drugs affecting the vasculature and blood pressure Flashcards
what classes of drugs are used to relax vascular smooth muscle?
- organic nitrates = used to treat angina, as prophylaxsis, pulmonary oedema
- calcium channel blockers = to treat hyertension, stable angina
what is angina?
pain that occurs when the O2 supply to the myocardium is insufficient to meet its metabolic demand
what are the 3 types of angina?
stable, unstable, variant
what causes stable angina?
a fixed narrowing (stenosis) of coronary vessels as a consequence of atherosclerosis
- characterised by predictable pain upon exertion
what causes unstable angina?
- due to platelet-fibrin thrombus in association with an atheromatous plaqur
- characterised by pain to less and less exertion
- danger of MI
what causes variant angina?
- associated with coronary artery spasm
what do organic nitrates do?
- relax all types of smooth muscles
- they act upon vasculature causing:
1. venorelaxation
2. arteriolar dilation
3. increased coronary blood flow
how do organic nitrates effect coronary circulation?
the nitrate dilates collateral and causes the blood flow to the ischaemic myocardium to increase
what are the clinical uses of organic nitrates in angina?
GTN
what does GTN do?
- short acting
- undergoes extensive first-pass metabolism
- administered sublingually
what is first pass metabolism?
- drugs that are swallowed are carried from the gut to the liver by the portal circulation
- they undergo variable metabolism by the liver before reaching the systemic circulation
- some drugs (GTN) are almost completely inactivated by the liver
what are the adverse effects of organic nitrates?
- headaches
- hypotension and fainting
- reflex tachycardia
- formation of mathaemoglobin
how are organic nitrates tolerated?
- repeat administration of organic nitrates may be associated with a diminished effect
what are they 3 main types of calcium channel blockers?
- verapamil
- amlodipine
- diltiazem
how do calcium blockers help hypertension?
- reduced Ca+ entry int vascular smooth muscle cells causes generalised arteriolar dilation, reducing TPR and MABP. the major effect is on the arteries
- drugs with selectivity for smooth muscle L-type channels are preferred to minimise unwanted effects upon cardiac muscle
- Ca+ channel blockers cause coronary vasodilation and are useful in angina and hypertension at the same time
how do calcium blockers help angina?
- they are prophlactic, often used in combination with GTN
- they causeperipheral arteriolar dillation decreasing afterload and myocardial oxygen requirement
- they produce coronary vasodilation
what does the RAAS system play a role in?
sodium excretion and vascular tone
what is the physiological response to the activation of RAAS?
- compensatory in the long term to restoration of blood pressure that may be dramatically reduced eg heart failure or haemorrhage
- contraction of smooth muscle is due to release of noradrenaline
what does ACE do?
- converts angiotensin 1 into angiotensin 2
- inactivates bradykinin
what do ACEIs do?
- cause venous/arteriolar dilation, decreasing arterial blood pressure and cardiac load
- no effect on cardiac contractility
- reduce release of alderstorone
- reduce growth action of angiontensin 2 upon the heart
what are the adverse effects of ACEIs?
- initial hypotension
- dry cough
- hyperkalaemia
- angioedema
what are the clinical uses of B-adrenoceptor antagonists?
- in the treatment of angina pectoris
why are b-clockers of value?
- there is a decreased myocardial O2 requirement
- counter elevated sympathetic activity associated with ischaemic pain
- increase the amount of time spent in diastole, improving perfusion of the left ventricle
what are potassium channel openers?
- they open ATP-modulated K+ channels in vascular smooth muscle
- they act by antagonising intracellular ATP
- they cause hyperpolarisation with switches off L-type Ca2+ channels
- they act potently and primarly upon arterial smooth muscle
what are a1-adrenoceptor receptor antagonists?
- cause vasodilation by blocking vascular a1-adrenoceptors
- decreased MABP
- eg prazosin and doxazosin
- they provide symptomatic relief in benign prostatic hyperplasia
- adverse effects: postural hypotension
