Материал: MasterPass _ Pharmacology in 7 Days for Medical Students
About the authors
Dr Fazal graduated from Army Medical College, Rawalpindi, Pakistan in 1999. After working in his home country for a few years in various capacities, he came to the UK in 2005. Here he has worked as Clinical Research Fellow in the Universities of Southampton and Bristol, and as a Medical SHO in various NHS trusts. Although a junior doctor, Dr Fazal has contributed appreciably in medical literature. He is the first and corresponding author of eight research papers published in different peerreviewed journals. He has contributed a 28-web-page section namely ‘Phenotyping’ in an online encyclopaedia entitled ‘Online Encyclopaedia of Genetic Epidemiology Studies’, www.oege.org. This section links and describes standardised research protocols and related information for clinical phenotyping on common diseases and risk traits. It is primarily of relevance and consumption of researchers and PhD students. Dr Fazal has three medical books to his credit – the book in your hand, Hospital Dermatology (a 226-page book for final-year medical students and postgraduate trainees) and Essential Lists of Differential Diagnoses for MRCP: with diagnostic hints (a 272-page book for postgraduate doctors preparing for MRCP (UK) and FCPS (Pakistan) examinations). He is currently working as a CT2 in Medicine at the Princess of Wales Hospital in Bridgend.
Ahmed Ehsan Rabbani is a final-year medical student and the younger brother of Dr Fazal. It was Ahmed who highlighted the need for a pharmacology book that medical students could refer to during the last few days before the exam. To realise his vision, he contributed substantially in the design, literature search, drafting, picture drawing and revision of the manuscript. His most valued contribution is giving his elder brother the all-critical insight regarding what to include and what to exclude in this revision book.
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Contributors
Salman S Koul MBBS FCPS-I (Pak) MCPS (Pak)
Registrar
Department of Medicine
Pakistan Institute of Medical Sciences (PIMS)
Islamabad, Pakistan
Fazal R Subhani MBBS FCPS-I (Pak)
Registrar
Department of Pediatrics
Holy Family Hospital
Rawalpindi, Pakistan
Saeeda Yasmin MBBS FCPS (Pak) MRCS (UK)
Consultant Surgeon
Shifa Hospital
Islamabad, Pakistan
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General pharmacology
Pharmacology
1Brief definition: Science that deals with drugs.
2Broad definition: Science that deals with the interaction between living systems and molecules, especially the chemicals introduced from outside the system.
3Comprehensive definition: Knowledge of history, source, physical and chemical properties; compounding absorption, bio-transformation, distribution, excretion, mechanism of action, structural activity relationship, bio-chemical and physiological effects, and therapeutic/other uses of drugs.
WHO deÞnition of drug
A drug is any substance or product that is used or intended to be used to modify or explore physiological symptoms or pathological states for the benefit of the recipient.
DeÞnition of rational drug therapy
Administration of the right drug indicated for the disease, in the right dose, through an appropriate route of administration, for the right duration.
Criteria for right drug
•Cost-effectiveness
•Efficacy
•Safety
Alkaloids
Characteristics
Mostly solid (rarely liquid), nitrogenous compounds, complex structure, found in plants, intensely bitter in taste, very active biologically, basic in nature and form water-soluble salts with acids, e.g. ephedrine, otherwise insoluble in water (soluble in alcohol). Their names end in the suffix ‘ine’.
Examples
Solid alkaloids: Morphine, codeine, ephedrine, atropine, hyoscine, quinine, ergotamine, strychnine.
Liquid alkaloids: Nicotine, lobeline, pilocarpine.
PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS
Glycosides
Characteristics
These are an ether-like combination of sugars with organic structure. They are complex-structured, non-nitrogenous compounds found in plants containing C, H and O2, very active biologically, hydrolysed by acids/enzymes into:
ASugar portions or glycone.
BNon-sugar portions or aglycone.
When the sugar portion is glucose, it is called glucosides, e.g. salicyclines. Their names end in the suffix ‘in’.
Examples
Cardiac glycosides: Like digoxin, digitoxin, gitoxin.
Table 1.1 Differences between Þxed and volatile oils
Fixed oils |
Volatile oils |
Non-volatile
Source: animals and plants
They are esters of higher fatty acids Insoluble in water
They give no smell or taste to water They give greasy marks on paper They are bland and non-irritant They form soaps with alkalis
They cannot be distilled without being decomposed
They become decomposed and smell rancid when kept for a long time
They usually have few pharmacological actions, e.g. nutrient and emollient
Volatile
Plants alone
They are hydrocarbons
Slightly soluble in water
They impart smell and taste to water
They do not give greasy marks on paper
Mildly irritant
They do not form soaps with alkalis
They can be transferred by the process of distillation
They do not decompose
They have many actions, e.g. carminatives, antiseptics, counter-irritants, expectorants and ßavouring agents
Intravenous (I/V) route of administration
Advantages
1Since absorption is not required, pharmacological action starts instantaneously.
2Since first-pass metabolism in the liver is bypassed, the bioavailability of intravenously administered drugs is 100%.
3Valuable for emergency/unconscious patients/patients having vomiting.
4Permits titration of dosage (increase or decrease the dose).
5Suitable for large volumes of fluids, blood, plasma and nutrients.
6Irritant drugs can be given in diluted form.
Disadvantages
1 Drugs once injected cannot be taken out.
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GENERAL PHARMACOLOGY
2More risk of side effects like sepsis, phlebitis, etc.
3Extravasation into the surrounding tissues with resultant possible side effects (like tissue necrosis).
4Not suitable for oily preparations.
5Drugs incompatible with blood cannot be given.
6Because of 100% bioavailability, more vigilant dose titration is required.
Biotransformation
DeÞnition
Biotransformation is a chemical change that a drug undergoes in a living system with consequent change in its solubility and activity.
Objectives
1Activation of pro-drugs.
2Inactivation and elimination of drugs.
Advantages of administration of pro-drug
1To make the drug more portable, e.g. chloramphenicol palmitate is given instead of chloramphenicol.
2To make a drug tasteless and more stable, e.g. propoxyphene hydrochloride, which is bitter and unstable, is given in the form of a pro-drug – propoxyphene naphsylate, which is tasteless and stable.
3To improve the rate of absorption of the drug or to remove its toxicity, e.g. talampicillin, pivampicillin and bacampicillin are given instead of ampicillin.
4To increase the concentration of the drug at the site of action, e.g. levodopa instead of dopamine.
5To increase the duration of action of the drug, e.g. in place of phenothiazine, fluphenazine derivatives (like fluphenazine enanthate or fluphenazine decanoate) are given.
Features of mixed function oxidase system (MFOS)
This system is under genetic control. It is inducible and inhabitable. This system has gradually evolved as a result of exposure to toxins in plants and environment. Hence a safety mechanism for humans and animals. Its activity is modified by various factors like age, sex, species, altitude, climate, etc. Cytochrome P450 has multiple isoforms (about 50). Cytochrome P450 enzymes are involved in biotransformation of drugs in human beings.
Drug metabolism and elimination
Drugs are eliminated from human body by two main processes: excretion and metabolism.
Drug excretion occurs via kidneys, liver or lungs (primarily gaseous anaesthetics). Since renal excretion is the commonest route of drug elimination, in patients with chronic renal impairment, dose reductions become necessary to avoid drug toxicities /side effects. Small amounts of some drugs are excreted in the milk (→ possible ill effects on the breast-feeding babies).
Drug metabolism primarily occurs in the liver, especially by the cytochrome P450 (CYP) enzyme system (also called ‘microsomal enzymes’) embedded in the smooth
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