Mechanism of Action:

An angiotensin-converting enzyme (ACE) inhibitor. It is a prodrug that is metabolised to the active agent Ramiprilat, mostly in the liver, but also in kidney.


  • Hypertension
  • Heart failure
  • Prophylaxis after myocardial infarction
  • Proteinuric renal disease, including diabetic nephropathy
  • Microalbuminuria caused by diabetes

The enzyme ACE is part of the renin angiotensin aldosterone system (RAAS). Circulating angiotensinogen is converted to angiotensin I [ATI] by the enzyme renin. ACE is responsible for the conversion of ATI to ATII. ATII is a potent vasoconstrictor, and AT III, a metabolite of ATII, stimulates aldosterone secretion. Aldosterone-mediated retention of salt and water leads to increased extracellular fluid volume and subsequently raises blood pressure and increases cardiac output. Lisinopril competes with angiotensin ATI for binding to ACE. Conversion of ATI to ATII is thus prevented and the effects of RAAS diminished.

Learning materials:


Alternative drug name
Not specified
Decreases angiotensin II production and so reduces effects on vasoconstriction and aldosterone release. This reduces arterial blood pressure. As well as reducing ‘afterload’ also venodilates and so reduces venous return (‘preload’) making it an effective agent in chronic heart failure.
Adverse actions
Persistent non-productive cough (~1 in 10 patients) which resolves with drug discontinuation, renal impairment (especially in patients with bilateral renal artery stenosis or impaired renal function), hypotension, hyperkalaemia (decreased aldosterone leading to increased potassium blood levels). Rash (uncommon).

The cough is the result of bradykinin accumulation in the lungs which acts as an irritant (ACE inhibitors prevent the breakdown of bradykinin). This is also an important mechanism in a rare but serious problem of angioedema (1 in 1000).

Renal impairment is attributed to the disruption of homeostatic mechanisms (e.g. renal blood flow) controlled by ATII which serves to support renal blood flow in circumstances such as hypotension or dehydration. Risk of severe drop in blood pressure with the first dose of ACE inhibitors (first dose hypotension) is mostly seen in those who are volume-deplete, usually through being on diuretics, but it can also be seen in those who have RAAS greatly upregulated for other reasons (e.g. renal artery stenosis).

ACE inhibitors are contraindicated in pregnancy, at least in mid-pregnancy, as they cause oligohydramnios and may cause other severe abnormalities if exposure in mid-pregnancy.

Rare but severe allergic reaction can occur affecting the bowel and secondarily causing abdominal pain. This “anaphylactic” reaction is very rare but requires immediate attention.

Usually once daily administration in the range 2.5 to 10 mg). Twice daily dosing is sometimes recommended in heart failure. Doses are usually doubled at intervals of 1-4 weeks for outpatients. Its half life is >24h after multiple doses at 2.5mg daily; 15h at 5-10mg daily.

Lower doses are recommended in patients with low GFR. (EMC on Ramipril)

Renal impairment with other drugs affecting renal blood flow e.g. NSAIDs, diuretics. Hypotension with other antihypertensives. Hyperkalaemia with other drugs tending to preserve potassium e.g. potassium sparing diuretics such as spironolactone.
Symptomatically very low blood presssure.
Other ACE inhibitors include enalapril, lisinopril, perindopril, captopril etc. They vary in their pharmacokinetics but all work in much the same way. Angiotensin receptor blockers such as Losartan have a similar clinical profile to ACE inhibitors.

Not directly related, but of interest for treatment of pulmonary hypertension: ET-1 (endothelin-1) is a potent vasoconstrictor acting via ETA receptors (plus weak dilator action via ETB receptors) and its effects can be antagonized by bosentan, which is slightly more effective at blocking ETA receptors in comparison with ETB. The antagonist is used in treating pulmonary hypertension.

Added by ANT Mar 2017 revised 2021


!! Under revision March 2017 !!


Diuretic, relatively weak but potassium-sparing. It has particular utility in resistant hypertension, heart failure, liver disease, and other high-aldosterone states.

Mechanism of Action:

A synthetic 17-lactone steroid which is a competitive antagonist of aldosterone. It inhibits aldosterone’s Na+-retaining K+ excreting action at the distal convoluted tubule of the nephron. This means that it is a diuretic (relatively weak), but unlike other diuretics which tend to waste potassium from the body it is a ‘potassium sparing’ diuretic. Spioronolactone is a prodrug, metabolized to the active entity, canrenone.

Lecture and CAL materials: (under review)



  • Chronic heart failure
  • Angina pectoris
  • Myocardial infarction
  • Cardiac arrhythmias
  • Hypertension

Mechanism of Action:

Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent. It has little affinity to beta2-receptors of the smooth muscle of bronchi and vessels as well as the beta2-receptors involved in metabolic regulation. Therefore bisoprolol is not likely to influence the airway resistance or has beta2-mediated metabolic effects.

Lecture and CAL materials: (under review)



  • Heart failure and other states of intravascular volume overload.
  • Emergency treatment of acute pulmonary oedema.
  • Oedema associated with generalised extravascular volume expansion (nephrotic syndrome and other low-albumin or other salt-retaining states).

Mechanism of Action

Loop diuretic: the most powerful and rapidly effective class of diuretics. In kidney inhibits Na+/K+/2Cl- cotransporter in (thick) ascending loop of Henle where the drug is concentrated. As NaCl is not absorbed, it passes on through the tubule with an osmotic equivalent of water. Also get loss of K+ and H+.

Further resources