Lecture 1, General Pharmacology PDF

Introduction and General Pharmacology Presented By: Mohammad Jaffar, Associate Professor, Department of Pharmacology, Pharmacy Program, BMC-Jeddah BMC Introduction and General Pharmacology  General Pharmacology Pharmacon (Active ingredient) + Logos (Discourse) = Pharmacology During the e...

Introduction and General Pharmacology Presented By: Mohammad Jaffar, Associate Professor, Department of Pharmacology, Pharmacy Program, BMC-Jeddah BMC Introduction and General Pharmacology  General Pharmacology Pharmacon (Active ingredient) + Logos (Discourse) = Pharmacology During the early times the treatments were made with the flesh, blood and excreta of animals along with plant and metal preparations Drug is derived from Drogue meaning Herb. As per WHO, a drug is defined as “Any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefits of the recipient” Pharmacology is the study of drugs, particularly their actions on animals, organs and tissues. The actions may be beneficial or harmful.  Medication: is a substance administered for diagnosis, cure, treatment, mitigation or prevention. Prescription: the written direction for the preparation and the administration of the drug. The therapeutic effect: is the primary effect intended, such as morphine sulfate is analgesia. Side effect: secondary effect of the drug is one that unintended, Diarrhoea with Mg - Antacids  Pharmacokinetics the study of the Absorption, Distribution, metabolism, and Excretion of drugs, and their relation with pharmacologic response (What the body does to the drug) Pharmacodynamics a quantitative study of the biological and therapeutic effects of drugs (What the drug does to the body), such studies elucidate the mechanism of actions of drugs Poisons are substances that cause harmful, dangerous or fatal symptoms in animals or human beings. Many drugs in large doses acts as poisons. Chemotherapy concerned with the effect of drugs upon micro- organisms and parasites, living and multiplying in a living organism. It now includes the drug treatment of cancer as well  Pharmacopoeia an official code containing a selected list of the established drugs and medicinal preparations with descriptions of their physical properties and test for their identity, purity, and potency. Ex: Indian Pharmacopoeia, US Pharmacopoeia, British Pharmacopoeia, European Pharmacopoeia Formulary provides to the subscriber information about the available drugs, based on original and reputed drug information sources as well as experts recommendations.  Drug toxicity: deleterious effect of the drug on an organism or tissue, result from overdose or external use. Drug allergy: is immunological reaction or hypersensitive reaction to a drug. Ex: Penicillin drug hypersensitivity. Drug interaction: occur when administration of one drug before or after alter effect of one or both drug. Ex: Caffeine + Alprazolam = No effect Tetracycline + Calcium = No effect Drug misuse: Is the improper use of common medications Ex: Vitamin B Complex are the most abused drug in the world  Drug abuse: is an inappropriate intake of substance either continually or periodically. Ex: Alcohol is the most abused drug in the whole world Drug dependence: is a persons reliance on or need to take drug or substance there are two type of dependence: Physiological dependence: is due to biochemical changes in the body tissue these tissue come to require substance for normal function. Ex: Drug addiction towards Morphine, Amphetamine Psychological dependence: is emotional reliance on a drug to maintain a since of wellbeing accompanied feeling of need. Ex: Smoking of cigarretes Drug Tolerance: is due to biochemical changes in the body tissue these tissue come to require substance for normal function with daily increase in the dose of the drug. Ex: Marijuana usage may cause drug tolerance in humans Drug habituation: denotes a mild form of psychological dependence. Ex: habituation to Coca leaves, Cigarette and hookah smoking etc Illicit drug: also called street drug are those sold illegally. Ex: Amphetamine, Cocaine Various names of drugs: The generic name: a shorthand version of the drug's chemical name, structure, or formula The official name: is the name under which its listed in one in the official publication. The chemical name: is the name by which the chemist knows it. The trade mark or brand name (proprietary name) : is name given by the drug manufacture Example: hydrochlorothiazide (official name). Esidrex: (brand name)  The Nature and Sources of the drugs The various sources of the drugs are; 1) Mineral source: Liquid Paraffin, Magnesium Sulphate, Magnesium Trisilicate, Kaolin 2) Animal source: Insulin, Thyroid extract, Heparin, Gonadotropins, Anti toxic sera 3) Plant source: Morphine, Digoxin, Quinine, Atropine, Reserpine 4) Micro-organisms source: Antibiotics like Penicillin, Polymixin B 5) Synthetic source: Analgesics, Hypnotics, Anticancer agents and antimicrobials 6) Genetic engineering: Insulin and growth hormone, Genes 7) Hybridoma Technique: Monoclonal Antibodies  Routes of drug administration: There are three different routes of drugs administration. i.e. (a) Local application (local route), (b) Oral route, (c) Parenteral route.  Local Application……… oSite of application: Like, Dusting Powder, Paste, Lotions, Drops, Ointments, Plasters exerts action at the. oLocal application: bougie for urethra, Pessary for vagina, Suppository for vagina and rectum. oOnly for the rectum: Evacuant enema: Soap solution enema, 600 ml  It is administered before the surgical operations, deliveries, radiological investigations of the GI tract.  Oral or Enteral route: the drugs administered through mouth. Eg: Tablets, Pills, Capsules Advantages, oMost common route of drug administration. oIt is safe, convenient and economical and the complications of parenteral route are avoided. Disadvantages, oOnset of drug action is slow. oIrritant and unpalatable drugs cannot be administered through this route. oNot used in the presence of vomiting or diarrhoea. oCannot be employed in an unconscious / uncooperative patients or in emergency. oDrugs destroyed by digestive juice cannot be administered. Ex. Insulin totally destroyed in the gastric mucosa, Testosterone is destroyed by gastric mucosa and liver enzymes (First pass metabolism) little reaches the systemic circulation. Paracetamol is 80 % metabolized in the liver where as, only 20 % reaches the systemic circulation.  Enteric coated pills and tablets: oTablets coated with cellulose acetate phthalate, gluten and anionic co polymers of meth acrylic acid and its esters. oTablets is disintegrated in the intestine (Enteric coated) but not in the stomach Enteric coating is done, oTo prevent gastric irritation and gastric alteration of the drug  Parenteral: Injections oIntradermal: it is given in to the layers of the skin in small quantities. Ex: BCG Vaccine, Montrox test. oSubcutaneous: Only non irritant substances can be injected by this route. Ex: Insulin. Drug absorption is slower than the IM route Sub cutaneous implants can be given through this route. Ex: Sex Hormone Implant. In pediatric preparation saline is sometimes injected through this route.  Intramuscular: oMild irritant, suspensions, colloids can be injected by this route. oThe rate of absorption is reasonably uniform. oOnset f action is rapid oThe volume of injection should not exceed 10 ml oBut, diazepam, hydrocortisone, digoxin, phenytoin are absorbed more slowly through IM than Orally. oProcedure may cause local pain, and even necrosis oIt should be given in to the gluteus maximus  Intravenous route: Drugs administered in to the veins directly Advantages: oVery rapid action with desired blood concentration oDrug may be injected as bolus (Furosemide), or diluted in 10 – 20 ml solution (Aminophylline) or as infusion 50 – 100 ml (Morphine), or to maintain a constant plasma level (Insulin), or to administered larger volumes (fluids in shock). Disadvantages: oOnce the drug is administered the action cannot be halted. oCan lead to phlebitis  Intra arterial: Drugs administered into arteries oUsed in diagnosis studies Intra-thecal: Drugs administered into CNS membranes (L2-L3) oIntroduction of the drugs directly in to the spinal cord. Ex: Spinal anesthesia (Sub Arachnoid space) oProduces high local concentration oEx: Drugs used in the treatment of infections Intra-peritoneal: Drugs administered into peritoneal cavities oMay be used in infants to give normal saline oIt is also used for peritoneal dialysis Intraosseous cannulation: Into the bone - Adrenaline in shock Specially injected in to the tibia  Parenteral route of drug administration: Advantages: oCan be employed in an unconscious and uncooperative patients ocan be employed in cases of vomiting and diarrhoea. oDrugs which irritate and are not absorbed orally can also be administered parenterally. oTo avoid drug modification in the alimentary and liver enzymes oRapid action and accuracy of dose are ensured. Disadvantage: oInconvenient for use, self medication being difficult. oLess safe and liable to cause infection if proper care is not exercised oLikely to inure veins, nerves etc oMore expensive  Inhalations: oPressurized metered dose aerosols: Eg: Salbutamol, Beclomethasone in bronchial asthma. Dry powders from inhalers activated by patients inhalation: Eg: Salmeterol in bronchial asthma. oOxygen or compressed air driven nebulized solutions: Eg: Salbutamol in bronchial asthma. Drugs given by this route produce rapid effects Drugs like nicotine, morphine, tetrahydrocannabinol are rapidly absorbed following the inhalation of tobacco, opium, or marihuana smoke. The drugs absorbed through this route may affect the cardiac tissue directly. And may also produce cardiac toxicity.  Transcutaneous Drug Administration: Iontophoresis: Galvanic current applied facilitates the absorption of the drugs in to the deeper tissues. Inunction: Drugs rubbed in to the skin can get absorbed and produce effect. (Nitroglycerin) Jet injection: Drug is injected with high velocity through the skin (Insulin) Adhesive units: Nicotine patches, Scopolamine for motion sickness.  Transmucosal: Sub lingual administration: Nitroglycerin Nifedipine, diazepam, Lorazepam, Domperidon etc can also be administered through sublingual route. Trans Nasal route: Vasopressin, Calcitonin. Trans rectal route: Rectum has rich supply of blood and lymph system. Aminophylline and diazepam. Endo-tracheal route: in patients with endo-tracheal tube drug shall be administered after dilution Ex: Adrenaline, Atropine, lignocaine, Naloxone etc Pharmacokinetics (ADME) Absorption: It is the process of entry of drugs from the site of administration into the systemic circulation Factors influencing the absorption: a)Physico-chemical properties: Valency: Ferrous salt is more absorbed than ferric salts (Vitamin – C increases absorption of iron) b) Pharmaceutical form of drug: 1) Absorption of solutions is more than suspensions or tablets Drugs are fast absorbed through lungs than Sublingual, Intestine than Gastric mucosa And I.M route drug administration is more faster than S.C route C) pH with in the gut: Weak acidic drugs are absorbed from stomach Weak basic drugs are absorbed from intestine d) Drugs which are gastric irritants (Salicylates) and which are destroyed by the gastric mucosa (Insulin) are Enteric coated e) Rate of dissolution and gut motility: If the rate of dissolution is more, the rate of absorption is also more. Sustain release form prolong their duration f) Presence of other substances in the lumen: Food, calcium, Iron decreases tetracycline absorption, Fatty meal enhances Griseofulvin absorption Grape juice increases the bioavailability of all the drugs G) First Pass Effect: (Also known as Pre-systemic metabolism) Benzyl penicillin is destroyed by the acid in the stomach mucosa Insulin is metabolised by the peptidases in the gastric mucosa Paracetamol 80% is metabolised in the liver during the first pass of the drug through the liver To overcome the hepatic first pass metabolism, a)Increase the oral dose of the drug, eg: Propranolol b)Use other routes like I.V. eg: lidocaine, Sublingual eg: Nitroglycerine Bioavailability The percentage of drug that reaches systemic circulation unchanged and becomes available for producing biological effect following administration by any route i.e. 100 % after IV administration. DISTRIBUTION  Passage of drugs to CNS, -Penicillin slightly pass through the normal barrier, but the drug penetrate readily in acute bacterial meningitis Passage of drug to the fetus -Drugs generally actively pass trough the fetal barrier, specially drugs like Thalidomide, Diphenylhydantoin, Tetracyclines, Corticosteroids, Anti-thyroid drugs, Aspirin passes through the fetal barrier easily. -Hence their usage must be carefully monitored Pharmacodynamics  Pharmacodynamics is the study of Biological and Therapeutic effects of the drugs And also the mechanism of action of the drugs Mechanism of action Physical action: (Adsorption), Eg: Kaolin adsorbs the Toxins during diarrhoea Chemical action: (Neutralization), Eg: Sodium bicarbonate neutralises the action of hydrochloric acid in the stomach during gastritis  Action on enzymes: Stimulation Inhibition Irreversible Reversible - Long lasting - Short lasting - Requires new enzyme synthesis Eg: Neostigmine Eg: Organo-phosphorous compounds Affinity: Tendency of a drug to bind to the receptor Potency: How much drug is required to elicit a response Efficacy: Biological response Competitive Antagonism: Displaced by an excess agonist Non-Competitive Antagonism: Not displaced by an excess agonist Partial Agonist: Stimulates and Blocks receptors Inverse agonist: Produce effects opposite to that of agonist  Elimination Half Life: Plasma half life of a drug : (t½) = 4 hours The concentration of each drug declines by half after every four hours It depends on drug clearance It is a measure for drug elimination Half – life (t½) is important to indicate the time required to attain steady state of drug in the body  Factors modifying the dosage and action of drugs Age: Newborn infants are premature and more susceptible to drug’s effects due to Underdevelopment of microsomal enzymes, Reduced excretion Underdeveloped BBB Adult dose X Weight in Kgs For infants: Clark’s formula =----------------------------------------------- 70 Adult dose X Age in years For children: Young’s formula = ------------------------------------------- Age + 12 Elderly: a)Between 60 – 70 years of age  ¾ of adult dose b)Above 70 years of age  ½ the dose of adult 2) SEX/GENDER Women needs smaller doses of drugs than Men This is due to: Fat Content more in females Enzyme inhibition effect of female sex hormones Enzyme induction effect of male sex hormones During menstruation avoid: Salicylates and caster oil During pregnancy avoid: Teratogenic drugs and uterine stimulants During lactation avoid: Chloramphenicol, Anticoagulants, Phenolphthalein  3) ROUTES OF ADMINISTRATION IV > Sublingual & Inhalation > IM > SC > Oral The action of the drug is also affected by the route of drug administration: Eg: magnesium sulphate: Orally  Purgative Rectally  Dehydrating agent IV  Anticonvulsant and antagonist to Calcium  4) Drug Intolerance: Because of super sensitivity , hence decrease the dose of the drug 5) Tolerance: Failure of response to the usual dose of a drug is known as tolerance May be due to, a) Congenital reasons: Racial, Species, Individual variations b) Acquired reasons: Repetitive drug administration Eg: Morphine, Ethyl alcohol, Nitrates, Ephedrine  Special types of tolerance: a)Tachyphylaxis: rapidly diminishing response to successive doses of a drug, Eg: Ephedrine in BP b) Cross tolerance: Tolerance between related drugs Eg: Ethyl alcohol and general anaesthetics 6) HYPERSENSITIVITY – Allergic reactions: It is because of exaggerated immune response, May not occur in the first dose but surely occurs in the second dose It is not dependent on the dose or concentration of the drug  7) IDIOSYNCRASY = PHARMACOGENETICS Abnormal effect to a drug because of genetics or enzyme effect Eg: Peripheral neuritis with slow Isoniazid metabolisers 8) DRUG DEPENDANCE Habituation: Emotional or psychological dependence on the drug If the habituation is stopped, emotional distress develops Ex: Cigarette smoking Addiction: Psychic craving for or physiological dependence If the addicted drug is stopped, Severe withdrawal reactions are seen Ex: Marijuana, Amphetamine  9) PATHOLOGICAL STATE Aspirin lowers temperature to normal but not lessthan normal 10) CUMMULATION If the rate of drug administration is more than the drug elimination, the drug undergoes cummulation and adverse drug reaction, drug interactions are seen Eg: Digitalis 11) EMOTIONAL STATE – PLACEBO EFFECT Placebo are inert dosage forms which produce their effect psychologically : They are used in testing new drugs  12) DRUG COMBINATIONS: Addition or summation: 1 + 1 = 2 Synergism: 1 + 1 = 3 Potentiation: 1 + 1 = 2 Antagonism: 1 + 1 = 0 Toxicity of drugs: Adverse drug Reactions (Unwanted) a) Unpredictable: Eg: Idiosyncrasy Allergic reactions (Hypersensitivity reactions) b) Predictable 1) Overdose toxicity 2) Teratogenic effect 3) Long acting sulphonamides can produce jaundice in babies 4) Chloramphenicol – blood complications 5) Smoking and radiation – Carcinogenic effect 6) Streptomycin can produce 8th cranial nerve damage 7) Prolong use of antibiotics – Superinfection and Vit B and Vit K deficiency Type A: Predictable and dose dependent (Augmented) Extension of pharmacological action Ex: Hypoglycemia by insulin Excess bleeding by warfarin Bronchoconstriction by Propranolol Pupil constriction by Prazosin  Type B: Unpredicted and dose dependent (Bizarre) Usually opposite reaction due to genetic abnormalities Ex: Benzodiazepines induced excitement in females Isoniazid induced peripheral neuritis Succinyl choline induced apnea Primaquine induced hemolysis Anaphylactic reaction with penicillin Type C: Continuous leading to cell damage Ex: Bleomycin induced pulmonary fibrosis Cyclosporine induced Nephrotoxicity Paracetamol induced Hepatotoxicity Anti cancer agents induced decreased sexual characteristics in males and females Type D: Delayed after long use of drugs Ex: Thalidomide induced phocomelia Phenytoin caused cleft lip and cleft palate Valproate induced spina bifida Warfarin caused microcephali Thank You