Introduction to Pharmacology Course: Pharmacology I Course Code: PHR 213 Course Instructor: Sabiha Chowdhury Lecturer Department of Pharmacy BRAC University

Definition of Pharmacology Pharmacology is the science of drug that deals with the detail study of history, source, physical and chemical properties, roots of administration, biochemical and physiological effects, mechanism of action, absorption, distribution, bio-transformation, excretion, side effects, therapeutic uses and other uses of drugs.

Pharmacology has two main areas: Pharmacokinetics: deals with absorption, distribution, biotransformation and excretion of drugs Pharmacodynamics: deals with biochemical and physiological effect and their mechanism of action of drugs.

Other areas of pharmacology Pharmacotherapeutics which deals with the therapeutic use of drugs in the prevention and treatment of diseases. Toxicology: adverse effects of the drugs

Definition of Medicine Chemical substance which is used in the diagnosis, treatment of disease and prevention of disease and also prevention of pregnancy. Diagnosis-Histamine is used for diagnosis of gastric secretion Treatment-Paracetamol is used in fever Prevention of disease-vaccine Prevention of pregnancy-contraceptives

Medicine Any drug which is therapeutically used in the treatment of disease. All medicines are drugs, but all drugs are not medicines.  Prodrugs are inactive compounds that are converted to active drugs in the body enzymatically or simultaneously or non enzymatically-usually by metabolism. They are inert molecule. E.g. Levodopa, Aspirin, Protonosil. Advantages of prodrug: -to increase absorption -to decrease degradation of drugs -to reduce toxicity -to prolong action, e.g. oral contraceptives as esterified form -site specific bio activation (drug molecules will be liberated and give action.

Side effects: With the therapeutic dose all drugs have some undesirable effects which is known as side effects.There is no drugs with out side effects. Ex- Aspirin causes gastric ulcer. Side effects cannot be avoided. Toxic effects: It is exaggerated pharmacological effect due to repeated or over doses of drugs. Ex- large doses of sulfanamide cause haematuria(blood comes in urine) Toxic effects can be minimized by careful use of drugs

Idiosyncrasy: is the abnormal reaction/ extraordinary response of drug due to genetic abnormality Agonist: when two drugs have similar reaction then they are called agonist to each other Drug Interaction: interference of one drug in the action of another. Synergism: increase the action of a drug by the presence of a second drug Antagonism: reduction of the action of a drug by the presence of a second drug

Teratogenicity: Teratogen: A teratogen is an agent that can disturb the development of the embryo or fetus. Teratogens halt the pregnancy or produce a congenital malformation (a birth defect). e.g. Birth defects., Thalidomide Tragedy. Drug Intolerance: intolerance of drug in case of individuals. Ex-Liver failure (possibly also kidney failure) after a normal dose of acetaminophenLiver failurekidney failureacetaminophen Drug Tolerance: if certain drug do not work due to continuous use then it is called drug tolerance.

Drug Dependence and Drug Abuse: Drug dependence is the body's physical need, or addiction, to a specific agent. There is therefore virtually no difference between dependency and addiction. Over the long term, this dependence results in physical harm, behavior problems, and association with people who also abuse drugs. Dose: the specific amount of medication to be taken at a given time. Dosage form: Dosage forms are the means by which drug molecules are delivered to sites of action within the body Bioavailability: Amount of intact drug that reaches the systemic circulation is termed as bioavailability of the drug. IV route bioavailability is highest 100%. Other routes which require absorption bioavailability is not 100%.

Routes of Drug Administration A route of administration in pharmacology and toxicology is the path by which a drug is taken into the body. Various routes of administration. Oral Route Sublingual route or buccal route Rectal route Parental route Nasal route Inhalation route Topical route

Oral Route Mostly solution, Tablet, Capsule Advantages: Most easiest, convenient, safest, painless, non-invasive Various forms of drugs can be administered Cost effective-no need of sterility Less risky Disadvantages: Very large amount cannot be given Unpleasant and irritant drugs cannot be given Absorption of drug take much time, not sufficient Late onset of action-not applicable during emergency Acid unstable drugs cannot be given-Many drugs may get degraded in GIT e.g insulin Can not be applied to unconscious or non-cooperative patients Unsuitable in diarrhoea & vomiting First pass metabolism

Sublingual or Buccal Drug is placed just beneath the tongue, drug will be absorbed by buccal mucosa. It will not go to the GIT. Drugs may be crushed or as a tablet. Advantages: Absorption is prompted Rapid onset of action: action will be obtained within few minutes Very small amount of drug can be administered Can split-if required the rest of the drug can be removed Disadvantages: Very large amount cannot be given Irritant drugs cannot be given Not suitable for unconscious patients

Rectal Route Drugs are given inside rectum, e.g : suppository Advantages: Preferable route of administration for unconscious and non- cooperative patients Easy to administer to pediatric and geriatric patients 50% first pass metabolism effect can be avoided Rapidly absorbed Suitable for vomiting and nausea/ GI surgery patients Less side effects Disadvantages: Sometimes absorption is uneven Only non-irritant or non-inflammatory drugs should be given The route is inconvenient and embarrassing

Parental Route Drug will be injected into tissue fluid or blood and drug need not to pass the intestinal mucosa -Subcutaneous (SC) -Intramuscular (IM) -Intravenous (IV) Advantages: Action, absorption of drug is faster and surer and is convenient when emergency Bioavailability is very high Do not provoke irritation or vomiting, by irritation and vomiting drug can be lost Interference of drug absorption/digestive juice can be escaped No first pass mechanism

Parental Route (cont) Disadvantages: The products must be sterile which increases the cost of drug Route of administration is invasive and painful Risky, vital parts of the body can be exposed to high concentration of drug Sometimes cause irritation and inflammation

Subcutaneous (SC) In this case the drug is injected in the connective alveolar tissue, just below the skin. Norephedrine in asthma patients. Norephedrine Advantages: Drug is absorbed slowly due to this depot preparation [sustained action-drug action will be prolonged] Oily solution/aqueous suspension can be given by this route Self administration can be possible since drug need not to be penetrated Disadvantages: Well supplied by SC Irritant drug cannot be given Relatively slow absorption

Intramuscular (IM): In the skeletal muscles, deep penetration. Mild irritant can be given because nerve supply is less Disadvantage: most painful, depot preparation cannot be applied Intravenous (IV): Drug is injected directly in the vein by bolus form or introduced to the vein or can be increased gradually for hours. e.g. saline

Intravenous (cont) Advantages: Rapid onset of action, instant action and very much useful during emergency As the drug is given directly to the vein, the drug will be diluted in the blood & circulated, highly irritant drug can be given Bio-availability 100% Convenient for life threatening condition and very useful Accurate dosing precision can be introduced Disadvantages: Self administration is not possible. Administration by this route can be very risky sometimes because vital organs are exposed to the drug Thrombophlebitis [clot formation in the vein]

Inhalation Volatile liquids/ gaseous drugs/ materials are administered in the pulmonary tissues, directly to the blood Advantages: There is a large surface area in pulmonary alveolar tissue that’s why drug administration is rapid and instant Local action can be obtained Lower doses compared to other routes can be taken Liver can be bypassed Disadvantages: Only volatile or gaseous drug material can be taken Irritant or inflammatory drugs cannot be taken Accurate dosage precision is very difficult Sometimes this route of administration cause embarrassing situations

Nasal Route The drug is introduced to the nasal mucosa and absorbed by nasal mucosa will be introduced to the blood. Few drugs. Desmopressin: Anti-diabetic Disadvantages: Appropriate Administration is trouble-some

Topical Route Drug is given for local action not for systemic action. e.g. dermatitis, antibiotic, nasal spray, ointment, mouthwash, steroid Skin-lotion(muscle pain), cream, ointment, eye & ear preparation, ointments, drops Advantages: Application of the drug is very easy and applied directly to the affected area. Self administration is possible. Healing procedure can be observed easily Usually this route causes less systemic toxicity. Other organs are less affected. Disadvantages: Accurate dosing is very difficult In some cases some systemic toxicity can be raised due to prolonged administration of drug

Drug Absorption Absorption is the movement of drug particle from the site of application to the circulation and the rate and extent at which the drug particles go to the systemic circulation is known as drug absorption.

Most of the drugs are absorbed by-  Passive diffusion:  driving force- concentration gradient High conc. to low conc. until equilibrium will exist. Absorption will be completed as the drug will be utilized. The rate of absorption depends on lipophilicity (lipid-water-partition- coefficient) which will determine how fast the drug will be absorbed. Passive diffusion does not involve a carrier, the process is not saturable.

 Carrier mediated absorption: some drugs are absorbed by this process by the help of carrier. In this process a carrier molecule will make a complex with the drug. Usually polar molecules are absorbed by this process. Hydrophobic coating will be made. Two types of this process- Active Transport: In this process drug will be passed against concentration gradient and energy will be needed. e.g. levodopa, methyldopa Facilitated diffusion: it is faster than passive diffusion. It is like passive diffusion with the help of carrier molecule.

Factors affecting drug absorption Concentration of drug molecule: As most of drugs are absorbed by passive diffusion concentration is very important. High drug conc. will be applied for better activity. e.g. Lidocaine-local anaesthetic 2% solution will produce anesthetia more rapidly than 0.2% solution of lidocaine if the amount is same. Mostly applicable when solution drug is applied. Physical state of drug: some drugs are solid, some are liquid, suspension, emulsion, solution, tablet. Before absorption drug must be in solution so drug in the solution or liquid dosage form is absorbed faster than solid dosage form. e.g. tablet must be disintegrated, dissolute then the whole process but for liquid or solution dosage form there is no need of disintegration/dissolution. Viscous product absorption will be slower than the diluted solution Surface area of the absorptive site: higher the surface area greater will be the absorption and better action. Large intestine, pulmonary alveoli, skin if high conc. of drug.

Route of administration: very important. IV route- no absorption required/ no loss of drug Blood circulation of the absorptive site: if the blood circulation of the absorptive site is maximum/efficient the absorption will be faster. Blood circulation fastens the absorption. Morphine toxicity-respiration depression Movement of the drug molecule: movement of the drug molecule will increase the absorption distance between capillary and site of action decrease drug absorption. Gastric emptying: the time how quickly the drug leaves the stomach, surface area of the stomach is smaller than intestine so most drug is absorbed in the intestine. So absorption is inversely proportional to gastric emptying. Presence of food: will dilute the drug particle and decrease absorption. As a result drug will be absorbed slower compared to when there is no food. milk+tetracyclin Ca-Cyclin complex (non-absorbent) So absorption is retarded but sometimes, beta-adrenergic propranolol absorption will be increased by the presence of food. Factors affecting drug absorption (cont)

Presence of other drug: presence of other drug will affect absorption of the drug. In case of Tetracyclin and iron preparation the absorption of both the drug will be reduced. Factors affecting drug absorption (cont)