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PHARMACOLOGY
for Medical Graduates
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FOURTH EDITION
( R E V I S E D A N D U P D AT E D E D I T I O N )
PHARMACOLOGY
for Medical Graduates
TARA V SHANBHAG MD
Professor and Head, Department of Pharmacology
Srinivas Institute of Medical Sciences and Research Centre
Mukka, Surathkal, Mangalore
Karnataka, India
Formerly, Professor, Department of Pharmacology
Kasturba Medical College, Manipal, Manipal Academy of Higher Education
Manipal, Karnataka, India
SMITA SHENOY MD
Additional Professor, Department of Pharmacology
Kasturba Medical College, Manipal, Manipal Academy of Higher Education
Manipal, Karnataka, India
RELX India Pvt. Ltd.
Registered Office: 818, 8th Floor, Indraprakash Building, 21, Barakhamba Road, New Delhi 110001
Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase II, Gurgaon-122002, Haryana, India
Pharmacology for Medical Graduates, 4e, Tara V Shanbhag and Smita Shenoy (Revised and
Updated Edition)
Copyright © 2020 by RELX India Pvt. Ltd.
Previous editions Copyrighted 2019, 2015, 2013, 2008
All rights reserved.
ISBN: 978-81-312-6259-7
eISBN: 978-81-312-6260-3
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechani-
cal, including photocopying, recording, or any information storage and retrieval system, without permission in
writing from the publisher. Details on how to seek permission, further information about the Publisher’s permis-
sions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright
Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher (other
than as may be noted herein).
Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds or experiments described herein. Because of rapid advances in
the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made.
To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors in
relation to the adaptation or for any injury and/or damage to persons or property as a matter of products li-
ability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.
Typeset by GW India
Printed and bound at
FOREWORD TO THE FIRST EDITION
It is common knowledge that books play a major complementary and contributing role
in any educational process. While they are envisioned to facilitate self-learning beyond
classroom exercises, not all of them promote learning; some, indeed, hinder it.
To be useful and worthwhile, a book has to be so designed as to present an appro-
priate body of knowledge in a style that suits students in a particular stage of learning:
undergraduate, postgraduate, or postdoctoral.
Accordingly, a book in pharmacology for MBBS phase-II students would have a
body of knowledge that relates with the study-course objectives and contains ‘must
know’ and ‘nice to know’ levels of factual, conceptual and applied aspects of the subject.
It has a presentation style that offers an integrated composite picture of the subject
interspersed with lucid explanations, cogent reasoning and logical networking of infor-
mation. Contents will enable students to grasp topics in proper perspective and trigger
students’ higher mental skills like critical thinking, logical reasoning, etc. Proficiency so
acquired would enable the students to not only clear qualifying tests but also to wisely
manage drug issues in future.
Designing such a book is a challenging task, especially if it is to be concise and compre-
hensive in scope. Such a version demands wise sifting, prudent pruning and meaningful
condensing of the enormous and variegated knowledge base of pharmacology.
Commendably, Dr (Mrs) Tara Shanbhag has accomplished this in her very first ven-
ture. A fairly large number of charts, diagrams and other forms of illustrations in the
text amply demonstrate this. No wonder, she has received ‘Good Teacher’ award time
and again.
A well written concise book as this one, serves twice as a preparatory tool: at the start
of the study-course it provides a road-map of the subject to be learnt and thus tunes the
students for deeper learning; and at the course-end (and examination time) it helps in
rapid review and recapitulation of what is learnt.
I am confident that this well thought out and well planned book, Preparatory Manual
of Pharmacology for Undergraduates by Dr Tara V Shanbhag will be of tremendous use
to the students.
With pleasure, I compliment Dr (Mrs) Tara V Shanbhag, an erstwhile postgraduate
student of mine, for such a fine piece of work.
Professor DR Kulkarni
Formerly: Head, Department of Medical Education, BM Patil Medical College, Bijapur;
Director of PG Studies, Head, Department of Pharmacology, KMC, Manipal;
Principal, Dr. Patil Medical College, Kolhapur;
Head, Department of Pharmacology, JNMC, Belgaum;
President, Pharmacological Society of India (1995)
v
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PREFACE TO THE FOUR TH EDITION
Pharmacology is a vast subject and one of the fast-growing branches of medical science
and requires addition of latest information from time to time. The present fourth
edition includes significant expansion and revision of the third edition. Some new
topics like drug dosage forms and calculation of dosage of drugs have been included.
The cardiovascular drug summary table also have been included for quick revision.
The style has been retained in the form of simple diagrams, self-explanatory flowcharts,
tables and student-friendly mnemonics. The textual presentation in tabular format
helps in quick reading and recall. Definitions and treatment schedules have been incor-
porated as per various guidelines.
This extensively revised and updated edition will be useful not only for the students
of medicine but also for the practicing doctors as well. This book will also help
postgraduates of pharmacology and other clinical subjects for quick revision of
pharmacology and therapeutics.
We are extremely thankful to our students and colleagues, who had given us valuable
feedback for this edition.
We hope this edition will meet the requirements of the undergraduate medical
students and serves as a better learning tool. We would sincerely appreciate critical
appraisal of this manual and suggestions for further improvement in future.
Tara V Shanbhag
Smita Shenoy
vii
PREFACE TO THE FIRST EDITION
Pharmacology is a vast subject with many crucial aspects related to drugs, their compo-
sition, uses, effects, interactions, etc. which make the subject complicated and difficult
to comprehend.
During the course of interaction with my students as well as those of other universi-
ties where I went as an examiner, I realized the difficulties faced by them while preparing
for their exams due to vastness of the subject. This motivated me to write a preparatory
manual that condenses this vital subject into essential elements and yet covers the
undergraduate syllabus.
The present book thus is a concise exam-oriented preparatory manual. The text is
presented in a simple, precise and point-wise manner. This style of presentation would
not only make it easier for the students to understand the subject in a better manner, but
would also help them to quickly review and revise the subject before examination.
Further, to make learning simpler and comprehension easier for the students, numerous
tables, flowcharts and line diagrams have been included.
A large number of people have helped me make this book possible. For this, I thank
my postgraduate students and colleagues.
I am grateful to Professor DR Kulkarni for his guidance and suggestions and for
writing the Foreword.
I would appreciate critical appraisal of this manual and suggestions for improvement.
Tara V Shanbhag
viii
BRIEF CONTENTS
1 General Pharmacology 1
2 Autonomic Pharmacology 46
11 Chemotherapy 367
Index 505
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CONTENTS
1 General Pharmacology 1
Introduction (Definitions and Sources of Drugs) 1
Routes of Drug Administration 3
Pharmacokinetics 8
Pharmacodynamics 23
Rational Use of Medicines 36
Adverse Drug Effects 37
Poison Information Centres 42
Pharmacoeconomics 43
New Drug Development 43
2 Autonomic Pharmacology 46
Introduction to Autonomic Nervous System 46
Cholinergic System 46
Cholinergic Agents (Cholinomimetics, Parasympathomimetics) 50
Anticholinergic Agents 62
Skeletal Muscle Relaxants 69
Adrenergic Agonists (Sympathomimetic Agents) 75
Adrenergic Receptor Blockers 88
!-Adrenergic Blockers 88
"-Adrenergic Blockers 91
xi
xii CONTENTS
11 Chemotherapy 367
Sulphonamides 375
Quinolones and Fluoroquinolones 378
Penicillins 383
Cephalosporins 390
Carbapenems 393
CONTENTS xiii
Monobactams 394
Aminoglycosides 394
Tetracyclines 398
Chloramphenicol 401
Macrolides 402
Miscellaneous Antibacterial Agents 405
Urinary Antiseptics 409
Drugs Useful in the Treatment of Sexually Transmitted Diseases 410
Antituberculosis Drugs 412
Antileprotic Drugs 419
Antifungal Agents 422
Antiviral Agents 430
Antimalarial Drugs 438
Antiamoebic Drugs 448
Anthelmintics 454
Anticancer Drugs 459
Index 505
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COMPETENCY MAP
Core Chapter
Code Competency Y/N No. Page No.
PHARMACOLOGY
Topic: Pharmacology
PH1.1 Define and describe the principles of pharmacology and Y 1 1
pharmacotherapeutics.
PH1.2 Describe the basis of Evidence based medicine and Y 1 21
Therapeutic drug monitoring.
PH1.3 Enumerate and identify drug formulations and drug Y 1, 12 8, 495
delivery systems.
PH1.4 Describe absorption, distribution, metabolism & Y 1 8 – 18
excretion of drugs.
PH1.5 Describe general principles of mechanism of drug action. Y 1 23 – 27
PH1.6 Describe principles of Pharmacovigilance & ADR Y 1 41
reporting systems.
PH1.7 Define, identify and describe the management of Y 1 37 – 41
adverse drug reactions (ADR).
PH1.8 Identify and describe the management of drug Y 1 35
interactions.
PH1.9 Describe nomenclature of drugs i.e. generic, branded Y 1 2
drugs.
PH1.10 Describe parts of a correct, complete and legible generic Y - -
prescription. Identify errors in prescription and correct
appropriately.
PH1.11 Describe various routes of drug administration, eg., oral, Y 1 3–8
SC, IV, IM, SL.
PH1.12 Calculate the dosage of drugs using appropriate Y 12 498 – 503
formulae for an individual patient, including children,
elderly and patient with renal dysfunction.
PH1.13 Describe mechanism of action, types, doses, side Y 2 75 – 97
effects, indications and contraindications of adrenergic
and anti-adrenergic drugs.
PH1.14 Describe mechanism of action, types, doses, side Y 2 46 – 68
effects, indications and contraindications of cholinergic
and anticholinergic drugs.
PH1.15 Describe mechanism/s of action, types, doses, side Y 2 69 – 75
effects, indications and contraindications of skeletal
muscle relaxants.
PH1.16 Describe mechanism/s of action, types, doses, side Y 6 230 – 254
effects, indications and contraindications of the drugs
which act by modulating autacoids, including: anti-
histaminics, 5-HT modulating drugs, NSAIDs, drugs for
gout, anti-rheumatic drugs, drugs for migraine.
PH1.17 Describe the mechanism/s of action, types, doses, side Y 5 181 – 189
effects, indications and contraindications of local
anesthetics.
(Continued)
xv
xvi COMPETENCY MAP
Core Chapter
Code Competency Y/N No. Page No.
PH1.18 Describe the mechanism/s of action, types, doses, side Y 5 173 – 181
effects, indications and contraindications of general
anaesthetics, and pre- anesthetic medications.
PH1.19 Describe the mechanism/s of action, types, doses, side Y 5 164 – 173,
effects, indications and contraindications of the drugs 192 – 229
which act on CNS, (including anxiolytics, sedatives &
hypnotics, anti-psychotic, anti- depressant drugs, anti-
maniacs, opioid agonists and antagonists, drugs used
for neurodegenerative disorders, anti-epileptics drugs).
PH1.20 Describe the effects of acute and chronic ethanol intake. Y 5 189 – 191
PH1.21 Describe the symptoms and management of methanol Y 5 191
and ethanol poisonings.
PH1.22 Describe drugs of abuse (dependence, addiction, Y 1, 5 39, 217
stimulants, depressants, psychedelics, drugs used for
criminal offences).
PH1.23 Describe the process and mechanism of drug Y 1, 5 39,
deaddiction. 190 – 191,
204 – 205
PH1.24 Describe the mechanism/s of action, types, doses, side Y 4 151 – 163
effects, indications and contraindications of the drugs
affecting renal systems including diuretics, antidiuretics-
vasopressin and analogues.
PH1.25 Describe the mechanism/s of action, types, doses, side Y 3, 8 285 – 296,
effects, indications and contraindications of the drugs 142 – 143
acting on blood, like anticoagulants, antiplatelets,
fibrinolytics, plasma expanders.
PH1.26 Describe mechanisms of action, types, doses, side Y 3, 4 98 – 104,
effects, indications and contraindications of the drugs 158 – 159
modulating the renin- angiotensin and aldosterone
system.
PH1.27 Describe the mechanisms of action, types, doses, side Y 3 98 – 111
effects, indications and contraindications of
antihypertensive drugs and drugs used in shock.
PH1.28 Describe the mechanisms of action, types, doses, side Y 3 112 – 122
effects, indications and contraindications of the drugs
used in ischemic heart disease (stable, unstable angina
and myocardial infarction), peripheral vascular disease.
PH1.29 Describe the mechanisms of action, types, doses, side Y 3 122 – 131
effects, indications and contraindications of the drugs
used in congestive heart failure.
PH1.30 Describe the mechanisms of action, types, doses, side N 3 131 – 138
effects, indications and contraindications of the
antiarrhythmics.
PH1.31 Describe the mechanisms of action, types, doses, side Y 3 138 – 142
effects, indications and contraindications of the drugs
used in the management of dyslipidemias.
PH1.32 Describe the mechanism/s of action, types, doses, side Y 6 256 – 262
effects, indications and contraindications of drugs used
in bronchial asthma and COPD.
PH1.33 Describe the mechanism of action, types, doses, side Y 6 254 – 256
effects, indications and contraindications of the drugs
used in cough (antitussives, expectorants/ mucolytics).
COMPETENCY MAP xvii
Core Chapter
Code Competency Y/N No. Page No.
PH1.34 Describe the mechanism/s of action, types, doses, side Y 7 277 – 284,
effects, indications and contraindications of the drugs 263 – 270,
used as below: 270 – 272,
1. Acid-peptic disease and GERD 274 – 276,
2. Antiemetics and prokinetics 272 – 273
3. Antidiarrhoeals
4. Laxatives
5. Inflammatory Bowel Disease
6. Irritable Bowel Disorders, biliary and pancreatic
diseases.
PH1.35 Describe the mechanism/s of action, types, doses, side Y 8 297 – 302,
effects, indications and contraindications of drugs used 302
in hematological disorders like:
1. Drugs used in anemias
2. Colony Stimulating factors.
PH1.36 Describe the mechanism of action, types, doses, side Y 9 341 – 354,
effects, indications and contraindications of drugs used 309 – 315,
in endocrine disorders (diabetes mellitus, thyroid 354 – 361
disorders and osteoporosis).
PH1.37 Describe the mechanisms of action, types, doses, side Y 9 316 – 326,
effects, indications and contraindications of the drugs 304 – 309
used as sex hormones, their analogues and anterior
Pituitary hormones.
PH1.38 Describe the mechanism of action, types, doses, side Y 9 331 – 341
effects, indications and contraindications of
corticosteroids.
PH1.39 Describe mechanism of action, types, doses, side Y 9 326 – 331
effects, indications and contraindications the drugs used
for contraception.
PH1.40 Describe mechanism of action, types, doses, side Y 9, 2 322, 91
effects, indications and contraindications of 1. Drugs
used in the treatment of infertility, and 2. Drugs used in
erectile dysfunction.
PH1.41 Describe the mechanisms of action, types, doses, side Y 10 362 – 366
effects, indications and contraindications of uterine
relaxants and stimulants.
PH1.42 Describe general principles of chemotherapy. Y 11 367–375
PH1.43 Describe and discuss the rational use of antimicrobials Y - -
including antibiotic stewardship program.
PH1.44 Describe the first line antitubercular dugs, their Y 11 412 – 417
mechanisms of action, side effects and doses.
PH1.45 Describe the dugs used in MDR and XDR Tuberculosis. Y 11 418
PH1.46 Describe the mechanisms of action, types, doses, side Y 11 419 – 422
effects, indications and contraindications of antileprotic
drugs.
PH1.47 Describe the mechanisms of action, types, doses, side Y 11 438 – 448,
effects, indications and contraindications of the drugs 453,
used in malaria, KALA-AZAR, amebiasis and intestinal 448 – 452,
helminthiasis. 454 – 458
PH1.48 Describe the mechanisms of action, types, doses, side Y 11 409 – 410,
effects, indications and contraindications of the drugs 430 – 438
used in UTI/ STD and viral diseases including HIV.
(Continued)
xviii COMPETENCY MAP
Core Chapter
Code Competency Y/N No. Page No.
PH1.49 Describe mechanism of action, classes, side effects, Y 11 459 – 469
indications and contraindications of anticancer drugs.
PH1.50 Describe mechanisms of action, types, doses, side Y 12 472 – 476
effects, indications and contraindications of
immunomodulators and management of organ
transplant rejection.
PH1.51 Describe occupational and environmental pesticides, Y 2 60 – 61
food adulterants, pollutants and insect repellents.
PH1.52 Describe management of common poisoning, Y 1 41 – 42,
insecticides, common sting and bites. 60 – 61
PH1.53 Describe heavy metal poisoning and chelating agents. N 12 470 – 472
PH1.54 Describe vaccines and their uses. Y 12 485 – 487
PH1.55 Describe and discuss the following National Health Y - -
Programmes including Immunisation, Tuberculosis,
Leprosy, Malaria, HIV, Filaria, Kala Azar, Diarrhoeal
diseases, Anaemia & nutritional disorders, Blindness,
Non-communicable diseases, cancer and Iodine
deficiency.
PH1.56 Describe basic aspects of Geriatric and Pediatric Y - -
pharmacology.
PH1.57 Describe drugs used in skin disorders. Y 12 487 – 491
PH1.58 Describe drugs used in Ocular disorders. Y 12 491 – 492
PH1.59 Describe and discuss the following: Essential medicines, Y 1 1, 21 – 22
Fixed dose combinations, Over the counter drugs,
Herbal medicines.
PH1.60 Describe and discuss Pharmacogenomics and N 1 43
Pharmacoeconomics.
PH1.61 Describe and discuss dietary supplements and N - -
nutraceuticals.
PH1.62 Describe and discuss antiseptics and disinfectants. Y 12 476 – 479
PH1.63 Describe Drug Regulations, acts and other legal aspects. Y - -
PH1.64 Describe overview of drug development, Phases of Y 1 43 – 45
clinical trials and Good Clinical Practice.
■ Pharmacology: It is the science that deals with the effects of drugs on living systems.
■ Drug: World Health Organization (WHO) defines drug as ‘any substance or
product that is used or intended to be used to modify or explore physiological systems
or pathological states for the benefit of the recipient’.
■ Pharmacokinetics: It means the movement of drug within the body; it includes
the processes of absorption (A), distribution (D), metabolism (M) and excretion
(E). It means ‘what the body does to the drug’.
■ Pharmacodynamics: It is the study of drugs – their mechanism of action, phar-
macological actions and their adverse effects. It covers all the aspects relating to
‘what the drug does to the body’.
■ Pharmacy: It is the branch of science that deals with the preparation, preserva-
tion, standardization, compounding, dispensing and proper utilization of drugs.
■ Therapeutics: It is the aspect of medicine concerned with the treatment of diseases.
■ Chemotherapy: It deals with treatment of infectious diseases/cancer with chemi-
cal compounds that cause relatively selective damage to the infecting organism/
cancer cells.
■ Toxicology: It is the study of poisons, their actions, detection, prevention and
treatment of poisoning.
■ Clinical pharmacology: It is the systematic study of a drug in man, both in
healthy volunteers and in patients. It includes the evaluation of pharmacokinetic
and pharmacodynamic data, safety, efficacy and adverse effects of a drug by com-
parative clinical trials.
■ Essential medicines: According to WHO, essential medicines are ‘those that sat-
isfy the healthcare needs of majority of the population’. They should be of assured
quality, available at all times, in adequate quantities and in appropriate dosage
forms. They should be selected with regard to disease prevalence in a country,
evidence on safety and efficacy, and comparative cost-effectiveness. The examples
are iron and folic acid preparations for anaemia of pregnancy, antitubercular
drugs like isoniazid, rifampicin, pyrazinamide, ethambutol, etc.
■ Orphan drugs: Drugs that are used for diagnosis, treatment or prevention of rare
diseases. The expenses incurred during the development, manufacture and marketing
of drug cannot be recovered by the pharmaceutical company from selling the drug, e.g.
digoxin antibody (for digoxin toxicity), fomepizole (for methyl alcohol poisoning), etc.
■ Over-the-counter drugs (OTC drugs, nonprescription drugs): These drugs can
be sold to a patient without the need for a doctor’s prescription, e.g. paracetamol,
antacids, etc.
■ Prescription drugs: These are drugs which can be obtained only upon producing the
prescription of a registered medical practitioner, e.g. antibiotics, antipsychotics, etc.
1
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2 PHARMACOLOGY FOR MEDICAL GRADUATES
Formulary: It provides information about the available drugs in a country – their use,
dose, dosage forms, adverse effects, contraindications, precautions, warnings and guid-
ance on selecting the right drug for a range of conditions.
*S Kopp-Kubel. International Nonproprietary Names (INN) for pharmaceutical substances. Bull World Health
Organ 1995;73(3):275–279.
1—GENERAL PHARMACOLOGY 3
SOURCES OF DRUGS
They are natural, semisynthetic and synthetic. Natural sources are plants, animals, min-
erals, microorganisms, etc. Semisynthetic drugs are obtained from natural sources and
are later chemically modified. Synthetic drugs are produced artificially.
The different sources of drugs:
1. Plants:
a. Alkaloids are nitrogen containing compounds, e.g. morphine, atropine, quinine,
reserpine, ephedrine.
b. Glycosides contain sugar group in combination with nonsugar through ether
linkage, e.g. digoxin, digitoxin.
c. Volatile oils have aroma. They are useful for relieving pain (clove oil), as carmi-
native (eucalyptus oil), flavouring agent (peppermint oil), etc.
d. Resins are sticky organic compounds obtained from plants as exudate, e.g. tincture
benzoin (antiseptic).
2. Animals: Insulin, heparin, antisera.
3. Minerals: Ferrous sulphate, magnesium sulphate.
4. Microorganisms: Penicillin G, streptomycin, griseofulvin (antimicrobial agents),
streptokinase (fibrinolytic).
5. Semisynthetic: Hydromorphone, hydrocodone.
6. Synthetic: Most of the drugs used today are synthetic, e.g. aspirin, paracetamol.
Drugs are also produced by genetic engineering (DNA recombinant technology), e.g.
human insulin, human growth hormone and hepatitis B vaccine.
Most of the drugs can be administered by different routes. Drug- and patient-related
factors determine the selection of routes for drug administration. These factors are
1. Characteristics of the drug.
2. Emergency/routine use.
3. Condition of the patient (unconscious, vomiting and diarrhoea).
4. Age of the patient.
5. Associated diseases.
6. Patient’s/doctor’s choice (sometimes).
Routes
Local Systemic
Enteral Parenteral
– Oral – Injection
– Sublingual – Inhalation
– Rectal – Transdermal
Routes of drug administration
4 PHARMACOLOGY FOR MEDICAL GRADUATES
LOCAL ROUTES
It is the simplest mode of administration of a drug at the site where the desired action
is required. Systemic side effects are minimal.
1. Topical: Drug is applied to the skin or mucous membrane at various sites for
localized action.
a. Oral cavity: As suspension, e.g. nystatin; as a troche, e.g. clotrimazole (for oral
candidiasis); as a cream, e.g. acyclovir (for herpes labialis); as ointment, e.g. 5%
lignocaine hydrochloride (for topical anaesthesia); as a spray, e.g. 10% ligno-
caine hydrochloride (for topical anaesthesia).
b. GI tract: As tablet which is not absorbed, e.g. neomycin (for sterilization of gut
before surgery).
c. Rectum and anal canal:
1) As an enema (administration of drug into the rectum in liquid form):
■ Evacuant enema (for evacuation of bowel): For example, soap water
colitis.
2) As a suppository (administration of the drug in a solid form into the
rectum), e.g. bisacodyl suppository for evacuation of bowel.
d. Eye, ear and nose: As drops, ointment and spray (for infection, allergic condi-
tions, etc.), e.g. gentamicin – eye and ear drops.
e. Bronchi: As inhalation, e.g. salbutamol, ipratropium bromide, etc. (for bronchial
asthma and chronic obstructive pulmonary disease).
f. Vagina: As tablet, cream, pessary, etc. (for vaginal candidiasis).
g. Urethra: As jelly, e.g. lignocaine.
h. Skin: As ointment, cream, lotion, powder, e.g. clotrimazole (antifungal) for
cutaneous candidiasis.
2. Intra-arterial route: This route is rarely employed. It is mainly used during diag-
nostic studies, such as coronary angiography and for the administration of some
anticancer drugs, e.g. for treatment of malignancy involving limbs.
3. Administration of the drug into deep tissues by injection, e.g. administration of
triamcinolone directly into the joint space in rheumatoid arthritis.
SYSTEMIC ROUTES
Drugs administered by this route enter the blood and produce systemic effects.
Enteral Routes
They include oral, sublingual and rectal routes.
Oral Route. It is the most common and acceptable route for drug administration.
Dosage forms are tablet, capsule, powder, syrup, linctus, mixture, suspension, etc., e.g.
paracetamol tablet for fever, omeprazole capsule for peptic ulcer are given orally. Tablets
could be coated (covered with a thin film of another substance) or uncoated. They are
also available as chewable (albendazole), dispersible (aspirin), mouth dissolving
(ondansetron) and sustained release forms. Capsules have a soft or hard shell.
Advantages
■ Safer.
■ Cheaper.
■ Painless.
1—GENERAL PHARMACOLOGY 5
Disadvantages
■ It is not suitable for/in:
■ unconscious patients
Sublingual Route. The preparation is kept under the tongue. The drug is absorbed
through the buccal mucous membrane and enters systemic circulation directly, e.g.
nitroglycerin(for acute attack of angina) and buprenorphine.
Advantages
■ Quick onset of action of the drug.
■ Self-administration is possible.
Disadvantages
■ It is not suitable for:
Parenteral Routes
Routes of administration other than enteral route are called parenteral routes.
Advantages
■ Onset of action of drugs is faster, hence suitable for emergency.
■ Useful in:
■ unconscious patient
■ Suitable for:
■ irritant drugs
Disadvantages
■ Require aseptic conditions.
Inhalation. Volatile liquids and gases are given by inhalation for systemic effects, e.g.
general anaesthetics.
Advantages
■ Quick onset of action.
Disadvantages
■ Local irritation may cause increased respiratory secretion and bronchospasm.
Advantages
■ Self-administration of drug is possible, e.g. insulin.
■ Depot preparations can be inserted into the subcutaneous tissue, e.g. norplant for
contraception.
Disadvantages
■ It is suitable only for nonirritant drugs.
Intradermal
Subcutaneous
Intravenous
Intra-arterial
Intramuscular
Intra-articular
Intramuscular (i.m.) Route. Drugs are injected into large muscles, such as deltoid, glu-
teus maximus and vastus lateralis, e.g. paracetamol, diclofenac, etc. A volume of 5–10 mL
can be given at a time.
Advantages
■ Absorption is more rapid as compared to oral route.
■ Mild irritants, depot injections, soluble substances and suspensions can be given
by this route.
Disadvantages
■ Aseptic conditions are needed.
Intravenous (i.v.) Route. Drugs are injected directly into the blood stream through
a vein. Drugs are administered as
1. Bolus: Single, relatively large dose of a drug injected rapidly or slowly into a vein,
e.g. i.v. ranitidine in bleeding peptic ulcer.
2. Slow intravenous injection: For example, i.v. morphine in myocardial infarction.
3. Intravenous infusion: For example, dopamine infusion in cardiogenic shock;
mannitol infusion in cerebral oedema; fluids infused intravenously in dehydration.
Advantages
■ Bioavailability is 100%.
severe dehydration.
■ Highly irritant drugs, e.g. anticancer drugs can be given because they get diluted in blood.
cerebral oedema.
■ By i.v. infusion, a constant plasma level of the drug can be maintained, e.g. dopamine
Disadvantages
■ Local irritation may cause phlebitis.
■ Extravasation of some drugs (e.g. noradrenaline) can cause injury, necrosis and
sloughing of tissues.
■ Depot preparations cannot be given by i.v. route.
Precautions
■ Drug should usually be injected slowly.
■ Before injecting, make sure that the tip of the needle is in the vein.
Intrathecal Route. Drug is injected into the subarachnoid space, e.g. lignocaine
(spinal anaesthesia), antibiotics (amphotericin B), etc.
Backing layer
D D D D
D D D Drug reservoir
D D D D
D D D D D Rate controlling
membrane
Adhesive layer
Disadvantages
■ Expensive.
Pharmacokinetics PH1.4
Pharmacokinetics is derived from two words: Pharmacon meaning drug and kinesis
meaning movement. In short, it is ‘what the body does to the drug’. It includes
1—GENERAL PHARMACOLOGY 9
absorption (A), distribution (D), metabolism (M) and excretion (E). All these pro-
cesses involve movement of the drug molecule through various biological membranes.
All biological membranes are made up of a lipid bilayer. Drugs cross various bio-
logical membranes by the following mechanisms:
1. Passive diffusion: It is a bidirectional process. The drug molecules move from a
region of higher to lower concentration until equilibrium is attained. The rate
of diffusion is directly proportional to the concentration gradient across the
membrane. Lipid-soluble drugs are transported across the membrane by passive
diffusion. It does not require energy and is the process by which majority of the
drugs are absorbed.
2. Active transport: Drug molecules move from a region of lower to higher concen-
tration against the concentration gradient. It requires energy, e.g. transport of
sympathomimetic amines into neural tissue, transport of choline into cholinergic
neurons and absorption of levodopa from the intestine. In primary active trans-
port, energy is obtained by hydrolysis of ATP. In secondary active transport, energy
is derived from transport of another substrate (either symport or antiport).
3. Facilitated diffusion: This is a type of carrier-mediated transport and does not
require energy. The drug attaches to a carrier in the membrane, which facilitates
its diffusion across the membrane. The transport of molecules is from the region
of higher to lower concentration, e.g. transport of glucose across muscle cell mem-
brane by a transporter GLUT 4.
4. Filtration: Filtration depends on the molecular size and weight of the drug.
If drug molecules are smaller than the pores, they are filtered easily through the
membrane.
5. Endocytosis: The drug is taken up by the cell through vesicle formation. Absorp-
tion of vitamin B12–intrinsic factor complex in the gut is by endocytosis.
BIOAVAILABILITY
It is the fraction of a drug that reaches systemic circulation from a given dose. Intrave-
nous route of drug administration gives 100% bioavailability as it directly enters the
circulation. The term bioavailability is used commonly for drugs given by oral route.
If two formulations of the same drug produce equal bioavailability, they are said
to be bioequivalent. If formulations differ in their bioavailability, they are said to be
bioinequivalent.
Factors Affecting Bioavailability. The factors which affect drug absorption (physico-
chemical properties of the drug, route of drug administration, pH and ionization, food,
1—GENERAL PHARMACOLOGY 11
presence of other drugs, area of absorbing surface, GI and other diseases) also affect bio-
availability of a drug. Other factors that affect the bioavailability of a drug are discussed
as follows:
1. First-pass metabolism (First-pass effect, presystemic elimination): When drugs
are administered orally, they have to pass via gut wall n portal vein n liver n
systemic circulation (Fig. 1.4). During this passage, certain drugs get metabolized
and are removed or inactivated before they reach the systemic circulation. This
process is known as first-pass metabolism. The net result is a decreased bioavail-
ability of the drug and diminished therapeutic response, e.g. drugs like lignocaine
(liver), isoprenaline (gut wall), etc.
Consequences of high first-pass metabolism:
1) Drugs which undergo extensive first-pass metabolism are administered
parenterally, e.g. lignocaine is administered intravenously in ventricular
arrhythmias.
2) Dose of a drug required for oral administration is more than that given by
other systemic routes, e.g. nitroglycerin.
2. Hepatic diseases: They result in a decrease in drug metabolism, thus increasing
the bioavailability of drugs that undergo high first-pass metabolism, e.g. pro-
pranolol and lignocaine.
3. Enterohepatic cycling: Some drugs are excreted via bile but after reaching the in-
testine they are reabsorbed n liver n bile n intestine and the cycle is repeated –
such recycling is called enterohepatic circulation and it increases bioavailability
as well as the duration of action of the drug, e.g. morphine and doxycycline.
Language: Spanish
EL 19 DE MARZO Y EL 2 DE MAYO
Es propiedad. Queda hecho el depósito que
marca la ley. Serán furtivos los ejemplares que no
lleven el sello del autor.
EL 19 DE MARZO
Y EL
2 DE M AYO
4 4. 0 0 0
MADRID
PERLADO, PÁEZ Y COMPAÑÍA
(Sucesores de Hernando)
ARENAL , 1 1
1907
EL 19 DE MARZO Y EL 2 DE MAYO
Cuatrocientos versos por este estilo nos tragamos Inés y yo, siendo
de notar que ella atendía a la lectura con tanta formalidad como si la
comprendiera, y aun en los pasajes más ruidosos hacía señales de
asentimiento y elogio para contentar al pobre viejo: ¡tal era su
discreción!
—Puesto que os ha agradado tanto, hijos míos —dijo D. Celestino
guardando su manuscrito—, otro día os leeré parte del poema. Lo dejo
para mejor ocasión y así se comparte el placer entre varios días
evitando el empacho que produce la sucesión de manjares demasiado
dulces y apetitosos.
—¿Y piensa usted leérsela también al Príncipe de la Paz?
—¿Pues para qué la he escrito? A Su Alteza Serenísima le encantan
los versos latinos... porque es un gran latino... y pienso darle un buen
rato uno de estos días. Y a propósito, ¿qué se dice por Madrid? Aqu
está la gente bastante alarmada. ¿Pasa allá lo mismo?
—Allá no saben qué pensar. Figúrese usted, la cosa no es para
menos. Temen a los franceses, que están entrando en España a más y
mejor. Dicen que el Rey no dio permiso para que entrara tanta gente, y
parece que Napoleón se burla de la Corte de España, y no hace
maldito caso de lo que trató con ella.
—Es gente de pocos alcances la que tal dice —repuso D. Celestino
—. Ya saben Godoy y Bonaparte lo que se hacen. Aquí todos quieren
saber tanto como los que mandan; de modo que se oyen unos
disparates...
—Lo de Portugal ha resultado muy distinto de lo que se creía. Un
general francés se plantó allá, y cuando la familia real se marchó para
América, dijo: «Aquí no manda nadie más que el Emperador, y yo en
su nombre. Vengan cuatrocientos milloncitos de reales; vengan los
bienes de los nobles que se han ido al Brasil con la familia real.»
—No juzguemos por las apariencias —dijo D. Celestino—: sabe Dios
lo que habrá en eso.
—En España van a hacer lo mismo —añadí—; y como los Reyes
están llenos de miedo, y el Príncipe de la Paz tan aturrullado, que no
sabe qué hacer...
—¿Qué estás diciendo, tontuelo? ¿Cómo tratas con tan poco respeto
a ese espejo de los diplomáticos, a esa natilla de los ministros? ¿Que
no sabe lo que se hace?
—Lo dicho, dicho. Napoleón les engaña a todos. En Madrid hay
muchos que se alegran de ver entrar tanta tropa francesa, porque
creen que viene a poner en el trono al Príncipe Fernando. ¡Buenos
tontos están!
—¡Tontos, mentecatos, imbéciles! —exclamó con enfado el Padre
Celestino.
—Lo que fuere sonará. Si vienen con buen fin esos caballeros, ¿po
qué se apoderan por sorpresa de las principales plazas y fortalezas?
Primero se metieron en Pamplona, engañando a la guarnición; después
se colaron en Barcelona, donde hay un castillo muy grande que llaman
el Montjuich. Después fueron a otro castillo que hay en Figueras, e
cual no es menos grande, el mayor del mundo, según dice Pacorro
Chinitas, y lo cogieron también, y, por último, se han metido en San
Sebastián. Digan lo que quieran, esos hombres no vienen como
amigos. El ejército español está trinando: sobre todo, hay que oír a los
oficiales que vienen del Norte y han visto a los franceses en las plazas
fuertes... le digo a usted que echan chispas. El Gobierno del Rey Carlos
IV está que no le llega la camisa al cuerpo, y todos conocen la
barbaridad que han hecho dejando entrar a los franceses; pero ya no
tiene remedio... ¿Sabe usted lo que se dice por Madrid?
—¿Qué, hijo mío? Sin duda alguna de esas vulgarísimas
aberraciones propias de entendimientos romos. Ya lo he dicho
nosotros no entendemos de negocios de Estado; ¿a qué viene e
comentar las combinaciones y planes de esos hombres eminentes, que
se desviven por hacernos felices?
—Pues allá dicen que la familia real de España, viéndose cogida en
la red por Bonaparte, ha determinado marcharse a América, y que no
tardará en salir de Aranjuez para Cádiz. Por supuesto, los partidarios
del Príncipe Fernando se alegran, y creen que esto les viene de perillas
para que el otro suba al trono.
—¡Necios, mentecatos! —exclamó el tío de Inés, incomodándose de
nuevo—. ¡Pensar que había de consentir tal cosa el señor Príncipe de la
Paz, mi paisano, mi amigo y aun creo que pariente!... Pero no nos
incomodemos fuera de tiempo, Gabriel, y por cosas que no hemos de
resolver nosotros. Vamos a comer, que ya es hora, y el cuerpo lo pide.
Inés, que se había retirado un momento antes, volvió a decirnos
que la comida estaba pronta. Durante ella, el respetable cura nos
comunicó el contenido de la misteriosa carta que había llegado a la
casa por la mañana.
—Hijos míos —dijo cuando los tres habíamos tomado asiento—: voy
a participaros un suceso feliz; tú, Inesilla, regocíjate. La fortuna se te
entra por las puertas, y ahora vas a ver cómo Dios no abandona nunca
a los desvalidos y menesterosos. Ya sabes que tu buena madre, que
santa gloria haya, tenía un primo llamado D. Mauro Requejo
comerciante en telas, cuya lonja, si no me engaño, cae hacia la calle
de Postas, esquina a la de la Sal.
—D. Mauro Requejo... —dije yo recordando—, justamente. Doña
Juana le nombró delante de mí varias veces, y ahora caigo en que ese
comerciante pone en el Diario unos anuncios que me dan bastante que
hacer.
—Le recuerdo —dijo Inés—. Él y su hermana eran los únicos
parientes que tenía mi madre en Madrid. Por cierto que siempre se
negó a favorecernos, aunque lo necesitábamos bastante: dos veces le
vi en casa. ¿Creería su merced que fue a consolarnos, a socorrernos?
No: fue a que mi madre le hiciera algunas piezas de ropa, y después
de regatear el precio, no pagó más que la mitad de lo tratado, y decía
É
«De algo ha de servir el parentesco.» Él y su hermana no hablaban
más que de su honradez o de lo mucho que habían adelantado en e
comercio, y nos echaban en cara nuestra pobreza, prohibiéndonos que
fuéramos a su casa, mientras no nos encontráramos en posición más
desahogada.
—Pues digo —afirmé con enfado— que ese D. Mauro y su señora
hermana son dos grandísimos pillos.
—Poco a poco —continuó el cura—. Déjenme acabar. El primo de tu
madre habrá faltado; pero lo que es ahora, sin duda, Dios le ha tocado
en el corazón, y se dispone a enmendar sus yerros, favoreciéndote
como buen pariente y hombre caritativo. Ya sabes que es bastante
rico, gracias a su laboriosidad y mucha economía. Pues bien: en la
carta que he recibido esta mañana me dice que quiere recogerte y
ampararte en su casa, donde estarás como una reina; donde no te
faltará nada, ni aun aquello de que gustan tanto las damiselas del día
tal como joyas, trajes bonitos, perfumes primorosos, guantes y otras
fruslerías. En fin, Dios se ha acordado de ti, sobrinita. ¡Ah! ¡si vieras
qué interés tan grande demuestra por ti en sus cartas; qué alabanzas
tan calurosas hace de tus méritos; si vieras cómo te pone por esas
nubes, cómo lamenta tu orfandad y cómo se enternece considerando
que eres de su misma sangre, y que, a pesar de esta natura
preeminencia, careces de lo que a él le sobra! Te repito que trabajando
mucho y ahorrando más, el Sr. Requejo ha llegado a ser muy rico. ¡Qué
porvenir te espera, Inesilla! El párrafo más conmovedor de la carta de
tus tíos —añadió sacando la epístola— es este: ¿A quién hemos de
dejar lo que tenemos, sino a nuestra querida sobrinita?
Inés, confundida ante tan inesperado cambio en los sentimientos y
en la conducta de sus antes cruelísimos parientes, no sabía qué pensar
Me miró, buscando sin duda en mis ojos algo que le diera luz sobre tan
inexplicable mudanza; mas yo, que algo creía comprender, me guardé
muy bien de dejarlo traslucir ni con palabras ni con gestos.
—Estoy asombrada —dijo la muchacha—; y por fuerza, para que
mis tíos me quieran tanto, ha de haber algún motivo que no
comprendemos.
—No hay más sino que Dios les ha abierto los ojos —dijo D
Celestino, firme en su ingenuo optimismo—. ¿Por qué hemos de pensa
mal de todas las cosas? D. Mauro es un hombre honrado: podrá tene
sus defectillos; pero ¿qué valen esos ligeros celajes del alma cuando
está iluminada por los resplandores de la caridad?
Inés, mirándome, parecía decirme:
—¿Y tú qué piensas?
Algunos meses antes de aquel suceso, yo hubiera acogido las
proposiciones de D. Mauro Requejo con el imprevisor optimismo, con e
necio entusiasmo que afluían de mi alma juvenil ante los
acontecimientos nuevos e inesperados; pero los contratiempos me
habían dado alguna experiencia: conocía ya los rudimentos de la
ciencia del corazón, y el mío principiaba a reunir ese tesoro de
desconfianzas, merced a las cuales medimos los pasos peligrosos de la
vida. Así es que respondí sencillamente:
—Puesto que ese tu reverendo tío era antes un bribón, no sé po
qué hemos de creerle santo ahora.
—Tú eres un chicuelo sin experiencia —me dijo D. Celestino algo
enojado—, y yo no debiera consultar esto contigo. ¡Si sabré yo
distinguir lo verdadero de lo falso! Y sobre todo, Inés, si él quiere
favorecerte, poniéndote en pie de gente grande; si él quiere gastarse
sus ahorros con su querida sobrina, ¿por qué no lo has de aceptar?
Mucho más podría decirte; pero él mismo en persona te explicará
mejor el gran cariño que te tiene.
—¿Pues qué —preguntó Inés turbada—, vendrá a Aranjuez?
—Sí, chiquilla —repuso el clérigo—. Yo te reservaba esta noticia para
lo último. El domingo próximo tendrás el gusto de ver aquí a tu amado
tío y protector. ¡Ah, Inés! Mucho sentiré separarme de ti; pero
servirame de consuelo la idea de que estás contenta, de que disfrutas
mil comodidades que yo no te puedo dar. Y cuando este viejo incapaz
eche un paseíto a Madrid para visitarte, espero que le recibirás con
alegría y sin orgullo; espero que no te ofuscará la ruin vanidad a
considerarte en posición superior a la mía, porque tío por tío, hermano
soy de tu difunto padre, mientras que el otro...
D. Celestino estaba conmovido, y yo también, aunque por distinta
causa.
—Sí —continuó el cura—. Dentro de ocho días tendremos aquí a ese
eminente tendero de la calle de la Sal. Me dice que habiendo
comprado unas tierras en Aranjuez, junto a la laguna de Ontígola
vendrá con el doble objeto de conocer su finca y de verte. Él espera
que irás a Madrid en su compañía y en la de su hermana Doña
Restituta, a quien también tendremos el gusto de ver en casa.
Después de oír esto, todos callamos. Revolviendo en mi cabeza
extraños y no muy alegres pensamientos, dije a Inés:
—Pero ese hombre, ¿es casado?
Ella leyó en mi interior con su intuición incomparable, y me
respondió con viveza:
—Es viudo.
Después volvimos a callar, y solo D. Celestino, tarareando una
antífona, interrumpía nuestro grave silencio.
III
Imposible decir si Doña Restituta sería más joven o más vieja que
su hermano: ambos parecían haber pasado bastante más allá de los
cuarenta; pero si en la edad se asemejaban, no así en la cara ni e
gesto, pues Restituta era una mujer que no se estorbaba a sí misma y
que sabía estarse quieta. Había en ella, si no fineza de modales, esa
holgada soltura, propia de quien ha hablado con gente por mucho
tiempo. Comparando aquellas dos ramas humanas de un mismo
tronco, se podía decir: «Mauro ha estado toda la vida cargando fardos
y Restituta midiendo y vendiendo; el uno es un sabandijo de almacén
y la otra la bestezuela enredadora de la tienda.»
Alta y flaca, con esa tez impasible y uniforme que parece un forro
de manos largas y feas, a quien el continuo escurrirse por entre telas
había dado cierta flexibilidad; de escaso pelo, tan lustrosamente
aplastado sobre el casco, que más parecía pintura que cabello; con su
nariz encarnadita y algo granulenta, aunque jamás fue amiga de oler lo
de Arganda; la boca plegada y de rincones caídos, la barba un poco
velluda, y un mirar así entre tarde y noche, como de ojos que miran y
no miran, Restituta Requejo era una persona cuyo aspecto no
predisponía a primera vista ni en contra ni en favor. Oyéndola hablar
tratándola, se advertía en ella no sé qué de escurridizo, que escapaba
a la observación, y se caía en la cuenta de que era preciso tratarla po
mucho tiempo para poder hacer presa con dedos muy diestros en la
piel húmeda de su carácter, el cual para esconderse poseía la presteza
del saurio y la flexibilidad del ofidio. Pero dejemos estas
consideraciones para su lugar, y por ahora conténtense ustedes con oí
hablar a los tíos de Inés.
—Este estaba tan impaciente por venir —dijo Restituta, señalando a
su hermano— que con la prisa nos fue imposible traer alguna cosita
como hubiéramos deseado.
D. Celestino les dio las gracias con su amable sonrisa.
—Tenía tanta impaciencia por venir a ver esas tierras —dijo D
Mauro— que... y al mismo tiempo el alma se me arrancaba en
cuajarones al pensar en mi querida sobrinita, huérfana y abandonada..
porque las tierras, señor D. Celestino, no son ningún muladar, Sr. Don
Celestino, y me han costado obra de trescientos cuarenta y ocho
reales, trece maravedís, sin contar las diligencias ni el por qué de la
escritura. Sí, señor: ya está pagado todo, peseta sobre peseta.
—Todo pagado —indicó Doña Restituta, mirando uno tras otro a los
tres que estábamos presentes—. A este no le gusta deber nada.
—¡Quiten para allá! Antes me dejo ahorcar que deber un maraved
—declaró D. Mauro, llevando la manopla a la garganta, oprimida por e
corbatín.
—En casa no ha habido nunca trampas —añadió la hermana.
—A eso deben ustedes el haber adelantado tanto —dijo D
Celestino.
—La suerte... eso sí; hemos tenido suerte —dijo Requejo—. Luego
esta es tan trabajadora, tan ahorrativa, tan hormiguita...
—Pero todo se debe a tu honradez —añadió Restituta—. Sí, créanlo
ustedes, a su honradez. Este tiene tal fama entre los comerciantes, que
le entregarían los tesoros del Rey.
—En fin... algo se ha hecho, gracias a Dios y a nuestro trabajo. S
fuera a hacer caso de esta, compraría tierras y más tierras. A esta no le
gustan sino las fincas.
—Y con razón: si este me hiciera caso —dijo la hermana, mirando
otra vez sucesivamente a los circunstantes—, todas nuestras ganancias
se emplearían en tierras de labor.
—Como yo soy así, tan... pues —indicó Requejo.
—Sin soberbia, Sr. D. Celestino —dijo Restituta—, bueno es
aparentar que se tiene lo que se tiene.
—Y me hace comprar vestidos, sombreros, alhajas —indicó D
Mauro—. Qué sé yo la tremolina de cosas que ha entrado en casa. Ello
como se puede... Vea usted esta cadena —añadió, mostrando a D
Celestino una que traía al cuello—; vea usted también este alfiler
¿Cuánto cree usted que me han costado? La friolenta de mil reales..
Psh: yo no quería; pero esta se empeñó, y como se puede...
—Son hermosas piezas.
—Y bien te dije que te quedaras también con la tumbaga de la
esmeralda, que ya recordarás la daban en poco más de nada. Es una
lástima que la haya tomado el Duque de Altamira.
Al decir esto nos miraban, y nosotros les contestábamos con señales
de asentimiento, pero sin palabras, porque ni a Inés ni a mí se nos
ocurrían.
—Pero ¿cómo está ahí mi sobrina tan calladita? —dijo Requejo
riéndose de improviso y quedándose muy serio un instante después.
Inés se sonrojó y no dijo nada, porque, en efecto, no tenía nada
que decir.
—¡Ay, no puede negar la pinta! ¡Cómo se parece a su madre, a la
pobre Juana, mi prima querida! —exclamó Requejo llevándose la
manopla a la boca para tapar un bostezo—. ¡Y qué pronto se murió la
pobrecita!
—Ya que pasó a mejor vida aquella santa y ejemplar mujer —dijo
Restituta—, no la nombremos, porque así se renueva nuestro dolor y e
de esa pobre muchacha, aunque ella es niña, y los niños se consuelan
más fácilmente.
Inés no dijo nada tampoco; pero el color encendido de su rostro se
trocó en intensa palidez. Creyó conveniente el cura variar la
conversación, dijo:
—¿Y ha visto usted esas tierras de la laguna de Ontígola?
—Todavía no —respondió Requejo—; pero me han dicho que son
magníficas. Psh... para mí, poca cosa. Esta se empeñó en que me
quedara con ellas, y al fin me decidí. Allá en el país tenemos muchas
más, que hemos ido comprando poco a poco.
—En su país de usted, hacia el Bierzo, si no me engaño.
—Más acá del Bierzo, en Santiagomillas, que es tierra de
Maragatería. De allí semos todos, y allí está todavía el solar de los
Requejos.
—Familia hidalga, según creo —afirmó el cura.
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