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The word Pharmacology is derived from Greek words pharmakon (=drug= remedy= to do good) and logos (= a study = science)

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BASIC PHARMACOLOGY Definition: Pharmacology is a subject of medical science which deals with the study of drugs or medicine that interact with the living system through chemical processes, specially by binding to regulatory molecules and activating or inhibiting body process. Medical Pharmacology: Branch of Pharmacology deals with the use of Drugs in human body for Diagnosis, Prevention, Suppression and Treatment of the Diseases. Clinical Pharmacology: Deals with the Scientific study of Drugs( Pharmacokinetics & Pharmacodynamic parameters) in the patients & also in the healthy persons for the safe & effective use of Drugs (Therapy).

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Pharmacokinetics Greek word-Pharmakon means drug, Kinein means: To move It deals with- Absorption – taken into the body Distribution – moved into tissues Metabolized – changed so can be excreted Excreted – removed from the body

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ABSORPTION OF DRUG The process by which the drug enters into the systemic circulation from the site of administration ( except intravenous or intra-arterial routes ) through the biological membrane is called absorption of drug . In case of intravenous or intra-arterial administration the drug is not absorbed and it enters into the circulation directly .

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DISTRIBUTION OF DRUG All the consequences of delivery of drug to the tissue is called distribution of drug. Distribution of drug means dividing and spreading of drug to the tissue. Selective distribution of drug: It means special distribution of drug in the certain tissue of the body due to special affinity between particular drug & particular body constituents Examples- Ephedrine > Iris Tetracycline > Ca++ containing tissue (bones/teeth) Heavy metal (arsenic) > hair and nail Dioxin > heart Thiopental Na+ > adipose tissue

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BIO-TRANSFORMATION OF DRUG (METABOLISM) Molecular alteration of drug in a living body with or without enzyme . Why necessary ? Drugs are chemical substance & interact with living organism. As we need drugs for treatment of diseases similarly we also want to get rid of them from the body to overcome their persistent effects. 100 mg of phenobarbitone would have a half life of greater than 100 years if it is not removed from the body by making some changes in its molecules . For this reason drug metabolism is necessary .

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Result of biotransformation: Active drug is converted to inactive drug e.g.. morphine >morphine glucouronide Inactive drug is converted to active drug e.g. Levedopa> Dopamine Active drug is converted to active metabolites e.g. Heroine> Morphine Toxic drug are converted to less toxic or nontoxic drug e .g. morphine >morphine glucouronide Nontoxic drug is converted to toxic drug e.g. Parathione >Paroxine

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ELIMINATION OF DRUG Elimination includes all the processes that terminate the presence of the drug in the body . Drugs are excreted from the body after being partly or wholly converted into polar metabolites .

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Routes of excretion of drug Major processes: Kidney: Frusemide,pathidine , Hepato-billiary process: Tetracycline, Chloramphenicol Gastro-intestinal: Antacid , BaSO4 Pulmonary: Inhalation anesthetics, Alcohol Minor processes: Skin/ sweat glands : Vit-C ,iron, Griseofulvin Saliva : morphine, caffeine Breast : morphine ,phenobarbitone Vagina :Metronidazole Tear: Rifampicin

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Factors affecting elimination Disease: Heart liver or kidney disease lowers perfusion to organs of elimination. Age: Reduced glomerular filtration, and liver metabolism Obesity: Slows elimination of lipid soluble drugs. Presence of other drugs: Phenobarbitol induces liver oxidizing enzymes. Cimetidine inhibits liver oxidizing enzymes

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PHARMACODYNAMICS It is a branch of Pharmacology which deals with the effects of Drug & Mechanism of action.

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Effects of Drugs Therapeutics (Beneficial effect) Toxicology (Adverse effect)

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Drug- Derived from Drouge (French word) = A Dry Herb Definition: According to the World Health Organization (WHO),1992- ‘’ A Drug is any substance or product that is used or intended to be used to modify or explore Physiological system or Pathological states for the benefit of the recipient.’’ Aim of Drugs: To improve quality of life.

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Basic use of drugs Diagnosis- BaS04 >GIT lesion Prevention- Vaccine, Contraceptives, toxins Suppression/Control- Insulin for DM, Anti-hypertensive drugs. Treatment- Antibiotics for infection, Diuretics for edema, analgesic for pain.

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Prodrug The drugs which do not produce any pharmacological effect until they are chemically altered within the body. Purpose of prodrug: To modify absorption ? To modify distribution ? To modify the duration of action ? To reduce adverse effect ? To overcome difficulties in Pharmaceutical formulation.? Examples- Castor oil, levodopa etc.

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Drug nomenclature Pharmacopoeia: It is an official publication written by legally authorized body constituted by law which describes drugs that are used commonly with their source, properties, action, standardization, indication, contraindication etc. B.P > British Pharmacopoeia. U.S.P > United States Pharmacopoeia I.P > Indian Pharmacopiea INN > International non-proprietary name (WHO recommended) JP > Japanese Pharmacopoeia

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Naming of Drugs Chemical Name Generic/Non-proprietary/Official/Approved name. Trade/Proprietary/Commercial/Brand name. Examples of a Drug with 3 types of name: Acetylsalicylic acid (Chemical name) Aspirin (Generic name) Eras ( Trade name)

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Receptor Receptor are macromolecular structures with which the drug binds & form a drug-receptor complex that initiates a chain of events leading to the pharmacologic/therapeutic action (s). Receptors are: protein or lipoprotein in nature situated on the cell membrane or within the cell (cytoplasm, nucleus) bound mostly reversibly Location of Receptor: On the cell membrane- Insulin Within cytoplasm- Steroid receptor Within nucleus- Thyroid receptor.

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Common Receptor and their Subtypes Cholinoceptor or cholinergic receptor Muscarinic nicotinic Adrenoceptor or adrenergic receptor Alpha Beta Histamine receptor H1 H2 H2 Dopamine receptor D1 D2

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Common Receptor and their Subtypes-- continued 5-hydroxytryptamine receptor 5-HT1 5-HT2 5-HT3 Opoid receptor Mu Kappa delta GABA receptor GABA1 GABA2 Prostaglandin receptor

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Drug-Receptor Terminologies Affinity: Affinity is the tendency of drug to bind with a receptor. Efficacy: The effect produce by a drug is called efficacy. Potency: The power of a drug to produce the desired effect is called potency. Agonist: Drugs having affinity as well as efficacy are called agonist. E.g. Sulbutamol > Beta-receptor agonist Antagonist: Drugs having affinity but lacking efficacy are called antagonist. E.g. Atropine > Muscarinic antagonist.

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Posology: Deals with dosage of Drug. Dose: Amount of drug or medicinal substance to be administered at one time is called dose Dosage: Determination of the amount , frequency and number of dose for a patient is called dosage. Therapeutic dose: Dose require to produce the optimal therapeutic effect is called therapeutic dose. Maximum dose: Largest dose of drug that is safe to administration and produce no toxic effect is called maximum dose. Minimum dose: Smallest dose of drug that will be effective is called minimum dose.

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POSOLOGY Lethal dose: Dose that cause death of some experimental animals. Toxic dose: Dose that causes signs and symptoms of drug toxicity. Pediatric drug dose: Calculation of dosage based on age or weight are conservatives and tend to underestimate the required dose. Age (Young’s rule): Dose=Adult dose x Age(years)/Age+12

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POSOLOGY Booster dose: An additional dose( of an immunizing agent) to increase the protection afforded by the original series of injections. The booster dose is given some months or years after the initial immunization. Loading dose: The “loading dose” is one or series of doses that may be given at the onset of therapy with the aim of achieving the target concentration rapidly. Maintenance dose: Dose required to maintain the desired effect that is achieved by preceding dose. Test dose: Amount of drug given initially ( before giving full therapeutic dose) to see the response of drug to tissue is called test dose. Fatal dose: Amount of dose that cause death of 100% of experimental animals.

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Plasma Concentration Time Plasma concentration vs. time profile of a single dose of a drug ingested orally

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POSOLOGY ED50(Median effective dose): The dose at which 50% of individual exhibit the specified quantal effect is called ED50 TD50(Median toxic dose): The dose required to produce a particular toxic effect in 50% of test animals is called TD50. LD50(Median lethal dose): The dose required to produce death in 50% of experimental animals is called the LD50.

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THERAPEUTIC INDEX Therapeutic index is the ratio between the median lethal dose and the median effective dose. So, therapeutic index =LD50/ED50 [In experimental animal] Or, Therapeutic index is the ratio between median toxic dose and the median effective dose. So, therapeutic index =TD50/ED50 [In clinical medicine]

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Half life Definition: The time by which the effect of a drug will come to half is called the Biological half life of that drug. Example: 4 mg of a drug is administered. Blood concentration become 2mg (50%) after 10 minutes. So, plasma half-life =10 minutes. Importance: Half life gives gross idea about the Pharmacokinetics and Pharmacodynamics of a drug. Half life gives idea about the duration of action of a drug. It can guide the dosage schedules. Low Half life > Frequent administration High half life> Should be given once or twice daily

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Bioavailability Definition: It is the amount or percentage of active drug that is being absorbed from a given dosage form & is made available to the site of action is called the Bioavailability of that particular from. e.g. Bioavailability of Paracetamol is 50%. It means if a patient orally takes 500 mg of Paracetamol, only 250mg (50%) of drug will reach to the systemic circulation.

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Bioavailability Dose Destroyed in gut Not absorbed Destroyed by gut wall Destroyed by liver to systemic circulation

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Plasma concentration Time (hours) i.v. route oral route Bioavailability (AUC)o (AUC)iv

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Drug interaction Drug interaction is a phenomenon which occurs when the effects of one drug are modified by the prior or concurrent administration of another drug. Drug interaction may result beneficial or harmful effects. Drug interaction may occur- Out side the body- Phenytoin + Infusion fluid = Precipitation At absorption level- Antacid + Tetracycline = Decreased absorption of Tetracycline At distribution level- Sulfonamide + Aspirin = Sulfonamide toxicity At bio-transformation level- Warfarin + Barbiturates = Decreased anticoagulation At excretion level- Penicillin + Probenecid = Increased penicillin level At receptor level (Pharmacodynamics) – Thiazide diuretic + Beta Blocker = Hypertension

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Route of Drug Administration: Oral Intravenous Intra-arterial Intramuscular Subcutaneous Intraperitoneal Topical Suppository Inhalation Sub-lingual Local injection Intrathecial

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