DRUGS FOR ARRHYTHMIAS

Adenosine

Mechanism of action

Adenosine is a purine nucleotide. It acts on adenosine receptors and enhances the flow of potassium out of myocardial cells and produces hyperpolarization of the cell membrane and stabilizes the cell membrane. It has potent effects on the SA node, producing sinus bradycardia, and slows impulse conduction through the AV node.

Indications

The main indication is reversion to sinus rhythm of atrioventricular junctional tachycardia.

Preparations and dose

3 mg/mL.

Intravenous injection By rapid i.v. injection into a central or large periph-eral vein, 6 mg over 2 seconds with cardiac monitoring and resuscitation equipment available; if necessary followed by 12 mg after 1-2 minutes, and then 12 mg after a further 1-2 minutes; increments should not be given if high-level AV block develops at any dose.

Side-effects

Unwanted effects are common; however, they are usually transient. Patients should be warned before drug administration of side-effects usually lasting less than 1 minute:

■ Bradycardia and AV block

■ Facial flushing, headache, chest pain or tightness

■ Bronchospasm.

Cautions/contraindications

Contraindicated in asthma, second- or third-degree AV block and sick sinus syndrome (unless pacemaker fitted).

Amiodarone hydrochloride

Mechanism of action

Class III (Vaughan Williams' classification) drug action which prolongs the duration of the action potential, thus increasing the absolute refractory period. Inhibits the potassium channels involved in repolarization.

Indications

Intravenous injection of amiodarone is used in cardiopulmonary resuscitation for ventricular fibrillation or pulseless tachycardia unresponsive to other interventions. Oral and i.v. amiodarone is used in the treatment of arrhyth-mias (supraventricular and ventricular tachycardia, atrial fibrillation and flutter) particularly when other drugs are ineffective or contraindicated. In the non-emergency setting it should only be initiated under specialist super-vision. Unlike many other antiarrhythmic drugs, amiodarone causes little or no myocardial depression.

Preparations and dose

Tablets: 100 mg, 200 mg; Injection: 30 mg/mL or concentrate 50 mg/mL.

Oral 200 mg three times daily for 1 week reduced to 200 mg twice daily for a further week; maintenance, usually 200 mg daily or the minimum required to control the arrhythmia.

Intravenous Via central line catheter (in an emergency, e.g. ventricular tachycardia, can be given via a large peripheral line, but is a vesicant drug and therefore requires caution), initially 5 mg/kg in 250 mL glucose 5% (drug incompatible with sodium chloride) over 20-120 minutes with ECG monitor-ing. This may be repeated if necessary to a maximum of 1.2 g in 24 hours in 500 mL. As soon as an adequate response has been obtained, oral therapy should be initiated and the i.v. therapy phased out.

Side-effects

Amiodarone contains iodine and can cause both hypothyroidism and hyper-thyroidism. Thyroid function tests including T3 should be measured before treatment and then every 6 months of treatment. Also liver toxicity and liver biochemistry should be measured before and then every 6 months of treat-ment. Other side-effects are reversible corneal microdeposits (drivers may be dazzled by headlights at night), phototoxic skin reactions (advise patients to use total sunblock creams), slate-grey skin pigmentation, pneumonitis and peripheral neuropathy.

Cautions/contraindications

It is contraindicated in sinus bradycardia or sinoatrial heart block, unless pacemaker fitted, iodine sensitivity and thyroid dysfunction.

Many drugs interact with amiodarone including warfarin and digoxin (check National Formulary for full list). It has a very long half-life (extending to several weeks) and many months may be required to achieve steady-state concentrations; this is also important when drug interactions are considered.

Flecainide

Mechanism of action

Class Ic (Vaughan Williams' classification) antiarrhythmic drug. It is a mem-brane-depressant drug that reduces the rate of entry of sodium into the cell (sodium-channel blocker). This may slow conduction, delay recovery or reduce the spontaneous discharge rate of myocardial cells.

Indications

AV nodal reciprocating tachycardia, arrhythmias associated with accessory conducting pathways (e.g. Wolff-Parkinson-White syndrome), paroxysmal atrial fibrillation. Occasionally it is used in ventricular tachyarrhythmias resist-ant to other treatments.

Preparations and dose

SVT - 50 mg twice daily increased to maximum 300 mg daily.

‘On demand’ treatment for AF - 200 mg or 300 mg if weight greater than 70 kg, at the onset of paroxysm.

Side-effects

These include dizziness, visual disturbances, dyspnoea, palpitations, pro-arrhythmic effects, headache, fatigue and nausea in 5-10% of patients. Rarely, bronchospasm, heart block, bone marrow suppression and increased ventricular rate in AF/flutter are seen.

Cautions/contraindications

These comprise significant coronary artery disease; left ventricular dysfunc-tion or other forms of significant structural heart disease; second degree or greater AV block and bundle branch block. Interactions with other drugs can occur including β-blockers and calcium channel blockers (check National Formulary for full list).

Lidocaine hydrochloride Mechanism of action

Class 1b (Vaughan Williams' classification) antiarrhythmic drug. This is a membrane-depressant drug that reduces the rate of entry of sodium into the cell (sodium-channel blocker). This may slow conduction, delay recovery or reduce the spontaneous discharge rate of myocardial cells. It shortens the duration of the action potential.

Indications

These include ventricular arrhythmias, especially after myocardial infarction.

Preparations and dose

Injection: 2%, 20 mg/mL; Infusion 0.1% (1 mg/mL), 0.2% (2 mg/mL).

Intravenous injection 100 mg as a bolus over a few minutes (50 mg in lighter patients or those whose circulation is severely impaired) followed immediately by infusion (with ECG monitoring) of 4 mg/min for 30 minutes, 2 mg/min for 2 hours, then 1 mg/min; reduce concentration further if infusion continued beyond 24 hours.

Side-effects

These primarily comprise dizziness, paraesthesias, drowsiness and confusion particularly if the injection is too rapid. Other side-effects are convulsions, hypotension, bradycardia and hypersensitivity.

Cautions/contraindications

It is contraindicated in sinoatrial disorders, all grades of AV block, severe myocardial depression, acute porphyria. There is increased myocardial depression with β-blockers and other anti-arrhythmics and also an increased risk of ventricular arrhythmias with anti-psychotics that prolong QT interval.

β-blockers

See page 495.

Digoxin

Mechanism of action

This drug blocks AV conduction and reduces heart rate by enhancing vagal nerve activity and inhibiting sympathetic activity. It is positively inotropic (enhancing strength of cardiac contraction) by inhibition of Na+/K+-ATPase and secondary activation of the Na+/Ca2+ membrane exchange pump thereby increasing intracellular calcium levels.

Indications

It is used in heart failure with atrial fibrillation or patients in sinus rhythm who remain symptomatic despite ACE inhibitor, p-blocker and diuretics.

It is also used for rate control in sedentary patients with atrial fibrillation/ flutter.

Preparations and dose

Tablets: 62.5, 125 and 250 ng. Injection: 250 ng/mL Check renal function and electrolytes before starting therapy; reduce dose in the elderly and in renal impairment.

Oral rapid digitalization for atrial fibrillation/flutter 0.75-1.5 mg in divided doses over 24 hours and then maintenance of 125-250 μg once daily according to heart rate and renal function. For heart failure (sinus rhythm) 62.5-125 μg once daily is given.

Intravenous infusion for emergency loading dose for atrial fibrillation or flutter 0.75-1 mg (diluted in glucose 5% or sodium chloride 0.9% to a concentration of not more than 62.5 μg/mL) over at least 2 hours and then maintenance dose the next day by mouth.

Side-effects

These include nausea, vomiting, diarrhoea, conduction disturbances blurred or yellow Vision and ventricular arrhythmias. Side-effects are common because of the narrow therapeutic index (the margin between effectiveness and toxicity). Hypokalamia and renal impairment (reduce dose) increase the risk of toxicity. In suspected toxicity, measure plasma potassium concen-tration first and correct if hypokalaemia is evident. Plasma digoxin con-centrations should be measured if toxicity is suspected; concentrations of > 2 mmol/L usually suggest toxicity. In severe toxicity give anti-digoxin antibodies.

Contraindications

Contraindications are arrhythmias associated with accessory conduction pathways, e.g. Wolff-Parkinson-White syndrome, because accessory pathway is not affected and intermittent complete heart block or second degree AV block. Caution should be demonstrated in left ventricular outflow tract obstruction. Diltiazem, verapamil, spirinolactone and amiodarone inhibit renal excretion of digoxin; avoid with amiodarone and measure plasma levels with other drugs (see National Formulaty for full interaction list). Tetracycline, erythromycin and possibly other macrolides enhance the effect of digoxin. Rifampicin reduces serum concentrations.

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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