Clinical Application Of Pharmacokinetics & Pharmacodynamics L1 Applied PK_PD (Part 1) PDF

Official (Closed) and Sensitive-Normal PART 1 CLINICAL APPLICATION OF PHARMACOKINETICS & PHARMACODYNAMICS Of...

Official (Closed) and Sensitive-Normal PART 1 CLINICAL APPLICATION OF PHARMACOKINETICS & PHARMACODYNAMICS Official (Closed) and Sensitive-Normal LEARNING OUTCOMES 1 2 3 Explain how the various Describe the concept of Changes in PK and PD pharmacokinetic receptors and their in young and older factors can modify drug clinical significance adults action or response Official (Closed) and Sensitive-Normal PHASES OF DRUG ACTIVIT Y Official (Closed) and Sensitive-Normal PHARMACOKINETICS Determine the ONSET, INTENSITY, and DURATION of drug action Official (Closed) and Sensitive-Normal PHARMACOKINETICS Studies what happens to the drug and its metabolites in the body following administration by any route. It looks at: Absorption (how well it is absorbed and its bioavailability) Distribution within the body Metabolism Excretion “What happens from the time drug enters the body to when all the drug has left the body” Official (Closed) and Sensitive-Normal THE 4 (FOUR) PROCESSES OF PHARMACOKINETICS: ABSORPTION, DISTRIBUTION, METABOLISM, EXCRETION Official (Closed) and Sensitive-Normal (1) ABSORP TION & DRUG ACTION How it moves from site of administration into the systemic circulation? Official (Closed) and Sensitive-Normal BIOAVAILABILIT Y Refers to the proportion of the administered drug that has reached the circulation, and that is available to have an effect. Official (Closed) and Sensitive-Normal BIOEQUIVALENCE & THERAPEUTIC EQUIVALENCE “Bioequivalent – when medications have the same bioavailability and same blood concentration of active ingredients” “Therapeutic equivalence” – when medications are pharmaceutically equivalent with similar clinical and safety profiles” Official (Closed) and Sensitive-Normal FACTORS AFFECTING ABSORP TION Official (Closed) and Sensitive-Normal RATE AND AMOUNT OF DRUG ABSORP TION IS INFLUENCED BY: Dosage forms and route of drug administration Effects of GI disorders, circulatory shock, congestive heart failure These are related to: (a) blood flow to site of absorption (b) total surface area for absorption (c) delayed gastric emptying affecting time needed for drug to reach site of absorption Presence of other substances (example - food or other drugs) Official (Closed) and Sensitive-Normal DOSAGE FORMS & DRUG ABSORP TION Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal RANKED THEM Tablet Suspension FROM FASTEST TO SLOWEST ABSORP TION Enteric FROM GI TRACT Capsule coated tablet Official (Closed) and Sensitive-Normal NOT TO BE CRUSHED, POUND, OR CHEWED CARBAMAZEPINE CR TAB ADALAT LA ® TAB POTASSIUM CHLORIDE SR TAB CLARITHRYOMYCIN MR TAB Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal DOSAGE FORMS THAT ARE NOT SUITABLE FOR CRUSHING Types of preparation Explanation CR EC ER, XR LA MR OROS REPETABS SA SR Official (Closed) and Sensitive-Normal FOOD & DRUG ABSORP TION Official (Closed) and Sensitive-Normal FOOD & DRUG ABSORP TION Official (Closed) and Sensitive-Normal DRUG-FOOD INTERACTION MSD Manual: A write up on drug-drug interactions & drug-food interactions Official (Closed) and Sensitive-Normal GRAPEFRUIT & DRUG ABSORP TION Official (Closed) and Sensitive-Normal EFFECTS OF FOOD ON DRUG ABSORPTION: Tablets FOSAMAX® (alendronate sodium, MSD) Bioavailability was decreased by approximately 40% when alendronate was administered one or one-half hour before a standardized breakfast when compared to dosing 2 hours before eating. Official (Closed) and Sensitive-Normal FIRST-PASS EFFECT The metabolism of a drug and its passage from the liver into the circulation A drug given via the oral route may be extensively metabolized by the liver before reaching the systemic circulation (high first-pass effect) Bioavailability is (high or low)?? The same drug—given IV—bypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation Official (Closed) and Sensitive-Normal TRUE OR FALSE IV Lasix 80 mg STAT = PO Lasix 80 mg STAT?? Official (Closed) and Sensitive-Normal PARENTERAL ROUTE & DRUG ABSORP TION Intravenous route (IV) No delay in absorption Intramuscular route (IM) Size of muscle & blood flow will affect absorption Subcutaneous route (SC) Slower absorption compared to IM route Official (Closed) and Sensitive-Normal TOPICAL ROUTE & DRUG ABSORP TION Skin (including transdermal patches) Fentanyl transdermal patch for pain Eyes Ears Nose Lungs (inhalation) Rectum Vagina Official (Closed) and Sensitive-Normal REVIEW QUESTION: CARBAMAZEPINE CR TAB ADALAT LA ® TAB POTASSIUM CHLORIDE SR TAB CLARITHRYOMYCIN MR TAB Question: Will bioavailability increased or decreased if these dosage forms are crushed, pound, or chewed? Official (Closed) and Sensitive-Normal (2) DISTRIBUTION & DRUG ACTION Journey of drug through the blood stream to reach target sites Official (Closed) and Sensitive-Normal DISTRIBUTION OF DRUGS After absorption, the drug need to be distributed via the blood stream to its site of action Some of the factors that will affect drug distribution include: Extent of plasma protein-binding Whether the drug is more water soluble or fat soluble Passage through barriers eg. blood-brain barrier (BBB), placenta Official (Closed) and Sensitive-Normal Fig. 4-9. Drug movement across the blood-brain barrier. Tight junctions between cells that compose the walls of capillaries in the CNS prevent drugs from passing between cells to exit the vascular system. Consequently, in order to reach sites of action within the brain, a drug must pass directly through cells of the capillary wall. To do this, the drug must be lipid soluble or be able to use an existing transport system. Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal (3) METABOLISM & DRUG ACTION How drug gets modified by enzymes and rendered ineffective? Official (Closed) and Sensitive-Normal METABOLISM (BIOTRANSFORMATION) Defined as enzymatically mediated alteration of drug structure (parent compound) into different compounds (metabolites) Most drugs are metabolised in the liver After metabolism, the resulting metabolites may have increased/decreased or no change in their drug effect Note: Prodrugs – need to be metabolised by the liver before it is active Besides the liver, the other sites of metabolism include: GIT, kidneys or lungs Official (Closed) and Sensitive-Normal FACTORS AFFECTING THE RATE OF DRUG METABOLISM Factors that decrease metabolism Cardiovascular dysfunction Renal insufficiency Starvation Obstructive jaundice etc. Factors that increase metabolism Fast acetylator Other drugs administered concurrently Official (Closed) and Sensitive-Normal IMPLICATIONS OF CHANGES TO DRUG METABOLISM Delaying drug metabolism causes: Accumulation of drugs Prolonged action of the drugs  drug toxicity Stimulating drug metabolism causes: Diminished pharmacologic effects Official (Closed) and Sensitive-Normal REVIEW QUESTION: For each of the following situations, state whether the drug action will be increased or decreased: Warfarin treatment in a patient with malnutrition and reduced blood plasma proteins Morphine treatment in a patient with liver disease Official (Closed) and Sensitive-Normal (4) EXCRETION & DRUG ACTION How the drug is removed from the body? Official (Closed) and Sensitive-Normal EXCRETION Defined as the movement of drugs and their metabolites out of the body The kidney is the major organ for drug excretion It is a sum of three processes (glomerular filtration, tubular reabsorption and tubular secretion) Other sites involved: intestines (biliary excretion), lungs, mammary glands Note: Combination of metabolism plus excretion -> Elimination Drug clearance refers to the volume of blood cleared of a drug per period of time (litres/hour) Official (Closed) and Sensitive-Normal Official (Closed) and Sensitive-Normal QUESTIONS?