Angina 2&3 Flashcards
nitrates are prodrugs, what are prodrugs?
drugs that need to be activated once they have been administered, once they have converted, they are active need to convert nitrate to nitric oxide
what are the 3 main treatments of stable coronary artery disease ( angina and INOC- variant/ microvascular)
nitrates and nitrites
B- adrenoreceptor antagonists
CALCIUM CHANNEL BLOCKERS
how do nitrates and nitrites work?
vasorelaxation-systemic vasodilatation -therapeutic effect
what is the mechanism of vasodilation in nitrates and nitrites?
- converted to NO (reduced)
- This would activate guanylate cyclase, which would convert GTP to cyclic GMP
- This would activate protein kinase G – cause blood vessels to relax.
how do nitrates and nitrites produce their anti-anginal effect?
- peripheral venodilatation decrease in-preload - and MVO2
- peripheral arterial& arteriolardilatation - decrease in :afterload and VO2
what are the 3 ways that nitrates and nitrites are used clinically?
1-relief of acute angina attacks –GTN, amyl
2-nitriteprophylaxis of chronic angina –GTN, ISDN, ISMN
3-choice & mode of therapy
what are 4 side effects of nitrates and nitrites?
1 flushing & throbbing headaches
2 postural hypotension & syncope (low bp- take sitting down)
3 reflex tachycardia & myocardial contractility (inc MOD- not desirable)
4 tolerance
depletion of thiol (-SH) groups
physiological adaptation
name 1 problems associated with nitrates
- must pass first pass metabolism
-
how long is a nitrate free period?
8-10 hours
what is the pharmacological action of b-adrenoceptor antagonists?
antagonise the effects of sympathetic nervous activation (i.e. noradrenaline & adrenaline) at β-adrenoceptors
how many subtypes of beta-adrenoceptors are there?
3 but focus on 1 and 2
1-ARs –heart & kidney
2-ARs –heart, smooth muscle (e.g. vascular & bronchial)
3-ARs –adipocytes
what are the two subclasses of b-Blockers?
1-‘non-selective’ –e.g. propranolol
2- B1-receptor selective (‘cardioselective’) –e.g. atenolol
what happens when b2 adrenoceptors activate?
- When B2 activate in blood vessels- relax
- When in lungs – cause bronchioles to dilate
- When activated on heart reduce force of contraction
how do b-b produce their anti-anginal effect?
haemodynamic effects dec myocardial O2demand
dec myocardial contractility
dec heart rate
dec system blood pressure
what is the first line treatment for prophylaxis of chronic stable angina
beta-adrenoceptor antagonists
what are the two classes of drugs used to treat chronic stable angina classified based on?
where they are eliminated:
1 eliminated via hepatic metabolism
2 eliminated unchanged via the kidney
what are the features of drugs eliminated via hepatic metabolism?
more lipid soluble almost completely absorbed from the gut largely metabolised in the liver very variable bioavailability short plasma half-life
what are the features of drugs eliminated via the kidney?
more water soluble incompletely absorbed from the gut largely eliminated unchanged less variable bioavailability longer plasma half-life
what happens if you withdraw a Beta-blocker from treatment abruptly?
rebound phenomenon- increase force of contraction and MOD on heart- don’t stop taking unless doctor says so/ dose tapered down slowly- risk of angina agitation
what are some adverse side effects of beta-blockers?
bronchoconstriction -exacerbation of asthma
peripheral vasoconstriction -cold extremities
myocardial depression -risk of heart failure
masking of signs of impending hypoglycaemiasexual dysfunction
poor patient compliance
CNS disturbances –nightmares, depression, confusion
inc LV size =inc myocardial O2consumption
what is the pharmacological action of Calcium channel blockers?
inhibit entry of Ca into cells via voltage-gated calcium channels i.e. if heart(node cells) blocks entry of calcium cells it reduces force of contraction
what are the vascular effects that CCB have?
block of Ca influx into arterioles -arteriolar dilatation
what are the two mechanisms of anti-anginal effects of CCB?
Reduced myocardial O2 demand
Increased myocardial blood flow
What is CCB a first line treatment for?
chronic stable angina
also for management of variant angina
