Essentials of Medical Pharmacology

168 Pages·2008·41.09 MB·English

E,ssentialso f
Medical
Pharmacology
Sixth Edition
KD TRIPATHIn no
Ex-Director-Professaonr d Heado f Pharmacology
MaulanaA zad MedicaCl ollegea nd associated
LN and GB PantH ospitals
NewD elhiI,n dia
JAYPEEB ROTHERSM EDICALP UBLISHER(SP )L TD
St Louis( USA) . PanamaC ity (Panama). New Delhi. Ahmedabad.B engaluru
Chennai. Hyderabad.K ochi. Kolkata. Lucknow. Mumbai. Nagpur
Published by
JitendaPr Vij
JaypeeB rothersM edicalP ublishers( P) Ltd
Corporate Otfice
4838124A, nsarRi oad,D aryaganNj, ew Delhi 1100 02, India,P hone:+ 91-11-43574357
Fax: [phone]
Registered Office
B-3,E MCAH ouse,23123A8 nsariR oad,D aryaganNj, ew Delhi 1100 02,I ndia
Phones:+ 91-11 -23272143+,9 1-11-232727Q+39,1 -11-2328202+19, 1-11-23245672
Rel: +9 1- 11 - 32558559,F ax: +91- 11 - 23276 490, +91- .11 - 23245683
e-mail:ja ypee@jaypeebrothers,cWome,b site:w wwj aypeebrothercso m
Branches
O 2/8, AkrutiS ocietyJ, odhpurG am BoadS atellite
Ahmedabad3 80 015, Phones:+ 91-79-2692623R3e, l:+ 91-79-32988717
Fax:+ 91-79-2692709e4-,m ail:a hmedabad@jaypeebrotchoemr
tr 202 BataviaC hambers8, KumaraK rupaR oad,K umaraP arkE ast
Bengaluru5 60 001, Phones:+ 91- 80-22285917, +91 - 80-22382956R,e l: [phone]
Fa x: +91 - 80-2228716 1, e-mail:b angalor@e j aypeebrothecrso m
D 282 lllrd Floor,K haleeSl hirazEi stateF, ountainP laza,P antheonB oad
Chennai6 00 008, Phones+: 91-44-2819326+59, 1-44-2819489R7e, l:+ 91-44-32972089
Fa x: [phone],e -mail:c henna@i j aypeebrothecrso m
A 4-2:1067/1-31,s t Floor,B alajiB uildingR, amkoteC rossR oad
Hyderabad5 00 095, Phones:+ 91-40-6661002+09, 1-40-2475849Rae, l:[phone]
Fax:[phone],e -mail:h yderaba@d j aypeebrothecro m
tr No.4 l13098B, & B'1,K uruvBi uildingS, t VincenRt oad
Kochi 682 018, Kerala,P hones+: 91-484-403610+99, 1-484-239573+99, 1-484-2395740
e-mail:k ochi@jaypeebrothecrosm
tr 1-AI ndianM irrorS treetW, ellingtoSn quare
Kofkata7 00 013, Phones+: 91-33-2265192+69, 1-33-222764Q+49,1 -33-22276415
Fax: [phone]e5-,m ail:k olkata@jaypeebrothceorms
D LekhraMj arketl ll, B-2,S ector-4F, aizabadR oad,I ndiraN agar
Lucknow2 26 016,P hones:+ 91-522-304055+39, 1-522-3040554
e-mail:l ucknow@ja ypeebrothercso m
tr 106A mitl ndustriaEl stale6, 1 Dr SS Rao Road,N earl \4cl\iHl ospitalP, arel
Mumbai4 00 012, Phones+: 91-22-2412486+39, 1-22-2410453R2e, l:+ 91-22-32926896
Fax:+ 91-22-2416082e8-m, ail:m umba@i j aypeebrothers,com
O "KAIVIALPUSHP3A8", ReshimbagO, pp MohotaS cienceC ollegeU, mredR oad
Nagpur4 40 009 (MS),P honesR: el:+ 91-712-324522F0a, x:+ 91-712-2704275
e-mail:n agpur@ja ypeebrothercso m
North America Office
1745,P heasantR un Drive,M arylandH eights( Missouri),M O 63043,U SA Ph: 001-636-6279734
e-mail: [email protected], [email protected]
Central America Oftlce
Jaypee-HighlightMs edicalP ublishersI nc,, City of Knowledge,81d.237C, layton,P anamaC ity, Panama Ph:507-317-0160
Essentials of Medical Pharmacology, 6th edition
ManagingE dltor M Tripathi
O 2008,K D TriDathi
All rightsr eseruedN o part of this publicatiosnh ouldb e reproduceds,t oredi n a retrievasl ystemo, r transmitteidn any form or by any
means:e lectronicm, echanicapl,h otocopyinrge,c ordingo,r otheruisew, ithoutth e priorw rittenp ermissioonf the authora nd the publisher
This book has been published in good laith that lhe material provided by author is original Every effort is made to ensure
accuracy of material, but the publisher,p rinter and author will not be held responsiblet or any inadvertente tro(s) In case of any
dispute, all legal matters to be settled under Delhi jurisdictiono nly
First Edition. 19 85
Second Edition: 1988
Third Edition: '1994
Foutth Edition: 1999
Updated Reprint:2 001
Fifth Edition: 2003
Sixth Edition: 2008
Beptint 2008
Repilnt 2009
rsBN 81-8448-085-7
Typeset at JPBMP typesetting unit
Printed at Ajanta Offset & Packagings Ltd , New Delhi
= unprecedented pace of developments over the recent years in the field of drugs (medicines) has
*:-iirer emphasized the relevance of Pharmacology to health professionals. Molecular targets of drug
: --rrri'rd r€ being defined at greater resolution, refining new drugs design. Practice of medicine is
-.rL.iorming from'experience (impression) based' to 'evidence based', since more and more credible
= , -.lencef rom well designed clinical studies is now available on the impact of different treatments
r :rortalitv, morbidity and other therapeutic outcomes. The present edition is oriented to reflect
:- .ontemporary advancements.
-
\dopting the'prototype drug' approach and a structured, systematica nd user-friendly format,
:.-. actions,m echanisms,k inetics and toxicological aspectso f drugs are described along with the
:::-rmacological basis of their use and role/status in the therapy of various diseases/conditions.
-- ;. r,rniques ynthesis of pharmacology with clinical medicine, the book is designed to be useful
:----:. to the uninitiated medical student, as well as to prescribing physicians.
\11c hapters have been updated to include recently introduced drugs and published information.
--:r:st therapeutic guidelines from leading professional bodies, WHO and National Health
l --i rammes have been incorporated, especially in areasl ike hypertension, hyperlipidaemias, stroke
:::-,'ention, surgical prophylaxis, tuberculosis, leprosy, malaria, and HIV-AIDS. Recentd evelopments
..-.e been highlighted, notably in hormone replacement therapy, aromatase inhibitors,
-:-.:hosphonates,s electiveC OX-2 inhibitors, atypical antipsychotics,t herapy of diabetesm ellitus,
-=-..:tf ailure, acute coronary syndromes, Alzheimer's disease,p arkinsonism, glaucoma, kala azar,
=.: -\ chapter is devoted to the principles of 'rational use of medicines',e lementso f 'evidenceb ased
:-edicine' and the processo f 'new drug development' to reflect current importance of theset opics.
::..rther new chapter compiles the clinically important drug interactions.S ome other topics added
,:; drug transporters, pharmacogenomics, pharmacovigilance, expiry date of pharmaceuticals, single
=::nliomer drugs, biological responsem odifiers, prescribing in pregnancy, etc.
\erv drugs marketed in India till mid 2007 are included, while obsolete ones are deleted.
-::equently used drugs and those not available in India are described briefly in extract type.
-::.:-ortant points are summarized in boxes. Leading trade names with dosage forms are given.
::rphasis is placed on the profile of diseasesa nd drug use in India and other tropical countries,
;: as to be particularly useful to students and doctors in these regions; a need not well addressed
:-. nanv texts.
Thanks are due to my colleaguesa nd students for their valuable feedbacka nd suggestions.A s
:::i'iously, the major impetus for this edition has come from Shri J.P Vij, the ever agile Chairman
-a\-pee
: Brothers.C ommendable type setting,p roof reading and improvement in illustrations has
-=en done respectively by Ms Sunita Katla, Ms Ceeta Srivastava and Mr Manoj. The editorial
:::-:'.agementa nd moral support of my wife has been a boon.
'-=-,''D elhi KD Tripathi
:.: \or'. 2007
Contents
Section 1'
q$ GeneralP harmacologicaPl rincipler qffi
@ &
1. Introduction, Routes of Drug Administration J
2. Pharmacokinetics:M embrane Transport, Absorption and Distribution of Drugs .............1..1
Pharmacokinetics:M etabolism and Excretion of Drugs, Kinetics of Elimination ..............2.3.
J.
1 Pharmacodynamics:M echanism of Drug Action; ReceptorP harmacology..............,.,.,.. ..,,..37
5. Aspects of Pharmacotherapy;C linical Pharmacology and Drug DeveIopment..................5.9.
5. Adverse Drug Effects .,,.....,,78
Autonomic Nervous System:G eneralC onsiderations. ................ ........................88
7. CholinergicSystemandDrugs... .............93
8. Anticholinergic Drugs and Drugs Acting on Autonomic Ganglia....... ...........1..0 5
9. Adrenergic System and Drugs ............1..1 5
10. Antiadrenergic Drugs (Adrenergic ReceptorA ntagonists) and
Drugs for Glaucoma ................... ,,..,,,,...,,132
11. Histamine and Antihistaminics .............. ................1.5..1.
12. S-Hydroxytryptamine, its Antagonists and Drug Therapy of Migraine.........................,....,.'1.62
13. Prostaglandins,L eukotrienes (Eicosanoids)a nd Platelet Activating Factor.........................773
14. Nonsteroidal Antiinflammatory Drugs and Antipyretic-Analgesics....... .......1. 84
15. Antirheumatoid and Antigout Drugs ................. ..,....,202
viii Contents
Section 4
f K
fiE '?+
RespiratoryS ystemD rugs
15. Drugs for Cough and Bronchial Asthma ...................213
Section 5
Hormones q4d-.'iRelated Drugs
. ,jl
Introduction.........
17.AnteriorP ituitaryH ormones.. ............. ........................233
18.Thyroid Hormonea ndThyroid Inhibitors... .............242
19.Insulin,O ralH ypoglycaemiDc rugsa ndG lucagon................... .........................254
20.Corticosteroids. ............
27. Androgens and Drugs for Erectile Dysfunction ......288
22. Estrogens,P rogestinsa nd Contraceptives........ .........297
23. Oxytocin and Other Drugs Acting on Uterus
24. Drugs Affecting Calcium Balance ..................3..2.5....
;'1,.\! :, nS eCtiOn b'
-a
Drugs Acting on Peripheral (Somatic) Nervous S
*
25. SkeletaMl uscleR elaxants .....................339
Section 7
Drugs Acting on Central Nervous Systqrn I.a-
27.
28.Ethyl and Methyl Alcohols .................. .............."...'.....380
29.Sedative-Hypnotics ...........388
30.Antiepileptic Drugs ...........401
31.Antiparkinsonian Drugs ..................'......414
32. Drugs Used in Mental Illness: Antipsychotic and Antimanic Drugs .........'....423
33.Drugs Used in Mental lllness: Antidepressant and Antianxiety Drugs .........439
34. Opioid Analgesics and Antagonists .....453
35.CNS Stimulants and Cognition Enhancers. .............
Contents ix
Section U
Cardiovas-cular Drugs
CardiacE lectrophysiological Considerations ....,......476
36.DrugsAffectingRenin-AngiotensinSystemandPlasmaKinins .......,.....,,,....479
J/. CardiacG lycosidesa nd Drugs for Heart Failure.............. ........,,...499
38.AntiarrhythmicDrugs .......508
39.Antianginal and Other Anti-ischaemic Drugs ..,......521
40.Antihypertensive Drugs ...539
Section 9
Drugs Acting on Kidney
41. Diuretics .......
42. Antidiuretics
Section 1-0
Drugs Affecting Blood and Blood Formation
43.Haematinics and Erythropoietin ........... ..................5..8..1
44. Drugs Affecting Coagulation" Bleeding and Thrombosis......... 593
45. Hypolipidaemic Drugs and Plasma Expanders ......672
Section 1T
GastrointestinalD rugs
45. Drugs for PepticU lcer............ .................627
47. Drags for Emesis,R eflux and Digestive Disorders ..................5..3..9
48. Drugs for Constipation and Diarrhoea ..................6..5..1
Section 12 .'
Antimicrobial Drugs
49. Antimicrobial Drugs: General Considerations ................. .............567
50. Sulfonamides, Cotrimoxazole and Quinolones .......G82
51. Beta-LactamA ntibiotics ............... ...........594
x Contents
52.Tetracyclinesa nd Chloramphenicol (Broad-SpectrumA ntibiotics) ............ ....710
53.Aminoglycoside Antibiotics............... ....719
54.Macrolide, Lincosamide, Glycopeptideand Other Antibacterial Antibiotics;
Urinary Antiseptics 727
55. AntitubercularDrugs 739
56. Antileprotic Drugs 7s7
5/. Antifungal Drugs ............. /Jt
58. 767
59. Antimalarial Drugs 780
50. Antiamoebic and Other Antiprotozoal Drugs 797
51..AnthelminticDrugs 808
Section 13
Chemotherapyo f NeoplasticD iseases
1,4
63. Immunosuppressants, Gene Therapy...... .................837
64. Drugs Acting on Skin and Mucous Membranes .....845
55. Antiseptics, Disinfectants and Ectoparasiticides.............. .............857
65. ChelatingAgents ................855
68. Vaccinesa nd Sera... .........,.879
69. Drug Interactions ...............889
SelectedR eferencesf or Further Reading...... ...,.......,897
Appendix 1: List of EssentialM edicines .............. .......9 03
Appendix 2: Prescribingi n Pregnancy ....................9..0..8
Appendix3: DrugsinBreastfeeding ......977
Appendix 4: Drugs anilFixedDose Combinations Banneilinlndia ....,,...,,...,, ....9 15
10
19
List of Abbreztiations
17
19
;1
)t A-r/il/r1l Angiotensin I/II/[I Asc LH Ascending tmb of Loop of Henle
)/ AA Arnino acid AT-III Antithrornbin III
t0 ABC ATP-binding cassette (transporter) ATG Antithymocyte globulin
ABLC Amphotericin B lipid compiex ATP Adenosine triphosphate
Y7 AB Antibody ATPase Adenosine triphosphatase
AC Adenylyi cyclase ATPIII Adult heatment panel III
I ACE Angiotensin II converting enz)'me ATS Antitetanic serum
ACh Acetylcholine A-V Atrioventricular
AChE Acetylcholinesterase AVP Arginine vasopressin
ACT Artemisinin-based combination therapy AZ't Zidovudine
ACTH Adrenocorticotropic hormone
AD Alzheimer's disease BAL British anti lewisite
ADE Adverse drug event BAN British approved name
ADH Antidiuretic hormone BB Borderline leprosy
ADP Adenosine diphosphate BCG Bacillus Calmette Gu6rin
Adr Adrenaline BCNU Bisctrloroethyl nitrosourea (Carmustine)
ADR Adverse drug reaction BD Twice daily
ADS Anti diphtheritic senxn P-ARK p adrenergic receptor kinase
AES Atrial extrasystole BHC Benzene hexachloride
AF Ahial fibrillation BHP Benign hypertrophy of prostate
AFI Atrial flutter BI Bacillary index
AG Antigen BL Borderline lepromatous leprosy
AGS Antigasgangrene serum BMD Bone mineral density
AHG Antihaemophilic globulin BMR Basal metabolic rate
AI Aromatase inhibitor BNP Brain nartriuretic peptide
AIDS Acquired immunodeficiency syndrome BOL 2-Bromolysergic acid diethylamide
AIP Aldosterone induced protein BP Blood pressure
ALA Alanine BPN Bisphosphonate
Am Amikacin BRMs Biologic response modiliers
AMA Antimicrobial agent BSA Body surface area
AMB Amphotericin B BT Borderline tuberculoid leprosv
amp Ampoule BuChE Butyryl cholinesterase
AMP Adenosine mono phosphate BW Body weight
AMPA o-Arninohydroxy methylisoxazole BZD Benzodiazepine
propionic acid
ANC Acid neutralizing capacity c-10 Decamethonium
ANP Atrial natriuretic peptide CA Catecholamine
ANS Autonomic nervous system CaBP Calcium binding protein
AP Action potential CAD Coronary artery disease
APC Antigen presenting cell CAM Calmodulin
APD Action potential duration cAMP 3', 5' Cyclic adenosine monophosphate
aPTT Activated partial thromboplastin time caP Capsule
ARB Angiotensin receptor blocker CAR Conditioned avoidance response
ARC AIDS related complex CAse Carbonic anhydrase
ARS Anti rabies serum CAT Computerized axial tomography
ARV Antiretrovirus CBF Cerebral blood flow
5-ASA S-Amino salicydic acid CBG Cortisol binding globulin
xii Abbreviations
CBS Colloidal bismuth subcitrate DI Diabetes insipidus
ccB Calcium channel blocker DIT Diiodotyrosine
CCNU Ciloroethyl cyclohexyl nitrosourea dl Decilitre
(lomustine) DLE Disseminated lupus erythematosus
CD Collecting duct DMA Dimethoxy amphetamine
CFTR Cystic fibrosis transport regulator DMARD Disease modi{zing antirheumatic dru:
CGMP 3', 5' Cyclic guanosine monophosphate DMPA Depot medrox),?rogesterone acetate
CGRP Calcitonin gene related peptide DMPP Dimethyl phenyl piperazinium
CH Cholesterol DMT Dimethyl tryptamine/Divalent metai
ChE Cholinesterase uansDorter
CHE Cholesterol ester DNA Deoxyribose nucleic acid
Chv Chylomicron DOC Deoxycholate
Chy rem. Chylomicron remnants DOCA Desoxy corticosterone acetate
CHF Congestive heart failure DOM Dimethoxymethyl amphetamine
CI Cardiac index dopa Dihydroxyphenyl alanine
CL Clearance DOPAC 3, 4, Dihydroxyphenyl acetic acid
CLcr Creatinine ciearance DOSS Dioctyl sulfosuccinate
CMI Ce1l mediated immunity DOTS Directly observed treatment short course
CMV Cytomegalovirus DPD Dihydropyrirnidine dehydrogenase
CNS Central nervous system DPT Diphtheria-pertussis-tetanus triple antige:
c.o. L4ruraL u^.u.tuP..u!r DRC Dose-response curve
CoEn-A -C^-oi:^e^ nzyme-A DT Drstal tubule
COMT Catechol-O-methyl transferase DT-DA Diphtheria-tetanus double antigen
COX Cyclooxygenase d-TC d-Tubocurarine
cPs. Cycles per second DTIC Dacarbazine
CPS Complex partial seizures DTPA Diethylene triamine pentaacetic acid
CPZ Chlorpromazine DYN Dlnorphin
CRABP Celluiar retinoic acid binding protein
CRBP Cellular retinol binding protein E Ethambutol
CRF Corticotropin releasing factor EACA Epsilon amino caproic acid
CSF Cerebrospinal fluid EAD Early after-depolarization
CTZ Chemoreceptor trigger zone e.c.f. Extracellular fluid
CV Cardiovascular ECG Electrocardiogram
CVP Central venous pressure ECT Electroconvulsive theraov
CVS Cardiovascular system ED Erecfile dysfunction
CWD Cell wall deficient EDTA Ethylene diamine tetraacetic acid
CYP45OCytochrome P450 EEG Electroencephalogram
cyt Cycloserine ELAM-I Endothelial leukocyte adhesion molecule-1
B-END p-Endorphin
DA Dopamrne ENS Enteric nervous system
DA-B12Deoxyadenosyl cobalamin ENT Extraneuronal amine transporter
DAD Delayed after-depolarization EPEC Enteropathogenic E. coli
DAC Diacyl glycerol EPO Erythropoietin
DAM Diacetyl monoxime EPP End :p.late Dotential
DAMP Diphenyl acetoxy-N-methyl piperidine tl(P -E.t.J ective refractorv oeriod
methiodide EPSP Excitatory postsynaptic potential
DAT Dopamine transporter ER Estrogen receptor
dDAVP Desmopressin ES Extrasystole
DDS Diamino diphenyl sulfone (Dapsone) ESR Erythrocyte sedimentation rate
DDT Dichloro diphenyl trichloroethane ETEC Enterotoxigenic E coll
DEC Diethyl carbamazine citrate Etm Ethionamide
DHA Dihydroartemisinin
DHE Dihydroergotamine FA Folic acid
DHFA Dihydro folic acid FAD Flavin adenine dinucleotide
DHFRase Dihydrofolate reductase 5-FC 5-Flucytosine
DHP Dihydropyridine FDT Fixed duration therapy (of leprosy)
DHT Dihydrotachysierol FEV1 Forced expiratory volume in 1 second