Name the category.
Antihypertensive therapy
List the main drug.
LISINOPRIL
Name an alternative drug.
RAMIPRIL
What kind of drugs are both lisinopril and ramipril?
Angiotensin-converting enzyme inhibitors (ACE inhibitors)
List indications.
Arterial hypertension
Diabetes mellitus (type I and type II) with
Nephroprotective indications, such as:
Microalbuminuria and proteinuria (especially ≥ 300 mg/g)
Coronary heart disease
Heart failure with reduced ejection fraction
Survival benefit (the exact mechanisms are poorly understood)
Any murmur that decreases with amyl nitrite has an etiology that is treatable with ACE inhibitors.
History of myocardial infarction
Nondiabetic chronic kidney disease with proteinuria
Scleroderma-associated hypertensive crisis (even if creatinine is elevated)
Describe the overall mechanism of action of ACE inhibitors.
inhibition of ACE → ↓ conversion of angiotensin I to angiotensin II
List the main physiological effects exhibited by ACE inhibitors.
↓ Angiotensin II
↓ Vasoconstriction → ↓ blood pressure
↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure
Dilation of efferent arteriole → ↑ renal plasma flow → ↓ GFR → ↓ filtration fraction
↑ Renin secretion (due to lack of feedback inhibition) → ↑ angiotensin I
↓ Breakdown of bradykinin → ↑ production of arachidonic acid metabolites → ↑ vasodilation → ↓ blood pressure
List other effects caused by ACE inhibitors.
↓ Proteinuria and ↓ progression of proteinuric chronic kidney disease: ↓ intraglomerular hydrostatic pressure attenuates thickening and sclerosis of the GBM
↓ Preload and afterload → ↓ cardiac remodeling after acute myocardial infarction or in chronic hypertensive disease
ACE Effects on renal filtration.
List adverse effects of ACE inhibitors.
Increase in bradykinin concentration, which can lead to:
Dry cough (can be treated by discontinuing ACE inhibitor, consider switching to ARB) [7][8]
Bradykinin-mediated angioedema due to increased vascular permeability and vasodilation
Hyperkalemia
↓ GFR (with ↑ creatinine): can cause acute kidney injury in patients with preexisting renal hypoperfusion (e.g., renal artery stenosis, hypovolemia, heart failure) [9]
Hypotension
Proteinuria
Pemphigus vulgaris (unknown mechanism) [10]
Teratogenicity: renal malformations
Leukopenia
Rash
Taste changes
Side effects of CAPTOPRIL: Cough, Angioedema, Pemphigus vulgaris, Teratogenicity, hypOtension, high Potassium, Renal failure, Increased creatinine, Low GFR.
List contraindications for both ACE inhibitors and ARBs.
Absolute contraindications
Hypersensitivity
C1 esterase inhibitor deficiency (due to predisposition to angioedema)
Pregnancy: risk of harm to the fetus (e.g., renal impairment, renal malformations, oligohydramnios, placental insufficiency)
Breastfeeding
Relative contraindications
Aortic stenosis
Renal dysfunction, consider altering dose if GFR < 60 mL/min
Bilateral renal artery stenosis or a solitary kidney: GFR is already decreased and further reduction may lead to acute kidney injury.
List important interactions of ACE inhibitors.
Other antihypertensive drugs → ↑ hypotensive effect
NSAIDs → ↓ antihypertensive effect
Potassium-sparing diuretics or other drugs that increase potassium level: ↑ hyperkalemia
↑ Level of lithium due to ↓ renal elimination
Allopurinol: ↑ risk of immunological reactions or leukopenia
List additional considerations of ACE inhibitors.
Starting with low doses (preferably in a controlled setting) is recommended to avoid severe hypotension.
Combine ACE inhibitors or ARBs with thiazide diuretics to offset the risks of hyperkalemia and hypokalemia.
When starting an ACE inhibitor or an ARB, monitor blood pressure, potassium, and creatinine.
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