Anti-Anginal

Question 1

Short acting (organic) nitrates

Answer 1

Glycerine Trinitrate - Nitroglycerine (sublingual), Isosorbide Dinitrate (sublingual)

Question 2

Long acting (organic) nitrates

Answer 2

Glycerine Trinitrate - Nitroglycerine (local), isosorbide trinitrate (oral), isosorbide mononitrate (oral), pentaerythrityl tetra nitrate (oral)

Question 3

Mechanism of action

Answer 3

most nitrates are prodrugs denigrated to NO, which activates guanyl cyclase, thereby increases cGMP, dephospho rylation of myosin light chain, results in Smooth muscle relaxation and vasodilation; venous dilation decreases preload and oxygen demand of the heart, dilation of coronaries increase blood flow and oxygen delivery to myocardium.

Question 4

Pharmacokinetics - Absorption

Answer 4

ISDN is completely absorbed oral by 20% enters systemic circulation intact, the rest is converted to ISMN

Question 5

Pharmacokinetics - Biotransformation

Answer 5

Hepatic first pass is high and oral bioavailability is low for GTN and ISDN, half life 3 min for GTN, 10 min for ISDN and 280 min for ISMN

Question 6

Indications

Answer 6

prophylaxis and treatment of angina, left ventricular failure

Question 7

Contraindications

Answer 7

hypersensitivity to nitrates, hypotension, hypovolemia

Question 8

Side effects

Answer 8

Postural hypotension, tachycardia (reflex mediated), headache, flushing, dizziness, drug rash (pentaerythrityl tetra nitrate)

Question 9

Notes

Answer 9

Sublingual route rapid (1-3 minutes) and effective in acute angina; oral and transdermal provide prolonged prophylaxis of attacks (3-10 hours); GTN given IV in emergencies, because of rapid onset of action, to avoid nitrate tolerance a drug free period of 8 hours is needed

Question 10

BB (calcium) mechanism

Answer 10

block L-type channels in heart and vascular smooth muscle, reduces CA entry into cardiac and vascular cells, reducing contractility and vasodilation: reduced preload and after load, increased CBF, reduced contractility, decreased heart rate; dihydropyridines block L type calcium in vascular cells, do not affect cardiac contractility/conduction

Question 11

Calcium block indicators

Answer 11

prophylaxis and treatment of angina, HBP

Question 12

CA contraindications

Answer 12

heart block/failure (Verapamil, Diltiazem), WPW syndrome, cariogenic shock, advanced aortic stenosis (digyropiridines)

Question 13

Ca side effects

Answer 13

hypotension, rash, bradycardia/heart block/constipation (Verapamil, diltiazem), tachycardia/per. edema/flushing/dizziness (dihydropiridines)

Question 14

Dihydropyridines are useful for

Answer 14

Angina with coronary vasospasm

Question 15

Nicorandil (K+ activator)

Answer 15

activates K+ channels of vascular smooth muscle and K+ flows out of cells, inhibiting Ca influx, and vasodilation (contraction)

Question 16

Nicorandil indication

Answer 16

prophylaxis of angina

Question 17

Nicorandil contraindications

Answer 17

cardiogenic shock, left ventricular failure, hypotension

Question 18

Nicorandil SE

Answer 18

headache, cutaneous vasodilation, nausea, vomitting