A Textbook of Clinical Pharmacology and Therapeutics

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FURTHER READING Goldman D, Oroszi G, Ducci F. The genetics of addictions: Uncovering the genes. Nature Reviews. Genetics 2005; 7: 521–32. Green AR, Mechan AO, Elliott JM et al. The pharmacology and clinical pharmacology of 3, 4-methylenedioxymethamphetamine. Pharmacological Reviews 2003; 55: 463–508. MISCELLANEOUS 443 Hall AP, Henry JA. Acute toxic effects of ecstasy (MDMA) and related compounds. British Journal of Anaesthesia 2006; 6: 675–85. Mottram DR (ed.). Drugs in sport, 4th edn. London: Routledge, 2005. Winger G, Woods JH, Hofmann FG. A handbook of drug and alcohol abuse, 4th edn. Oxford: Oxford University Press, 2004.
● Intentional self-poisoning 444 ● Accidental poisoning 449 INTENTIONAL SELF-POISONING CHAPTER 54 DRUG OVERDOSE AND POISONING Self-poisoning creates 10% of the workload of Accident and Emergency departments in the UK. Opioids (diamorphine (heroin), morphine and methadone), compound analgesics (e.g. codeine plus paracetamol), paracetamol alone and antidepressants are the most common drugs used in fatal overdose. Temazepam, cocaine, MDMA/ecstasy, lithium, paraquat, salicylates, digoxin and aminophylline continue to cause fatalities. This list of agents that cause death from overdose does not reflect the drugs on which individuals most commonly overdose. Self-poisoning often involves multiple drugs and alcohol. Benzodiazepines (often taken with alcohol) are commonly taken in an overdose, but are seldom fatal if taken in isolation. Around 75% of deaths from overdose occur outside hospital, with the mortality of those treated in hospital being less than 1%. The majority of cases of self-poisoning fall into the psychological classification of suicidal gestures (or a cry for help). However, the prescription of potent drugs with a low therapeutic ratio can cause death from an apparently trivial overdose. DIAGNOSIS HISTORY Self-poisoning may present as an unconscious patient being delivered to the Accident and Emergency Department with or without a full history available from the patient or their companions. Following an immediate assessment of vital functions, as full a history as possible should be obtained from the patient, relatives, companions and ambulance drivers, as appropriate. A knowledge of the drugs or chemicals that were available to the patient is invaluable. Some patients in this situation give an unreliable history. A psychiatric history, particularly of depressive illness, previous suicide attempts or drug dependency, is relevant. EXAMINATION A meticulous, rapid but thorough clinical examination is essential not only to rule out other causes of coma or abnormal behaviour (e.g. head injury, epilepsy, diabetes, hepatic ● Criminal poisoning 449 encephalopathy), but also because the symptoms and signs may be characteristic of certain poisons. The clinical manifestations of some common poisons are summarized in Table 54.1. The effects may be delayed. LABORATORY TESTS Routine investigation of the comatose overdose patient should include blood glucose (rapidly determined by stick testing) and biochemical determination of plasma electrolytes, Table 54.1: Clinical manifestations of some common poisons Symptoms/signs of Common poisons acute overdose Coma, hypotension, flaccidity Benzodiazepines and other hypnosedatives, alcohol Coma, pinpoint pupils, Opioids hypoventilation Coma, dilated pupils, Tricyclic antidepressants, hyper-reflexia, tachycardia phenothiazines; other drugs with anticholinergic properties Restlessness, hypertonia, Amphetamines, MDMA, hyper-reflexia, pyrexia anticholinergic agents Convulsions Tricyclic antidepressants, phenothiazines, carbon monoxide, monoamine oxidase inhibitors, mefenamic acid, theophylline, hypoglycaemic agents, lithium, cyanide Tinnitus, overbreathing, Salicylates pyrexia, sweating, flushing, usually alert Burns in mouth, dysphagia, Corrosives, caustics, paraquat abdominal pain MDMA, methylenedioxymethylamphetamine.
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A Textbook of Clinical Pharmacology
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A Textbook of Clinical Pharmacology
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This fifth edition is dedicated to
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FOREWORD viii PREFACE ix ACKNOWLEDG
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PREFACE Clinical pharmacology is th
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PART I GENERAL PRINCIPLES
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● Use of drugs 3 ● Adverse effe
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and acquired factors, notably disea
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100 Effect (%) 0 0 5 10 1 10 100 (a
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Dose ratio -1 100 50 The relationsh
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● Introduction 11 ● Constant-ra
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In reality, processes of eliminatio
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lood (from which samples are taken
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● Introduction 17 ● Bioavailabi
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ROUTES OF ADMINISTRATION ORAL ROUTE
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Transdermal absorption is sufficien
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FURTHER READING Fix JA. Strategies
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and thromboxanes are CYP450 enzymes
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and lorazepam. Some patients inheri
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Orally administered drug Parenteral
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● Introduction 31 ● Glomerular
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ACTIVE TUBULAR REABSORPTION This is
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DISTRIBUTION Drug distribution is a
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Detailed recommendations on dosage
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DIGOXIN Myxoedematous patients are
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● Introduction 41 ● Role of dru
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25 20 10 Life-threatening toxicity
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● Introduction 45 ● Harmful eff
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vagina in girls in their late teens
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an anti-analgesic effect when combi
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Case history A 20-year-old female m
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METABOLISM At birth, the hepatic mi
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lifelong effects as a result of tox
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DISTRIBUTION Ageing is associated w
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DIGOXIN Digoxin toxicity is common
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FURTHER READING Dhesi JK, Allain TJ
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Factors involved in the aetiology o
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analgesic. Following its release, t
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antibiotics, such as penicillin or
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predisposes to non-immune haemolysi
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● Introduction 71 ● Useful inte
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Response Therapeutic range Toxic ra
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Table 13.1: Interactions outside th
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Table 13.5: Competitive interaction
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● Introduction: ‘personalized m
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Table 14.2: Variations in drug resp
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lipoprotein (LDL) is impaired. LDL
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Key points • Genetic differences
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• Discovery • • Screening Pre
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Too many statistical comparisons pe
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ETHICS COMMITTEES Protocols for all
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Table 16.1: Recombinant proteins/en
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duration and benefit. Adenoviral ve
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● Introduction 97 ● Garlic 97
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A case report has suggested a possi
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including hypericin and pseudohyper
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PART II THE NERVOUS SYSTEM
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● Introduction 105 ● Sleep diff
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and daytime sleeping should be disc
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Key points • Insomnia and anxiety
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Box 19.1: Dopamine theory of schizo
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The Boston Collaborative Survey ind
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Oral medication, especially in liqu
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e.g. interpersonal difficulties or
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Partial response to first-line trea
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Key points Drug treatment of depres
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Case history A 45-year-old man with
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Levodopa PRINCIPLES OF TREATMENT IN
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• pulmonary, retroperitoneal and
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CHOREA The γ-aminobutyric acid con
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Cholinergic crisis Treatment of mya
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● Introduction 133 ● Mechanisms
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absolute arbiter. The availability
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Table 22.2: Metabolic interactions
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FURTHER ANTI-EPILEPTICS Other drugs
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Case history A 24-year-old woman wh
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Assessment of migraine severity and
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● General anaesthetics 145 ● In
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is the theoretical concern of a ‘
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• Respiratory system - apnoea fol
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Competitive antagonists (vecuronium
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have also proved useful in combinat
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● Introduction 155 ● Pathophysi
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ASPIRIN (ACETYLSALICYLATE) Use Anti
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Key points Drugs for mild pain •
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increases, correlating with the hig
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• If possible, use oral medicatio
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PART III THE MUSCULOSKELETAL SYSTEM
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● Introduction: inflammation 167
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Chapter 33). All NSAIDs cause wheez
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• Stomatitis suggests the possibi
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Pharmacokinetics Allopurinol is wel
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PART IV THE CARDIOVASCULAR SYSTEM
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esponsible for the strong predilect
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Ezetimibe Fat Muscle Dietary fat In
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educed). The risk of muscle damage
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Each of these classes of drug reduc
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AT 1 receptor) produce good 24-hour
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Table 28.2: Examples of calcium-cha
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Key points Drugs used in essential
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Case history A 72-year-old woman se
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Assess risk factors Investigations:
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Persistent ST segment elevation Thr
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Mechanism of action GTN works by re
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Because of the risks of haemorrhage
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Intrinsic pathway XIIa XIa the acti
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that the pharmacodynamic response i
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used with apparent benefit in acute
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The drugs that are most effective i
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therapeutic plasma concentration ca
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● Common dysrhythmias 217 ● Gen
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BASIC LIFE SUPPORT CARDIOPULMONARY
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arrest. The electrocardiogram is li
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should be given to insertion of an
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Drug interactions Amiodarone potent
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effect when treating sinus bradycar
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Case history A 24-year-old medical
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PART V THE RESPIRATORY SYSTEM
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CHAPTER 33 THERAPY OF ASTHMA, CHRON
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STEP 5: CONTINUOUS OR FREQUENT USE
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Adenylyl cyclase Table 33.1: Compar
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Drug interactions Although synergis
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use in asthma has declined consider
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α 1-antitrypsin deficiency, neutro
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PART VI THE ALIMENTARY SYSTEM
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● Peptic ulceration 247 ● Oesop
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PEPTIC ULCERATION 249 • With rega
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Ranitidine has a similar profile of
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Vestibular stimulation ? via cerebe
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cortical centres affecting vomiting
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• in hepatocellular failure to re
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Ciprofloxacin is occasionally used
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withdrawal), small doses of benzodi
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Table 34.7: Dose-independent hepato
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● Introduction 265 ● General ph
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dinucleotide (NAD) and nicotinamide
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Table 35.1: Common trace element de
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PART VII FLUIDS AND ELECTROLYTES
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● Introduction 273 ● Volume ove
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Key points Diuretics Diuretics are
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is sometimes caused by drugs, notab
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or with potassium-sparing diuretics
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Greger R, Lang F, Sebekova, Heidlan
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PART VIII THE ENDOCRINE SYSTEM
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in prefilled injection devices (‘
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Metformin should be withdrawn and i
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FURTHER READING American Diabetes A
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deficiency. Potassium iodide (3 mg
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fertility. It is contraindicated du
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● Introduction 297 ● Vitamin D
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effective in life-threatening hyper
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Further reading Block GA, Martin KJ
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Table 40.1: Actions of cortisol and
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injection may be useful, but if don
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CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
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elease by the pituitary via negativ
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Treatment with depot progestogen in
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infusion using an infusion pump to
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significant proportion of men who r
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with symptoms caused by the release
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FURTHER READING Birnbaumer M. Vasop
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PART IX SELECTIVE TOXICITY
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● Principles of antibacterial che
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2. transfer of resistance between o
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Pharmacokinetics Absorption of thes
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Mechanism of action Macrolides bind
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asic quinolone structure dramatical
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Case history A 70-year-old man with
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PRINCIPLES OF MANAGEMENT OF MYCOBAC
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Pharmacokinetics Absorption from th
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MYCOBACTERIUM LEPRAE INFECTION Lepr
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POLYENES AMPHOTERICIN B Uses Amphot
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therapy is adequate though more fre
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NUCLEOSIDE ANALOGUES ACICLOVIR Uses
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Table 45.3: Summary of available ac
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Uses Interferon-α when combined wi
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● Introduction 351 ● Immunopath
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Table 46.1: Examples of combination
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NON-NUCLEOSIDE ANALOGUE REVERSE TRA
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FUSION INHIBITORS Uses Currently, e
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salvage therapy include azithromyci
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● Malaria 361 ● Trypanosomal in
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Pharmacokinetics Chloroquine is rap
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Table 47.2: Drug therapy of non-mal
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Table 48.1: Classification of commo
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Polymorph count/mm 3 (a) (b) 10 000
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doses are used to prepare patients
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Adverse effects Methotrexate Inhibi
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Table 48.7: Summary of clinical pha
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Table 48.9: Summary of the clinical
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Plasma membrane Signal transduction
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Table 48.10: Monoclonal antibodies
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INTERFERON-ALFA 2B Interferon-alfa
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PART X HAEMATOLOGY
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● Haematinics - iron, vitamin B 1
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one marrow to produce red cells. Th
Page 404 and 405: EPO Erythroid precursors Erythrocyt
Page 406 and 407: Therapeutic principles The extent o
Page 408 and 409: PART XI IMMUNOPHARMACOLOGY
Page 410 and 411: ● Introduction 399 ● Immunity a
Page 412 and 413: Key points Antigen recognition Expr
Page 414 and 415: Table 50.1: Novel anti-proliferativ
Page 416 and 417: Key points Treatment of anaphylacti
Page 418 and 419: DRUGS THAT ENHANCE IMMUNE SYSTEM FU
Page 420 and 421: PART XII THE SKIN
Page 422 and 423: ● Introduction 411 ● Acne 411
Page 424 and 425: DERMATITIS (ECZEMA) PRINCIPLES OF T
Page 426 and 427: SPECIALISTS ONLY SPECIALISTS ONLY E
Page 428 and 429: TREATMENT OF OTHER SKIN INFECTIONS
Page 430 and 431: effect of too high a dose of UVB in
Page 432 and 433: PART XIII THE EYE
Page 434 and 435: ● Introduction: ocular anatomy, p
Page 436 and 437: to cause pupillary dilatation, name
Page 438 and 439: Table 52.3: Antibacterial agents us
Page 440 and 441: Table 52.6: Common drug-induced pro
Page 442 and 443: PART XIV CLINICAL TOXICOLOGY
Page 444 and 445: ● Introduction 433 ● Pathophysi
Page 446 and 447: Table 53.2: Central nervous system
Page 448 and 449: which provide anonymized data to th
Page 450 and 451: Peak plasma levels after smoking ci
Page 452 and 453: Key points Acute effects of alcohol
Page 456 and 457: Table 54.2: Common indications for
Page 458 and 459: Table 54.5: Antidotes and other spe
Page 460 and 461: Commission on Human Medicines (CHM)
Page 462 and 463: Note: Page numbers in italics refer
Page 464 and 465: atrial fibrillation 217, 221 digoxi
Page 466 and 467: Cushing’s syndrome 302 cyclic ade
Page 468 and 469: 5-fluorouracil 375-6 fluoxetine, mo
Page 470 and 471: children 54 diazepam 108 iron prepa
Page 472 and 473: non-steroidal anti-inflammatory dru
Page 474 and 475: puberty (male), delay 314 puerperiu
Page 476: tolerance 9, 433 benzodiazepines 10
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A Textbook of Clinical Pharmacology and Therapeutics

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