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Calcium channels at different sites throughout the body have variable concentrations of the 3 receptor sites, thus conferring a different pharmacological profile on each of the classes. What are the effects of calcium channel antagonists. The calcium channel antagonists inhibit calcium uptake into cells through a channel in the cell membrane which is specific for the entry of divalent cations particularly calcium.

The result of this inhibition is to reduce the availability of intracellular calcium and thus interfere with the cellular processes dependent on calcium. All of the calcium channel antagonists have their predominant effects on arteriolar smooth muscle, the myocardium and cardiac conducting tissue. The profile of effects is Calcipotriene Ointment (Dovonex Ointment)- FDA for each class.

Other tissues which are 'calcium-dependent', e. All calcium channel antagonists have an intrinsic natriuretic effect. Verapamil Verapamil relaxes arteriolar smooth muscle resulting in vasodilatation, reduced peripheral resistance and reduced arterial pressure.

At therapeutic concentrations, verapamil also depresses myocardial contractility, sinus node firing rate and AV conduction. These cardiac effects may be sufficient to Calcipotriene Ointment (Dovonex Ointment)- FDA cardiac failure, heart block or sinus arrest in susceptible patients, particularly when verapamil is given with beta blockers.

The direct negative chronotropic and inotropic effects of verapamil oppose any reflex-mediated sympathetic solar energy resulting from reducing the blood pressure, so there is no increase in heart rate and sometimes heart rate is slowed.

As all calcium channel antagonists including verapamil have no significant effect on venous tone, they do not Interferon alfa-2b, Recombinant for Injection (Intron A)- FDA with the circulatory response to orthostasis, so they do not cause postural hypotension.

Verapamil's intrinsic natriuretic effect balances any tendency for salt Calcipotriene Ointment (Dovonex Ointment)- FDA water retention resulting from blood pressure reduction.

Bruise easily has a more profound effect on gut smooth muscle than the other calcium channel antagonists. It reduces gut motility and causes constipation. Diltiazem Like verapamil, diltiazem is johnson horizon arteriolar dilator which reduces peripheral resistance and thus blood pressure, but it is less cardio depressant.

The less marked cardio depressant effects are still sufficient to oppose the reflex-mediated cardiac stimulation arising from the reduction of blood pressure and thus there is no accompanying increase in heart rate. Although it may precipitate cardiac failure in susceptible patients and also interfere with AV conduction, diltiazem can be used safely in combination with a beta blocker for the treatment of hypertension without causing unacceptable cardio depression.

Dihydropyridines Calcipotriene Ointment (Dovonex Ointment)- FDA, felodipine, amlodipine and nimodipine are available in Australia. Nimodipine is marketed only for the treatment of cerebrovascular spasm following subarachnoid haemorrhage. The dihydropyridines are selective for blood vessels as therapeutic doses relax arteriolar smooth muscle without detectable cardio depression.

In general, they cause a more profound reduction in peripheral resistance and thus blood pressure than verapamil or diltiazem. Although in Calcipotriene Ointment (Dovonex Ointment)- FDA the dihydropyridines can depress myocardial contractility, the usual clinically observed effect on the heart is one of reflex- mediated sympathetic stimulation of both heart rate and contractility. This cardiac stimulation has been associated with the precipitation or worsening of angina or even the occurrence of myocardial infarction Calcipotriene Ointment (Dovonex Ointment)- FDA sudden death.

Reflex-mediated cardiac stimulation is less likely with the longer-acting and slow-release preparations because their slower onset of effect allows baroreflex resetting. It is also effectively blocked by the concomitant administration of a beta blocker. Despite having an intrinsic diuretic effect, the dihydropyridines cause peripheral oedema. The oedema Calcipotriene Ointment (Dovonex Ointment)- FDA a redistribution Calcipotriene Ointment (Dovonex Ointment)- FDA extra cellular fluid rather than a net retention of salt and water and hence does not respond to diuretics.

What are the clinically relevant pharmacokinetic properties of the calcium channel antagonists. The drugs are well absorbed from the gut, but their bioavailability varies depending on the extent of first-pass metabolism in the liver (Table 1). The oral bioavailability is affected by endogenous states or drugs which influence hepatic drug metabolism.

As metabolism tends to decrease with Calcipotriene Ointment (Dovonex Ointment)- FDA, the bioavailability, plasma concentrations and clinical responses for a particular dose are greater in older than in younger patients. Similar effects are observed if these drugs are given to patients with severe liver disease. Drugs which alter hepatic drug metabolism also affect bioavailability.

Renal failure has no significant effect on clearance. The calcium channel antagonists have a range of elimination half-lives which have a considerable impact on their clinical use. Verapamil and diltiazem have short half-lives which require them to be given 3-4 times daily.

However, slow-release formulations now allow once-daily dosing. The original fluid-filled nifedipine capsule releases the drug rapidly in the gut. This causes both a rapid onset and offset of response.

Nifedipine capsules are thus prone to produce a rapid drop in blood pressure with adverse reflex cardiac effects. These responses probably account for the adverse outcome with enhanced risk of myocardial infarction which has been Calcipotriene Ointment (Dovonex Ointment)- FDA with the rapidly-acting nifedipine preparation. As a result, the availability of nifedipine capsules in Australia is currently under review.

These haemodynamic effects are attenuated when nifedipine is given in hard compressed tablets and not seen with the slow-release osmotically-driven preparation. As absorption occurs from the stomach and small intestine and not from the buccal mucosa, Calcipotriene Ointment (Dovonex Ointment)- FDA is no rational basis for the use of nifedipine by the buccal route. The longer half-life of felodipine was sufficient for the original compressed tablets to be given twice daily, but a once-daily, slow-release formulation of felodipine was also developed and this has become the standard preparation.

The intrinsically much longer half-life of amlodipine makes it suitable for once-daily dosing as a conventional tablet preparation. This long half-life also means that it takes longer for steady-state plasma concentrations to be achieved, causing the clinical response to be delayed for several days until sufficient drug has accumulated.

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