Week 10- antianginal pharmacology

Question 1

what is angina pectoris?

Answer 1

When oxygen supply to myocardium is

insufficient for its needs, latin for tight chest

Question 2

what is the pain feeling like?

Answer 2

intense, diffuse, gripping, constricting,
suffocating chest pain
 “bear hug”
 may radiate to arms, neck & jaw
 difficult to distinguish from “heart burn”

Question 3

what is athersclerosis?

Answer 3

a blockage in the coronary artery

Question 4

what happens during athersclerosis?

Answer 4

atherosclerosis causes artery to narrow due to growth which will block the artery and the placque over time will become unstable and will rupture and will release plaque material and trigger platelet activation and clotting and will form a thrombus that will block the artery

Question 5

what are the aims for treatment of angina?

Answer 5

 Alleviate acute symptoms
 Minimise frequency of ischaemia (lack of block and oxygen supply to cardiomyocytes)
 Reduce progression of atherosclerosis
(secondary prevention – statins, aspirin, ACEI in
diabetes etc)

Question 6

what are the triggers for angina?

Answer 6

when there is an unbalance in the oxygen needs and oxygen supply. limited o2 supply to cardiomycocytes causes angina

Question 7

how to reduce oxygen demand?

Answer 7

-reduce cardia output
 e.g. rest, stress, smoking, weight
-Reduce pre-load
 venodilator e.g. nitrates
-Reduce afterload
 arterial dilator e.g. calcium channel blocker, nitrates
-Reduce cardiac rate/contractility
 negative inotrope/chronotrope e.g b- blocker, calcium
channel blocker
-Improve efficiency of heart
 exercise, stop smoking

Question 8

how to improve oxygen supply?

Answer 8

-increase coronary flow
 arterial dilator eg calcium channel blocker, nitrate
 surgery e.g. bypass, angioplasty, stent

Question 9

what are the anti-anginal agents?

Answer 9

 Organic nitrates – acute attacks
 Calcium channel blockers
 b-adrenoreceptor antagonists
 Slow heart rate so reduce metabolic demand
 Potassium channel activators
 Vasodilators

Question 10

what are organic nitrates?

Answer 10

- Glyceryl trinitrate (nitroglycerin)
 explosive (Nobel)
 effective in angina
 quick onset/short duration of action
- Isosorbide mononitrate
 longer duration of action

Question 11

what is the mechanism of action of nitrates?

Answer 11

• Nitric oxide (NO) released from organic nitrates
   Relaxes all smooth muscle
   Main effects on CV system
• Lower doses
   marked dilatation of large veins
   reduction in Central Venous Pressure (reduced pre-load)
   reduction in Cardiac output & oxygen consumption
   little effect on arterioles/little change in BP
  -Higher doses/chronic use
   arteriolar dilatation, fall in BP, reduced CO, headache

Question 12

how is sheer stress and nitric oxide helping vaso dilation?

Answer 12

-nitric oxide is used in the CV system as a vasodilator and normally the endotheial cells will send sheer stress which will will trigger them to make nitric oxide which will diffuse across membrane and go to smooth muscle cellsa and cause vasodilation due to dephosphorylation of myosin light chain?

Question 13

what are the effects of nitrates on the coronary circulation?

Answer 13

• Increase coronary flow in normal subjects
   Reduction of vascular resistance
• Dilation of coronary arteries despite a fall in BP
• Diverts blood from normal to ischaemic areas
   Pharmacological “By pass” of narrowed segments

Question 14

what is the pharmacokinetics and stability of Glycerol trinitrate (Nitroglycerin) ?

Answer 14

 Absorbed sublingually (under the
tongue) - rapid relief
 Rapidly metabolised in liver (30 min
activity)
 Can’t be swallowed (1st Pass
effect)
-come as sprays, tablets glass bottles as volatile substances
-patches

Question 15

what does beta blcokers do for angina?

Answer 15

-reduce oxygen consumption only, so slow heart rate
-the depress the mycoardium
 no effect on coronary arteries
 provide secondary prevention
 improve exercise capacity
 contraindicated in coronary spasm
 slow withdrawal (up-regulated receptors)
- Indications
 Angina prophylaxis
 Unstable angina

Question 16

what are the 3 main classes of calcium channel blocker?

Answer 16

 Phenylalkylamines eg verapamil
 Dihydropyridines eg nifedipine, amlodopine
 Benzothiazepines eg diltiazem

Question 17

how do calcium channel blockers work?

Answer 17

 Block calcium ions entering cells through preventing
opening of voltage-gated L-type calcium channels
 Bind a1 subunit of the cardiac L-type calcium channels but at
different sites

Question 18

what is the pharmacological effects of calcium channel blockers?

Answer 18

-Main effects on cardiac and vascular smooth muscle, inhibiting Ca2+
entry caused by depolarisation in these tissues
 verapamil is relatively cardioselective
 nifedipine is relatively smooth muscle selective
 diltiazem is intermediate

Question 19

what are the direct cardiac actions of calcium channel blockers?

Answer 19

 Antidysrhythmic effects(mainly atrial tachycardia) because of impaired
atrioventricular conduction
 Reduced contractility
 Negative inotropic and chronotropic effect (but little effect on CO -due to
reduction in peripheral resistance)
 Verapamil – contra-indication in heart failure

Question 20

what are the direct vascual smooth muscle affects of CCB mainly nifedipine?

Answer 20

 arteriolar dilatation – reduce blood pressure (reduce afterload)
 coronary vasodilatation –used in patients with variant angina (spasm)