Views
5 years ago

A Textbook of Clinical Pharmacology and Therapeutics

A Textbook of Clinical Pharmacology and Therapeutics

in prefilled injection

in prefilled injection devices (‘pens’) which are convenient for patients. The small dose of soluble insulin controls hyperglycaemia just after the injection. The main danger is of hypoglycaemia in the early hours of the morning. When starting a diabetic on a two dose per day regime, it is therefore helpful to divide the daily dose into two-thirds to be given before breakfast and one-third to be given before the evening meal. If the patient engages in strenuous physical work, the morning dose of insulin is reduced somewhat to prevent exercise-induced hypoglycaemia. Insulin is also required for symptomatic type 2 diabetics in whom diet and/or oral hypoglycaemic drugs fail. Unfortunately, insulin makes weight loss considerably more difficult because it stimulates appetite, but its anabolic effects are valuable in wasted patients with diabetic amyotrophy. Insulin is needed in acute diabetic emergencies such as ketoacidosis, during pregnancy, peri-operatively and in severe intercurrent disease (infections, myocardial infarction, burns, etc.). Insulin requirements are increased by up to one-third by intercurrent infection and patients must be instructed to intensify home blood glucose monitoring when they have a cold or other infection (even if they are eating less than usual) and increase the insulin dose if necessary. The dose will subsequently need to be reduced when the infection has cleared. Vomiting often causes patients incorrectly to stop injecting insulin (for fear of hypoglycaemia) and this may result in ketoacidosis. Patients for elective surgery should be changed to soluble insulin preoperatively. During surgery, soluble insulin can be infused i.v. with glucose to produce a blood glucose concentration of 6–8 mmol/L. This is continued post-operatively until oral feeding and intermittent subcutaneous injections Key points Type 1 diabetes mellitus and insulin • Type 1 (insulin-dependent) diabetes mellitus is caused by degeneration of β-cells in the islets of Langerhans leading to an absolute deficiency of insulin. • Without insulin treatment, such patients are prone to diabetic ketoacidosis (DKA). • Even with insulin treatment, such patients are susceptible to microvascular complications of retinopathy, nephropathy and neuropathy, and also to accelerated atherosclerotic (macrovascular) disease leading to myocardial infarction, stroke and gangrene. • Management includes a healthy diet low in saturated fat (Chapter 27), high in complex carbohydrates and with the energy spread throughout the day. • Regular subcutaneous injections of recombinant human insulin are required indefinitely. Mixtures of soluble and longer-acting insulins are used and are given using special insulin ‘pens’ at least twice daily. Regular selfmonitoring of blood glucose levels throughout the day with individual adjustment of the insulin dose is essential to achieve good metabolic control, which reduces the risk of complications. • DKA is treated with large volumes of intravenous physiological saline, intravenous soluble insulin and replacement of potassium and, if necessary, magnesium. DRUGS USED TO TREAT DIABETES MELLITUS 287 of insulin can be resumed. A similar regime is suitable for emergency operations, but more frequent measurements of blood glucose are required. Patients with type 2 diabetes can sometimes be managed without insulin, but the blood glucose must be regularly checked during the post-operative period. Ketoacidosis The metabolic changes in diabetic ketoacidosis (DKA) resemble those of starvation since, despite increased plasma glucose concentrations, glucose is not available intracellularly (‘starving amidst plenty’). Hyperglycaemia leads to osmotic diuresis and electrolyte depletion. Conservation of K� is even less efficient than that of Na� in the face of acidosis and an osmotic diuresis, and large amounts of intravenous K� are often needed to replace the large deficit in total body K� . However, plasma K� concentration in DKA can be increased due to a shift from the intracellular to the extracellular compartment, so large amounts of potassium chloride should not be administered until plasma electrolyte concentrations are available and high urine output established. Fat is mobilized from adipose tissue, releasing free fatty acids that are metabolized by β-oxidation to acetyl coenzyme A (CoA). In the absence of glucose breakdown, acetyl CoA is converted to acetoacetate, acetone and β-hydroxybutyrate (ketones). These are buffered by plasma bicarbonate, leading to a fall in bicarbonate concentration (metabolic acidosis – with an increased ‘anion gap’ since anionic ketone bodies are not measured routinely) and compensatory hyperventilation (‘Küssmaul’ breathing). There are therefore a number of metabolic abnormalities: • Sodium and potassium deficit A generous volume of physiological saline (0.9% sodium chloride), given intravenously, is crucial in order to restore extracellular fluid volume. Monitoring urine output is necessary. When blood glucose levels fall below 17 mmol/L, 5% glucose is given in place of N-saline. Potassium must be replaced and if the urinary output is satisfactory and the plasma potassium concentration is �4.5 mEq/L, up to 20 mmol/hour KCl can be given, the rate of replacement being judged by frequent measurements of plasma potassium concentration and ECG monitoring. • Hyperglycaemia Intravenous insulin is infused at a rate of up to 0.1 unit/kg/hour with a syringe pump until ketosis resolves (judged by blood pH, serum bicarbonate and blood or urinary ketones). • Metabolic acidosis This usually resolves with adequate treatment with physiological sodium chloride and insulin. Bicarbonate treatment to reverse the extracellular metabolic acidosis is controversial, and may paradoxically worsen intracellular and cerebrospinal fluid acidosis. If arterial pH is �7.0, the patient is often given bicarbonate, should be managed on an intensive care unit if possible and may need inotropic support. • Other measures include aspiration of the stomach, as gastric stasis is common and aspiration can be severe and may be fatal, and treatment of the precipitating cause of coma (e.g. antibiotics for bacterial infection).

288 DIABETES MELLITUS Hyperosmolar non-ketotic coma Less insulin is required in this situation, as the blood pH is normal and insulin sensitivity is retained. Fluid loss is restored using physiological saline (there is sometimes a place for halfstrength, 0.45% saline) and large amounts of intravenous potassium are often required. Magnesium deficiency is common, contributes to the difficulty of correcting the potassium deficit, and should be treated provided renal function is normal. In this hyperosmolar state, the viscosity of the blood is increased and a heparin preparation (Chapter 30) should be considered as prophylaxis against venous thrombosis. Mechanism of action Insulin acts by binding to transmembrane glycoprotein receptors. Receptor occupancy results in: 1. activation of insulin-dependent glucose transport processes (in adipose tissue and muscle) via a transporter known as ‘Glut-4’; 2. inhibition of adenylyl cyclase-dependent metabolism (lipolysis, proteolysis, glycogenolysis); 3. intracellular accumulation of potassium and phosphate, which is linked to glucose transport in some tissues. Secondary effects include increased cellular amino acid uptake, increased DNA and RNA synthesis and increased oxidative phosphorylation. Adverse reactions 1. Hypoglycaemia is the most important and severe complication of insulin treatment. It is treated with an intravenous injection of glucose in unconscious patients, but sugar is given as a sweet drink in those with milder symptoms. Glucagon (1 mg intramuscularly, repeated after a few minutes if necessary) is useful if the patient is unconscious and intravenous access is not achievable (e.g. to ambulance personnel or a family member). 2. Insulin-induced post-hypoglycaemic hyperglycaemia (Somogyi effect) occurs when hypoglycaemia (e.g. in the early hours of the morning) induces an overshoot of hormones (adrenaline, growth hormone, glucocorticosteroids, glucagon) that elevate blood glucose (raised blood glucose on awakening). The situation can be misinterpreted as requiring increased insulin, thus producing further hypoglycaemia. 3. Local or systemic allergic reactions to insulin, with itching, redness and swelling at the injection site. 4. Lipodystrophy: the disappearance of subcutaneous fat at or near injection sites. Atrophy is minimized by rotation of injection sites. Fatty tumours occur if repeated injections are made at the same site. 5. Insulin resistance, defined arbitrarily as a daily requirement of more than 200 units, due to antibodies, is unusual. Changing to a highly purified insulin preparation is often successful, a small starting dose being used to avoid hypoglycaemia. Pharmacokinetics Insulin is broken down in the gut and by the liver and kidney, and is given by injection. The t1/2 is three to five minutes. It is metabolized to inactive α and β peptide chains largely by hepatic/renal insulinases (insulin glutathione transhydrogenase). Insulin from the pancreas is mainly released into the portal circulation and passes to the liver, where up to 60% is degraded before reaching the systemic circulation (presystemic metabolism). The kidney is also important in the metabolism of insulin and patients with progressive renal impairment often have a reduced requirement for insulin. There is no evidence that diabetes ever results from increased hepatic destruction of insulin, but in cirrhosis the liver fails to inactivate insulin, thus predisposing to hypoglycaemia. ORAL HYPOGLYCAEMIC DRUGS AND TYPE 2 DIABETES Oral hypoglycaemic drugs are useful in type 2 diabetes as adjuncts to continued dietary restraint. They fall into four groups: 1. biguanides (metformin); 2. sulphonylureas and related drugs; 3. thiazolidinediones (glitazones); 4. α-glucosidase inhibitors (acarbose). Most type 2 diabetic patients initially achieve satisfactory control with diet either alone or combined with one of these agents. The small proportion who cannot be controlled with drugs at this stage (primary failure) require insulin. Subsequent failure after initially adequate control (secondary failure) occurs in about one-third of patients, and is treated with insulin. Inhaled insulin is effective but expensive. Its bioavailability is affected by smoking and by respiratory infections, and currently should only be used with great caution in patients with asthma/ COPD. BIGUANIDES: METFORMIN Uses Metformin is the only biguanide available in the UK. It is used in type 2 diabetic patients inadequately controlled by diet. Its anorectic effect aids weight reduction, so it is a first choice drug for obese type 2 patients, provided there are no contraindications. It must not be used in patients at risk of lactic acidosis and is contraindicated in: • renal failure (it is eliminated in the urine, see below); • alcoholics; • cirrhosis; • chronic lung disease (because of hypoxia); • cardiac failure (because of poor tissue perfusion); • congenital mitochondrial myopathy (which is often accompanied by diabetes); • acute myocardial infarction and other serious intercurrent illness (insulin should be substituted).

  • Page 2 and 3:

    A Textbook of Clinical Pharmacology

  • Page 4 and 5:

    A Textbook of Clinical Pharmacology

  • Page 6 and 7:

    This fifth edition is dedicated to

  • Page 8 and 9:

    FOREWORD viii PREFACE ix ACKNOWLEDG

  • Page 10 and 11:

    PREFACE Clinical pharmacology is th

  • Page 12 and 13:

    PART I GENERAL PRINCIPLES

  • Page 14 and 15:

    ● Use of drugs 3 ● Adverse effe

  • Page 16 and 17:

    and acquired factors, notably disea

  • Page 18 and 19:

    100 Effect (%) 0 0 5 10 1 10 100 (a

  • Page 20 and 21:

    Dose ratio -1 100 50 The relationsh

  • Page 22 and 23:

    ● Introduction 11 ● Constant-ra

  • Page 24 and 25:

    In reality, processes of eliminatio

  • Page 26 and 27:

    lood (from which samples are taken

  • Page 28 and 29:

    ● Introduction 17 ● Bioavailabi

  • Page 30 and 31:

    ROUTES OF ADMINISTRATION ORAL ROUTE

  • Page 32 and 33:

    Transdermal absorption is sufficien

  • Page 34 and 35:

    FURTHER READING Fix JA. Strategies

  • Page 36 and 37:

    and thromboxanes are CYP450 enzymes

  • Page 38 and 39:

    and lorazepam. Some patients inheri

  • Page 40 and 41:

    Orally administered drug Parenteral

  • Page 42 and 43:

    ● Introduction 31 ● Glomerular

  • Page 44 and 45:

    ACTIVE TUBULAR REABSORPTION This is

  • Page 46 and 47:

    DISTRIBUTION Drug distribution is a

  • Page 48 and 49:

    Detailed recommendations on dosage

  • Page 50 and 51:

    DIGOXIN Myxoedematous patients are

  • Page 52 and 53:

    ● Introduction 41 ● Role of dru

  • Page 54 and 55:

    25 20 10 Life-threatening toxicity

  • Page 56 and 57:

    ● Introduction 45 ● Harmful eff

  • Page 58 and 59:

    vagina in girls in their late teens

  • Page 60 and 61:

    an anti-analgesic effect when combi

  • Page 62 and 63:

    Case history A 20-year-old female m

  • Page 64 and 65:

    METABOLISM At birth, the hepatic mi

  • Page 66 and 67:

    lifelong effects as a result of tox

  • Page 68 and 69:

    DISTRIBUTION Ageing is associated w

  • Page 70 and 71:

    DIGOXIN Digoxin toxicity is common

  • Page 72 and 73:

    FURTHER READING Dhesi JK, Allain TJ

  • Page 74 and 75:

    Factors involved in the aetiology o

  • Page 76 and 77:

    analgesic. Following its release, t

  • Page 78 and 79:

    antibiotics, such as penicillin or

  • Page 80 and 81:

    predisposes to non-immune haemolysi

  • Page 82 and 83:

    ● Introduction 71 ● Useful inte

  • Page 84 and 85:

    Response Therapeutic range Toxic ra

  • Page 86 and 87:

    Table 13.1: Interactions outside th

  • Page 88 and 89:

    Table 13.5: Competitive interaction

  • Page 90 and 91:

    ● Introduction: ‘personalized m

  • Page 92 and 93:

    Table 14.2: Variations in drug resp

  • Page 94 and 95:

    lipoprotein (LDL) is impaired. LDL

  • Page 96 and 97:

    Key points • Genetic differences

  • Page 98 and 99:

    • Discovery • • Screening Pre

  • Page 100 and 101:

    Too many statistical comparisons pe

  • Page 102 and 103:

    ETHICS COMMITTEES Protocols for all

  • Page 104 and 105:

    Table 16.1: Recombinant proteins/en

  • Page 106 and 107:

    duration and benefit. Adenoviral ve

  • Page 108 and 109:

    ● Introduction 97 ● Garlic 97

  • Page 110 and 111:

    A case report has suggested a possi

  • Page 112 and 113:

    including hypericin and pseudohyper

  • Page 114 and 115:

    PART II THE NERVOUS SYSTEM

  • Page 116 and 117:

    ● Introduction 105 ● Sleep diff

  • Page 118 and 119:

    and daytime sleeping should be disc

  • Page 120 and 121:

    Key points • Insomnia and anxiety

  • Page 122 and 123:

    Box 19.1: Dopamine theory of schizo

  • Page 124 and 125:

    The Boston Collaborative Survey ind

  • Page 126 and 127:

    Oral medication, especially in liqu

  • Page 128 and 129:

    e.g. interpersonal difficulties or

  • Page 130 and 131:

    Partial response to first-line trea

  • Page 132 and 133:

    Key points Drug treatment of depres

  • Page 134 and 135:

    Case history A 45-year-old man with

  • Page 136 and 137:

    Levodopa PRINCIPLES OF TREATMENT IN

  • Page 138 and 139:

    • pulmonary, retroperitoneal and

  • Page 140 and 141:

    CHOREA The γ-aminobutyric acid con

  • Page 142 and 143:

    Cholinergic crisis Treatment of mya

  • Page 144 and 145:

    ● Introduction 133 ● Mechanisms

  • Page 146 and 147:

    absolute arbiter. The availability

  • Page 148 and 149:

    Table 22.2: Metabolic interactions

  • Page 150 and 151:

    FURTHER ANTI-EPILEPTICS Other drugs

  • Page 152 and 153:

    Case history A 24-year-old woman wh

  • Page 154 and 155:

    Assessment of migraine severity and

  • Page 156 and 157:

    ● General anaesthetics 145 ● In

  • Page 158 and 159:

    is the theoretical concern of a ‘

  • Page 160 and 161:

    • Respiratory system - apnoea fol

  • Page 162 and 163:

    Competitive antagonists (vecuronium

  • Page 164 and 165:

    have also proved useful in combinat

  • Page 166 and 167:

    ● Introduction 155 ● Pathophysi

  • Page 168 and 169:

    ASPIRIN (ACETYLSALICYLATE) Use Anti

  • Page 170 and 171:

    Key points Drugs for mild pain •

  • Page 172 and 173:

    increases, correlating with the hig

  • Page 174 and 175:

    • If possible, use oral medicatio

  • Page 176 and 177:

    PART III THE MUSCULOSKELETAL SYSTEM

  • Page 178 and 179:

    ● 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 196 and 197:

    ● Introduction 185 ● Pathophysi

  • 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 222 and 223:

    ● Introduction 211 ● Pathophysi

  • 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 230 and 231:

    BASIC LIFE SUPPORT CARDIOPULMONARY

  • 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
  • Page 280 and 281: Table 35.1: Common trace element de
  • Page 282 and 283: PART VII FLUIDS AND ELECTROLYTES
  • Page 284 and 285: ● Introduction 273 ● Volume ove
  • Page 286 and 287: Key points Diuretics Diuretics are
  • Page 288 and 289: is sometimes caused by drugs, notab
  • Page 290 and 291: or with potassium-sparing diuretics
  • Page 292 and 293: Greger R, Lang F, Sebekova, Heidlan
  • Page 294 and 295: PART VIII THE ENDOCRINE SYSTEM
  • Page 296 and 297: ● Introduction 285 ● Pathophysi
  • Page 300 and 301: Metformin should be withdrawn and i
  • Page 302 and 303: FURTHER READING American Diabetes A
  • Page 304 and 305: deficiency. Potassium iodide (3 mg
  • Page 306 and 307: fertility. It is contraindicated du
  • Page 308 and 309: ● Introduction 297 ● Vitamin D
  • Page 310 and 311: effective in life-threatening hyper
  • Page 312 and 313: Further reading Block GA, Martin KJ
  • Page 314 and 315: Table 40.1: Actions of cortisol and
  • Page 316 and 317: injection may be useful, but if don
  • Page 318 and 319: CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
  • Page 320 and 321: elease by the pituitary via negativ
  • Page 322 and 323: Treatment with depot progestogen in
  • Page 324 and 325: infusion using an infusion pump to
  • Page 326 and 327: significant proportion of men who r
  • 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

  • Page 358 and 359:

    Table 45.3: Summary of available ac

  • 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 376 and 377:

    Table 47.2: Drug therapy of non-mal

  • 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

  • Page 384 and 385:

    doses are used to prepare patients

  • 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

  • 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 454 and 455:

    FURTHER READING Goldman D, Oroszi G

  • 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

A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
World Journal of Gastrointestinal Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
Clinical Pharmacology of Sleep
World Journal of Gastrointestinal Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
World Journal of Gastrointestinal Pharmacology and Therapeutics
Role of Quantitative Clinical Pharmacology in Guiding Drug
Diagnosis and pharmacological management of Parkinson's - SIGN
An Anatomico-Clinical Overview - Advances in Clinical ...
2012 EDUCATIONAL BOOK - American Society of Clinical Oncology
CLINICAL PHARMACOLOGY AND THERAPEUTICS FOR THE ...
CLINICAL PHARMACOLOGY THERAPEUTICS
Pharmacology and therapeutics, clinical trial - Dermage