calciumblockers
Table of Contents
calcium channel blockers
see also:
- excessive dosing of alpha adrenergic agonists may cause hypertensive crisis which may be fatal, and attempts to treat such alpha agonist crises with beta adrenergic blockers or calcium channel blockers may cause acute pulmonary oedema (APO) and thus these agents are contra-indicated in this situation!!
high specificity calcium channel blockers:
- act via specific membrane sites;
non-dihydropyridines:
Phenylalkylamine group:
- marked suppression of SA automaticity & conduction;
- moderate coronary vasodilatation & -ve inotropy;
- thus the reflex tachycardia due to decreased total peripheral resistance is blunted;
- may increase LV performance if no CCF but if CCF,
- marked decrease in contractility & LV function may occur.
- verapamil (Isoptin): (Isoptin, Veracaps SR)
Benzothiazepine group:
- marked suppression of SA automaticity;
- moderate suppression of SA conduction;
- moderate coronary vasodilatation;
- mild -ve inotropy;
- diltiazem: (Cardizem)
- ie. similar effects to verapamil;
T-gated blockers:
- mibefradil: [Posicor]
- less -ve inotropy?
- still suppress AV node
Dihydropyridine group:
- bind to the large alpha1 subunit & also inhibits Pdiesterase;
- marked coronary vasodilatation & arteriolar vasodilatation:
- → decreases BP → increases symp.N.S. → increases HR, increases contractility & increases cardiac output;
- minimal -ve inotropy, & suppression of SA automaticity/cond.
- contra-indications:
- unstable angina
- uncontrolled congestive cardiac failure
- immediately post-AMI
- LV outflow obstruction
- pregnancy
- severe liver or renal impairment
- strong inhibitors of the liver enzyme CYP3A4
- use with cyclosporin
- adverse effects
- generally well tolerated
- headaches and flushes may occur
- tachycardia / palpitations
- leg oedema - less so with the newer lercanidipine
- rarely, HS reactions
- nifedipine: (Adalat)
-
- may be some selectivity for cerebral vessels
- nicardipine:
- may be some coronary selectivity for vasodil. ⇒ nifedipine;
- a little less -ve inotropy cf nifedipine;
- → incr. exercise tolerance & decr. angina in pts with effort-angina;
- felodipine: (Plendil ER)
- peak 3-5hrs; once daily if ER as pre-systemic metabolism resulting in 20% bioavail. & minimising post-absorption peak;
- 99% plasma protein bound;
- Extensively metabolised by liver;
- amlodipine: (Norvasc) Aust. '94;
- peak blood levels 6-12hrs post-dose - shorter (6-8hrs) if hepatic insufficiency
- once daily dosing; steady state by 7-8days;
- 97.5% plasma protein bound; Vd ~20 l/kg; metab. by liver;
- lercanidipine (Zanidip):
- newer generation with apparently less leg oedema
low specificity calcium antagonists:
- bepridil:
- perhexiline maleate:
- used in refractory cases of angina where:
- awaiting revascularisation in whom Rx will be < 3 months duration, or,
- long term Rx in pt who is unsuitable or unwilling to have revascularisation.
- need to measure plasma levels:
- Rx range:
- 0.15-0.6mg/L - adequate for most
- 0.6-1.2mg/L - for those not responding to above dose range
- Toxicity:
- > 1.2mg/L ⇒ hepatotoxicity, peripheral neuropathy (if chronic high levels)
- adverse effects in Rx range:
- 60% have some dose dependent adverse effects but most are mild:
- dizziness, nausea during loading phase
- diabetics may develop hypoglycaemia in 1st few days Rx
- relative C/I's:
- liver disease
- peripheral nerve disease
- ~10% popn are slow metabolisers of perhexilene & require very low maintenance doses (eg. 50-100mg once weekly).
- these pts can be idientified by relatively high plasma concentrations after the initial week's Rx together with absence of detectable circulating metabolite
- administration:
- 200mg orally bd for 3 days, then,
- 200mg daily after taking a blood sample
- further dose adjustments at monthly intervals should be based on plasma levels
- usual maintenance dose: 100-400mg daily aiming for plasma level 0.15-0.6mg/L
- flunarizine:
clinical uses of calcium antagonists:
- Exertional Angina:
- see angina
- Supraventricular tachycardia:
- see SVT
- mainly verapamil
- Hypertension:
- see hypertension
- Hypertensive crises:
- esp. the dihydropyridines in perioperative HT:
- as effective as nitroprusside, trimetaphan or nitrates & safer;
calciumblockers.txt · Last modified: 2020/03/19 10:30 by 127.0.0.1