Introduction to Pharmacology Lecture 2: Pharmacokinetics PDF

Introduction to Pharmacology pharmacokinetic 2 Dr. Nesreen Elgayar  Pharmacodynamic Body Drug Pharmacokinetic Oct 18, 2024  Outlines Pharmacokinetics Cont. Bioavailability of Drug. Factors Affecti...

Introduction to Pharmacology pharmacokinetic 2 Dr. Nesreen Elgayar  Pharmacodynamic Body Drug Pharmacokinetic Oct 18, 2024  Outlines Pharmacokinetics Cont. Bioavailability of Drug. Factors Affecting Bioavailability. Distribution of Drug. Factors Affecting Distribution of Drug. Metabolism of Drug. Factors Affecting Metabolism of Drug. Oct 18, 2024  III. Patient Factors blood flow: ↓ in SC → ↓ Rate of absorption -1 Adding EP (VC) to Local anesthetics ↑ prolong action + ↓ bleeding GIT Motility: ↑ G.M. by prokinetic → ↑ Absorption -2 e.g. Add Metoclopramide to ergotamine (TTT of Migraine) + Anti-emetic 3- GIT Content : e.g. Tetracycline → ↓ Absorption of Ca ++ (chelation) Oct 18, 2024  Part of drug may be metabolized before reaching Blood (First pass metabolism) & lost. The remaining part reach Blood is called Bioavailability (available for action). Oct 18, 2024  Bioavailability (F) Fraction (%) of dose of the drug reaching systemic circulation unchanged & available for biological action. F IV = 100% AUC Bioavailability = certain route AUC IVI Oct 18, 2024  serum concentration AUC t max Time Oct 18, 2024  Factors Affecting Bioavailability I. Factors affecting GI absorption. II. Factors affecting First-pass metabolism. Oct 18, 2024  Factors affecting GI absorption Factors related to Factors related to Drug Patient 1- Formulation 1- pH of gut 2- ↓ Molecular weight 2- Rate of gastric emptying 3- Lipophilicity 3- GI Surface area (200m2) 4- Stability in gut 4- GI disease Oct 18, 2024 5- pKa  Factors affecting First-pass metabolism 1- Route of administ.: FPM can be avoided by parenteral, Sublingual and to a lesser extent rectal routes 2- Nature of drug: Hepatic FPM Oral Nitroglycerin & Propranolol Oral Intestinal FPM Estrogen inhal Pulmonary FPM Nicotine Oct 18, 2024  Routes By passing the First-pass Effect Sublingual Parenteral Rectal (to some extent) Oct 18, 2024  Distribution Oct 18, 2024  Factors Affecting Vd 1- Binding to plasma proteins (PPB) 2- Permeability of tissue to drug: (↓ MW, Lipophilicity → ↑ Vd ) 3- Perfusion of tissue (↑ blood flow → ↑ Vd ) 4- Binding to tissue Chloroquine Retina, Liver Tetracyclines &Ca Oct 18, 2024 Bone and Teeth  Lipophilicity Oct 18, 2024  Plasma Proteins Binding (PPB) (Albumin & Globulin) Drug Equilibrium Inactive (Reservoir) Active Non-diffusible Diffusible Not metabolized Metabolized Not excreted Excreted Oct 18, 2024  Significance of PPB 1. Acts as reservoir 2. Absorption (down Conc. Gradient) 3. Vd & tissue penetration 4. Metabolism 5. Excretion 6. t½ 7. Drugs Interaction Drugs higher affinity to PP (Aspirin) can displace drugs with lower affinity (Warfarin) → ↑ Free part → Bleeding Oct 18, 2024  Drug Clearance Lipophilic Drugs Hydrophilic Drugs Oct 18, 2024  Metabolism Oct 18, 2024  Metabolism Site Liver (main site) other organs, e.g. intestinal, lung, plasma, skin and kidney. Aim Hydrophilic excreted Oct 18, 2024  Types of M. Reactions Phase I Phase II (Non-Synthetic) (Synthetic) = Conjugation Oxidation Acetaylation. Reduction Methylation Hydrolysis Glucoroniation converts parent drugs to → formation of non toxic more polar metabolites highly polar, rapidly eliminated conjugates. Oct 18, 2024  Factors Affecting Metabolism 1- Physiological factors: Age……., Sex………. 2- Pathological F.: liver cell failure & CHF 3- Environmental F: smoking & pesticides (enzyme induction) 4- Drugs: (enzyme inducers and enzyme inhibitors) Oct 18, 2024  Enzyme Inducers + + + + Microsomal enz. →↑ their own & other drugs metabolism Examples Phenytoin - Phenobarbitone →↑ warfarin metabolism → ↓effect Oct 18, 2024  Enzyme Inhibitors - - - Drugs inhibit drug metabolism serious drug interactions (Toxicity) It occurs faster than enzyme induction. Examples: Chloramphenicol - Erythromycin warfarin metabolism → Toxicity → Bleeding ↓→ Oct 18, 2024  Drug Clearance Renal Excretion Lipophilic Drugs Hydrophilic Drugs Oct 18, 2024  Drug clearance Definition: clearance is the volume of plasma from which a drug is cleared per unit of time. Oct 18, 2024  Conc. C 1/2 C T ime Steady t State Concentration (Css) 1/2. It is the concentration of the drug in plasma when the rate of absorption = the rate of elimination. Elimination half life ( t 1/2) It is the time required to reduce the plasma concentration of the drug to the half of its initial concentration Oct 18, 2024  Importance of t1/2 1) t1/2 shows the time required for a drug to reach CSS after its administration.The drug needs 4-5 times its half life to reach its CSS Oct 18, 2024  2) t1/2 shows the time required for a drug to be removed from blood after stoppage of drug, usually it takes 4-5 time half life. 3) t1/2 determines dose interval (frequency) of drug administration:  Most drugs are given at intervals equal to their t1/2 to avoid interdose fluctuation in blood level away from CSS.  Drugs with short t1/2 < 3 hours are given by continuous infusion.  Drugs with long t1/2 > 3 days are given as initial loading dose followed by maintenance dose. Oct 18, 2024  Loading dose (LD):  The dose given at the onset of therapy to achieve target concentration (CSS) i.e. the dose which saturate Vd.  Loading dose = CSS x VD Maintenance dose (MD):  The dose given for maintaining the drug steady state concentration. It is given at dose rate equal to elimination rate of the drug  Maintenance dose = CSS x CL Oct 18, 2024 Oct 18, 2024