Calcium channel blockers- Cardiovascular system drugs.pptx

drugs used in cardiovascular system- calcium channel blockers

1. Calcium channel blockers Presentation by- Sarayu O Sringeri Roll no:115 CLASSIFICATION MECHANISM OF ACTION AND PHARMACOLOGICAL ACTIONS

2. 3 TYPES OF CALCIUM CHANNELS HAVE BEEN DESCRIBED IN SMOOTH MUSCLES VOLTAGE SENSITIVE CHANNELS Activated when membrane potential drops to around –40 mV or lower. RECEPTOR OPERATED CHANNELS Activated by Adrenaline and other agonists Independent of membrane depolarization (NA contracts even depolarized aortic smooth muscle LEAK CHANNELS Small amounts of Ca2+ leak into the resting cell and are pumped out by Ca2+ATPase Mechanical stretch promotes inward movement of Ca2+ 3 TYPES

3. WHAT ARE THE TYPES OF CALCIUM CHANNELS???

4. CLASSIFICATION OF CALCIUM CHANNEL BLOCKERS PHENYL ALKALAMINES DIHYDROPYRIDINE BENZOTHIAZIPINE hydrophilic papaverine congener. Ex: Verapamil Lipophilic Dihydropyridines (DHPs) are the most potent Ca2+ channel blockers, and this subclass has proliferated exceptionally. Ex: Nifedipine , Felodipine, Amlodipine, Lacidipine, Nimodepine Hydrophilic Ex: Diltiazem

5. MECHANISM OF ACTION

6. PHARMACOLOGICAL ACTIONS VERAPAMIL - phenyl alkalamine Dilates arterioles and has some α adrenergic blocking activity HR generally decreases, A-V conduction is slowed, but cardiac output is maintained by reflex sympathetic stimulation and reduction in aortic impedance Nausea, constipation and bradycardia are more common than with other CCBs, while flushing, headache and ankle edema are less common. Hypotension is occasional Verapamil should not be given with β blockers as additive sinus depression, conduction defects or asystole may occur.

7. DILTIAZEM- benzothiazepine Less potent vasodilator than nifedipine and verapamil modest direct negative inotropic action, but direct depression of SA node and A-V conduction are equivalent to verapamil Clinical doses produce consistent fall in BP with little change or decrease in HR Diltiazem dilates coronaries Side effects are milder , increases plasma digoxin level Diltiazem should not be given to patients with preexisting sinus, A-V nodal or myocardial disease

8. NIFEDEPINE- dihydropyridine Prototype DHP with a rapid onset and short duration of action Overriding action of nifedipine is arteriolar dilatation The direct depressant action on heart requires much higher dose, but a weak negative inotropic action can be unmasked after β blockade Does not depress SA node or A-V conduction Reflex sympathetic stimulation of heart predominates producing tachycardia, increased contractility and cardiac output Frequent side effects are palpitation, flushing, ankle edema, hypotension, headache, drowsiness and nausea. These are related to peaks of drug level in blood

9. OTHER DHPs Felodipine It differs from nifedipine in having greater vascular selectivity, larger tissue distribution and longer t½ Amlodipine Pharmacokinetically it is the most distinct DHP and the most popular. Oral absorption is slow, but complete Because of less extensive and less variable first pass metabolism, its oral bioavailability is higher and more consistent. Diurnal fluctuation in blood level is small and action extends over the next morning. Nitrendipine Oral bioavailability of 10–30% . It has been shown to release NO from the endothelium and inhibit cAMP phosphodiesterase. These may be the additional mechanisms of vasodilator action

10. Lacidipine A highly vasoselective newer DHP suitable for once daily administration. It is claimed to attain higher concentration in vascular smooth muscle membrane, and is approved only for use as antihypertensive. Nimodipine Short-acting DHP which penetrates blood-brain barrier due to high lipid solubility. Selectively relax cerebral vasculature and is approved for prevention and treatment of neurological deficit Lercanidipine Similar to nifedipine, but with longer duration of action. Peak plasma concentrations occur at 1.5–3 hours Benidipine Long-acting DHP that owes its long duration of action to slow dissociation from the DHP receptor on the smooth muscle cell.

11. PHARMACOKINETICS All CCBs are 90–100% absorbed orally , peak occurring at 1–3 hr (except amlodipine 6–9 hr ). All are highly plasma protein bound (min: diltiazem 80%, max: felodipine 99%). The Ca2+ channel blockers are high clearance drugs with extensive tissue distribution . All are > 90% metabolized in liver and excreted in urine. Some metabolites are active.

12. SOURCES Essentials of Medical Pharmacology Seventh Edition KD TRIPATHI--- Pg: 546-550 Clinical roles of calcium channel blockers in ischemic heart diseases | Hypertension Research

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