Оглавление
Группа авторов. Clinical Pharmacology and Therapeutics
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Clinical Pharmacology and Therapeutics. Lecture Notes
Preface
Contributors
1 Pharmacodynamics and pharmacokinetics. Clinical scenario
Introduction
KEY POINTS – PHARMACODYNAMICS AND PHARMACOKINETICS
Principles of drug action (pharmacodynamics)
Mechanism of drug action. Action on a receptor
Action on an enzyme
Action on membrane ionic channels
Cytotoxic actions
Dose–response relationship
Principles of pharmacokinetics. Absorption
Distribution
Clinical relevance of volume of distribution
Plasma protein binding
Clearance
Single intravenous bolus dose
Linear versus non‐linear kinetics
Principles of drug elimination. Drug metabolism
Metabolic drug interactions
Clinical scenario
Induction
KEY POINTS ‐ ENZYME INDUCTION AND INHIBITION
Clinical scenario
Inhibition
Genetic factors in metabolism
Renal excretion
Clinical pharmacokinetics: dosage individualisation. Clinical scenario
KEY POINTS
Introduction
Therapeutic drug monitoring
Clearance estimates
Interpretation of serum concentrations
Clinical examples of therapeutic drug monitoring. Digoxin. Clinical scenario
Is this concentration expected?
What dose adjustment should be made?
Gentamicin. Clinical scenario
What dosage regimen should be prescribed?
Has steady state been reached?
How should the dose be adjusted?
Phenytoin. Clinical scenario
Why was the first concentration so low?
Why was the second concentration so high?
Influence of renal function on pharmacokinetics and pharmacodynamics
Clinical scenario
Influence of impaired renal function. KEY POINTS
Altered pharmacokinetics. Elimination
Decreased protein binding
Influence hepatic disease on pharmacokinetics and pharmacodynamics. Hepatic metabolism
Altered drug effect
Worsening of the existing clinical condition
Enhancement of adverse drug effects
Influence of liver disease
Altered pharmacokinetics
Decreased first‐pass metabolism
Decreased elimination by liver metabolism and decreased protein binding. High extraction drugs
Low extraction drugs
Altered drug effect deranged brain function
Decreased clotting factors
Worsening of metabolic state. Drug‐induced alkalosis
Fluid overload
Hepatotoxic drugs
Prescribing for the young and the elderly. Prescribing for the young. Clinical scenario
Introduction
Pharmacokinetics
Pharmacodynamics
Practical aspects of prescribing in children
Safety
Development and regulation of medicines for children
Prescribing for the elderly. Clinical scenario
Introduction
Drug absorption
Drug distribution
Drug metabolism and age
Renal excretion
Receptor sensitivity
Impairment of homeostasis
Polypharmacy
KEY POINTS: PRESCRIBING FOR THE ELDERLY
Drugs in pregnant and breastfeeding women. Drugs in pregnancy
Clinical scenario
KEY POINTS
Introduction
Effect of drugs on the foetus
Fertilisation and implantation period
Organogenesis
Growth and development
Drugs given at the end of pregnancy
Effect of pregnancy on drug absorption, distribution and elimination
Drug distribution
Drug elimination
Drug treatment of common medical problems during pregnancy. Infection
Nausea and vomiting
Diabetes
Asthma
Epilepsy
KEY POINTS IN THE MANAGEMENT OF PREGNANT WOMEN WITH EPILEPSY
Hypertension
Hyperthyroidism
Thrombosis
Depression
Connective tissue disease
Drug use in breastfeeding. Clinical scenario
KEY POINTS
2 Clinical trials and drug development. Clinical scenario
KEY POINTS
Introduction
Drug discovery
Models of drug development
Preclinical development
In vitro studies
In vivo animal studies of efficacy and toxicity
Clinical trials
Phase I clinical trials
Specific types of Phase I clinical studies. First in human studies
Dose ranging studies
Interaction studies
Safety studies
Phase II clinical trials
Phase III clinical trials
Factors to consider in Phase III trial design
Newer approaches to Phase III clinical trial design
Clinical scenario
Phase IIIb and IV studies
Pharmacovigilance
Yellow card scheme
3 Pharmacoeconomics: the economic evaluation of new drugs. Clinical scenario
Introduction – why do we need economic evaluations?
KEY POINTS
Economic evaluation
Perspective
Costs
Linking costs to benefits
Cost‐minimisation analysis
Cost‐effectiveness analysis
Cost–benefit analysis
Cost–utility analysis
Why use CUA and QALYs?
How are the constituent parts of QALYs estimated?
How is cost‐effectiveness then assessed?
Sensitivity analysis
Pharmacoeconomics and decision‐making
REFERENCES
4 Practical prescribing
Good prescribing: questions to ask yourself before prescribing a drug. Is drug treatment really necessary?
Which drug should I choose?
By what route should it be administered?
What dose and how often?
Writing the prescription: practical aspects
General pointers on good prescribing
Adverse drug reactions
Drug allergy
Drug interactions
Pharmacodynamic interactions
Pharmacokinetic interactions
Adherence
Clinical scenario
Emergency prescribing
5 Gastrointestinal system. Introduction
Gastro‐oesophageal reflux disease. Clinical scenario
Relevant pathophysiology
Drugs used in the treatment of gastro‐oesophageal reflux disease
Drugs used in the treatment of gastro‐oesophageal reflux disease. Antacids and antacid/alginate preparations
Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use and dosage
Drugs that inhibit gastric acid secretion. Proton pump inhibitors (PPIs): omeprazole, lansoprazole, pantoprazole and esomeprazole. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use and dosage
Histamine H2‐receptor antagonists
Drugs that act on oesophageal and/or gastric motility. Metoclopramide, domperidone
Prescribing points
Peptic ulcer. Clinical scenario
Relevant pathophysiology
Drugs used in the treatment of peptic ulcer
Drugs used in the treatment of peptic ulcer. Proton pump inhibitors (see Section ‘GORD’)
H2‐receptor antagonists
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use and dosage
Sucralfate (sucrose aluminium octasulphate) Mechanism
Clinical use and dosage
Pharmacokinetics
Adverse effects
Drug interactions
Drug combinations to eradicate H. pylori
Prescribing points
Nausea and vomiting. Relevant pathophysiology
Prescribing points
Drugs used in treatment of vomiting. Anticholinergic drugs: hyoscine. Mechanism
Adverse effects
Clinical use
Antihistamines: cyclizine and promethazine. Mechanism
Adverse effects
Clinical use
Dopamine antagonists – phenothiazines: chlorpromazine, prochlorperazine. Mechanism
Adverse effects
Clinical use and dose
Dopamine antagonist: metoclopramide. Mechanism
Adverse effects
Drug interactions
Clinical use and dose
Dopamine antagonist: domperidone. Mechanism
Adverse effects
Clinical use and dose
Serotonin antagonists: ondansetron. Mechanism
Adverse effects
Clinical use and dose
Cannabinoids: nabilone. Mechanism
Adverse effects
Clinical use and dose
Neurokinin‐1 receptor antagonists: aprepitant, fosaprepitant. Mechanism
Interactions
Adverse effects
Clinical use and dosage
Diarrhoea and constipation. Diarrhoea
Irritable bowel syndrome (IBS)
Pancreatic insufficiency
Drugs used in non‐specific diarrhoea. Codeine phosphate
Diphenoxylate
Loperamide
Constipation
Drugs that increase faecal bulk
Stimulant laxatives
Stool softeners
Osmotic laxatives
5‐HT4 agents
Prescribing points
Inflammatory bowel disease. Clinical scenario
Relevant pathophysiology
Drugs used in the treatment of inflammatory bowel disease – (box/flow chart for management of IBD) Corticosteroids
Aminosalicylates
Mechanism
Adverse effects
Clinical use
Thiopurines (azathioprine, 6‐mercaptopurine) Mechanism
Side effects
Clinical use
Other immunosuppressants
Anti‐tumour necrosis factor antibodies
New treatments (often second line)
Prescribing points
Drugs adversely affecting gastrointestinal function
KEY POINTS
6 Cardiovascular system: Management of coronary artery disease and its complications. Introduction
Angina pectoris and acute coronary syndromes. Aims of treatment
Relevant pathophysiology
Stable angina
Unstable angina
Clinical scenario
Drugs used in angina – glyceryl trinitrate (GTN) Mechanism
Pharmacokinetics
Adverse effects
Clinical use and dose
Isosorbide dinitrate and isosorbide mononitrate
Dose
ß‐receptor blockers
Clinical pharmacology
Pharmacologically predictable adverse effects of β‐receptor blockade. Bradycardia and impairment of myocardial contractility
Peripheral vasoconstriction
CNS effects
Bronchospasm
Tiredness and fatigue
Masking of hypoglycaemia
Additional pharmacological characteristics
Adverse effects
Clinical use
Dose
Calcium antagonists
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use
Dose
Clinical scenario
Potassium channel activators
Selective sinus node inhibitors – ivabradine
Pharmacokinetics
Dose
Adverse effects
Ranolazine
General principles of management of angina
Stable angina
Prescribing points
Clinical scenario
Unstable angina and non‐ST elevation myocardial infarction
Cardiac arrhythmia
Relevant pathophysiology. Normal electrophysiology
Mechanisms of arrhythmias
Classification of anti‐arrhythmic drugs
Class I action
Class II action
Class III action
Class IV action
Clinical scenario
Class I agents. General
Class Ia agents
Class Ib agents
Class Ic agents – flecainide. Mechanism
Pharmacokinetics
Adverse effects
Clinical use and dose
Class Ic agents – propafenone
Pharmacokinetics
Adverse effects
Clinical use and dose
Class II agents. β‐adrenoceptor antagonists
Clinical use
Class III agents. Amiodarone. Mechanism
Pharmacokinetics
Adverse effects
Clinical use and dose
Drug interactions
Clinical scenario
Dronedarone
Clinical scenario
Sotalol. Mechanism
Clinical use
Class IV agents. Verapamil. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use and dose
Diltiazem
Digitalis glycosides
Mechanism
Digoxin. Pharmacokinetics
Adverse effects
Drug interactions
Clinical use and doses
Treatment of digoxin‐induced toxicity
Adenine nucleotides. Adenosine. Mechanism
Pharmacokinetics
Adverse effects
Clinical use and dose
Drug interactions
Heart failure. Clinical scenario
Definition
Relevant pathophysiology
Neuroendocrine activation in heart failure
Diuretics
Loop diuretics – furosemide (frusemide), bumetanide, torasemide. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Dose
Neuroendocrine antagonists. ACE inhibitors
Mechanism
Adverse effects
Drug interactions
Dose
β‐adrenoceptor antagonists
Dose
Angiotensin II receptor blockers
Dose
Angiotensin receptor‐neprilysin inhibitors
Dose
Prescribing points
Mineralocorticoid receptor antagonists
Adverse effects
Dose
Hydralazine and isosorbide dinitrate
Ivabradine
Drugs with a positive inotropic effect. Digoxin
Clinical scenario
Adrenoceptor agonists: dopamine and dobutamine
Mechanism
Pharmacokinetics
Adverse effects
Dose
Levosimendan
Drugs affecting preload. Glyceryl trinitrate and isosorbide dinitrate
Drugs affecting preload and afterload. Sodium nitroprusside
Nesiritide
Prescribing points
General principles of management of heart failure. Acute left ventricular failure or pulmonary oedema
Long‐term management of chronic heart failure
KEY POINTS
Primary and secondary prevention of cardiovascular disease. Introduction
Clinical scenario
KEY POINTS
Hypertension
Relevant pathophysiology
Primary and secondary hypertension
Causes of secondary hypertension
Benefits of treatment
Hypertension management
Principles of antihypertensive treatment
Prescribing points
Antihypertensive drugs
Calcium antagonists. Mechanism
Clinical pharmacology
Pharmacologically predictable adverse effects
Prescribing points
ACE inhibitors. Mechanism
Clinical pharmacology
Pharmacologically predictable adverse effects
Other adverse effects
Prescribing points
Angiotensin (AT1) receptor antagonists
Diuretics. Mechanism
Clinical pharmacology
Pharmacologically predictable adverse effects. Hypokalaemia
Hyperuricaemia
Hyperglycaemia
Hypercalcaemia
Other adverse effects. Hyperlipidaemia
Impotence
Others
Prescribing points
β‐adrenoceptor antagonists (beta‐blockers)
Prescribing points
Mechanism. Prescribing points
α1‐antagonists
Centrally acting agents
Hypertensive emergencies
Cholesterol and lipids. Aim
Relevant pathophysiology
Primary and secondary lipid disorders
Familial hypercholesterolaemia
Polygenic lipid disorders
Secondary lipid disorders
Risks of hypercholesterolaemia
Lipid‐lowering treatment. Benefits of lipid‐lowering treatment
Principles of lipid‐lowering treatment
Dietary and lifestyle advice
Lipid‐lowering drugs
HMG CoA reductase inhibitors: mechanism
Prescribing points
Ezetimibe
PCSK9 inhibitors
Fibrates
Bile acid sequestrant resins
Other lipid‐lowering drugs
Antiplatelet drugs. Approach to the management of thrombosis
Aspirin. Pharmacology
Effects on haemostasis
Pharmacokinetics
Clinical use of aspirin
Prescribing points
Adverse effects of aspirin
Contraindications
P2Y12 receptor antagonists. Clopidogrel, ticagrelor and prasugrel
Ticagrelor
Prasugrel
Dipyridamole
Glycoprotein IIb/IIIa receptor antagonists
7 Respiratory system. Introduction
Diseases of airflow obstruction
Asthma
Aim of therapy
COPD
Aim of therapy
Management of asthma and COPD
Treatment of chronic airways disease. Clinical scenario
Inhaled therapies
Bronchodilators: β2‐adrenoceptor agonists. Mechanism of action
Pharmacokinetics
Adverse effects
Interactions
Clinical use
Prescribing points – stepwise escalation of drug treatment of stable/chronic asthma
Prescribing points – stepwise escalation of drug treatment of stable COPD
Bronchodilators: anticholinergics. Mechanism
Pharmacokinetics
Adverse effects
Interactions
Clinical use
Dose
Bronchodilators: Cys leukotriene receptor antagonists. Mechanism
Pharmacokinetics
Adverse effects
Interactions
Clinical use
Dose
Bronchodilators: theophyllines. Mechanism
Pharmacokinetics
Adverse effects
Interactions
Clinical use
Dose
Preventer Medications
Inhaled corticosteroids. Mechanism
Pharmacokinetics
Adverse effects
Interactions
Clinical use
Dose
Biological agents
Anti‐IgE therapy. Mechanism of action
Pharmacokinetics/dose
Interactions
Clinical use
Anti‐IL‐5 Therapy. Mechanism of action
Pharmacokinetics/dose
Interactions
Adverse effects
Clinical use
Mucolytics
Sodium cromoglicate
Prednisolone
Steroid‐sparing agents in severe asthma
Treatment of acute airways disease. Clinical scenario
Magnesium sulphate
Management of acute asthma
Management of acute exacerbations of COPD. Clinical scenario
Other therapy for airways diseases. Smoking cessation
Nicotine replacement therapy
Bupropion
Varenicline
Oxygen. Acute oxygen therapy
Chronic oxygen therapy
Short‐burst oxygen therapy
Long‐term oxygen therapy
Notes on other respiratory diseases. Bronchiectasis. Clinical scenario
Aims of management
Drugs
Interstitial lung disease. Clinical scenario
Aims of treatment
Disease targeted treatment
Pirfenidone
Adverse effects
Dose
Pulmonary hypertension. Clinical scenario
Supportive therapy
Specific drug therapy
8 Nervous system. Introduction
Epilepsy. Clinical scenario
Pathophysiology
Aetiology of seizures
Prescribing points
Anti‐epileptic drugs in common use
Carbamazepine. Mechanism
Pharmacokinetics
Adverse effects
Valproate. Mechanism
Pharmacokinetics
Adverse effects
Phenytoin. Mechanism
Pharmacokinetics
Adverse effects
Fosphenytoin
Lamotrigine. Mechanism
Pharmacokinetics
Adverse effects
Topiramate. Mechanism
Pharmacokinetics
Adverse effects
Levetiracetam. Mechanism
Pharmacokinetics
Adverse effects
Anti‐epileptic drug therapy in pregnancy
Headache
KEY POINTS
Clinical scenario
Migraine
KEY POINTS
Acute treatment of migraine attack
Migraine prophylaxis
Antimigraine drugs in common use. Sumatriptan – acute treatment. Mechanism
Pharmacokinetics
Adverse effects
Beta‐blockers
Amitriptyline
Candesartan
Topiramate
Pizotifen
Medication‐overuse headache
Prescribing points
Cerebrovascular disease. Pathophysiology
Aim and principles of treatment. Intracranial haemorrhage
Acute treatment of ischaemic stroke
Secondary prevention of stroke
Prescribing points
Infections of the nervous system
Drug‐induced neurological disorders
Neuroinflammatory disorders. Pathophysiology
Prescribing points
Methylprednisolone
Intravenous human immunoglobulin (IVIg)
Plasma exchange
Multiple sclerosis
Movement disorders. Clinical scenario
Pathophysiology
Parkinson's disease
Prescribing points
Drugs used for parkinsonism
Levodopa
COMT inhibitors
Dopamine agonists
Monoamine‐oxidase B inhibitors
Amantadine
Anticholinergics
KEY POINTS – PARKINSON'S DISEASE
Treatment of psychiatric disorders
Clinical scenario
Antipsychotic drugs
Adverse effects of antipsychotics
Relevant pathophysiology
First‐generation antipsychotics. Mechanism
Pharmacokinetics
Adverse reactions
Clinical use and dose
Second‐generation antipsychotics
Depot antipsychotics
Dose
Prescribing points
Clinical scenario
Antidepressants. Aims
Relevant pathophysiology
SSRIs
Mechanism
Pharmacokinetics
Adverse effects
Tricyclic antidepressants. Mechanism
Pharmacokinetics
Adverse effects. Adverse effects of tricyclic antidepressants
Clinical use and dose
Other related antidepressants
Monoamine oxidase inhibitors. Mechanism
Adverse effects
Other antidepressants. Venlafaxine
Mirtazapine
Agomelatine
Mood‐stabilising agents. Relevant pathophysiology
Lithium carbonate. Mechanism
Pharmacokinetics
Adverse effects (see above)
Drug interactions
Adverse effects of lithium carbonate
Dose
Other mood stabilisers. Carbamazepine
Sodium valproate
Antipsychotic drugs
Anxiolytics. Aim
Relevant pathophysiology
Benzodiazepines. Mechanism
Pharmacokinetics
Adverse effects
Adverse effects of benzodiazepines
Drug interactions
Clinical use and dose
Other drug treatment for anxiety. β‐receptor blockers
Dose
Serotonergic agents
Tricyclic antidepressants, SSRIs and MAOIs
Hypnotic drugs and the treatment of insomnia. Aim
Relevant pathophysiology
Benzodiazepines. Mechanism
Adverse effects
Clinical use and dose
Zopiclone, zolpidem and zaleplon
Melatonin
Drug‐induced psychiatric disorder
Abuse of psychoactive drugs
Benzodiazepines
Disulfiram
Acamprosate
Opiate dependence
Treatment of dementia. Aim
Relevant pathophysiology
Donepezil
Rivastigmine
KEY POINTS
9 Infection. Introduction
KEY POINTS: GENERAL PRINCIPLES OF ANTIMICROBIAL THERAPY
Clinical scenario
Principles of anti‐infective treatment
The patient
The organism
Bacteria
Resistance. Innate/intrinsic resistance
Acquired resistance
Viruses
Fungi and protozoa
The drug
Absorption
Route of elimination
Adverse effects
Drug interactions
Antimicrobial prophylaxis
Antibacterial drugs. Penicillins. Mechanism
Pharmacokinetics. Oral absorption
Distribution
Elimination
Adverse effects. Immediate hypersensitivity
Delayed hypersensitivity
Toxicity
Drug interactions
Antibacterial spectrum
Penicillinase‐sensitive penicillins
Examples of adult doses
Penicillinase‐resistant penicillins
Examples of adult doses
Co‐amoxiclav
Examples of adult doses
Piperacillin‐tazobactam
Dose
Carbapenems
Doses
Cephalosporins. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Antibacterial spectrum
Example of adult dose
Pivmecillinam
Aminoglycosides. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Antibacterial spectrum
Sulphonamide–trimethoprim combinations. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Antibacterial spectrum
Dose
Trimethoprim
Tetracyclines. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Antibacterial spectrum
Dose
Metronidazole
Dose
Macrolides
Drug interactions
Dose
Sodium fucidate
Dose
Clindamycin
Dose
Nitrofurantoin
Dose
Glycopeptides (vancomycin and teicoplanin)
Dose
Quinolones
Ciprofloxacin. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Antibacterial spectrum
Dose
Levofloxacin
Dose
Linezolid. Mechanism
Pharmacokinetics
Adverse events
Drug interactions
Antibacterial spectrum
Dose
Daptomycin. Mechanism
Pharmacokinetics
Adverse events
Drug interactions
Antibacterial spectrum
Dose
Tigecycline. Mechanism
Pharmacokinetics
Adverse events
Drug interactions
Antibacterial spectrum
Dose
Fidaxomicin
Fosfomycin
Antituberculous drugs
Isoniazid. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Dose
Rifampicin. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Dose
Ethambutol. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Dose
Pyrazinamide. Mechanism
Pharmacokinetics
Adverse effects
Dose
Second‐line anti‐tuberculous drugs
Antifungal drugs. Amphotericin B. Mechanism
Pharmacokinetics
Adverse effects
Drug interaction
Antifungal spectrum
Dose
Imidazoles and related compounds. Mechanism
Miconazole and clotrimazole. Pharmacokinetics
Antifungal spectrum
Fluconazole, itraconazole, ketoconazole, voriconazole. Pharmacokinetics
Antifungal spectrum
Adverse effects
Drug interactions
Dose
Nystatin
Echinocandins (caspofungin, micafungin and anidulofungin)
Antiviral drugs
HIV. Introduction
Clinical scenario
KEY POINTS
Overview of HIV replication and drug targets
Nucleoside/nucleotide reverse transcriptase inhibitors
Pharmacokinetics
Food and drug interactions
Adverse effects
Non‐nucleoside reverse transcriptase inhibitors (NNRTIs)
Pharmacokinetics
Food and drug interactions
Adverse effects
Protease inhibitors (PIs)
Pharmacokinetics
Food and drug interactions
Adverse effects
Fusion and entry inhibitors
Integrase strand transfer inhibitors (INSTIs)
Pharmacokinetics
Food and drug interactions
Adverse effects
Antiretroviral therapy (ART)
Drug resistance
Indications for ART therapy
Preferred first‐line regimens
Monitoring
Treatment adherence
Changing therapy
Using HIV medication to reduce HIV transmission
HIV‐2 infection
Prescribing points
Hepatitis B (HBV) Introduction
Clinical scenario
KEY POINTS
Overview of HBV replication and treatment
Interferon
Pharmacokinetics
Food and drug interactions
Adverse effects
Nucleoside/nucleotide analogues (NAs)
Drug resistance
Hepatitis C (HCV) Introduction
Clinical scenario
KEY POINTS
Overview of HCV structure and treatment
NS3‐4A protease inhibitors
NS5A inhibitors
NS5B polymerase inhibitors
Sofosbuvir
Fixed dose combinations
Goals of treatment
HCV treatment and genotype
Other antiviral drugs. Aciclovir, valaciclovir and famciclovir. Mechanism
Pharmacokinetics
Adverse effects
Drug interactions
Clinical use
Dose
Zanamivir and oseltamivir
10 Drugs and endocrine disease. Diabetes mellitus. Pathophysiology
Clinical scenario
Aims of treatment
Non‐pharmacological therapy
Drug treatments in diabetes mellitus
Insulin. Mechanism
Pharmacokinetics and insulin preparations
Dose and regimens
Adverse effects
Oral and other injectable hypoglycaemic agents. Biguanides (metformin) Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Sulphonylureas. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Thiazolidinediones (glitazones) Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Glucagon‐like peptide 1 receptor agonists. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Dipeptidyl peptidase‐4 (DPP‐4) inhibitors. Mechanism
Pharmacokinetics
Clinical use and dose
Sodium‐glucose co‐transporter 2 inhibitors. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Cardiovascular outcomes trials
Diabetic emergencies in adults. Clinical scenario
Ketoacidosis. Causes
Clinical features
Treatment
KEY POINTS
Hyperosmolar hyperglycaemic state. Cause
Features
Treatment
Hypoglycaemic coma. Causes
Clinical features
Treatment
Thyroid disease. Thyrotoxicosis (hyperthyroidism) Clinical scenario
Pathophysiology
Aims of treatment
Drug treatments inthyrotoxicosis. Thionamide (thiourylene) antithyroid drugs. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Radioactive iodine
Potassium iodide
β‐adrenoreceptor blockade
Thyroid crisis
Hypothyroidism. Clinical scenario
Pathophysiology
Treatment – thyroid replacement therapy
Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Obesity. Clinical scenario
Pathophysiology
Aims of treatment
Non‐pharmacological therapy
Drug treatments of obesity
Pancreatic lipase inhibitors (Orlistat) Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Liraglutide. Mechanism and pharmacokinetics
Clinical use and dose
Adverse effects
Bone metabolism. Clinical scenario
Introduction
Calcium salts
Calcium preparations
Vitamin D compounds
Mechanism
Pharmacokinetics
Clinical use and doses
Adverse effects
Bisphosphonates. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Other drugs for osteoporosis. Monoclonal antibodies – denosumab
Dosage
Adverse effects
Hormone‐replacement therapy. Mechanism
Pharmacokinetics
Clinical use
Adverse effects
Selective oestrogen‐receptor modulators. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Calcitonin. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Teriparatide. Mechanism
Pharmacokinetics
Clinical use and dose
Adverse effects
Strontium ranelate
Pituitary and adrenal cortex disease. Hypopituitarism
Cranial diabetes insipidus
Drug treatment of pituitary tumours. Dopamine agonists. Mechanism
Clinical use
Adverse effects
Somatostatin analogues. Mechanism
Clinical use
Adverse effects
Adrenal steroid replacement
11 Genitourinary system. Drugs for bladder outlet obstruction. Clinical scenario
Adrenergic α‐antagonists (alpha‐blockers) Mechanism
Adverse effects
Prescribing points
5‐α‐reductase inhibitors. Mechanism
Adverse effects
Prescribing points
Drugs for overactive bladder
Clinical scenario
Anticholinergic agents. Mechanism
Adverse effects
Prescribing points
Others
Drugs for prostate cancer. Clinical scenario
Hormone (androgen ablation) therapy
Anti‐androgens. Mechanism
Adverse effects
Gonadotrophin‐releasing hormone analogues and antagonists. Mechanism
Adverse effects
Prescribing points
Oestrogens
Other agents
Drugs for erectile dysfunction. Clinical scenario
Phosphodiesterase inhibitors. Mechanism
Adverse effects
Prescribing points
Testosterone
Adverse effects
Prescribing points
Other agents
Drugs and the reproductive system. Hormonal contraception. Clinical scenario
Introduction
Hormonal contraception
Composition
Mechanism
Pharmacokinetics
Adverse effects
Venous thromboembolic disease
Arterial disease (myocardial infarction and ischaemic stroke)
Focal migraine
Hypertension
Oral contraceptives and cancer
Bone mineral density
Irregular bleeding patterns and return to fertility
Other adverse effects
Hormonal contraception and breastfeeding
Drug interactions
Clinical use of hormonal contraception
KEY POINTS
Contraindications
Drugs used in the treatment of menopausal symptoms. Clinical scenario
Introduction
Composition
HRT and cancer risk
HRT, cardiovascular disease and venous thrombotic disease
HRT and bone health
Non‐hormonal alternatives to treat hot flushes
Progestogens – non‐contraceptive uses
KEY POINTS
Drugs used to modify the pregnant uterus and cervix. Prostaglandins. Mechanism
Pharmacokinetics
Adverse effects
Oxytocin. Mechanism
Pharmacokinetics
Adverse effects
Tocolytics
Ovulation‐induction agents. Anti‐oestrogens. Mechanism
Clinical use and dose. Female subfertility
Breast cancer
Metformin
Ovarian suppression. Danazol. Mechanism
Adverse effects
Drug interactions
Clinical use
Gonadotrophin‐releasing hormone analogues. Mechanism
Adverse effects
Anti‐androgens
12 Malignant disease. Clinical scenario
KEY POINTS
Introduction
Chemotherapy
Patient selection
Principles of drug treatment
Chemotherapeutic agents
Pharmacokinetics
Adverse effects
General adverse reactions
Specific adverse reactions
Drug interactions
Methotrexate and salicylates
6‐Mercaptopurine and allopurinol
Procarbazine and alcohol
Targeted therapy: signal transduction inhibitors
Targeted therapy: hormone therapies
Targeted therapy: antiangiogenic agents
Targeted therapy: immunotherapy
Clinical scenario
Dabrafenib/trametinib – BRAF/MEK inhibitors. Mechanism
Adverse effects
Pembrolizumab – immunotherapy. Mechanism
Adverse effects
Clinical scenario
Carboplatin and paclitaxel chemotherapy. Mechanism
Adverse effects
Olaparib. Mechanism
Adverse effects
Prescribing points
13 Drugs and the blood. Clinical scenario
KEY POINTS
Introduction
Primary haemostasis
Activation of the coagulation cascade
Fibrinolysis
Pathophysiology
Anticoagulant drugs. Parenteral anticoagulants
Heparins. Chemistry and pharmacology
Clinical use of unfractionated heparin
Clinical use of low molecular weight heparin
Monitoring of heparin
Adverse effects
Reversal of anticoagulation with heparin
Contraindications to heparin
Heparinoids and hirudins
Fondaparinux
Oral anticoagulants. Vitamin K antagonists
Pharmacology
Monitoring of warfarin therapy
Pregnancy
How to initiate anticoagulation with warfarin
Drug interactions
Adverse effects
Treatment of haemorrhage and reversal of warfarin anticoagulation
Contraindications to warfarin anticoagulation
Direct oral anticoagulants
Oral direct thrombin inhibitor – dabigatran
Treatment of haemorrhage and reversal of dabigatran anticoagulation
Oral direct Xa inhibitors – apixaban, rivaroxaban and edoxaban
Treatment of haemorrhage and reversal of oral Xa inhibitors
Thrombolytic agents. Clinical use of thrombolytic agents
General aspects of thrombolysis
Streptokinase
Alteplase (tPA)
Other thrombolytic agents
Anaemia and haematinics. Aims
Relevant pathophysiology
Iron deficiency anaemia
Adverse effects
Dose
Parenteral iron
Megaloblastic anaemia
Adverse effects
Dose
Folic acid
Dose
Haemopoetic growth factors
Recombinant erythropoietin (epoetin, darbepoetin alfa)
Recombinant human granulocyte‐colony stimulating factor (filgrastim, lenograstim, pegfilgrastim)
Recombinant thrombopoietin receptor agonists (romiplostim and eltrombopag)
Drug‐induced blood conditions. Drug‐induced blood loss
Drug‐induced megaloblastic anaemia
Drug‐induced sideroblastic anaemia
Drug‐induced marrow depression: aplastic anaemia
Drug‐induced haemolytic anaemia
Direct toxins
Interaction with hereditary defects in red cells
Immune mechanisms
Immune haemolytic anaemia
Autoimmune haemolytic anaemia
Neutropenia
Drug‐induced thrombocytopenia
14 Musculoskeletal system. Clinical scenario
KEY POINTS
Principles of management
Principles of drug treatment
Simple analgesia
Non‐steroidal anti‐inflammatory drugs (NSAIDs)
Important adverse effects
Examples of non‐selective NSAIDs
Examples of COX‐2 inhibitors
Drug interactions
Prescribing points
Management of RA
Management of spondyloarthropathies (SpA)
Management of PsA and other pSpA
Management of AS and other axSpA
Prescribing points
Management of OA
Drugs used in gout and pseudogout. Clinical scenario
Introduction
KEY POINTS
Management of the acute attack
Long‐term management
Xanthine oxidase inhibition. Allopurinol
Febuxostat
Uricosuric drugs
15 Immunopharmacology. Clinical scenario
KEY POINTS
Introduction
Innate or natural immunity
Acquired or adaptive immunity
Drugs that suppress immune responses
Corticosteroids
Clinical scenario
KEY POINTS
Glucocorticoids. Cortisol and its derivatives
Pharmacological effects
Adverse effects
Adrenal suppression
Topical therapy
Clinical use and doses of commonly used corticosteroids. Hydrocortisone
Prednisolone
Beclometasone
Dexamethasone
Triamcinolone
Mineralocorticoids. Pharmacological effects
Clinical use and dose
Small chemical agents that modify immune response
Azathioprine
Ciclosporin
Cyclophosphamide
Dimethyl fumarate
Hydroxychloroquine
Leflunomide
Methotrexate
Mycophenolate mofetil
Sulfasalazine
Tacrolimus
Targeted small molecule inhibitors. Phosphodiesterase type 4 (PDE4) inhibitors
Tyrosine kinase inhibitors
Biological therapies
Targeting cells, cell receptors and co‐stimulatory molecules. B‐cells
Targeting both T‐cells and B‐cells
T‐cells
Targeting cytokines
IL‐1
IL‐6
IL12/23
IL‐17
TNF
Immunomodulatory and immunostimulatory agents
Cytokines
Other immunostimulatory agents
Cancer immunotherapy (see Chapter 12)
Other drugs that act by their effect on the immune system. Antihistamines
Drugs that block mediator release
β2‐adrenoceptor agonists
Theophylline derivatives
Cromoglicate and related therapies
Leukotriene receptor antagonists
16 Travel medicine. Introduction
KEY POINTS: ASSESSING THE NEED FOR PROPHYLAXIS
Principles of immunisation. Passive immunisation
Active immunisation
Live vaccines
Vaccine contraindications
Vaccines used for preventing infection in travellers
Malaria prevention and treatment
Life cycle
Disease risk areas
Chemoprophylaxis against malaria
Drug resistance
Treatment of malaria
Treatment of other common imported parasitic infections
17 Analgesia and anaesthesia. Introduction
Clinical scenario
Pathophysiology of pain
Management of pain
KEY POINTS
Paracetamol
Non‐steroidal anti‐inflammatory drugs (NSAIDS)
Opioids
Strong opioid agonists. Morphine
Absorption
Distribution
Metabolism
Elimination
Diamorphine
Methadone
Oxycodone
Pethidine
Fentanyl
Alfentanil
Remifentanil
Weak Opioid Agonists. Codeine
Tramadol
Opioid antagonists
Partial agonists
Adjunctive agents
Anaesthesia. Clinical scenario
IV anaesthetic agents
Non‐barbiturate agents. Propofol
Etomidate
Ketamine
Barbiturates. Thiopental
Inhalational anaesthetics
Local anaesthetics
Lidocaine
Bupivacaine
Levobupivacaine
Prilocaine
Mepivacaine
Ropivacaine
Procaine
Cocaine
Benzocaine
Mixes of local anaesthetics
Neuromuscular blocking drugs (NMBDs)
Critical care considerations. Introduction
Specific considerations in ICU. Pain, agitation and delirium (PAD)
Shock
Extracorporeal support
Venous thromboembolism (VTE)
Stress ulcer
Glucose control
18 Poisoning and drug overdose. Clinical scenario
KEY POINTS
Introduction
General approach to the poisoned patient
Assessment and diagnosis
Toxicological analyses
Immediate management
Interpretation of investigations in poisoning of unknown cause
The management of specific complications
Specific treatments
Toxicokinetics
Enhanced drug elimination
Haemodialysis
Haemoperfusion
Physiological support systems
Features of common drug overdose
Antidepressant drugs. Tricyclic antidepressants
Selective serotonin reuptake inhibitors
Other antidepressants
Monoamine oxidase inhibitors
Sedatives and benzodiazepine‐related compounds
Opioids
Management
Non‐steroidal anti‐inflammatory agents
Salicylates
Paracetamol
Management
Treatment
Assessing severity of hepatic damage
Drugs of abuse
Other substances. Digoxin
Lithium
Iron
Lead
Antiepileptic agents
Mushrooms
Summary
Index
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