- The main stay of acute relief in ischaemia
- vasodilation, venous and coronary arteries at lower concentrations than arterioles –> decrease ventricular preload –> decreased CO–> drop BP
- Compensatory tachycardia, increased contractility, Na and water retension
- SE – orthostatic hypotension, headache
- NO activates guanyl cyclase –> increases cGMP–> decreased Calcium–>dephosphorylation of myosin light chain –> prevents actin and myosin interacting–> reduce smooth muscle vascular tone.
- Tolerance/tachyphylaxis can be developed with continuous use(decrease in sulfhydryl groups) after some hours.
- Sildenafil is contraindicated in GTN users cos it also increases cGMP but via decreased breakdown of cGMP(inhibits phosphodiesterase)
Reduces platelet aggregation
- Organic nitrates have Low oral bioavailability due to hepatic bd with nitrate reductase. (<10-20%)
- S/L and transdermal used, Duration of effect 10-15mins
- Oral used for longer duration of action
- Isosorbide mononitrate (an active metabolite) has 100% oral bioavailabilty.
- Renal excretion.
What is the coronary steal syndrome ?
- When you use vasodilators in the context of pre-existing coronary artery stenosis you risk coronary steal syndrome
- The stenosed vessels are already maximally dilated, so when you dilate all the coronary vessels the blood is shunted away from the ischaemic areas resulting in more ischaemia
Calcium channel blockers:
- vasodilation – arterioles more sensitive than veins. Not much orthostatic hypotension.
- Cardiac effects – decrease HR, decrease contractility,
- Decreased intracellular Ca (which otherwise binds to calmodulin)–> which inhibits activation of myosin light chain kinase.
- Dyhydropyiridines bind to one site on a1 subunit of L type Ca channels, verapamil and diltiazem bind at another site on the subunit(non selective block).
- Dyhydropyridines have a higher ratio of vascular smooth muscle effects relative to cardiac effects compared to verapamil and diltiazem.
Drug Nifedipine Amlodipine Felodipine Verapamil Oral Bio availablity 45-70% 65-90% 15-20% 20-35% Half life (hrs) 4 30-50 11-16 6 Indication Anginga, HTN, Raynauds Angina, HTN HTN, Raynauds Angina, HTN, arrhythmias, migraine
- High first pass effect
- High plasma protein binding
- Extensive metabolism
Passing familiarity with Nimodipine.
- It is a dihydropyridine with high afinity for cerebral blood vessels
- Apprear to reduce morbidity after subarachnoid haemorrhage
Tell me about the drugs used for angina
Physiology concepts to answer this question: