Calcium antagonists.pptx 1

Calcium Antagonists
Department of pharmacy,
Institute of Medicine, MMC. Nepal

1. CALCIUM ANTAGONISTS Presented by Bibek Nepal Kuber B ajgain

2. EXCITATION–CONTRACTION COUPLING MUSCLE Stimulation of the cardiac cell initiates the process of excitation, which has been related to ion fluxes through the cell membrane . Depolarization of the tissue in the atria of the heart is mediated by two inwardly directed ionic currents. Fast sodium current via Na + channel Current caused by slow activation of an L-type Ca ++ channel

3. EXCITATION–CONTRACTION COUPLING MUSCLE Contraction of cardiac and other muscle occurs from a reaction between actin and myosin the contractile process in cardiac muscle involves a complex of proteins (troponins I, C, and T and tropomyosin ) attached to myosin, which modulates the interaction between actin and myosin.

4. EXCITATION–CONTRACTION COUPLING MUSCLE

5. CALCIUM CHANNEL BLOCKERS Three important classes of CCBs Verapamil - a phenyl alkylamine (hydrophilic papaverine ) Nifedipine - a dihydropyridine ( lipohilic ) Diltiazem – a hydrophilic benzothiazepine

6. CALCIUM CHANNEL BLOCKERS Pharmacolgical actions All three subclasses of CCBs inhibit calcium mediated slow channel component of AP in Smooth muscle : The CCBs decrease intracellular availability of Ca +2 and causes relaxation Dihydropyridines ( nifedipine ) has most marked smooth muscle relaxant property.

7. CALCIUM CHANNEL BLOCKERS Pharmacolgical actions b ) Heart CCBs have negative inotropic effect Verapamil has shown to have higher cardiodepressant action * Diltiazem has shown to have intermediate cardio depressant effect and vasodilation

8. CALCIUM CHANNEL BLOCKERS Indications Angina Hypertension Raynaud’s syndrome Supraventricular tachycardia and arrhythmias Atrial fibrillation Delay of preterm labor Prophylaxis of cluster headache

9. CALCIUM CHANNEL BLOCKERS Adverse effect Myocardial effects : hypotension , heart failure Conduction effect : heart block , arrhythmias Vascular smooth muscle : flushing , edema , headache rashes Other effect : constipation , nausea , photosensitivity

10. VERAPAMIL Verapamil is chemically 5-[( 3,4 dimethoxyphenethyl ) methylamino ]-2-( 3,4 dimethoxyphenyl )- 2-isopropylvaleronitrile ( Calan , Isoptin ) a coronary vasodilator and is the prototype of the Calcium antagonists used in cardiovascular diseases.

11. VERAPAMIL Properties It is white crystalline powder, soluble in water freely soluble in methanol, sparingly soluble in ethanol It should be stored in well closed container

12. VERAPAMIL Synthesis:

13. NIFEDIPINE Nifedipine is chemically 1,4-dihydro-2, 6-dimethyl-4-( 2- nitrophenyl )-3,5-pyridinedicarboxylate dimethyl ester ( Adalat , Procardia )

14. NIFEDIPINE It is yellow crystalline powder sparingly soluble in ethanol, insoluble in water but freely soluble in acetone When exposed to day light or artificial light of certain wavelength it readily converts to nitrosophenylpyrimidine derivative and exposure to UV rays leads to formation of nitrophenylpyrimidine . Hence it should be stored in light resistant airtight container

15. NIFEDIPINE Synthesis Step 1:preparation of Methyl-[2-acetyl-3-(2-nitropheny)]- 2-propionate

16. NIFEDIPINE Step 2 : preparation Methyl 3-amino 2-butenoate

17. NIFEDIPINE Step 3: condensation of step 1 and step 2 product

18. DIPYRIDAMOLE Dipyridamole is chemically 2,2,2,2-[(4,8-di- 1piperidinylpyrimido[5,4- d ]pyrimidine-2,6-diyl) dinitrilo ]- tetrakisethanol ( Persantine ),

19. DIPYRIDAMOLE Properties It is bitter, yellow crystalline powder, soluble in dilute acids, methanol and chloroform A formulation containing dipyridamole and aspirin (Aggrenox) is currently being marketed as an antithromobotic .

20. DIPYRIDAMOLE Pharmacological actions : Dipyridamole is a long-acting vasodilator. Its vasodilating action is selective for the coronary system. The drug also inhibits adenosine deaminase in erythrocytes and interferes with the uptake of the vasodilator adenosine by erythrocytes. These actions potentiate the effect of prostacyclin (PGI2), which acts as an inhibitor to platelet aggregation.

21. DIPYRIDAMOLE Side effect More common : Abdominal or stomach cramps, diarrhea, dizziness or lightheadedness Less common: Flushing, headache, nausea or vomiting, weakness Rare General discomfort and/or unusual tiredness or weakness, hair loss, joint pain or swelling, muscle pain, runny nose, sneezing