardia, -ve inotrope, constipation
