A Textbook of Clinical Pharmacology and Therapeutics

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BASIC LIFE SUPPORT CARDIOPULMONARY RESUSCITATION AND CARDIAC ARREST: BASIC AND ADVANCED LIFE SUPPORT 219 Table 32.1: Anti-dysrhythmic drugs: the Vaughan–Williams/Singh classification Class Example Mode of action Comment I Rate-dependent block of Na� conductance a Quinidine Procainamide Disopyramide Intermediate kinetics between b and c Prolong cardiac action potential b Lidocaine Rapid dissociation from Na� Mexiletine channel Useful in ventricular tachydysrhythmias c Flecainide Slow dissociation from Na� channel Prolong His–Purkinje conduction: worsen Propafenone survival in some instances II Atenolol Beta blockers: slow pacemaker Improve survival following myocardial depolarization infarction III Amiodarone Prolong cardiac action potential Effective in supra-, as well as ventricular Sotalol tachydysrhythmias. Predispose to torsades de Dofetilide Ibutilide pointes (a form of ventricular tachycardia) IV Verapamil Calcium antagonists: block cardiac Used in prophylaxis of recurrent SVT. Largely Diltiazem voltage-dependent Ca2� conductance superseded by adenosine for treating acute attacks. Negatively inotropic Table 32.2: Drugs/ions not classified primarily as anti-dysrhythmic, but used to treat important dysrhythmias Digoxin (rapid atrial fibrillation) Atropine (symptomatic sinus bradycardia) Adenosine (supraventricular tachycardia) Adrenaline (cardiac arrest) Calcium chloride (ventricular tachycardia caused by hyperkalaemia) Magnesium chloride (ventricular fibrillation) When a person is found to have collapsed, make a quick check to ensure that no live power lines are in the immediate vicinity. Ask them, ‘Are you all right?’, and if there is no response, call for help. Do not move the patient if neck trauma is suspected. Otherwise roll them on their back (on a firm surface if possible) and loosen the clothing around the throat. Assess airway, breathing and circulation (ABC). Tilt the head and lift the chin, and sweep an index finger through the mouth to clear any obstruction (e.g. dentures). Tight-fitting dentures need not be removed and may help to maintain the mouth sealed during assisted ventilation. If the patient is not breathing spontaneously, start mouthto-mouth (or, if available, mouth-to-mask) ventilation. Inflate the lungs with two expirations (over about 2 seconds each) Unresponsive? Shout for help Open airway Not breathing normally? 2 rescue breaths Check pulse No pulse? Precordial thump if arrest witnessed 30 chest compressions 2 breaths 30 compressions Continue until breathing and pulse restored of emergency services arrive Figure 32.1: Adult basic life support.
220 CARDIAC DYSRHYTHMIAS Shockable (VF/pulseless VT) 1 Shock 150–360 J biphasic or 360 J monophasic Immediately resume: CPR 30:2 for 2 min Unresponsive? Open airway look for signs of life CPR 30:2 Until defibrillator/monitor attached Assess rhythm During CPR: • Correct reversible causes* • Check electrode position and contact • Attempt/verify: i.v. access airway and oxygen • Give uninterrupted compressions when airway secure • Give adrenaline every 3–5 mins • Consider: amiodarone, atropine, magnesium *Reversible causes Hypoxia Tension pneumothorax Hypovolaemia Cardiac tamponade Hypo/hyperkalaemia/other metabolic disturbance Toxins Hypothermia Thrombosis (coronary or pulmonary) and check that the chest falls between respirations. If available, 100% oxygen should be used. Check for a pulse by feeling carefully for the carotid or femoral artery before diagnosing cardiac arrest. If the arrest has been witnessed, administer a single thump to the precordium. If no pulse is palpable, start cardiac compression over the middle of the lower half of the sternum at a rate of 100 per minute and an excursion of 4–5 cm. Allow two breaths per 30 chest compressions. Drugs can cause fixed dilated pupils, so do not give up on this account if drug overdose is a possibility. Hypothermia is protective of tissue function, so do not abandon your efforts too readily if the patient is severely Call resuscitation team Non-shockable (pulseless electrical activity/asystole) Immediately resume: CPR 30:2 for 2 min hypothermic (e.g. after being pulled out of a freezing lake). Mobilize facilities for active warming. ADVANCED LIFE SUPPORT Figure 32.2: Adult advanced life support. (Redrawn with permission from the European Resuscitation Council Guidelines, 2005.) Basic cardiopulmonary resuscitation is continued throughout as described above, and it should not be interrupted for more than 10 seconds (except for palpation of a pulse or for administration of DC shock, when personnel apart from the operator must stand well back). ‘Advanced’ life support refers to the treatment of cardiac dysrhythmias in the setting of cardiopulmonary
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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
Page 180 and 181: Chapter 33). All NSAIDs cause wheez
Page 182 and 183: • Stomatitis suggests the possibi
Page 184 and 185: Pharmacokinetics Allopurinol is wel
Page 186 and 187: PART IV THE CARDIOVASCULAR SYSTEM
Page 188 and 189: ● Introduction 177 ● Pathophysi
Page 190 and 191: esponsible for the strong predilect
Page 192 and 193: Ezetimibe Fat Muscle Dietary fat In
Page 194 and 195: educed). The risk of muscle damage
Page 198 and 199: Each of these classes of drug reduc
Page 200 and 201: AT 1 receptor) produce good 24-hour
Page 202 and 203: Table 28.2: Examples of calcium-cha
Page 204 and 205: Key points Drugs used in essential
Page 206 and 207: Case history A 72-year-old woman se
Page 208 and 209: Assess risk factors Investigations:
Page 210 and 211: Persistent ST segment elevation Thr
Page 212 and 213: Mechanism of action GTN works by re
Page 214 and 215: Because of the risks of haemorrhage
Page 216 and 217: Intrinsic pathway XIIa XIa the acti
Page 218 and 219: that the pharmacodynamic response i
Page 220 and 221: used with apparent benefit in acute
Page 224 and 225: The drugs that are most effective i
Page 226 and 227: therapeutic plasma concentration ca
Page 228 and 229: ● Common dysrhythmias 217 ● Gen
Page 232 and 233: arrest. The electrocardiogram is li
Page 234 and 235: should be given to insertion of an
Page 236 and 237: Drug interactions Amiodarone potent
Page 238 and 239: effect when treating sinus bradycar
Page 240 and 241: Case history A 24-year-old medical
Page 242 and 243: PART V THE RESPIRATORY SYSTEM
Page 244 and 245: CHAPTER 33 THERAPY OF ASTHMA, CHRON
Page 246 and 247: STEP 5: CONTINUOUS OR FREQUENT USE
Page 248 and 249: Adenylyl cyclase Table 33.1: Compar
Page 250 and 251: Drug interactions Although synergis
Page 252 and 253: use in asthma has declined consider
Page 254 and 255: α 1-antitrypsin deficiency, neutro
Page 256 and 257: PART VI THE ALIMENTARY SYSTEM
Page 258 and 259: ● Peptic ulceration 247 ● Oesop
Page 260 and 261: PEPTIC ULCERATION 249 • With rega
Page 262 and 263: Ranitidine has a similar profile of
Page 264 and 265: Vestibular stimulation ? via cerebe
Page 266 and 267: cortical centres affecting vomiting
Page 268 and 269: • in hepatocellular failure to re
Page 270 and 271: Ciprofloxacin is occasionally used
Page 272 and 273: withdrawal), small doses of benzodi
Page 274 and 275: Table 34.7: Dose-independent hepato
Page 276 and 277: ● Introduction 265 ● General ph
Page 278 and 279: 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
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EPO Erythroid precursors Erythrocyt
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Therapeutic principles The extent o
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PART XI IMMUNOPHARMACOLOGY
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● Introduction 399 ● Immunity a
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Key points Antigen recognition Expr
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Table 50.1: Novel anti-proliferativ
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Key points Treatment of anaphylacti
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DRUGS THAT ENHANCE IMMUNE SYSTEM FU
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PART XII THE SKIN
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● Introduction 411 ● Acne 411
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DERMATITIS (ECZEMA) PRINCIPLES OF T
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SPECIALISTS ONLY SPECIALISTS ONLY E
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TREATMENT OF OTHER SKIN INFECTIONS
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effect of too high a dose of UVB in
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PART XIII THE EYE
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● Introduction: ocular anatomy, p
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to cause pupillary dilatation, name
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Table 52.3: Antibacterial agents us
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Table 52.6: Common drug-induced pro
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PART XIV CLINICAL TOXICOLOGY
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Table 53.2: Central nervous system
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which provide anonymized data to th
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Peak plasma levels after smoking ci
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Key points Acute effects of alcohol
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FURTHER READING Goldman D, Oroszi G
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Table 54.2: Common indications for
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Table 54.5: Antidotes and other spe
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Commission on Human Medicines (CHM)
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Note: Page numbers in italics refer
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atrial fibrillation 217, 221 digoxi
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Cushing’s syndrome 302 cyclic ade
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5-fluorouracil 375-6 fluoxetine, mo
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children 54 diazepam 108 iron prepa
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non-steroidal anti-inflammatory dru
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puberty (male), delay 314 puerperiu
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tolerance 9, 433 benzodiazepines 10
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