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97

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Pharmacology

Cardiovascular

Question 110 of 180

Which of the following is NOT a pharmacological effect of ACE inhibitor therapy:

Answer:

Angiotensin-converting enzyme inhibitors (ACE inhibitors) e.g. captopril inhibit the conversion of angiotensin I to angiotensin II, and thus have a vasodilatory effect, lowering both arterial and venous resistance. The cardiac output increases and, because the renovascular resistance falls, there is an increase in renal blood flow. This latter effect, together with reduced aldosterone release, increases Na+ and H2O excretion, contracting the blood volume and reducing venous return to the heart.

ACE Inhibitors

Mechanism of Action

Angiotensin-converting enzyme inhibitors (ACE inhibitors) e.g. captopril inhibit the conversion of angiotensin I to angiotensin II, and thus have a vasodilatory effect, lowering both arterial and venous resistance. The cardiac output increases and, because the renovascular resistance falls, there is an increase in renal blood flow. This latter effect, together with reduced aldosterone release, increases Na+ and H2O excretion, contracting the blood volume and reducing venous return to the heart.

Blocking ACE also diminishes the breakdown of the potent vasodilator bradykinin which is the cause of the persistent dry cough. Angiotensin-II receptor blockers do not have this effect, therefore they are useful alternative for patients who have to discontinue an ACE inhibitor because of persistent cough.

Indications

ACE inhibitors have many uses and are generally well tolerated. They are indicated for:

  • Heart failure
  • Hypertension
  • Diabetic nephropathy
  • Secondary prevention of cardiovascular events

Contraindications

ACE inhibitors should be avoided in:

  • History of angioedema associated with previous exposure to an ACE inhibitor
  • Recurrent angioedema
  • Bilateral renal artery stenosis
  • Pregnancy and breastfeeding

Cautions

The use of ACE inhibitors is cautioned in:

  • Renal impairment
  • Afro-Caribbean patients (may respond less well to ACE inhibitors)
  • Peripheral vascular disease or generalised atherosclerosis (risk of clinically silent renovascular disease)
  • Primary aldosteronism (patients may respond less well to ACE inhibitors)
  • History of idiopathic or hereditary angioedema
  • Patients with hypertrophic cardiomyopathy
  • Patients with severe or symptomatic aortic stenosis (risk of hypotension)

Concomitant treatment with NSAIDs increases the risk of renal damage, and with potassium-sparing diuretics (or potassium-containing salt substitutes) increases the risk of hyperkalaemia. Hyperkalaemia and other side effects of ACE inhibitors are more common in the elderly and in those with impaired renal function and the dose may need to be reduced.

Side Effects

Side effects of ACE inhibitors may include:

  • Deterioration in renal function
  • Hyperkalaemia
  • Hypotension
  • Persistent dry cough
  • Angioedema (non-allergic drug reaction)
  • Dizziness and headaches (usually secondary to hypotension)
  • Other common adverse effects include abdominal discomfort, dyspepsia, diarrhoea, nausea and vomiting, rash (in particular maculopapular rash), myalgia, muscle spasms, dyspnoea, chest pain, and fatigue

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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