Rapid Clinical Pharmacology E-Book

Andrew Batchelder

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: Rapid
• Sprache: Englisch

Seitenzahl: 160

Veröffentlichungsjahr: 2011

Beschreibung

This pocket reference guide is a must for all medical students and junior doctors preparing for exams in pharmacology or needing a rapid reminder during a clinical attachment.

In light of the growing pressures on those who prescribe drugs to patients, increasing emphasis has been placed on the importance of pharmacology in the undergraduate medical curriculum. Rapid Clinical Pharmacology, with its concise, easy-to-use approach, offers an appealing format for students to use in both clinical practice and exam preparation and its ‘one-page per drug/class' layout easily facilitates the generation of a personal student formulary.

Each chapter of the book mirrors each section of the BNF to allow easy cross-referencing and then each chapter is divided into consistent sections as per other books in the Rapid series.

Rapid Clinical Pharmacology will also be available as a mobile application for iPhone, iPod Touch, iPad and Blackberry. See wiley.com/go/mededapps for further details.

Leseprobe

Contents

Preface

List of abbreviations

BASIC PHARMACOKINETIC CONCEPTS

Basic pharmacokinetic concepts

GASTROINTESTINAL SYSTEM

Histamine type 2 receptor antagonists

Laxatives

Proton pump inhibitors (PPIs)

CARDIOVASCULAR SYSTEM

α-adrenoceptor antagonists (α blockers)

Adenosine

Aldosterone antagonists

Amiodarone

Angiotensin-converting enzyme inhibitors (ACEIs)

Angiotensin II receptor blockers (ARBs)

Antimuscarinics

Aspirin

(β-adrenoceptor antagonists (β blockers)

Calcium channel blockers (CCBs)

Cardiac glycosides

Clopidogrel

Dipyridamole

Fibrates

Fibrinolytics

Flecainide

Glycoprotein IIb/IIIa inhibitors

Inotropic sympathomimetics

Loop diuretics

Low molecular weight heparins (LMWH)

Nitrates

Potassium channel activators

Statins

Thiazide diuretics

Tranexamic acid

Vasoconstrictor sympathomimetics

Warfarin

RESPIRATORY SYSTEM

ß2 adrenoceptor agonists

Histamine type 1 receptor antagonists

Inhaled antimuscarinics

Leukotriene receptor antagonists

Oxygen

Theophylline

CENTRAL NERVOUS SYSTEM

5-HT1 agonists (triptans)

5-HT3 antagonists

Antihistamine anti-emetics

Antipsychotics – atypical

Antipsychotics – typical

Benzodiazepines

Carbamazepine

Dopamine antagonist anti-emetics

Drugs for dementia

Gabapentin and pregabalin

Levodopa (L-dopa)

Lithium

Monoamine oxidase inhibitors (MAOIs)

Non-steroidal anti-inflammatory drugs (NSAIDs)

Opioid analgesia

Other antiepileptics

Other antiparkinsonian drugs

Paracetamol

Phenothiazine anti-emetics

Phenytoin

Selective serotonin reuptake inhibitors (SSRIs)

Sodium valproate

Tricyclic antidepressants (TCAs)

INFECTIONS

Aciclovir

Aminoglycosides

Antifungals

Antiretroviral agents

Antituberculosis drugs

Cephalosporins and other β lactams

Penicillins

Glycopeptide antibiotics

Macrolides

Metronidazole

Nitrofurantoin

Quinolones

Tetracyclines

Trimethoprim

ENDOCRINE SYSTEM

5α-reductase inhibitors

Antidiuretic hormone (ADH) analogues

Biguanides

Bisphosphonates

Carbimazole

Corticosteroids

Dipeptidylpeptidase-4 (DDP-4) inhibitors

Gonadotrophin-releasing hormone (GnRH) agonists

Hormone replacement therapy (HRT)

Incretin mimetics

Insulins

Levothyroxine

Propylthiouracil

Sulfonylureas

Thiazolidinediones

OBSTETRICS, GYNAECOLOGY AND URINARY

Contraceptives

Mifepristone

Oxybutynin

Oxytocin

Phosphodiesterase type 5 inhibitors

MALIGNANT DISEASE AND IMMUNOSUPPRESSION

Alkylating agents

Anthracyclines

Anti-androgens

Antimetabolites

Antiproliferative immunosuppressants

Calcineurin inhibitors

Other antineoplastic drugs

Selective oestrogen receptor modulators (SERMs)

Trastuzumab (Herceptin®)

Vinca alkaloids

MUSCULOSKELETAL AND JOINT DISEASES

Allopurinol

Aminosalicylic acid compounds (ASAs)

Colchicine

Methotrexate

EYE

Antiglaucoma drugs

ANAESTHESIA

Depolarising neuromuscular blocking agents

Etomidate

Inhalational anaesthetics

Lidocaine

Non-depolarising blocking agents

Propofol

Thiopental sodium

INTRAVENOUS FLUIDS

Intravenous fluids

BLOOD AND TRANSFUSION MEDICINE

Blood and transfusion medicine

Index of drugs

This edition first published 2011 © 2011 by John Wiley and Sons, Ltd

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Library of Congress Cataloging-in-Publication Data

Rapid clinical pharmacology : a student formulary / Andrew Batchelder... [et al.]. – 1st ed.p. ; cm. – (Rapid series)Includes index.

ISBN 978-0-470-65441-5 (pbk. : alk. paper)

1. Clinical pharmacology-Handbooks, manuals, etc. I. Batchelder, Andrew. II. Series: Rapid series.

[DNLM: 1. Pharmacology, Clinical-methods-Handbooks. 2. Pharmaceutical Preparations-administration & dosage-Handbooks. QV 39]RM301.28.R37 2011615’.1-dc22

2011007199

Preface

In light of the growing pressures on prescribers, increasing emphasis has been placed on the importance of pharmacology in the undergraduate medical curriculum. Clinical pharmacology is a topic with which many students and clinicians struggle because of the large volumes of factual information that they are required to assimilate. In addition, medical students frequently have difficulty identifying the core learning material.

The British Pharmacological Society has recommended that learning be focused on a core list of commonly used drugs and suggests that students create a personal formulary. Rapid Clinical Pharmacology provides a concise structured approach for readers, be they students preparing for pharmacology examinations, junior doctors starting out in clinical practice or members of allied health professions involved in prescribing and dispensing medications. The familiar format of the Rapid series emphasises the key headings for each drug class, directing readers to the main points. Special considerations are also given under the ‘Important points’ heading to highlight features unique to certain drugs or classes.

Good prescribing practice requires knowing which drug to use and why; however, it also requires consideration of comorbidities, potential adverse effects and polypharmacy. Emphasising clinically relevant information about the most commonly used medications, this book provides a good foundation of pharmacological knowledge upon which to build. Additionally, it includes useful tips on prescribing in the context of intravenous fluids and blood components.

We would like to thank Dr Adrian Stanley for the wealth of time and effort he has dedicated to editing this text; without his invaluable assistance this book would not have been possible.

Andrew BatchelderCharlene RodriguesZiad Alrifai

List of abbreviations

5-HT5-hydroxytryptamine (serotonin)ACEIsAngiotensin-converting enzyme inhibitorsAChAcetylcholineACSAcute coronary syndromeADHAntidiuretic hormoneADPAdenosine diphosphateAFAtrial fibrillationAIDSAcquired immunodeficiency syndromeAPTTActivated partial thromboplastin timeARBsAngiotensin receptor blockersASAAminosalicylic acidATPAdenosine triphosphateAVAtrioventricularAVNRTAV nodal re-entry tachycardiaBMBoehringer Mannheim (finger-prick blood glucose)BPBlood pressureBTSBritish Thoracic SocietyCa2+Calcium ioncAMPCyclic adenosine monophosphateCCBsCalcium channel blockersCCFCongestive cardiac failureCD4+Cluster of differentiation 4cGMPCyclic guanosine monophosphateCl-Chloride ionCMVCytomegalovirusCNSCentral nervous systemCO2Carbon dioxideCOCPCombined oral contraceptive pillCOMTCatechol-O-methyl transferaseCOPDChronic obstructive pulmonary diseaseCOXCyclo-oxygenaseCSFCerebrospinal fluidCTComputed tomographyCTGCardiotocographyCTZChemoreceptor trigger zoneCVPCentral venous pressureDICDisseminated intravascular coagulationDKADiabetic ketoacidosisDNADeoxyribonucleic acidDVTDeep vein thrombosisEBVEpstein Barr virusECGElectrocardiographyESRErythrocyte sedimentation rateFBCFull blood countFFPFresh frozen plasmaFSHFollicule-stimulating hormoneG6PDGlucose-6-phosphate dehydrogenase deficiencyGABAGamma aminobutyric acidGFRGlomerular filtration rateGIGastrointestinalGLUTGlucose transportersGnRHGonadotrophin-releasing hormoneGPIIb/IIIaGlycoprotein IIb/IIIaGTNGlyceryl trinitratGTPGuanosine triphosphateGUGenito-urinaryH+Hydrogen ionH1Histamine type 1 receptorH2Histamine type 2 receptorHDLHigh density lipoproteinsHER2Human epidermal growth factor receptor 2HIVHuman immunodeficiency virusHMG CoA3-hydroxy-3-methylglutaryl coenzyme AHONKHyperosmolar non-ketotic stateHRTHormone replacement therapyIHDIschaemic heart diseaseINIntranasalINRInternational normalised ratioISMNIsosorbide mononitrateJVPJugular venous pressureK+Potassium ionL-dopaLevodopaLDLLow-density lipoproteinsLFTsLiver function testsLHLuteinising hormoneLMWHLow molecular weight heparinLRTILower respiratory tract infectionLVLeft ventricularLVFLeft ventricular failureM2Muscarinic type 2 receptorsM3Muscarinic type 3 receptorsMAOMonoamine oxidaseMAOIsMonoamine oxidase inhibitorsMIMyocardial infarctionMMSEMini-mental state examinationmRNAMessenger ribonucleic acidN2ONitrous oxideNa+Sodium ionNICENational Institute for Health and Clinical ExcellenceNMDAN-methyl-D-aspartic acidNNRTIsNon-nucleoside reverse transcriptase inhibitorsNRTIsNucleoside reverse transcriptase inhibitorsNSAIDNon-steroidal anti-inflammatory drugsO2OxygenOCPOral contraceptive pillPCAPatient-controlled analgesiaPCOSPolycystic ovarian syndromePEPulmonary embolismPGsProstaglandinsPIsProtease inhibitorsPOBy mouth (per os)POPProgesterone-only pillPONVPost-operative nausea and vomitingPPARPeroxisome proliferator-activated receptorsPPIProton pump inhibitorPRPer rectumPSAProstate-specific antigenQTcCorrected QT intervalRNARibonucleic acidSASino-atrialSERMSelective oestrogen receptor modulatorSLESystemic lupus erythematosusSNRIsSerotonin and noradrenaline reuptake inhibitorsSSRIsSelective serotonin reuptake inhibitorsSVTSupraventricular tachycardiat½Half-lifeT3Tri-iodothyronineT4Tetra-iodothyronineTCAsTricyclic antidepressantsTFTsThyroid function testsTIATransient ischaemic attackTPRTotal peripheral resistancetRNATransfer ribonucleic acidTSHThyroid-stimulating hormoneU&EsUrea and electrolytesUTIUrinary tract infectionVFVentricular fibrillationVLDLVery low-density lipoproteinsVTVentricular tachycardiaVTEVenous thromboembolism

Abbreviations of routes of administration

IMIntramuscularINIntranasalINHInhaledIVIntravenousNEBNebulisedPOOralPRPer rectumPVPer vaginaSCSubcutaneousSLSublingualTOPTopical

Abbreviations of dosing

ODOnce dailyOMOnce in the morningONOnce at nightBDTwice dailyTDSThree times a dayQDSFour times a dayPRNAs required

BASIC PHARMACOKINETIC CONCEPTS

Basic pharmacokinetic concepts

PHARMACOKINETICS The study of the movement of drugs into, within and out of the body. The key pharmacokinetic parameters from a dosing point of view are bioavailability (F), clearance (Cl), volume of distribution (Vd) and elimination half-life (t½).

PHARMACODYNAMICS The study of the effect of a drug on the body.

BIOAVAILABILITY (F)

F is defined as the percentage of an administered dose that reaches the systemic circulation unchanged. Bioavailability is 100% for the intravenous route.

Oral bioavailability varies and is dependent on the degree of absorption, formulation of some drugs (e.g. nitrates) and the degree of first-pass hepatic metabolism. If plasma concentration is plotted against time, bioavailability is represented as the area under the curve.

VOLUME OF DISTRIBUTION (Vd)

Vd represents the theoretical volume into which a given drug dose must be distributed in the body to achieve a concentration equal to that of plasma. Drugs that are highly lipid soluble, such as digoxin, have a high Vd. Drugs that are lipid insoluble, such as neuromuscular blockers, remain predominantly in the plasma and will have a low Vd.

Clinically, the larger the volume of distribution the longer it will take to reach a therapeutic level and, therefore, a loading dose may be necessary. The volume of distribution can be calculated as:

LOADING DOSE

Defined as the initial dose of a drug required to rapidly achieve a desired plasma concentration. The time required to achieve a steady state plasma concentration will be long if a drug has a long t½ (time taken to reach steady state is approximately 4 ½ half-lives). Therefore it is desirable to administer a loading dose to attain a therapeutic plasma concentration immediately. Examples of drugs requiring a loading dose regime include amiodarone, digoxin and warfarin.

The main factor determining a loading dose is the volume of distribution (Vd). In order for a drug to reach a steady state plasma concentration (Cp), the tissues into which the drug distributes must be saturated first. The relationship between loading dose and volume of distribution is defined below:

elimiation half-life(t1/2)

t½ is the time taken for the plasma concentration of a drug to fall by 50%. The elimination rate constant (K) is the fraction of the total amount of drug in the body removed per unit time. K is represented by the slope of the line of the log plasma concentration versus time.

Elimination rate constant and t½ can be used clinically to estimate the time to reach steady state concentrations after drug initiation or a change in maintenance dose.

FIRST-ORDER KINETICS

In first-order kinetics a constant fraction of the drug is eliminated per unit time. The rate of elimination is, therefore, proportional to the amount of drug in the body. The majority of drugs follow first-order kinetics.

ZERO-ORDER KINETICS

In zero-order kinetics the rate of drug elimination is linear and independent of drug concentration. Many important drugs, such as phenytoin and theophylline, follow zero- order kinetics at higher doses. Alcohol also follows zero-order kinetics with a decline in plasma levels at a constant rate of approximately 15 mg/100 ml/h.

CLEARANCE

Clearance is the theoretical volume of plasma from which the drug is completely removed per unit time. It is not the amount of drug removed from the body. Some of the factors that alter clearance include: degree of protein binding, body surface area, cardiac output, hepatic function and renal function.

Clearance can be calculated from the elimination rate constant and the volume of distribution:

GASTROINTESTINAL SYSTEM

Histamine type 2 receptor antagonists

EXAMPLES Ranitidine, cimetidine

MECHANISM OF ACTION Competitive inhibitors of all histamine type 2 receptors. Inhibit histamine- and gastrin-stimulated gastric acid secretion by their action on parietal cells in the stomach.

INDICATIONS

Gastric and duodenal ulcersGastro-oesophageal refluxTreatment and prophylaxis of NSAID-associated ulcers

CAUTIONS AND CONTRA-INDICATIONS

HypersensitivityIf red flag features of malignancy, need to investigate prior to initiating treatment

SIDE-EFFECTS

GI disturbance, especially diarrhoeaGynaecomastia (cimetidine)

METABOLISM AND HALF-LIFE These drugs are excreted largely unchanged in urine. t½ is 2–3 h.

MONITORING No specific drug monitoring required.

DRUG INTERACTIONS

Cimetidine inhibits Cytochrome P450 activity in the liver and therefore potentiates the action of drugs such as warfarin, phenytoin and theophylline

IMPORTANT POINTS

Ranitidine can be used prior to general anaesthesia in patients at high risk of aspiration particularly in obstetric practice (Mendelson’s syndrome)

Laxatives

MECHANISM OF ACTION

Bulk laxatives (e.g. ispaghula husk) – polysaccharide polymers that are not broken down by digestion and thereby increase stool volume. This stimulates intestinal peristalsis (via the stretch reflex) as well as softening faeces.

Osmotic laxatives (e.g. lactulose, Movicol®) – these poorly absorbed solutes increase the volume of water in the bowel lumen by osmosis hence increasing transit.

Stimulant laxatives (e.g. senna, docusate sodium) – the primary effect is via direct stimulation of myenteric plexus resulting in smooth muscle contraction and increased peristalsis.

Faecal softeners (e.g. arachis oil) – these are surfactants that reduce surface tension and allow water to penetrate and soften faeces.

INDICATIONS

ConstipationHepatic encephalopathy (lactulose)

CAUTIONS AND CONTRA-INDICATIONS

Bowel obstructionGalactosaemia (lactulose only)Acute inflammatory bowel diseaseSevere dehydration

SIDE-EFFECTS

FlatulenceDiarrhoeaAbdominal crampsElectrolyte disturbances

METABOLISM ANDHALF-LIFE Variable – most are broken down locally in the GI tract with minimal absorption.

MONITORING No specific drug monitoring required.

DRUG INTERACTIONS

Lactulose may enhance warfarin effects in severe liver disease

IMPORTANT POINTS

Before prescribing a laxative ensure constipation is not secondary to an underlying pathology such as bowel cancerIt requires at least 2–3 days for osmotic or bulking laxatives to take full effectAvoid laxatives if bowel obstruction is suspected due to risk of perforationLactulose reduces ammonia-producing organisms and is used in the treatment of hepatic encephalopathyChronic laxative use can cause tolerance (stimulant laxatives)

Proton pump inhibitors (PPIs)

EXAMPLES Omeprazole, lansoprazole, esomeprazole, pantoprazole

MECHANISM OF ACTION Inhibit H+/K+ ATPase on luminal surface of gastric parietal cells and thereby reduce gastric acid secretion.

INDICATIONS

Gastric/duodenal ulcerationAs part of triple therapy for eradication of Helicobacter pyloriGastro-oesophageal reflux diseaseAcid-related dyspepsiaHyper-secretory conditions, including Zollinger-Ellison syndromePrevention and treatment of NSAID-associated ulcers

CAUTIONS AND CONTRA-INDICATIONS

HypersensitivityIf red flag features of malignancy need to investigate prior to initiating treatment

SIDE-EFFECTS

GI disturbance (e.g. abdominal pain, nausea, vomiting, diarrhoea)Increased risk of gastric infections due to hypochlorhydria

METABOLISM AND HALF-LIFE Extensively metabolised by liver and excreted by both renal and biliary routes. t½ varies from 40 min to 2 h.

MONITORING No specific drug monitoring required.

DRUG INTERACTIONS

PPIs are inducers of Cytochrome P450 with some variation in potency between the individual drugs and, therefore, may enhance effects of drugs metabolised by the liver (e.g. phenytoin, carbamazepine, warfarin)

IMPORTANT POINTS

PPIs reduce acid secretion by >90% and are therefore more effective at healing peptic ulcers than H2 receptor antagonists (which reduce acid secretion by 50–60%)IV PPIs can be used in the management of acute upper GI bleeds under specialist supervision

CARDIOVASCULAR SYSTEM

α-adrenoceptor antagonists (α blockers)

EXAMPLES Doxazosin, prazosin, tamsulosin, alfuzosin

MECHANISM OF ACTION Inhibit α1-adrenoceptors in arterioles, thereby reducing tone of vascular smooth muscle and reducing total peripheral resistance. Inhibition of α1-adrenoceptors in periurethral prostatic stroma results in relaxation of internal urethral sphincter and some relief of obstructive urinary symptoms in males.

INDICATIONS

Hypertension (i.e. doxazosin, particularly in resistant cases as part of polytherapy)Benign prostatic hyperplasia

CAUTIONS AND CONTRA-INDICATIONS

Caution in patients with a susceptibility to heart failure

SIDE-EFFECTS

Postural hypotensionDizzinessWeakness and fatigueReflex tachycardiaHeadacheDry mouthEjaculatory failure