Lecture 30 Flashcards
(7 cards)
B blockers
B-adrenoceptor antagonists compete with noradrenaline and adrenaline. When noradrenaline/adrenaline bind to adrenoceptors in cardiac notch tissues (sinoatrial and atrioventricular node and myocytes, more B1 than B2) adenylyl cyclase forms cAMP from ATP which activates PKA which phosphorylates L-type Ca2+ - channels causing Ca2+ influx = contraction. Blocking B1 = decrease Ca2+ influx = decrease cell excitability. Decreases HR and force of contraction = decrease CO = decrease BP. Useful for stress induced increase BP, in kidneys decreases renin release = decreased BP.
Angiotensin-converting enzyme (ACE) inhibitors
Inhibition of ACE stops angiotensin 1 to angiotensin 2 therefore, less angiotensin 2 to bind to AT1 receptor e.g catopril, enalapril and perindopril. Only causes small decrease in arterial pressure in people who consume salt contained in Western diet but, large decrease in hypertensive patients. ACE inhibitors acts preferentially on angiotensin sensitive vascular beds incl. those of kidney, heart and brain. Selectivity important for sustaining adequate perfusion of organs in the face of decreased perfusion pressure.
AT1 receptor antagonists
ACE inhibitors can have bad side effects. Antagonise angiotensin II type 1 (AT1) receptors therefore AKA angiotensin receptor blockers (ARBs)
-Candesartan
- Telmisartan
-Irbesartan
Effect similar to ACE inhibitors.
Non-selective vs selective B blockers
Non-selective: Bind to B1 and B2 e.g timilol
selective: B1 only metoprolol. Decrease side-effects than non-selective.
Ca channel blockers
Block L-type Ca2+ channel in cardiac muscle and SM. Involved in vasoconstriction/dilation but dihydropyridines more potent. Inhibiting Ca2+ movement by blocking L-Ca2+ channels, decrease cell’s contractibility. In heart = decreased rate and contraction force. In SM = decreased contractility = relaxation. Decreased CO and vasoconstriction = decreased BP.
Side effect comparison
Dry cough common with ACE inhibitors due to bradykinin accumulation which may also cause angioedema. Combination may occur with ARBs but much less likely. ACE inhibitors may also cause hypotension esp. after first dose and in heart failure treated in diuretics. ACE inhibitors and ARBs are teratogenic therefore, avoided in pregnant/planning women as it can cause birth defects and they can cause reversible renal failure. Ca2+ have limited side effects incl. ankle oedema, headache and impotence (some). B-blockers cause bronchospasm, fatigue and impotence.
Other considerations
B-blockers are less well tolerated than ACE and ARBs and are less effective as other hypertensive drugs therefore, not usually first-line treatment (used when other conditions present and stress induced hypertension). Also, must not be combined with non-dihydropyridine Ca2+ channel blockers due to bradycardia and atrioventricular block. Cannot be given to asthmatics or COPD patients due to bronchospasm risk. Usually begin with with ACE inhibitor or ARBs in people with normal/raised renin levels (usually younger, Europeans). Ca2+ blockers given to people with low plasma renin levels (older/African patients). When dry cough is problem, ACE swapped with ARBs.
