Dr Sharon Rees @reesprescribe
The concept for the first angiotensin converting enzyme inhibitor (ACEI) was derived from snake venom in the 1950s. An orally active version was eventually found, and captopril was licensed in 1981 for hypertension and heart failure #prescribing
Dr Sharon Rees @reesprescribe
Improved me-too ACEI versions followed, such as #ramipril, which was approved in the UK in 1989. Captopril is now out-moded, but is still used in paediatrics #prescribing
Dr Sharon Rees @reesprescribe
Long-acting, high affinity ACEIs, such as #ramipril, are highly successful in cardiovascular and renal medicine for hypertension, heart failure, post-MI prophylaxis and nephropathy. #ramipril is one of the most prescribed ACEI in the UK: In January 2019, 2.5 million items were prescribed at the cost of over £3 million #prescribing
Dr Sharon Rees @reesprescribe
Mechanism of action (MOA): #ramipril inhibits the conversion of angiotensin I to the active ATII. Less ATII means less SNS stimulation, less aldosterone output (<circulating volume) and less peripheral vasoconstriction, so <pre-load and afterload #prescribing
Dr Sharon Rees @reesprescribe
ATII (and aldosterone) drives remodelling (fibrosis etc) in the myocardium, ultimately leading to heart failure decompensation. Less ATII/aldosterone levels restrain progress of heart failure. Effects on nephropathy are unclear, but may be by reducing intra-glomerular pressure, there is less basement membrane damage, which slows diabetic nephropathic damage #prescribing
Dr Sharon Rees @reesprescribe
Why the cough? The angiotensin converting enzyme also breaks down circulating bradykinin (BK). An ACEI drug cause levels of BK to rise. BK dilates vascular smooth muscle, which enhances lowering blood pressure, BUT BK has the opposite effect in bronchial smooth muscle, where it causes broncho-constriction, dry cough, bronchospasm, or an asthma attack #prescribing
Dr Sharon Rees @reesprescribe
#ramipril is a pro-drug, metabolised to the active metabolite ramiprilat (mainly in the liver). #ramipril has a triphasic half-life (t½): The 1st is 2–4 hours, the 2nd provides free drug up to 18 hours, and the 3rd t½ is over 50 hours as angiotensin converting enzyme-bound drug slowly dissociates. Mainly renal excretion. Renal or hepatic impairment can cause toxicity, hypotension and shock #prescribing
Dr Sharon Rees @reesprescribe
Common adverse drug reactions with #ramipril: dry tickly cough, sinusitis, bronchitis, headache, dizziness, GI disturbance, myalgia, chest pain, rash, hyperkalaemia. Serious: Stevens-Johnson syndrome, pancytopenia, hepatic toxicity, vascular stenosis, anaphylactoid reactions, angioedema (not exhaustive) #prescribing
Dr Sharon Rees @reesprescribe
Ethnic differences: genetic polymorphisms mean angioedema (allergic reaction) is more likely in the Afro-Caribbean population. Renin levels are lower in the Afro-Caribbean population, so ACEIs are less effective. This is reflected in hypertension decision-making protocols #prescribing
Dr Sharon Rees @reesprescribe
There are many drug–drug interactions for #ramipril, but few ‘severe’. These include lithium, azathioprine, allopurinol, aliskiren. Most enhance >K+ or cause hypotension, but several herbs also oppose anti-hypertensive effects (eg ephedra, ginger and licorice) #prescribing
Dr Sharon Rees @reesprescribe
Recent links with ACEIs (including #ramipril) to slight increased risk of lung cancer, especially if used for over 5 years. Putative mechanism is accumulation of lung BK and substance P, which are associated with lung tumour growth #prescribing