A Textbook of Clinical Pharmacology and Therapeutics

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Table 47.2: Drug therapy of non-malarial protozoan infections Protozoan species Drug therapy Additional comments HELMINTHIC INFECTION 365 Trichomonas vaginalis Metronidazole or tinidazole The most common protozoan infection. Treat the patient and their sexual partner T. cruzi (American) Benznidazole or nifurtimox Effective in the early acute stages T. gambiense and Pentamidine and suramin are Later neurological disease – melarsoprol or T. rhodesiense (African) effective in the early stages eflornithine or nifurtimox Toxoplasma gondii Pyrimethamine/sulfadiazine Add folinic acid to reduce risk of bone marrow suppression Pneumocystis carinii Sulfamethoxazole/trimethoprim – high dose Alternatives: pentamidine, atovaquone, see Chapter 46 Leishmania (visceral) Sodium stibogluconate or meglumine Resistant cases – add allopurinol plus pentamidine antimoniate with or without amphotericin B Leishmania (cutaneous) Intralesional – antimonials Lesions usually heal spontaneously Giardia lamblia Metronidazole or tinidazole Treat family and institutional contacts Table 47.3: Drug therapy for common helminthic infections Helminthic species Drug therapy Comment Tapeworms Taenia saginata Praziquantel or niclosamide or gastrograffin A single dose of praziquantel is curative Cysticercosis Taenia solium Praziquantel or gastrograffin Diphyllobothrium latum Praziquantel or niclosamide or gastrograffin Hydatid disease Echinococcus granulosus Albendazole or mebendazole Surgery for operably treatable cysts Hookworm Ancylostoma duodenale Mebendazole/albendazole, bephenium or pyrantel pamoate Necator americanus Strongyloides stercoralis Albendazole Threadworm Enterobius vermicularis Mebendazole/albendazole, bephenium or pyrantel pamoate Whipworm Trichuris trichiuria Tissue nematodes Thiabendazole Ancylostoma braziliensae Guinea worm Thiabendazole Dracunculus medinensis Visceral larvae/roundworms Metronidazole Symptoms quickly relieved Toxocara canis Diethylcarbamazine Progressively increasing dose, allergic Toxocara catis reactions to dying larvae, glucocorticosteroids required for ocular disease (continued)
366 MALARIA AND OTHER PARASITIC INFECTIONS Table 47.3: Continued Helminthic species Lymphatic filariasis Drug therapy Comment Wuchteria bancrofti Onchocerciasis Diethylcarbamazine Onchocerca volvulus Schistosomiasis/blood flukes Ivermectin Single dose is curative Schistosoma mansoni Schistosoma japonicum Praziquantel Oxamiquine (S. mansoni) Schistosoma hematobium Liver flukes/fascioliasis Metriphonate (S. hematobium) Fasciola hepatica, etc. Other gut nematodes Ascariasis Praziquantel Ascaris lumbricoides Trichinosis Pyrantel pamoate or levamisole Trichinella spiralis Mebendazole, albendazole or pyrantel pamoate Case history A 27-year-old male student goes on elective medical internship at a rural hospital in West Africa. He is taking malaria prophylaxis with chloroquine 250 mg weekly, and proguanil 200 mg daily. Two weeks after arriving at his destination he complains of lethargy, breathlessness on exertion, ankle swelling and paraesthesiae in his hands. He is seen by a physician’s assistant who gives him some iron tablets as he looks pale and investigations show a haemoglobin level of 6.8 g/dL with 5% reticulocytes. Question What is the underlying problem here that has not been completely defined? How should he be further managed? Answer This patient has a significant haemolytic anaemia, which is of recent onset and is thus most likely to be due to his treatment with prophylactic antimalarial drugs. He was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency and found to have a low activity of this enzyme in his red cells. The lack of this enzyme often only becomes clinically manifest when the red cell is stressed, as in the presence of an oxidant such as chloroquine (other common drugs that precipitate haemolysis include primaquine, dapsone, sulphonamides, the 4-quinolones, nalidixic acid and ciprofloxacin, nitrofurantoin, aspirin and quinidine). The patient’s erythrocytes cannot handle the increased oxidation stress and cannot utilize the hexose monophosphate shunt to synthesize NAPDH in order to reduce oxidized glutathione (which is the only way to achieve this in red cells) and are thus damaged by excessive redox stress. The patient should be asked whether anyone in his family has ever experienced a similar condition, as it is inherited as an X-linked defect. Patients whose ethnic origins are from Africa, Asia, southern Europe (Mediterranean) and Oceania are more commonly affected. Stopping the chloroquine and treating with folate and iron should improve the anaemia and symptoms. The patient should be warned about other drugs that can precipitate G6PD deficiencyrelated haemolysis and advised to inform his physician that he has this condition. He should also carry a card or bracelet that bears this information. FURTHER READING Bradley DJ, Bannister B, on behalf of the Health Protection Agency Advisory Committee on Malaria Prevention for UK Travellers. Guidelines for malaria prevention in travellers from the United Kingdom for 2003. Communicable Diseases and Public Health 2003; 6: 180–99. Liu LX, Weller PF. Antiparasitic drugs. New England Journal of Medicine 1996; 334: 1178–84. Molyneux M, Fox R. Diagnosis and treatment of malaria in Britain. British Medical Journal 1993; 306: 1175–80. Pasvol G. The treatment of complicated and severe malaria. British Medical Bulletin 2006; 75: 29–47. White NJ. The treatment of malaria. New England Journal of Medicine 1996; 335: 800–6. Zuckerman JN. Preventing malaria in UK travellers. British Medical Journal 2004; 329: 305–6.
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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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Page 328 and 329: with symptoms caused by the release
Page 330 and 331: FURTHER READING Birnbaumer M. Vasop
Page 332 and 333: PART IX SELECTIVE TOXICITY
Page 334 and 335: ● Principles of antibacterial che
Page 336 and 337: 2. transfer of resistance between o
Page 338 and 339: Pharmacokinetics Absorption of thes
Page 340 and 341: Mechanism of action Macrolides bind
Page 342 and 343: asic quinolone structure dramatical
Page 344 and 345: Case history A 70-year-old man with
Page 346 and 347: PRINCIPLES OF MANAGEMENT OF MYCOBAC
Page 348 and 349: Pharmacokinetics Absorption from th
Page 350 and 351: MYCOBACTERIUM LEPRAE INFECTION Lepr
Page 352 and 353: POLYENES AMPHOTERICIN B Uses Amphot
Page 354 and 355: therapy is adequate though more fre
Page 356 and 357: NUCLEOSIDE ANALOGUES ACICLOVIR Uses
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Page 360 and 361: Uses Interferon-α when combined wi
Page 362 and 363: ● Introduction 351 ● Immunopath
Page 364 and 365: Table 46.1: Examples of combination
Page 366 and 367: NON-NUCLEOSIDE ANALOGUE REVERSE TRA
Page 368 and 369: FUSION INHIBITORS Uses Currently, e
Page 370 and 371: salvage therapy include azithromyci
Page 372 and 373: ● Malaria 361 ● Trypanosomal in
Page 374 and 375: Pharmacokinetics Chloroquine is rap
Page 378 and 379: ● Introduction 367 ● Pathophysi
Page 380 and 381: Table 48.1: Classification of commo
Page 382 and 383: Polymorph count/mm 3 (a) (b) 10 000
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Page 386 and 387: Adverse effects Methotrexate Inhibi
Page 388 and 389: Table 48.7: Summary of clinical pha
Page 390 and 391: Table 48.9: Summary of the clinical
Page 392 and 393: Plasma membrane Signal transduction
Page 394 and 395: Table 48.10: Monoclonal antibodies
Page 396 and 397: INTERFERON-ALFA 2B Interferon-alfa
Page 398 and 399: PART X HAEMATOLOGY
Page 400 and 401: ● Haematinics - iron, vitamin B 1
Page 402 and 403: 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
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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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