admin Comment(0)

As of today we have 76,, eBooks for you to download for free. No annoying ads, no download limits, Essentials of Medical Pharmacology, 6th Edition. Download (tripathi) essentials of medical pharmacology This, the 6th edition ot the Textbook of Medical Parasitology comes after 18 years By the same . Essentials of. Medical. Pharmacology. Seventh Edition. KD TRIPATHI MD Medical pharmacology is a unique synthesis of basic pharmacology with clinical .. FFA Free fatty acid . SERDs Selective estrogen receptor down regulators.

Language: English, Spanish, Indonesian
Country: Hungary
Genre: Children & Youth
Pages: 155
Published (Last): 07.03.2016
ISBN: 246-9-29419-831-2
ePub File Size: 28.79 MB
PDF File Size: 17.75 MB
Distribution: Free* [*Free Regsitration Required]
Downloads: 31357
Uploaded by: JANUARY

Professor of Medicine, Pharmacology and Toxicology at Dartmouth Medical exciting new website featuring the images from the book for you to download. Check our section of free e-books and guides on pharmacology now! This page Author(s): The National Department of Health, Pretoria, South Africa. s license, which allows users to download, copy and build upon published articles even for commercial A free online edition of this book is available at www. Additional . Department of Experimental and Clinical Medicine .

Not in United States? Choose your country's store to see books available for purchase. Widely recognised as the best starting point for pharmacology study, the internationally best-selling Medical Pharmacology at a Glance is an ideal companion for all students of the health sciences. Key principles are supported by coloured schematic diagrams - invaluable as both an introduction to medical pharmacology, and revision in the run-up to pharmacology exams. Revised and thoroughly updated throughout, and reflecting changes to the content and assessment methods used by medical schools, Medical Pharmacology at a Glance:. Saunders Nursing Drug Handbook

Michael S. Carolan Sherman. Hematology E-Book. David Hudnall. Cancer Drug Design and Discovery. Stephen Neidle. Oxford Handbook of Practical Drug Therapy. Duncan Richards. Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics. Hartmut Derendorf. Ian Todd. Forensic Toxicology. Fetal and Neonatal Physiology E-Book. Richard A. Renal Cell Carcinoma. Robert A. Diabetes Risks from Prescription and Nonprescription Drugs. Samuel Dagogo-Jack. Principles and Practice of Gynecologic Oncology.

Dennis Chi. Pharmaceutical Extrusion Technology. Isaac Ghebre-Sellassie. The Hands-on Guide to Clinical Pharmacology. Sukhdev Chatu. Bertram Katzung. Andrew J Lawrence. Endogenous ADP-Ribosylation.

Friedrich Koch-Nolte. Mark Kester. Doping in Sports. Detlef Thieme. Immunology for Medical Students E-Book. Matthew Helbert. Preserving the Promise. Scott Dessain. Netter Collection of Medical Illustrations: Endocrine System E-book.

William F. Young Jr.

Free Pharmacology eBooks Download

Nina Dragicevic. Drug Therapy and Interactions in Pediatric Oncology. Carolina Witchmichen Penteado Schmidt. Nikki P. Advances in Nitrate Therapy. Adam Schneeweiss. Applied Pharmacology E-Book. Stan Bardal.

Oxidative Injury in Dermatopathology. Marshal Shlafer. Handbook of Biologically Active Peptides. Abba Kastin. Robert J. Analytical and Chromatographic Techniques in Radiopharmaceutical Chemistry.

Donald M. How to write a great review.

Ebook download free pharmacology medical

The review must be at least 50 characters long. The title should be at least 4 characters long. Your display name should be at least 2 characters long. At Kobo, we try to ensure that published reviews do not contain rude or profane language, spoilers, or any of our reviewer's personal information. You submitted the following rating and review.

We'll publish them on our site once we've reviewed them. Continue shopping. Item s unavailable for purchase. Please review your cart. You can remove the unavailable item s now or we'll automatically remove it at Checkout. Remove FREE. Unavailable for purchase. Continue shopping Checkout Continue shopping. Chi ama i libri sceglie Kobo e inMondadori.

Medical Pharmacology at a Glance by Michael J.

Join Kobo & start eReading today

Neal series At a Glance Buy the eBook Price: Choose Store. Revised and thoroughly updated throughout, and reflecting changes to the content and assessment methods used by medical schools, Medical Pharmacology at a Glance: In this series. Skip this list. Ratings and Book Reviews 0 0 star ratings 0 reviews.

Overall rating No ratings yet 0. How to write a great review Do Say what you liked best and least Describe the author's style Explain the rating you gave Don't Use rude and profane language Include any personal information Mention spoilers or the book's price Recap the plot.

Close Report a review At Kobo, we try to ensure that published reviews do not contain rude or profane language, spoilers, or any of our reviewer's personal information. Would you like us to take another look at this review? No, cancel Yes, report it Thanks! You've successfully reported this review. When these lamellar membranes are isolated by homogenization and fractionation of the cells, they reform into vesicles called microsomes.

NADPH donates an electron to the flavoprotein reductase, which in turn reduces the oxidized cytochrome P— drug complex. A second electron is introduced from NADPH, via the same flavoprotein reductase, which serves to reduce molecular oxygen and to form an activated oxygen-cytochrome P— substrate complex.

This complex in turn transfers activated oxygen to the drug substrate to form the oxidized product. Oxidation Reactions are A. Microsomal a.

Hydroxylation of aromatic ring, i. Phenytoin is changed to para- hydroxyphenytoin b. Aliphatic side chain hydroxylation, i.

Tolbutamide is metabolized to hydroxytolbutamide c. N-dealkylation, i. Q-dealkylation, i. Encainide to 0- demethyl encainide e. S-dealkylation, i. Deamination, i. Amphetamine is changed to Phenylacetone g. Desulfuration, i. Parathion is changed to paroxon h. Sulfoxidation, i. Chlorpromazine to Chlorpromazine sulfoxide i. N-oxidation, i.

Meperidine is converted to Meperidine N-oxide. Nonmicrosomal Ethyl alcohol to acetaldehyde. Reductions a. Nitroreductions, i. Chloramphenicol is reduced to arylamine b. Azoreduction, i. Prontocil to Sulfanilamide c. Chloralhydrate to Trichloroethanol alcohol hydrogenation.

Hydrolysis Enalapril to active Enalaprilat. Conjugation By these processes, there occurs— i. Inactivation of parent compound ii. Addition of endogenous substance with the help of energy and synthesis of larger molecular new substances. Hence, the reactions are also known as synthetic reactions.

The reactions are— a. Glucuronidation b. Acetylation c. Methylation d. Sulfate conjugation e. Glycine conjugation. The metabolite of the drug like Digoxin, Morphin, Diazepam, Aspirin, etc. Subsequently, activated by uridine diphosphate UDP. The active complex, viz.

Essentials of Medical Pharmacology, 6th Edition

UDP, glucuronic acid, conjugates with the drug metabolite. The whole process is shown here. Converting active drug to inactive substance ii. Active drug to active metabolite iii. Inactive drug to active substance iv.

More toxic drug to less toxic drug, so that they can be easily excreted out from the body. Barbiturates can induce the hepatic microsomal enzyme which will reduce the theraputic effects of coumarin anticoagulants, similarly Rifampicin can reduce the effect of oral contraceptives similarly enzyme inhibition is a phenomenon by which the activity of drug metabolizing enzymes in the endoplasmic reticulum is decreased.

So that the drug degradation rate is slowed and drug effect is increased. Coadministration of Cimetidine with Diazepam cause increased effects of Diazepam, similarly INH can increase the effect of Tolbutamide.

Most of the drugs are eliminated from the body after metabolism but some drugs do not follow the process, e. Digoxin, Ephedrine, Proctalol and Inhalation anesthetics. First order kinetics ii.

Zero order kinetics. First order kinetics Exponential clearing —A constant fraction of drug is eliminated per unit time. Zero order Linear clearing —A constant quantity of drug is eliminated per unit time. If we followed of zero order kinetics, the quantity moving was a fixed amount. To continue with the previous example, let the quantity of the drug in the body was mg and its excretion followed zero order kinetics and a fixed quantity, i.

Metabolism b. Three processes are involved in renal excretion of drugs as: Passive glomerular filtration—Directly proportional to the excretion b. Active tubular secretion—Inversely proportional to excretion c. Passive tubular reabsorption—Directly proportional to excretion. Alkaline drugs are excreted to a greater extent, if the urine is acidic; whereas acidic compounds are excreted more readily, if the urine is alkaline.

A practical application of this principle is in the treatment of poisoning by weak acids like phenobarbital and salicylic acid; where alkalization of urine increases the proportion of ionized drug, thereby decreasing reabsorption and enhancing excretion.

Administration of sodium bicarbonate is a therapeutically useful strategy for management of either type of poisoning. Since, urine is normally acidic, the elimination of weakly acidic drugs by excretion alone would require a long time. Fortunately, metabolism tends to transform these drugs into stronger electrolytes, thereby increasing the percentage in the ionic form and limiting tubular reabsorption.

An overview of the mechanism of drug action shows that drug acts on— A. Cell membrane by the following approaches: Action on receptors 2. Interference with selective passes of ions across membranes https: Inhibition of membrane bound enzymes and pumps 4. Physicochemical interactions.

Metabolic processes within the cell by: Enzyme inhibition 2. Inhibition of the transport processes 3. Incorporation into large molecules 4. Inhibition of cell wall synthesis. Outside the cell: Surface adsorption 2.

Chemical neutralization 3. Chelation process 4. Deinition Receptors are part of the cells that can interact with a drug or endogenous material so that a series of chemical events occurs leading to the biological effect of the drug.

Chemistry All receptors are macromolecules proteins , following cellular structures behave as receptors. Regulatory proteins — Act as receptors, e. Some enzymes — Dihydrofolate reductase for methotrexate. Structural proteins — Tubulin for colchicines. Activation Types on the basis of site, they are of three types, but according to MOA they are: Receptors present in the cell membrane— a They act, via G-proteins and b Act, via ligand gated channels.

Present as transmembrane receptors have tyrosine kinase and realeted kinase activities. Present in the cytosol or on the nucleus. Cytokine receptors. Acetylcholine, gaba, glutamic acid, butyric acid receptors have a central canal or channel within the cylinder. Normally they remain closed but when the ligand gets attached with the acetylcholine receptors AChR the channel opens up.

Depends upon the concentration of drug, reaching the receptors, upto a point, greater the number of drug molecules reaching the receptors, greater will be the effect. It also depends upon the quality of receptors.

After formation of the drug receptors complex that is, RLC, if the receptors are not sufficiently activated, response will be weaker. It also depends upon the presence of antagonists competitive or irreversible. On the basis of above facts, two important clinical issues, viz. Efficacy is defind as the maximal response given by a drug. Potency means how much drug concentration is required to obtain a given response, usually the fifty percent of the maximal response.

This means, EC50 of ED50 is a measure of potency, a drug whose ED50 is low, is a highly potent drug whereas a drug whose ED50 is high, has a low potency.

Formation Receptor molecules are synthesized by the cells. They have a fixed lifespan, i. After expiry of the life- span, they become degraded by the cell and is replaced by a new one.

Structure activity relationship they are closely similar in chemical structure. Ligand-receptor complex formation After the ligand has combined with a receptor, a ligand-receptor complex LRC is formed.

This LRC can stimulate the postreceptor signals causing biological effects. Thus, a ligand may be agonist or an antagonist. Site They may be present in the— 1. Cell membrane—Type I 2. In the cytosol— Type II 3. In the nucleus— Type III. Number of receptors Recently, with the help of radioligand binding technique, the receptors in a cell can be counted. The count can increase, a phenomenon called up regulation, the reverse is called down regulation.

Speciicity of receptor Receptors are specific, that is, a receptor supposed to bind with a particular drug will not bind with any other drug. This explains the phenomenon of specificity of drug action. As for example, AD causes vasoconstriction and bronchodilatation and NA causes vasoconstriction but not with b2-receptors of bronchial muscle to produce bronchodilatation, as bronchodilatation.

The reason is that the ligand drug must combine well as, it must combine with a1-receptors of vascular smooth muscle to produce vasoconstriction. That is why, the target cells of NA is smooth muscle of blood vessels but not the smooth https: Agonist-antagonist on receptor site After LRC formation, if the complex stimulates the postreceptor signals to cause biological effect in such cases the ligand is called agonist, if no effect is produced then called antagonist.

Calcium channel blockers are the drugs used for the treatment of hypertension to reduce BP, because calcium enters into the smooth muscle cell of blood vessels. After entry into the cells, they combine with calmodulin.

Subsequently, the 'cal-cam complex' causes the stimulation of excitation-contration coupling actin-myosin. So that there is vasoconstriction and rise of BP. Calcium channel blocker Nifedipine blocks the entry of calcium through the channels. So that, there is interference of exitation contraction coupling and vasodilatation and finally fall of BP.

Inhibition of membrane bound enzymes and pumps: Membrane bound ATPase is inhibited by cardiac glycosides which is used in the treatment of congestive cardiac failure, where there is fall of cardiac output. Permeability of calcium to membrane and release from sarcoplasmic reticulum is also increased.

All these three factors as a whole increase the intracellular calcium concentration. This increased intracellular calcium concentration with the involvement of troponin, finally stimulates the excitation—contraction coupling of actin and myosin. So that, there is increased force of contraction and cardiac output. This is the rationality of using cardiac glycosides in the treatment of congestive cardiac failure CCF.

Physicochemical interactions: They do not act on specific receptors but they prevent some metabolic functions probably by reaching a certain level of saturation at some cellular sites. But there are some hypothesis, i. Metabolic Processes within the Cell 1. Enzyme inhibition: It is believed that bronchodilatation by xanthines produced is due to suppression of cAMP degradation, resulting from inhibition of degrading enzyme phosphodiesterase, i.

Theophylline administration leads to rise of intracellular cAMP and bronchodilatation. In gouty arthritis there is increased concentration of uric acid due to excessive activity of xanthine oxidase. Allopurinol inhibits, xanthine oxidase, as a result uric acid formation is reduced. Inhibition of the transport process: Inhibition of transport process that carry substances across cells—Probenecid competes with Penicillin for the same excretory process in the kidney.

So Penicillin is retained in blood for a longer period. Which is required in the treatment of resistant cases of venereal disease to get the maximum effect of Penicillin. By competing with the same reabsorption process in the kidney aspirin reduces uric acid concentration in blood of gouty arthritic patients. Incorporation into large molecules: Constituents of mRNA is as follows.

Inhibition of cell wall synthesis: The basic structure of bacterial cell wall is composed of a complex polymer, called mucopeptide murein. The murein is a liner polymer, consisting of alternating units of two amino sugars N-acetyl glucosamine and N-acetyl muramic acid.

To each molecule of N-acetyl muramic acid, a tetrapeptide is attached. Tetrapeptide consists of L-alanine, D-alanine, Lysine and D-glutamic acid. Finally, these polymer strands are cross-linked by amino acid bridges formed by glycine which connect the L-lysine of one tetrapeptide to D-alanine of another.

This cross linking transpeptidation is carried out by an enzyme called transpeptidase, gives rigidity of the cell wall. Penicillin binds to D-alanine site of the enzyme transpeptidase in the bacterial cell wall and inhibits the enzyme transpeptidase and suppress transpeptidation reaction cross linking. So that, there is defective formation of cell wall and lysis of bacterial cell wall due to higher internal osmotic pressure and there is extrusion of protoplasmic contents and death of the bacteria.

Outside the Cell Biological activity of some drug depends on 1. Surface adsorption—Some chemically inert substances adsorbed, dissolved or suspended substances such as gases, toxins and bacteria, i. Chemical neutralization—Protamine sulfate positively charged acts as an antidote of heparin negatively charged by neutralizing it.

The chelating agent form a ring sructure with the metal which is nontoxic, highly water-soluble and excreted in the urine, e. Osmosis—Osmotic diuretics like mannitol, osmotic purgatives like magnesium sulfate act by osmosis. But pharmacokinetic and pharmacodynamic effects are involved and the issues fall in two general categories.

Factors related to patient and drugs— Fig. Factors modifying drug action https: Patients are II. Special examples exists, e. After the first week of life, the drug metabolic capacity increases rapidly. Glomerular filtration, tubular secretion and reabsorption are also low in neonates.

The incidence of adverse drug reactions rises with age, in the adult, specially after 65 years of age because of— 1. The increasing number of drugs that they need to take because they tend to have multiple diseases.

Poor compliance with dosing regime. Bodily changes of the aging that requires modification of dosage regimens. Absorption of drugs may be slightly slower because GI blood flow and motility are reduced but the effect is rarely important. Distribution is influenced by the following changes: There is a significant decrease in lean body mass so that standard adult slower.

Drugs that are normally extensively eliminated in 1st pass through the liver appear in higher concentrate in the systemic circulation and persists here for longer periods, e. Major tranquillisers, TCAs cardiac antidysrhythmic agents. Capacity to hepatic enzyme induction appears to be lessened. Particular risks of adverse effects arises with drugs that are eliminated mainly by the kidney and that have a small therapeutic ratio, i. Sex Women may show increased sensitivity to certain drugs due to hormonal effects.

Sex difference in drug metabolism is due to males having higher MFO activity than females as testosterone can induce microsomal enzymes whereas estradiol decreases their activity.

Body Weight Usually big bodied persons bigger surface area require bigger dose.

The Last Black Unicorn by Tiffany Haddish

A special problem arises with the children, they have smaller body weight and the physiology differs from that of the adults.

Then how to adjust the dose? Alternatively with the help of charts, one can calculate the drug dose of a child. Nutrition i. Because of the diseases patient may remain in a state of starvation or semistarvation.

The patient may be on a severe diet restriction for reduction of obesity. Some persons specially the poor may be in a stage of malnutrition with edema or malnutrition without edema. While prescribing drugs, the pertinent question is whether the conditions alter the pharmacology of the drugs. Major features of starvation are loss of— i. Total body wt. Loss of body wt. Fall of plasma albumin. In some cases, e. As for example, the plasma half-life of Tolbutamide an oral hypoglycemic agent of a nonalcoholic person is 5 to 9 hours.

And it can reduce upto 2 to 7 hours in a case of chronic alcoholics. Increased rate of biotransformation of drug in chronic alcoholic is due to increased hepatic microsomal cytochrome P activity and proliferation of the smooth endoplasmic reticulum.

Cigaret Smoking The biotransformation of some drugs such as Theophylline, Caffeine and Imipramine are several times higher in cigaret smokers than in nonsmokers. Cigaret smoke is a rich source of Benzopyrine which is a potent enzyme inducer.

There is a 12 fold increase in pulmonary mono- oxygenase activity after continuous exposure of rates to a mixture of cigaret smoke and air for five hours daily for 3 days. The elimination half-life of Theophylline is about 8 hours in adult nonsmokers and about 4 hours in adult smokers. Pregnancy While prescribing drugs to the pregnants, the clinician has to consider two special points, viz.

Special problem due to altered physiology in the mother ii. Special problems regarding whether the proposed drug is going to harm the fetus—This requires considerations of placental barrier as well as teratogenicity of the drug. Relevant physiological changes in pregnancy: Total body water increases in pregnancy 2. Body fat increases to some extent 3. Plasma albumin fall remarkably 4. Renal clearance increases. Expected effects therefore might be: Vd of water-soluble drug will increase and the total concentration of drug in plasma should fall.

Free form of the drug in plasma should rise and in cases of drugs which are mostly bound with the plasma protein risks increase. Vd of fat-soluble drugs increased. Drugs like Penicillin will be excreted even more quickly. Glucosephosphate dehydrogenase deficiency: Strandard dose of Primaquine may cause acute hemolysis and hematuria of a patient having deficiency of the above enzyme.

Pseudocholinesterase deficiency: During surgery the decrease metabolism of Suxamethonium by pseudocholinesterase can cause apnea after surgery. In this case fresh blood transfusion is the management. Pathological Condition In liver damage, drugs that are inactivated by liver can accumulate and may produce toxic effect.

Antipyretics—It acts only when there is pyrexia. Antiemetics—It acts only when there is vomiting. Antibiotics—It acts only when there is infection. Antihypertensives—It acts only when there is hypertension. Chlorpromazine in low dose acts as an antiemetic but in high dose acts as antipsychotics. Aspirin in low dose shows its antiplatelet effect, but in high dose it is anti-inflammatory. Routes Magnesium sulfate given orally acts as a purgatives but when given intramuscularly acts as sedatives.

Benzodiazepines given orally acts as an anxiolytics but when given IV, it acts as an anesthetics. Time Sedative effect of Benzodiazepines is more marked at night than the day time.

Drug Combination and Drug interaction See later Tolerance: Gradual diminish of tissue response to a drug due to repeated administration is termed tolerance. Morphine, pethidine, heroin. Predictable ADRs are due to extension of pharmacological response. Causes of predictable ADRs are— i. Excess dose intake ii. Slow metabolism iii. Hyperreactivity iv. Drug interaction v. Extremes of age vi. Fault of kidney, liver, heart vii. Hypoalbuminemia viii. Their subfamilies are — 1. Allergic or hypersensitivity reactions 2.

Cytotoxic or pseudoallergic reactions. Hypersensitivity or Allergic Reactions Most drugs are relatively low molecular weight and only become antigenic when they are combined covalently and irreversibly with other substances of high molecular weight, usually proteins. Allergic reactions to drugs are the results of interactions of drug or metabolite or a nondrug element in the formulation with the patient, and subsequent reexposure.

The chief target organs of hypersensitivity reactions are skin, respiratory tract, GIT and blood vessels. Hypersensitivity reactions may be of four types. Any of which can be produced by drugs. Warfarin resistance 2. Glaucoma after corticosteroid eyedrops 3. Malignant hyperpyrexia after general anesthesia. Cytotoxic or pseudoallergic reaction: Dose independent type of allergic reactions without immunological basis are the cytotoxic or pseudoallergic reaction.

These reactions are produced by compounds that are able to release histamine and other mediators directly from mast cells without involving an antigen—antibody reaction. The basic mechanism of cytotoxicity is as follows: Unwanted Efects Undesirable effects, produced by therapeutic dose, severe form of which necessitate the cessation of treatment, e. Toxic Efect The potential harmful effects of a drug in the living human body. Toxic effects may be acute or chronic, e. Supersensitivity or Intolerance It is a phenomenon, where some persons began to show responses, when the dose of the drug is very small in contrast to subjects requiring heavier doses for the response.

This people are said to have intolerance or are supersensitive to the particular drug. There are certain adverse reactions which are encountered on clinical practice but they do not fall under the types mentioned above.

Teratogenic 2. Mutagenic https: Carcinogenic 4. Drug intolerance 5. Teratogenic Reaction—Some drugs given in the first three months of pregnancy may cause congenital abnormalities and are said to be teratogenic.

Efects of teratogen Effects are due to direct action on the fetus. This drug affect cell division, e. Thalidomide, anticancer drugs and many antibiotics. Primary effects of the drugs are on the uterus placenta and so on. Effects on the fetus are secondary here, e. Uterine vasoconstrictors fetal anoxia, isotretinoin used in acne placenta fetal damage. Teratogenicity may be— 1. Anatomic when there is phokomelia 2. Growth retarding 3. Behavioral 4. Sex related 5. Even carcinogenic.

Following drugs are highly teratogenic thalidomide, androgenic steroids, anticonvulsants, antineoplastic, diethylstilbesterone, lithium, penicillamine, warfarin, and tricyclic antidepressants. Mutagenic and carcinogenic: Some drugs produce adverse effects only after prolonged treatment. The precise mechanism is unknown. For example, cataract due to chloroquine and corticosteroid, nephropathy with phenacetin, gold salts and penicillamine. Carcinogenesis and mutagenesis are caused by alkylating agents, Niridazole and estrogens.

A minority group begin to respond show the effect when the dose of the drug is very small. This minority group of persons are said to be supersensitive or drug intolerant. Some drugs play important role in the pathogenesis of photoallergy and phototoxicity which together constitute photosensitivity. They may be beneficial or harmful to the patient.

Interactions may increase the effect i. They may occur both in vitro and in vivo. Again in vivo reactions may be Pharmacokinetic or Pharmacodynamic.

Similarly, addition of more than one drug to the same infusion fluid may result in interactions causing loss of activity. The immediate effect of soluble insulin is reduced if it is drawn up with potassium zinc insulin in the same syringe and drip. Interactions during drug absorptions Drugs may interact in the GIT resulting in either decreased or increased absorption. Altered absorption may be due to any of the following mechanism. Direct chemical interactions; aluminium and magnesium containing drugs can interact and calcium and calcium form chelation with tetracycline causing reduced bioavailability of tetracyclines.

Similar interactions occur between iron and tetracycline. Furthermore, cholestyramine interferes with absorption of thyroxin, digoxine and warfarin by the process of absorption.

Examples are: Interactions during distribution Immediately after absorption, drug may exist in two forms, free or active and binding or inactive form. A drug, which is extensively bound to protein, can be displaced from its binding site by another drug having more binding capacity, thereby raising the free concentration of displaced drug.

Aspirin displaces Warfarin from binding site resulting in increased adverse effects of Warfarin. Other examples are given below: Interactions during metabolism Most drugs are metabolized by hepatic enzymes. Many drugs can induce, i. Examples are— a. Enzyme inducer Induced drug Result Explanation Barbiturates Coumarin anti- Failure of coum- Increased coagulants arine effect coagulation Phenytoin Digoxin Failure of digo- Due to low xin to produce concentration of desirable action digoxin Rifampicin Oral contrace- Failure of Chance of ptive contraception conception Contd Interactions during excretion Drugs, which are excreted, via kidneys, may be interfered in two ways: Interference with active transport ii.

Interference with passive diffusion. Probenecid competes with Penicillins for active transport process and prolongs the action of Penicillin, which is beneficial. Other examples are given in the Table 1. Table 1.

Thus, basic drugs are better excreted in acidic urine and acidic drugs are better excreted in alkaline urine. Enhanced excretion of barbiturate occurs if sodium bicarbonate is given, similarly Benzodiazepine is rapidly excreted if ammonium chloride is added. Pharmacodynamic interactions: All these are the examples of chemical antagonism. Physiological antagonism: When two drugs produce opposite ef- fect on the same physiological system, one drug canceling the effect of other, i.

Pharmacological antagonism: When two drugs competes for the same receptor and the inactive drug prevent the access of active drug.

It is of two types: Competitive ii. Atropine nullifies the a. Thus propranolol b-blocker nullifies the effects of adrenaline by effects of acetylcholine on the muscarinic receptors and so on. In this type of antagonism the antagonist may combine irreversively with the receptor or portion of the receptor in which cases increasing the concentration of the agonist will never fully overcome the inhibi- tion, e.

Acetylcholine and decamethonium at the neuromuscular junction. Inhibition —— insulin sympathetic of glucose activity recovery from hypo- glycemia b.

Inhibition of sympto- ms of hyp- oglycemia c. Clearence CL 2. Maintenance dose MD 3. Dose interval DI 4. Fraction oral 'F'oral 5. Steady-state concentration Css 6. Volume of distribution Vd 7. Loading dose LD 8. Secreted by specialized cells ii.

Acts locally iii. Protects the body from some adverse situations iv. Degraded quickly are termed as autacoids.

Free download medical pharmacology ebook

From Greek, autos self coid remedy , i. However, in spite of such distinct features the status of a substance as autacoids may remain uncertain, i.

Mast cells situated at the base of gastric parietal cells exert a paracrine effect by histamine on the parietal cells. Here, histamine acts as a neuromodulators. Histamine is secreted by some CNS neurons, where histamine acts as a neurotransmitter.

A and PGs prostaglandins may be considered to be the derivatives of prostanoic acid, which however is a hypothetical acid not occurring in the nature. Platelet aggregation—A particular type of cells can produce one or two but not all the varieties of eicosanoids. Different eicosanoids can https: TXA2 produced by platelets help in platelet aggregation, while PGI2 secreted by the vascular endothelium opposes it. Reproductive system 1.

Regression of size of pregnancy occurs by PGE2. High conc. Inflammation ii. Bronchial asthma iii. Patent ductus arteriosus PDA iv. Dysmenorrhea v.

Bartter syndrome vi. Rheumatoid arthritis vii. Hypercalcemic states. A which has 20 carbon atoms and contain 4 double bonds. Antihistamines a. Physiological antagonist—Adrenaline b.

Ebook medical download pharmacology free

Mast-cell stabilizer—Cromoglycate c. Receptor blockers i. H1 ii. Ethanolamines —Diphenhydramine 2. Ethylaminediamines — Pyrilamine 3.

Piperazine derivatives — Meclizine 4. Alkalamines — Chlorpheniramine 5. Phenothiazine — Promethazine 6. Others — a. Piperidines— Loratadine b. Others — Astemizole. Deinition Asthma is a chronic inflammatory disorder of airway which is charac- terized by episodic, reversible bronchospasm resulting from an exagger- ated bronchoconstrictor response to various stimuli.

Types 1. Extrinsic a. Allergic b. Occasional c. Atopic 2. Allergens—Pollen, mite, dust, feather of pillow, specific foods 2. Exercise—Emotion, environment 3. Infection—Respiratory tract infection 4. Occupation—Industrial chemicals 5. Drugs—Aspirin, Propranolol. Basic Pathology of Bronchial Asthma 1. Bronchial smooth muscle contraction. Persistent inflammation of bronchial tree and damage to epithelium of bronchus. Increased mucus production by goblet cells.

Exaggerated bronchoconstrictor response. Or, bronchial hyperresponsiveness or increased airway reactivity to various stimuli i. Vasoconstriction, 2. Platelet plugging, 3. Coagulation in the local region. Aspirin in low dose , Sulfinpyrazone and Dipyridamole. Anticoagulants They effect by opposing procoagulant, i. Heparin, Warfarin and the other coumarin anticoagulants. Streptokinase, Urokinase, tissue plasminogen activator tPA.

Antithrombotics or antiplatelets Platelets are the smallest of the formed elements of blood, are enclosed by a membrane containing receptors thromboxanes concerned mainly with homeostasis, the cessation of bleeding. Normally, they can a negative surface charge and are therefore separated by mutual repulsion and remain in inactive state. But following an injury platelets are activated. ADP induces platelet aggregation and is thought to act by converting AA into thromboxanes, via cyclooxygenase pathway, after proper stimulation.

This thromboxane combines with the membrane receptors of neighboring platelets causing reversible platelet aggregation. Platelet aggregation is also produced by collagen, thromboxanes, serotonin, catecholamines, and POE2.

The aggregate induced by these substances undergo a viscious metamorphosis in which platelets become fused, i. Thus, the clotting process is facilitated by the release of platelet factor- III and the vascular endothelium released PGI2 combines with platelet membrane, this binding causes production of cAMP within the platelet. Prevention of degradation of cAMP leads to cAMP accumulation, and more vigorous inhibition of release of platelet contents.

Since aggregation of platelets serves as a focus for initiation of blood clotting, it is thought that inhibitors of platelet aggregation may be value in the Rx of thrombotic diseases with antithrombotics.

Mechanism of platelet aggregation Individual drugs Aspirin: There are two sets of chemicals acting on the platelets— https: TxA2 cause platelet activation, i. The other set, i. TxA2 is produced by the platelet through cyclooxygenase pathway but PGI2 from vascular endothelium although through cyclooxygenase pathway.

Aspirin in low doses inhibits the platelet cyclooxygenase pathway but not the endothelium cyclooxygenase pathway in other words TxA2 synthetase but not the PGI2 synthetase so that Aspirin in low doses opposes homeostasis by suppressing TxA2 but, PGI2 is not suppressed.

The great use of aspirin as antihomeostatic agent is as prophylaxis where there is increased risk of blood clotting, i. Angina pectoris ii. Early in MI iii. Coronary artery bypass graft iv. Atrial fibrillation particularly in the elderly where use of warfarin can be risky. Further details of aspirin see in CNS. Dipyridamole It inhibits the phosphodiesterase enzyme. Inhibition of phosphodiesterase causes accumulation of cAMP. However, as an antiplatelet agent, it is weak and usually given with aspirin.

There are three main hypothesis. First one is that the genes controlling the synthesis of protein clotting factors operate in conjunction with a gene that produces a repressor substance. The inhibitory effect of the repressor substance is prevented by vitamin K. Therefore, synthesis proceeds. In the absence of vitamin K, synthesis is suppressed.

The second hypothesis depends on the fact that the vitamin K, dependent clotting factors are glycoproteins and invokes the following scheme in the attachment of the carbohydrate moiety to the peptide chain.

This final stage is the Y-carboxylation of some of the glutamic acid residues in the protein. In the first hypothesis, vitamin K antagonists are thought to prevent the inhibitory effect of vitamin K on the suppressor.

In the second hypothesis, it is thought that antagonists prevent the reinstitution of vitamin K by inhibiting the FAD-dependent enzyme diaphorase. In the third hypothesis, the antagonist prevent the role of vitamin K in the Y-carboxylation of glutamic acid residues. In Vivo Anticoagulants a.

Parenteral — Heparin b. Coumarin derivatives—Dicumarol, Warfarin sodium, Warfarin potassium ii. Table 3. So factor requires time mints.

So used routinely used to be exhausted in emergency Contd Antithrombin-III is an a-globulin, normally present in the blood, is an important controlling protein. It forms a complex with active serine proteases which interact with its arginine containing site. In absence of exogenous heparin, the complex forms very slowly.

After combining with exogenous heparin, it potentiates the action upto folds. Pharmacological actions of heparin 1. Apart from its effects on coagulation, heparin can cause. Plasma clearing effect—After a fatty meal. Normally, after heavy fat ingestion, plasma becomes milky. This milkiness can be cleared up by heparin. These triglycerides are hydrolyzed by lipoprotein lipase causing clearance of milkiness.

Reduction of aldosterone secretion. Delay in wound healing. Vitamin K antagonists are known collectively as systemically acting or indirect acting anticoagulant.

They cause a decrease in plasma levels of vitamin K dependent clotting factors and thereby reduce the coagulability of the blood. Two of them, tPA and urokinase are endogenous whereas streptokinase is exogenous.

Tissue plasminogen activator tPA also called tPA. Recombinant tPA. It is a naturally occurring substance, synthesized from vascular endothelium. Commercially, tPA is now prepared by DNA recombinant technology which can be used for therapeutic purposes. Normally, plasminogen as well as tPA are present in circulating blood, but as tPA has originally very weak action so that no plasmin is formed.

Streptokinase is obtained from group C-b-hemolytic streptococci. It combines with plasminogen molecule and streptokinase plasminogen complex is formed. Streptokinase alone has no enzyme activity.

In the form of a complex, it can act on both 1 Circulating plasminogen as well as. Therefore, tPA acts only on the plasminogen in clot. Whereas streptokinase also acts on circulating plasminogen, so it should produce more bleeding disorders. As Streptokinase is obtained from streptococcus, so it is a foreign protein. Most persons in their lifetime have had streptococcal infections causing antistreptococcal antibodies to appear.

These antibodies can and does neutralize with the Streptokinase. There will be Two Fall Outs 1. Dose of Streptokinase should be high to overcome neutralization by the antibodies. There can be allergic reaction when IV Streptokinase is given, urticaria anaphylaxis can develop with IV Streptokinase. Urokinase is an enzyme obtained from fetal kidney. In many respect, it has similarity with Streptokinase. However, allergic reactions are less frequent and is usually mild.

Source b. Chemistry c. Indication d. Hematopoietic growth factor. Oral and parenteral forms of iron b. Total requirements c. Though erythropoietin should also be called hematinic because hematinic means blood forming agents. Source It is normally produced by the kidneys. Hypoxia stimulates its secretion. It acts on the most primitive precursors of erythrocytes. On the cell membrane of the such progenitor cells, erythropoietin receptors are present. It stimulates erythrocyte proliferation and erythroid cell maturation and differentiation.

It follows, where kidneys are grossly damaged, anemia would develop. Chemistry It is a amino acid containing peptide and is given parenterally, but surprisingly despite the chemistry it is not antigenic. Indication Major therapeutic indications of erythropoietin are— i.

Patients of chronic renal failure on chronic dialysis with anemia ii. Hematopoietic Growth Factor In recent times, a new term, hematopoietic growth factors has been introduced, erythropoietin is one of them.

The well known hematopoietic growth factors include: Erythropoietin ii.