Anti anginal agents

Question 1

Organic nitrates

Answer 1

1. Venodilation-reduces preload>antianginal,hypotensive activity
2. Coronary b/v dilation -Antianginal activity

Fast and short acting- Glyceryl trinitrate
sublingual onset 1-3 min,
duration of operation 20-30 min
First-pass metabolism
=>Angina attack

Long-acting (GTN metabolites)-Isosorbide Dinitrate (ISDN),Isosorbide Mononitrate (ISMN) d.i. 6-8 h

=> Prevention of angina attacks

SE: headache, hypotension, reflextachycardia
Interaction (MI): PDE-5 inhibitors→life-threatening hypotensive reaction!

A nitrate free interval of 10-12 hrs is needed or nitrate intolerance develops

Question 2

Dihydropiridine CCB

Answer 2

1.Dilation of peripheral arteries-reduces
afterload→ ↓ oxygen consumption
2.Coronary artery dilation-↑oxygen supply

Nifedipine
Amlodipine d.a. 24 h

 Prophylaxis of angina attacks
 IHD (*vazospastic form)

SE: headaches,
flushing,
fatigue, peripheral edema
(ankle), constipation

*vasospastic or
Princmetal’s Angina -
coronary b / v spasms at rest / sleep

Question 3

Non dihydropiridine CCB

Answer 3

Verapamil
Diltiazem

Explicit cardio-depressants:

1. Decreases HR, * contractility → ↓ oxygen consumption → antianginal effect
2. Reduces AV conduction → ** antiarrhythmic effects

Question 4

BAB

Answer 4

1. «-» chronotropic and «-» *inotropic effect-
   ↓oxygen consumption at rest and during physical activity
2. Reduces AV conduction ** antiarrhythmic
   activity

Metoprolol
Bisoprolol
Propranolol

 Prophylaxis of angina attacks

SE: bradycardia, AV block,
bronchospasms, cold extremities

Question 5

Ivabradine

Answer 5

Sinus node inhibitor

inhibits flow (* Na + ion flow) in the sinus node (inhibits ** HCN channels)
Causes dose-dependent decrease in heart rate
↓ O2 consumption, does not induce vasoconstriction and does not affect contractility

 IHD

BAB intolerance or contraindications, as well as in combination

SE: light phenomena in the retina (photopsy), pronounced bradycardia

Question 6

Sodium channel blockers

Answer 6

Ranolazine
causes late blockade of Na + channels - indirectly reduces intracellular Ca2 + concentration and as a result - ↓ myocardial diastolic tension → ↓ oxygen consumption.
improves myocardial perfusion in diastole
Reduces need of GTN use

Question 7

Rosuvastatin

Atorvastatin

Answer 7

HMG-coenzyme A reductase
inhibition
\+ pleiotropic effects
for instance,
plaque stabilization,
antioxidant effect
HMG-Coenzyme A analogs,blocks mevalonic acid - cholesterol Precursor - synthesis in the liver →
↑ LDL receptor expression in hepatocytes(upregulation) → ↓ LDL in plasma

SE: hepatic function impairment
(hepatopathy), myopathy

Question 8

Fibric acid derivatives

Answer 8

Fenofibrate- PPAR-α agonists

Activation of cell nuclear receptor-peroxisome proliferative alpha receptor (PPAR-α) in b/v endothelium → LPL gene expression→
serum lipoprotein lipase activation →lipolysis→TG ↓
additional ↑LDL receptor expression in hepatocytes

Question 9

Cholesterol absorption inhibitors

Answer 9

Ezetimib
inhibits cholesterol absorption in the small intestine
by blocking the transport protein NPC1L1 in the enterocyte villi,
without affecting the fat soluble vitamins, triglycerides and
absorption of bile acids  ↓LDL

Question 10

PCSK9 inhibitors

Answer 10

Evolokumab

Inhibition of LDL receptor-degrading enzyme
Human IgG2 monoclonal antibody.

The antibody selectively binds to * PCSK9 and prevents circulating PCSK9 from binding to LDL receptors on the surface of liver cells,
thereby preventing PCSK9-mediated degradation of LDL receptors.

Increase in the density of hepatic LDL receptors causes natural decrease in serum LDL cholesterol (LDL-C)