L11: Alpha blockers and Ca2+ channel blockers Flashcards
What are the 2 alpha adrenergic receptors, what are their different types, locations and actions with normal substrate. What is the normal substrate
Both have normal substrate of NE, Epinephrine and isoproterenol
Alpha 1: Normal SM constriction - post synaptic
- a1a : prostate SM: maintain bladder tone/urinary continence
- a1b: Vascular smooth muscle : Increase BP
- a1d
Alpha 2: pre-synaptic and post synaptic on adrenergic neurons
- Inhibits NE and insulin release as part of negative feedback
- a2a,a2b,a2c.
What are the indications for Alpha blocker use
- Essential hypertension as 3rd line therapy (in combo w diuretic + acei) to reduce vasoconstriction
- Phaeochromocytoma: Perioperative period for removal of rare symp ns tumour that produces NE which greatly increases BP-> risk of heart attack or stroke
- Prostatism: to reduce prostatic tone and improve flow in older men with enlarged prostate and urinary incontinence
What is the go-to Alpha blocker, which receptors, actions, how is it given and metabolised
Doxazosin
- Reversible competitive inhibitor of all a1»_space;»a2
- Vasodilator and reduces prostatic symptoms
Given once daily, starting at a low dose and increased over wk/mo to attenuate to SE
-1st pass hepatic metab with active metabolites, faecally eliminated
What are the 2 rarely give a-blockers: for phaeochromocytoma
- compare when used, how delivered, and which receptors blocked
Phenoxybenzamine
- irreversible alpha (5ht,Ach) antagonist
- pre-operatively
- oral
Phentolamine
- competitive a1 and a2 (+Ach…) inhibitor
- acute intraoperative
- IV
Lots of SE
What are the 5 SE of a-blockers
- Orthostatic hypotension (dizziness/postural symptoms) –> can start at night
- Lassitude: tiredness/ fatigue
- Nasal stuffiness : vasodilation of nasal mucosa
- Dry mouth: reduced saliva production via symp
- Urinary incontinence in women
What is the benefit of using a-blocker Tamsulosin vs the normal one
It is a competitive antagonist blocking a1a and d subtypes but not a1b therefore helps prostatism but doesn’t affect vascular SM so less SE.
- Good for prostatism w/out high BP.
What are the 4 indications for using Ca2+ channel blockers and why
- Hypertension: (3rd line) causes vasodilation
- Angina: -ly chronotropic so reduces cardiac work for ischaemic heart and vasodilates
- Supraventricular tachyarrhythmias
- in AF they inhibit depolarisation at AV node to slow down transmitted ventricular rate (no rhythm control)
- In SVT dependent on an abnormal AV node they can help get to sinus rhythm
4.Vasospasm: help vasodilate in Raynauds phenomenon (CT problem) or Cerebral vasospasm after sub arachnoid haemorrhage irritates resistant vessels
What are the channels blocked by Ca2+ channel blockers, where does this act and what actions does it do
Voltage gated L-type Ca2+ channels in
- Vascular SM
- reduce arteriolar SM tone
-reduce BP and afterload
(also affects other SM to get SE) - Cardiac cells
- Reduce contractility - Conducting tissue: SA, AV node, conducting tree
- Reduce depolarisation and automaticity of sinus node rate and transmission through AV node.
- Thus HR reduced to reduce ischameic episodes at exertion in angina
What are the 3 classes of Ca2+ channel blockers, give name example and the tissue it acts on thus SE
- Dihydropyridines
eg. Nifedipine
- Resistance vessels so gets
- Oedema (precapillary arterioles vasodilating)
- Flushing
- Headache
- Phenylalkylamine
eg. Verapimil
- Cardiac tissues (conducting tree + myocytes)
- Heart block, bradyarrythmia (negative chronotrope)
- Negative inotropic effect (not good in HF, good for angina)
- Constipation (GI sm)
- Benzothiazepine
eg. Diltiazem
- slight mix of the two up there.
Compare the indications of use for Nifedipine, Diltiazem and Verapamil (all oral)
All 3 can do Hypertension but Verapamil very little.
- Nifedipine also good for vasospasm
- Diltiazem also good for Long term angina and AF rate control (+ BB)
- Verapamil also good for SVT and AF rate control (-chronotrope)
Compare the cautions of use for Nifedipine, Diltiazem and Verapamil
(all oral, significant 1st pass hepatic metabolism)
- Nifedipine should not be used sublingually as lipophilic causes quick drop in BP but then fast compensatory tachycardia
- Diltiazem can be used with BB, should be started at low dose to see control of AF
- Verapamil cannot be used with BB
- It inhibits CytP450-3A4 which inhibits breakdown of statins, and increases risk of rhabdomyolysis
- It inhibits P-glycoprotein involved in metabolism/excretion which increases digoxin/cyclosporin conc
