Basic Pharmacology of Pharmacokinetics.pptx

A presentation on pharmacokinetics

1. Introduction to Pharmacology Pharmacokinetics Dr. Faisal Amir

2. Principles of Rational Drug Therapy Proper indication for therapy Establish a diagnosis (at least provisional). Define therapeutic problems--- pain, infection. Define the therapeutic goals to be achieved , e.g. relief of symptoms , cure or prevention of complications Selection of a class of drug capable of achieving the desired goal. Select the appropriate / right drug. Select appropriate dose , route of administration & duration of drug therapy.

3. Prefer mono drug therapy. Provide proper information & instructions about the medication, to the patient for proper compliance. Monitor adherence to the medication (compliance). Instruct the patient to avoid change of drug brand un-necessarily. Monitor the extent of achievement of goal, where possible. Monitor adverse drug reactions. Modify therapy if needed.

4. Selection of the appropriate / right drug depends upon the following criteria: Efficacy Safety Cost effectiveness

5. Pharmacokinetics : (Greek : Kinesis – movement) Pharmacokinetics is‘ What the body does to the drugs’ It is the branch of pharmacology which deals with the quantitative study of absorption, distribution, binding, biotransformation & excretion of drugs. Together with dose of drugs these parameters determine the onset, intensity & duration of action. Pharmacodynamics ( Greek : dynamis – power) ‘What the drug does to the body’ This includes physiological and biochemical effects of drugs and their mechanism of action at macromolecular/sub-cellular/organ system levels.

6. Pharmacokinetics Absorption Distribution Metabolism Excretion

7. Pharmacokinetics Absorption First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma. Distribution Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.

8. Pharmacokinetics Metabolism Third, the drug may be biotransformed by metabolism by the liver or other tissues. Excretion Finally, the drug and its metabolites are excreted from the body in urine, bile, or feces.

9. Routes Enteral (Through the Gastrointestinal tract) Orally (swallowed) through Mucus Membranes Oral Mucosa (e.g. sublingual) Nasal Mucosa (e.g. insufflated) Topical/ Transdermal (through skin)

10. Routes Faster Absorption Parenterally (injection) Intravenous (IV) Intramuscular (IM) Subcutaneous (SC) Inhaled (through lungs)

11. Fastest Absorption General Principle The faster the absorption, the quicker the onset, the higher the addictiveness, but the shorter the duration

12. Mechanisms of absorption of drugs from the GI tract Passive diffusion Facilitated diffusion Active transport Endocytosis and exocytosis

13. Bioavailability Bioavailability the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is 0.7 or 70%. Intravenous administration has 100% bioavailability.

14. Factors that influence bioavailability First-pass hepatic metabolism Solubility of the drug Chemical instability Nature of the drug formulation

15. Drug distribution: Compartments 2/13/2024 Interstitial volume (15% body weight) Intravascular volume (5% body weight) Intracellular volume (40% body weight) Body fat (several % body weight)

16. On entering blood a portion of drug is bound to plasma proteins mainly Albumin and is inactive pharmacologically Unbound (free) drug is active pharmacologically 17

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18. Transfer of drugs across placenta is important Selection of drugs should be done carefully The Placental Barrier in fetus is not well developed Congenital anomalies especially in first trimester 19

19. Volume of Distribution Definition: Vd can be defined as a hypothetical fluid volume necessary to contain all the drug in the body at the same concentration as in the blood or plasma, considering the body as a single compartment . Vd relates the amount of drug in the body to the concentration of drug (C) in blood or plasma. 20

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21. Biotransformation/ Metabolism BIO derived from GREEK Word BIOS meaning life Transformation meaning alteration / change Chemical alteration that a drug molecule undergoes in a living organism with consequent change in its solubility & activity

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23. Phase I: Most commonly involve cytochrome P450 system. Involve oxidation, reduction, and hydrolysis to convert drug into more polar (water soluble form) Different drugs can interact. Phase II: Conjugation. Converted into inactive, more water soluble compounds which can be excreted via kidney or bile.

24. BIOTRANSFORMATION…. Inactivation of Drugs Elimination of Drugs Activation of Pro-drugs

25. EXCRETION OF DRUGS is the movement of drug (metabolites or unchanged) from tissues and blood to the external environment Routes of excretion 1. Kidneys 2. Bile & faeces 3. Other: Lungs Saliva, sweat, tears Hair & Skin Breast milk

26. Renal excretion of drugs may decrease in impaired renal function due to: Renal disease Old age Some drugs are nephrotoxic i.e. Streptomycin, Gentamicin they are not metabolized and can produce toxicity, if dose adjustments are not done according to creatinine clearance

27. BILE EXCRETION Liver cell transfer drugs / metabolites ( conjugates) by active transport in to bile : These metabolites may be: Excreted in to the feces Absorbed into the blood and excreted in the urine May undergo Entero-hepatic circulation

28. Clearance (CL) Definition: Clearance of a drug is defined as volume of biological fluid that is cleared off the drug per unit time to account for elimination. CL predicts the rate of elimination in relation to drug concentration (C) . CL = Rate of elimination Concentration

29. Significance CL is a measure of body’s ability to eliminate a drug CL can ↓ in diseases of organs of elimination i.e. liver & kidneys CL is less at extremes of age ---- Dose should be ↓ Dosing interval ↑ CL affects plasma half life of drugs. If CL is ↓ --- t ½ prolonged So CL is important for rational long term dosage regimens

30. Elimination of Drug “Disappearance of the active molecules from the bloodstream or body is known as elimination of the drug” Determine the duration of action for most drugs Rate of elimination = CL x C Note: Drug elimination is not the same as drug excretion ( drug may be eliminated by metabolism long before the modified molecules are excreted from the body)

31. First Order Kinetics ( Flow-Dependent Elimination) The rate of elimination is directly proportional to the conc. of the drug in plasma Higher the concentration of drug, the greater amount of drug eliminated per unit time A constant fraction of drug is eliminated per unit time. Have a characteristic of half life elimination The systems for elimination are not saturated. e.g. Most of the drugs.

32. Zero Order/ Capacity-Limited Elimination: The rate of elimination is not proportional to the conc. of the drug in plasma. A constant amount of drug is eliminated per unit time DOA is more strongly dependant on dose If dosing rate exceeds the elimination, steady state can not be achieved & plasma conc. continues to rise Exp: Phenytoin, Ethanol, Aspirin in high doses.