DRUGS AFFECTING THE RENIN-ANGIOTENSIN SYSTEM

Renin produced by the kidney in response to glomerular hypoperfusion cata-lyzes cleavage of angiotensinogen (produced by the liver) to angiotensin (AT), which in turn is cleaved by angiotensin-converting enzyme (ACE) to angiotensin II, which acts on two receptors. The AT1 receptor mediates the vasoconstrictor effects of AT. The actions of the AT2 receptor are less well defined.

Angiotensin-converting enzyme inhibitors

Mechanism of action

These drugs inhibit the conversion of angiotensin I to angiotensin II and

reduce angiotensin II mediated vasoconstriction.

Indications

The main indicators are heart failure, hypertension, diabetic nephropathy and ischaemic heart disease.

Preparations and dose

Perindopril

Tablets: 2 mg, 4 mg, 8 mg.

■ Hypertension, initially 4 mg once daily (use 2 mg if in addition to diuretic, in the elderly, in renal impairment) subsequently adjusted according to response to maximum 8 mg daily

■ Heart failure: initially 2 mg once daily, increased after at least 2 weeks to maintenance usually 4 mg daily

■ Ischaemic heart disease, diabetic nephropathy: 4 mg daily increased after 2 weeks to 8 mg daily.

Lisinopril

Tablets: 2.5 mg, 5 mg, 10 mg, 20 mg.

■ Hypertension: initially 10 mg once daily (2.5-5 mg if in addition to diuretic, in the elderly, in renal impairment), usual maintenance 20 mg daily, maximum 80 mg daily

■ Heart failure: initially 2.5 mg once daily, increased by 10 mg every 2 weeks if tolerated to maintenance 35 mg daily

■ Ischaemic heart disease, diabetic nephropathy: 5-10 mg daily. Immedi-ately post STEMI start at 2.5 mg if systolic BP 100-120 mm Hg and gradually increase to maintenance dose of 5-10 mg. Do not give if systolic BP < 100 mm Hg.

Ramipril

Tablets: 1.25 mg, 2.5 mg, 5 mg, 10 mg.

■ Hypertension: initially 1.25 mg daily, increased weekly to maintenance

2.5-5 mg daily, maximum 10 mg once daily

■ Heart failure: initially 1.25 mg daily, increased if necessary to maximum 10 mg daily

■ Ischaemic heart disease, diabetic nephropathy: 2.5 mg twice daily, main-tenance 2.5-5 mg daily.

Side-effects

After the first dose side-effects can include hypotension (use small initial doses) in heart failure and patients taking diuretics, dry cough, hyperkal-aemia, sudden deterioration in renal function in patients with renal artery stenosis and in patients taking NSAIDs (check urea and electrolytes 1-2 weeks after starting treatment), loss of taste, rashes and hypersensitivity reactions.

Cautions/contraindications

These include bilateral renal artery stenosis, pregnancy, angio-oedema, severe renal failure, severe or symptomatic mitral or aortic stenosis and hypertrophic obstructive cardiomyopathy (risk of hypotension).

Angiotensin II receptor antagonists

Mechanism of action

These are antagonist of the type 1 subtype of the angiotensin II receptor (AT1 receptor).

Indications

Indications include hypertension, heart failure or diabetic nephropathy in patients intolerant to ACE inhibitors because of cough.

Preparations and dose

Candesartan

Tablets: 2 mg, 4 mg, 8 mg, 16 mg, 32 mg.

■ Hypertension: initially 8 mg daily, increased as necessary to 32 mg daily

■ Heart failure: initially 4 mg once daily increased at intervals of at least 2 weeks to target dose of 32 mg.

Valsartan

Capsules: 40 mg, 80 mg, 160 mg.

■ Hypertension: 80 mg once daily (40 mg in caution groups) and increased if necessary after 4 weeks to 160 mg daily

■ Ischaemic heart disease: 20 mg twice daily increased gradually to 160 mg twice daily.

Side-effects

These include postural hypotension, rash, abnormalities in liver biochemistry and hyperkalaemia.

Caution/contraindications

Lower doses should be given in liver and renal impairment, patients taking high-dose diuretics and the elderly (over 75 years). Caution should be applied in renal artery stenosis, aortic or mitral valve stenosis and in obstructive hypertrophic cardiomyopathy.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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