Angina 2&3 Flashcards
nitrates are prodrugs, what are prodrugs?
-drugs that need to be converted in vivo to the biologically active principle/metabolites
- nitrates + nitrites –> NO (in vivo)
what are the main treatments of stable coronary artery disease ( angina and INOC- variant/ microvascular)
nitrates and nitrites
B- adrenoreceptor antagonists
CALCIUM CHANNEL BLOCKERS
Misc Agents - Nicorandil, Ranolazine, Ivabradine
how do nitrates and nitrites work?
action on blood vessels -> 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 preload MVO2
-peripheral arterial and arteriolar dilatation –> decrease afterload and MVO2 - coronary vasodilatation –> reverse/prevent spasm and inc collateral BF
what are the 3 ways that nitrates and nitrites are used clinically?
1-relief of acute angina attacks –GTN, amyl nitrate
2-prophylaxis of chronic angina –GTN, ISDN, ISMN
3-choice & mode of therapy (influenced by pharmacokinetic profile - sublingual, buccal, transdermal, inhaler, IV)
what are 4 side effects of nitrates and nitrites?
1) flushing & throbbing headaches (dilation of arterioes in the temples)
2) postural hypotension & syncope (low bp- take sitting down)
3) reflex tachycardia & inc myocardial contractility
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 and why does it matter?
8-10 hours, body cant be saturated with nitrates 24/7 or else tolerance will build since thiols don’t replenish
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 and effects of inhibiting?
3 but focus on 1 and 2
1-ARs –heart & kidney –> dec cardian output
2-ARs –heart, smooth muscle (e.g. vascular & bronchial) –> peripheral vasoconstriction, bronchoconstriction
3-ARs –adipocytes
what are the two subclasses of b-Blockers?
1) ‘non-selective’ –e.g. propranolol
2) ‘B1-receptor selective’ or ‘cardioselective’ -eg. atenolol, acebutolol, metoprolol
how do b-b produce their anti-anginal effect?
1) haemodynamic effects –> dec myocardial O2 demand
-dec myocardial contractility
-dec heart rate
-dec system blood pressure
2) Ancillary Effects
-inc diasoltic filling time –> inc myocardial perfusion
-antiarryhthmic activity –> inc electrical stability
-antiatherogenic and antithrombotic
Heart spends longer in diastole, promoting coronary flow and reduce isch
what is the first line treatment for prophylaxis of chronic stable angina (effeort induced)
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 because more B receptors available for NA/AD to cause sympathetic effect- don’t stop taking unless doctor says/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 hypoglycaemia
-sexual dysfunction –>poor patient compliance - CNS disturbances –nightmares, depression, confusion
inc LV size =inc myocardial O2 consumption
BB are contraindicated for patients with…
-Variant Angina (use CCB)
-Asthma with non-selctive BB
what is the pharmacological action of Calcium channel blockers?
-inhibit entry of Ca into cells via L-type voltage-gated calcium channels i.e. if heart(node cells) blocks entry of calcium cells it reduces force of contraction
What are the 3 types of CCBs
1 - Phenylalkylamines (verapamil)
2 - Dihydropyridines (nifedipine)
3 - Benzothisazepines (diltiazem)
Most CCBs are dihydropyridines
Diltiazem + verapamil are rate limiting
What are the cardiac effects of rate limiting CCBs
- block Ca influx into cadiac muscle cells, dec cardiac contractility
- block Ca influx into nodal and conducting cells, dec HR
what are the vascular effects that CCB have?
**Block of Ca influx into arterioles –> arteriolar dilatation
**-peripheral vasodilatation, dec SVR, dec arterial BP
-coronary dilatation, inc coronary BF, reversal of spasm, prevention of spasm
what are the two mechanisms of anti-anginal effects of CCB?
1) Reduced myocardial O2 demand
-dec arterial BP
-dec myocardial contractility and HR (for RLCCB)
2) Inc myocarial blood flow
-coronary vasodilatation, inc CBF, spasm reversal and prevention
What is CCB a first line treatment for?
chronic stable angina
also for management of variant angina
The Adverse Effects of Dihydropridines
Amplodipine, Nifedipine
-Hypertension
-Light headedness
-Flushing
-Headache
-Peripheral Oedema
The Adverse Effects of Non-dihydropyridines
Verapamil, Diltiazem
-AV block
-Bradycardia
-Cardiodepression
-Constipation
-Headache
-Hypotension
- Peripheral Oedema
what does sublingual mean?
under tongue
what does buccal mean?
between cheek and gum
what are the 3 miscellaneous treatments of SCAD?
1-Potassium channel openers (Nicorandil)
-venodilatation, dec preload, dec MVO2
-arterial dilatation, dec afterload, dec MVO2
2-Sinus node (If current) inhibitors (Ivabradine)
-Inhibit If, dec HR, dec MVO2
3-Late Sodium Current Blockers (Ranolazine)
-Inhibit late sodium channel, anti-ischaemic effect
what are the two revascularisation procedures?
Percutaneous Coronary intervention (PCI)-balloon
Coronary artery by-pass graft (CABG) -sew
when do you consider a 3rd anti-anginal drug?
when 2 don’t satisify
