Hypnotics
Hypnotics should be reserved for short courses (because dependence and tolerance may occur with long-term use) to alleviate acute conditions after causal factors have been established. Benzodiazepines are the most com-monly used hypnotics.
Mechanism of action
Benzodiazepines bind to specific receptor sites that are closely linked to the GABAa receptor, inducing a conformational change that enhances the action of the inhibitory neurotransmitter GABA. Zopiclone is not a benzodiazepine but binds to the same receptor.
Indications
Transient or short-term insomnia due to extraneous factors such as shift work or an emotional problem or serious medical illness. Short-term use only - up to 4 weeks.
Preparations and dose
Temazepam
Tablets: 10 mg, 20 mg; oral solution: 10 mg/5 mL.
Oral 10-20 mg at bedtime.
Zopiclone
Tablets: 3.75 mg, 7.5 mg.
Oral 7.5 mg at bedtime; elderly, initially 3.75 mg.
Side-effects
Drowsiness and lightheadedness, confusion and ataxia, especially in the elderly (avoid if possible). Hangover effects of a night-time dose may impair driving the following day. Paradoxical increase in anxiety and aggression; adjustment of the dose up or down usually improves the problem. Tolerance may develop within 3-14 days.
Cautions/contraindications
Contraindicated in respiratory depression, acute breathlessness, severe liver disease, myasthenia gravis, sleep apnoea syndrome. Withdrawal symptoms (may be delayed for 3 weeks with long-acting preparation) if drug stopped abruptly after long-term use, consisting of anxiety, insomnia, depression, psychosis and convulsions.
Anxiolytics
Anxiolytics, as with hypnotics, should only be prescribed in short courses (danger of dependence and tolerance following long-term use) to alleviate acute conditions after establishing the causal factors. Benzodiazepines are again the most commonly used anxiolytics.
Mechanism of action
As above.
Indications
■ Short-term relief in severe anxiety
■ In panic disorders resistant to antidepressant treatment
■ Intravenously for short-term sedation with medical procedures, e.g. colonoscopy
■ Prevention of the alcohol withdrawal syndrome
■ Benzodiazepines also used in the acute management of status epilepticus.
Preparations and dose
Diazepam
Tablets: 2 mg, 5 mg, 10 mg; oral solution: 2 mg/5 mL, 5 mg/5 mL; emulsion injection: 10 mg/2 mL; rectal solution: 2.5 mg/1.25 mL, 5 mg/2.5 mL, 10 mg/2.5 mL.
Oral Anxiety: 2 mg three times daily, increasing if necessary to 15-30 mg daily in divided doses. Elderly: half adult dose. Insomnia associated with anxiety: 5-15 mg at bedtime.
IMμV for severe acute anxiety and control of panic attacks: 10 mg repeated if necessary after not less than 4 hours (into a large vein at a rate not more than 5 mg/min). In status epilepticus: 10-20 mg i.v. repeated if necessary after 30-60 minutes; may be followed by infusion to maximum 3 mg/kg over 24 hours.
By rectum 500 μg/kg up to maximum 30 mg (elderly, half dose) repeated after 12 hours if necessary.
Lorazepam
Tablets: 1 mg, 2.5 mg; injection 4 mg/mL.
Oral Anxiety: 1-4 mg daily in divided doses (elderly, half dose). Insomnia associated with anxiety: 1-2 mg at bedtime.
IMμV for severe acute anxiety and control of panic attacks: 25-30 μg/kg, repeated if necessary every 6 hours (into a large vein by slow injection). In status epilepticus: 4 mg, by intravenous injection into a large vein.
Chlordiazepoxide
Capsules: 5 mg, 10 mg; tablets: 5 mg, 10 mg.
Oral Anxiety: 10 mg three times daily in anxiety, increased if necessary to 60-100 mg daily. In alcohol withdrawal: 10-50 mg four times daily (under supervision) and reduced gradually over 7-14 days.
Oxazepam
Tablets: 10 mg, 15 mg, 30 mg.
Oral Anxiety: 15-30 mg three to four times daily (half dose in elderly). Insomnia associated with anxiety: 15-25 mg (max. 50 mg) at bedtime.
Short acting and used as an alternative to chlordiazepoxide in alcohol with-drawal for patients with severe liver dysfunction, 15-30 mg four times daily (under supervision) and reduced gradually over 7-14 days.
Antipsychotics (‘neuroleptics’)
Mechanism of action
Blockade of CNS dopamine (D2) receptors.
Indications
In the short term to quieten disturbed patients whatever the underlying psychopathology, e.g. schizophrenia, mania, toxic delirium. Used in the long-term management of schizophrenia. Also used in intractable hiccup and nausea and vomiting.
Preparations and dose
Chlorpromazine
Tablets: 10 mg, 25 mg, 50 mg, 100 mg; oral solution: 25 mg/5 mL, 100 mg/5 mL; suppositories: 100 mg.
Initially 25-50 mg three times daily or 75 mg at night; adjust according to response.
Haloperidol
Capsules: 500 μ; tablets: 500 μg, 1.5 mg, 5 mg, 10 mg, 20 mg; oral liquid: 5 mg/5 mL, 10 mg/5 mL; inịection: 5 mg/mL, 20 mg/mL
Oral Psychoses: initially 1.5-3 mg (3-5 mg in severe cases) two to three times daily, may be increased to maximum 30 mg daily in divided doses and then reduced to maintenance dose when control achieved. Hiccup and vomiting: 1-1.5 mg three times daily.
IMμV 2-10 mg repeated every 4-8 hours according to response to a maximum of 18 mg daily.
Side-effects
Acute drowsiness, hypotension, tachycardia, convulsions, antimuscarinic symptoms (dry mouth, constipation, difficulty with micturition, blurred Vision), neuroleptic malignant syndrome (hyperthermia, fluctuating conscious level, muscular rigidity, autonomic dysfunction). Extrapyramidal, haematological and endocrine side-effects with longer-term use (check a National Formularự).
Cautions/contraindications
Use with caution in liver disease, renal impairment, cardiovascular disease, Parkinson's disease, epilepsy, myasthenia gravis, glaucoma. Contraindicated in coma and phaeochromocytoma. Many drug interactions (check a National Formularự).
Antiepileptics
Drug of choice for seizure type in adults. The newer antiepileptic drugs are not described here and should be initiated by a specialist.
Carbamazepine
Mechanism of action
Inhibition of repetitive neuronal firing is produced by reduction of trans-membrane Na+ influx, by use-dependent blockade of Na+ channels.
Indications
Drug of choice for simple and complex partial seizures, and for tonic-clonic seizures secondary to a focal discharge.
Preparations and dose
Tablets: 100 mg, 200 mg, 400 mg; liquid: 100 mg/5 mL; suppositories: 100 mg; modified-release tablets: 200 mg, 400 mg.
Initially 100 mg once or twice daily increased slowly to usual dose of 0.8-1.2 g daily (epilepsy) or 200 mg three to four times daily (trigeminal neuralgia). Total daily doses are the same for modified release preparations but given twice daily (may provide better steady-state levels).
Side-effects
Nausea and vomiting, especially early in treatment. Central nervous system toxicity leads to double vision, dizziness, drowsiness and ataxia. Transient leucopenia is common, especially early in treatment - severe bone marrow depression is rare. Hyponatraemia caused by potentiation of antidiuretic hormone.
Cautions/contraindications
Contraindicated in AV conduction abnormalities (unless paced), history of bone marrow depression, porphyria. Hepatic enzyme induction leading to accelerated metabolism of the oral contraceptive pill (dose of oestrogen should be increased to avoid failure of contraception), warfarin (reduced anticoagulant effect), ciclosporin and others (check with a National Formu-larý). Interactions also with other antiepileptic drugs.
Valproate
Mechanism of action
Blockade of transmembrane Na+ channels, thus stabilizing neuronal membranes.
Indications
Effective for all forms of epilepsy.
Preparations and dose
Tablets: 100 mg, 200 mg; solution: 200 mg/5 mL; inịection powder for reconstitution: 400 mg.
600 mg daily in two divided doses, increasing by 200 mg/day at 3-day intervals to usual dose of 1-2 g daily in divided doses.
Side-effects
Gastrointestinal upset (nausea, vomiting, anorexia, abdominal pain, acute pancreatitis), increased appetite and weight gain, transient hair loss, dose-related tremor, thrombocytopenia, rarely severe hepatotoxicity. Drug concentration in plasma does not correlate with therapeutic effect and monitoring is only necessary to assess complications of suspected toxicity.
Cautions/contraindications
Acute liver disease, porphyria. Monitor liver biochemistry 6-monthly in those most at risk of severe liver damage (check with a National Formularỷ). Many drug interactions with antiepileptics and other drugs (check with a National Formularự).
Phenytoin
Mechanism of action
Inhibit sodium influx across the cell membrane, reduce cell excitability.
Indications
All forms of epilepsy except absence seizures, but used much less in devel-oped countries. Also used in management of status epilepticus and in trigemi-nal neuralgia.
Preparations and dose
Capsules: 25 mg, 50 mg, 100 mg, 300 mg; suspension: 30 mg/5 mL; injection: 50 mg/mL.
Oral 150-300 mg daily (single dose or two divided doses) increased gradu-ally as necessary (with plasma-phenytoin concentration monitoring); usual dose 200-500 mg. Reference range for concentration 4080 |imol/L (10-20 mg/L) immediately before the next dose.
IV Give with blood pressure and ECG monitoring. 18 mg/kg diluted to 10 mg/ mL in 0.9% sodium chloride at a rate not exceeding 50 mg/min (average-sized adult 1000 mg over 20 min) as a loading dose. Maintenance dose
100 mg i.v. at intervals of 6-8 hours monitored by measurement of plasma conentration.
Side-effects
Intravenous injection may cause CNS, cardiovascular (hypotension, heart block, arrhythmias) and respiratory depression. If hypotension occurs, reduce infusion rate or discontinue. Other side-effects are dose related and include impaired brainstem and cerebellar function (nystagmus, double vision, vertigo, ataxia, dysarthria), chronic connective tissue effects (gum hyper-plasia, coarsening of facial features, hirsutism), skin rashes (withdraw treat-ment), folate deficiency, increased vitamin D metabolism and deficiency, blood dyscrasias, lymphadenopathy and teratogenic effects.
Cautions/contraindications
Contraindicated in sinus bradycardia, heart block and porphyria. Many drug interactions (check with a national formulary). Highly protein bound and can be displaced by valproate and salicylates, which therefore enhance the effect. Induction of hepatic drug-metabolizing enzymes and metabolism of warfarin and ciclosporin increased (see a National Formulary for full list).
Fosphenytoin
Mechnism of action
As for phenytoin.
Indications
As for phenytoin.
Preparations and dose
Injection: 75 mg/mL.
Pro-drug of phenytoin which can be given more rapidly and causes fewer infusion site reactions. Dose expressed as phenytoin sodium equivalent (PE) (fosphenytoin 1.5 mg = phenytoin sodium 1 mg).
Status epilepticus: initially 15 mg PE/kg by i.v. infusion (with blood pres-sure, ECG and respiratory rate monitoring during and for at least 30 minutes after infusion) at a rate of 100-150 mg PE/min. Maintenance 4-5 mg PE/kg daily (in one to four divided doses) by i.v. infusion at a rate of 50-100 mg PE/min.
Side-effects
As for phenytoin.
Cautions/contraindications
As for phenytoin.
1. Ethics and communication
2. 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
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