drugs for angina pectoris

Question 0

nitrates 
3 examples 
nature 
MOA 
consequences 
uses 
pharmacokinetics 
SEs

Answer 0

nitroglycerin, isosorbide, mononitrate
nitrate is a prodrug – metabolised to release NO which activates guanyl cyclase so on.

1) maintain platelets in resting phenotype and prevent their activation
2) vasodilate keeping vessels open – target SMCs
- guanyl cyclase activate GTP ->cGMP cause increase dephosphorylation of myosin light chain it and hence inactivating it - massively reducing uptake of Ca
- reduction of Ca – REXLAXATION inhibit vasoconstriction, promote vasodilation.

consequence:

• relax SMC - esp vascular ones
• relax large arteries - reduce central aortic pressure and cardiac afterload - more efficient pump blood out
• coronary vasodilation - collaterals
• venorelaxation and reduction in central venous pressure - preduce preload hence reduce SV (might result in postural hypotension)
• relief of coronar spams (variant)

use - stable angina prevention, unstable angina and acute heart failure

pharmacokinetics:
nitroglycerin
– well absorbed mouth, sublingual/transdermal
- ineffective orally due to 1st pass metabolism
- poor shelf life - self metabolism
- peaks 4 min, half life 30 mins

isosorbide mononitrate
- swallow > sublingual
- long lasting 4hours
not for acute angina but for stable > unstable

S/Es:

• postural hypotension
• headache
• tolerance w chronic use

Question 1

what are the few drug groups used for treatment of angina pectoris

Answer 1

nitrates
CCB
beta blockers
– reduce venous return, and HR hence reduce BP – reduce oxygen demand and improve coronary flow

Question 2

ca channel blockers 
3 groups w 1 example each
MOA
consequence wrt to angina 
pharmacokinetics
SEs

Answer 2

phenylalkamines - verapamil – heart >SM
benzodiazepines - eg diltiazem
dihydropyridines - eg nifedipine SM> heart

L type Ca antagonist

• block L type Ca channels on heart/SM
• 3 types bind to distinct sites on channel - specificity
• interact allosterically w each other and w the gating machinery to prevent opening - reduce Ca entry
• reduce Ca entry - decrease (ca)i
• vascular SM relaxation and reduction in arteriolar pressure (aftload)
• reduce cardiac contractility
• reduce HR

use stable > unstable (but does not dilate collaterals =)
variant angina (w spasms)
arrhythmias (verapamil)
HTN (dihydropyridines)

pharmacokinetics

• oral well absorbed
• vary in half life

SEs
- shot acting flushing 
-headaches
-swelling
-hypotension
Q free from adverse SEs