NITRATES, CALCIUM-CHANNEL BLOCKERS AND POTASSIUM-CHANNEL ACTIVATORS

Nitrates, calcium-channel blockers and potassium-channel activators have a vasodilating effect leading to a reduction in venous return, which reduces left ventricular work and dilatation of the coronary circulation.

Nitrates

Mechanism of action

An increase in cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells causes a decrease in intracellular calcium levels and smooth muscle relaxation with dilatation of veins and arteries, including the coronary circulation. They reduce venous return which reduces left ventricular work.

Indications

These drugs are used as a prophylaxis for and in the treatment of angina, as an adjunct in congestive heart failure and intravenously in the treatment of acute heart failure and acute coronary syndrome.

Preparations and dose

Glyceryl trinitrate - short acting

Sublingual tablets: 300 μg 500 μg 600 μg (expire after 8 weeks once bottle opened); spray 400 μg/dose.

■ Angina: one or two tablets or sprays under the tongue (sublingual use avoids hepatic first-pass metabolism) repeated as required. More effective if taken before exertion known to precipitate angina. Tablets (unlike spray) can be spat out if side-effects occur (headache, hypotension).

Glyceryl trinitrate - transdermal

Patches releasing approx: 5 mg, 10 mg, 15 mg/24 h.

■ Angina: apply patch to chest or outer arm and replace at different site every 24 hours. If tolerance (with reduced therapeutic effect) is sus-pected, the patch should be left off for 4-8 consecutive hours - usually at night as this is the least symptomatic period.

Glyceryl trinitrate - long-acting tablets

Buccal tablets: 2 mg, 3 mg, 5 mg.

■ Angina: 1-5 mg three times daily

■ Heart failure: 5 mg (increased to 10 mg in severe cases) three times daily.

Glyceryl trinitrate injection

5 mg/mL, diluted to 100 μg/ml, i.e. 5 mg in 50 ml, in glucose 5% or sodium chloride 0.9% administered Via a syringe pump.

■ 0.6-0.9 mg/h i.v., then increase dose cautiously until response is achieved, keeping systolic BP > 100 mmHg. Usual range 2-10 mg/h.

Isosorbide mononitrate

Tablets: 10 mg, 20 mg, 40 mg.

■ 10-40 mg twice daily, 8 hours apart rather than 12 to prevent nitrate tolerance.

Isosorbide mononitrate (modified release)

Tablets: 25 mg, 50 mg, 60 mg.

■ 25-60 mg once daily. Reserve for patients where twice-daily dosing (above) has proved unacceptable. Build up dose gradually to avoid head-aches. Up to 120 mg daily may be required.

Side-effects

These are mainly due to vasodilating properties and are minimized by initiating therapy with a low dose. They include flushing, headache, postural hypotension, and methaemoglobinaemia (p. 826) with excessive dosage.

Cautions/contraindications

Nitrates are contraindicated in hypotension and hypovolaemia, hypertrophic obstructive cardiomyopathy, aortic stenosis, mitral stenosis, cardiac tampon-ade and constrictive pericarditis. Nitrates potentiate the effect of other vasodilators and hypotensive drugs. Sildenafil is contraindicated in patients taking nitrates.

Calcium-channel blockers

This group of drugs includes different modified-release preparations of calcium channel blockers that have different bioavailabilities and so the brand should be stated on the prescription.

Mechanism of action

These drugs block calcium channels and modify calcium uptake into myo-cardium and vascular smooth muscle cells. The dihydropyridine calcium-channel blockers (e.g. amlodipine, nifedipine, nimodipine) are potent vasodilators with little effect on cardiac contractility or conduction. In con-trast, verapamil and to a lesser extent diltiazem are weak vasodilators but depress cardiac conduction and contractility.

Indications

Indicators for use are hypertension and prophylaxis for angina. Verapamil is used in the treatment of some arrhythmias. Nimodipine is for the prevention of ischaemic neurological deficits following aneurysmal subarachnoid haemorrhage.

Preparations and dose

Amlodipine

Tablets: 5 mg, 10 mg.

■ 5-10 mg once daily.

Verapamil

Tablets: 40 mg, 80 mg, 120 mg, 160 mg; oral solution: 40 mg/5mL; modi-fied-release (slow-release, SR) tablets: 120 mg, 240 mg; injection: 2.5 mg/ mL.

■ Angina: 80-120 mg three times daily. SR 240 mg once or twice daily

■ Hypertension: 240-480 mg daily in two to three divided doses. SR 120240 mg once or twice daily

■ Supraventricular arrhythmias: oral 40-120 mg three times daily, i.v. 5-10 mg over 10 minutes, further 5 mg after 5-10 minutes if required.

Nifedipine modified release

Adalat® LA tablets: 20 mg, 30 mg, 60 mg.

■ Angina: initially 30 mg once daily, increased if necessary to 90 mg once daily

■ Hypertension: initially 20 mg once daily, increased if necessary.

Diltiazem

Tablets: 60 mg.

■ Angina: 60 mg three times daily.

Diltiazem slow release

Capsules for twice daily use: 90 mg, 120 mg, 180 mg; capsules for once daily use: 120 mg, 180 mg, 240 mg, 300 mg.

■ Hypertension: 120 mg twice daily

■ Angina: 90 mg twice daily increased to 180 mg twice daily if required

■ Angina and hypertension: 240 mg once daily increased to 300 mg once daily.

Side-effects

These are mainly due to vasodilator properties: flushing, dizziness, tachy-cardia, hypotension, ankle swelling and headache. Side-effects are minimized by starting with a low dose and increasing slowly. Constipation occurs with verapamil. Worsening heart failure can be seen with verapamil and diltiazem.

Cautions/contraindications

The major contraindication is aortic stenosis. Verapamil and diltiazem dimin-ish cardiac contractility and slow cardiac conduction; thus they are relatively contraindicated in patients taking β-blockers, left ventricular failure, sick sinus syndrome, heart failure. Verapamil is contraindicated for treatment of arrhythmias complicating Wolff-Parkinson-White syndrome. Short-acting calcium antagonists increase mortality and are contraindicated immediately after myocardial infarction.

Potassium-channel activators

Mechanism of action

The mechanism of action here is a hybrid of nitrates (p. 499) and potassium channel activators. The latter causes an increase in potassium flow into the cell and indirectly leads to calcium-channel blockade and arterial dilatation.

Indications

Use is indicated in cases of refractory angina in patients who are uncontrolled on standard regimens of aspirin, β-blockers, nitrates, calcium antagonists and statins.

Preparations and dose

Nicorandil

Tablets: 10 mg, 20 mg.

■ 5-30 mg twice daily.

Side-effects

These include headache (often temporary), flushing, nausea, vomiting, dizzi-ness, hypotension, tachycardia.

Cautions/contraindications

Use is contraindicated in left ventricular failure and cardiogenic shock. Silde-nafil is contraindicated in patients taking nicorandil.

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

KEYWORD : Phác Đồ Chữa Bệnh, Bệnh Viện Bạch Mai, Từ Dũ , 115, Bình Dân, Chấn thương chỉnh hình, Chợ Rẫy, Đại học Y Dược, Nhân Dân Gia Định, Hoàn Mỹ, Viện Pasteur, Nhi Đồng Ung bướu, Quân Đội 103, 108,Phụ Sản Trung Ương, Bộ Y Tế,Phòng Khám, Hà Nội, Hải Dương, Thái Bình, Hồ Chí Minh, Sài Gòn, Đà Nẵng, Huế, Vinh, Đồng Nai, Bình Dương, Hải Phòng, Quảng Ninh, Hiệu Quả Cao, Chữa Tốt, Khỏi Bệnh, Là Gì, Nguyên Nhân, Triệu Chứng, Ăn Uống, Cách Chữa, Bài Thuốc
Thông Tin Trên Web Là Tài Liệu Lưu Hành Nội Bộ Cho Các Bạn Sinh Viên - Y, Bác Sĩ Tham Khảo : Liên Hệ : Maikhanhdu@gmail.com