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Series 8 starting today #ramipril Day 1:The concept for the 1st angiotensin converting enzyme inhibitor (ACEI) was derived from snake venom in the 1950s. An orally active version was eventually found & captopril was licensed in 1981 for hypertension & heart failure #prescribing
Day 1 #ramipril (cont): Improved ‘me too’ ACEI versions followed, such as #ramipril, approved in the UK in 1989. Captopril now out-moded, but still used in paediatrics #prescribing
Day 2: Long-acting, high affinity ACEIs, e.g #ramipril, highly successful in cardiovascular and renal space, re h-tension, heart failure, post-MI prophylaxis & nephropathy. Ramipril one of the most prescribed ACEI in UK: Jan 2019 total CCG items ~ 2.5 mill & cost >3m #prescribing
Day 3: MOA #ramipril inhibits the conversion of angiotensin(AT) I to the active ATII. Less ATII means less SNS stimulation, less aldosterone output (< circulating volume) & less peripheral v-constriction, so <pre-load & afterload #prescribing
Day (cont).ATII (& aldosterone) drive re-modelling (fibrosis etc) in myocardium > HF decompensation. < ATII/aldo levels restrain progress of HF. Effects on nephropathy unclear, but ? by < intra-glomerular pressure, less basement membr damage slows diabetic nephropathic damage
Day 4: Why cough? The AC enzyme also b-down circul bradykinin (BK). An ACEI drug >levels of BK to rise. BK dilates vasc smooth muscle/assists with < BP, BUT opposite effect in bronchial sm muscle, where it > broncho-constriction, dry cough, b-spasm, or >asthma attack #prescribing
