Pharmacokinetics DR FIDIA MUMTAHANA What is Pharmacology Pharmacology

Pharmacokinetics DR. FIDIA MUMTAHANA

What is Pharmacology ? Pharmacology Pharmacokinetics Pharmacodynamics What body does to drug What drug does to body

Pharmacokinetics What the body does to the drug (movement of the drug in body) Pharmacodynamics What the drug does to the body Mechanism of action Absorption Pharmacological Distribution actions Biotransformation Adverse effects Excretion Drug interactions

Pharmacokinetics mainly deals with the change of drug concentration in the body following administration. Pharmacokinetic process of a drug. Absorption Distribution Metabolism Excretion

Pharmacokinetic movement of drug Drug is administered absorbed in blood distributed to various sites but must reach the site where the drug needs to act the drug is degraded or metabolized excreted via (usually) urine, feces etc

Pharmacodynamics deal with the action, mechanisms, effects of drug with its concentration, indications, adverse reactions, and contraindications of drugs.

Pharmacokinetics

Pharmacokinetics Drug at site of administration Absorption Distribution Drug in plasma Metabolism Drug / metabolites in tissues Liver Drug / metabolites in urine, feces, bile Elimination Kidney

Pharmacokinetics Knowledge of pharmacokinetics helps the doctor to determine: How much drug is present in the body at any given time. How long does it take to reach a constant level of drug in the body during chronic drug administration. How long does it take for the body to get rid of drug once intake of drug has stopped.

Absorption

Absorption of drugs • The process by which drug enters into systemic circulation from the site of administration (except intravenous) through the membrane is called absorption. • Drugs can cross cell membranes by : – Simple diffusion – Facilitated diffusion – Active transport

Drug Absorption by Simple diffusion Transfer of drug from one component to another along the concentration, electro-chemical or pressure gradient without energy & carrier protein is called simple diffusion. • • Common process of drug absorption Energy & carrier not required Slow process 70% drugs are transported by this way

Drug Absorption by Simple diffusion • Lipid soluble drugs are absorbed mainly by this process –(propranolol, antianxiety drug, Morphine, barbiturates, Glucose, Paracetamol, Aspirin etc). • lipid solubility of a drug depends on its state of ionization- only non ionized form can cross the membrane by simple diffusion.

Absorption by Active transport It is the process by which drugs pass across the biological membrane against their concentration gradient with the help of carriers along with the expenditure of energy. • Need energy & carrier protein • Very rapid process • Less common • Exhibits selectivity Levo-dopa, α-methyl dopa, Streptomycine, 5 -fluorouracil

Absorption by Facilitated diffusion Movement of drug molecules & other substances through a biological membrane along the electro-chemical gradient with the help of carrier protein. • Downhill transport process • Need carrier protein but no energy • Speed is medium • Vit-b, Fat soluble vitamin, Glucose, Tetracycline, Pyrimidine etc

Factors modifying drug absorption 1. • • • Lipid solubility More lipid soluble drug more absorption Less lipid soluble drug less absorption More water soluble drug less absorption 2. Molecular weight • Drugs with low MW : 10 -1000 more rate of absorption • Iron-dextrose complex has high MW, so less absorption 3. Size of drug For lipid soluble drug size is not a matter but for water soluble drug smaller size more absorption

Factors modifying drug absorption 4. Degree of ionization • More ionization more water soluble less absorption • Less ionization less water soluble more absorption 5. Concentration of drug. More drug conc. more absorption 6. Presence of 2 nd drug VIT C • Fe +++ ------- Fe++ more absorption • Tetracycline in the presence of Antacid less absorption

Factors modifying drug absorption 7. p. H of the environment • Acidic drug in acid media & Alkaline drug in alkaline media Less ionization less water soluble more lipid soluble more absorption. • Acidic drug in alkaline media & Alkaline drug in acidic media more ionization more water soluble less lipid soluble less absorption.

Factors modifying drug absorption • p. H of drug & environment same more absorption • Aspirin is an acidic drug. In stomach (p. H: 1 -3), it remains unionized. So good absorption. But in duodenum (p. H: 8 -9), it becomes ionized, so less absorption.

Factors modifying drug absorption 8. Presence of food • Food enhances the absorption of some drug, so that drug is given with food- Riboflavin, griseofulvin, propranolol • Food also interferes with absorption of some drugs- Ampicillin, levodopa, tetracycline - given 1 hr before meal. 9. Inactivation- Insulin, oxytocin etc metabolized in gut if given orally --so less/no absorption.

Weak acidic drug Ampicillin Sulfonamide Aspirin Phenobarbitone Weak basic drug Morphine Amphetamin Chlorpromazine Propranolol

Bioavailability of Drugs The rate at which an administered drug is absorbed unchanged by the body's circulatory system. ex- Bio-availability of Digoxin is 62% - if patient takes 250 mg of digoxin, only 155 mg(62%) of drug will reach in blood.

Factors influence bioavailability 1. Route of administration. Intravenous B. A 100% Intramuscular 75 to =/< 100% Subcutaneous 75 to =/< 100% Transdermal 80 to =/< 100% Rectal 30 to <100% Oral 5 to <100% Inhalation 5 to <100% 2. Dosage form of a drug- Liquid > solid 3. Size of drug- Crystalloid > colloid 4. Ionization of drug 5. Presence of food 6. Presence of other agents