Pharmacology
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Cardiovascular
A patient who is taking ramipril for high blood pressure complains of a dry persistent cough. What is the mechanism of cough in ACE inhibitor therapy:
Answer:
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.ACE Inhibitors
Pharmacology / Cardiovascular
Last Updated: 17th April 2019
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 |
