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NTA Level 5 • Semester 1 • PST05104 Drug Receptor Interaction Pharmacology and Therapeutics • Source Session/Topic 5 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 5: Drug Receptor Interaction Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe the drug-receptor interaction Describe the types of receptors Explain the concept of receptor regulation Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD Projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning tasks Introduction, Learning tasks 2 2 30 minutes 30 minutes Presentation/ Drug-Receptor Interaction Drug-Receptor Interaction 2 2 30 minutes 30 minutes Buzzing Drug-Receptor Interaction Drug-Receptor Interaction Buzzing 3 3 45 minutes 45 minutes Presentation/ Types of Receptor Types of Receptor 3 3 45 minutes 45 minutes brainstorming Types of Receptor Types of Receptor brainstorming 4 4 30 minutes 30 minutes Presentation Concept of Receptor Regulation Concept of Receptor Regulation 5 5 05 minutes 05 minutes Presentation Key Points Key Points 6 6 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 33 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Drug-Receptor Interaction (30 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes How does drug interact with receptors? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below A drug receptor is a specialized target macromolecule, present on the cell surface or intracellularly, that binds a drug and mediates its pharmacologic actions. It describes protein molecules whose function is to recognise and respond to endogenous chemical signals. The term is most often used to describe the target molecules through which soluble physiological mediators-hormones, neurotransmitters, inflammatory mediators, etc.-produce their effects. Examples are acetylcholine receptors, cytokine receptors, steroid receptors, and growth hormone receptors Pharmacological effects, therefore, require, in general, that drug molecules must be 'bound' to particular constituents of cells and tissues in order to produce an effect. Four main kinds of regulatory protein are commonly involved as primary drug targets, namely: o receptors o enzymes o carrier molecules (transporters) o ion channels The function of a cell alters when a drug interacts with a receptor cell. At its most fundamental level, the interaction of drug and receptor follows the law of mass action. PST 05104 Pharmacology & Therapeutics 34 NTA Level 5 Semester 1 Facilitator Guide The law of mass action dictates that: o The combination of drug (also called ligand) and receptor depends on the concentrations of each o The amount of drug-receptor complex formed determines the magnitude of the response o A minimum number of drug receptor complexes must be formed for a response to be initiated (threshold) o As drug concentration increases, the number of drug-receptor complexes increases and drug effect increases o A point will be reached at which all receptors are bound to drug, and therefore no further drug-receptor complexes can be formed and the response does not increase any further (saturation) Law of Mass Action Applied to Drugs: Drug +Receptor ↔ Drug-Receptor Complex →Effect Occupation of a receptor by a drug molecule may or may not result in activation of the receptor. By activation, we mean that the receptor is affected by the bound molecule in such a way as to elicit a tissue response agonists, which 'activate' the receptors If a drug binds to the receptor without causing activation and thereby prevents the agonist from binding, it is termed a receptor antagonist. • The tendency of a drug to bind to the receptors is governed by its affinity, whereas the tendency for it, once bound, to activate the receptor is denoted by its efficacy. PST 05104 Pharmacology & Therapeutics 35 NTA Level 5 Semester 1 Facilitator Guide Selectivity of Drug Responses Drug molecules exhibit preferential affinity for receptors as follows: The cell will respond only to the spectrum of drugs that exhibit affinity for the receptors expressed by the cell. The greater the extent to which a drug molecule exhibits high affinity for only one receptor, the more selective will be the drug‘s actions, with lower potential for side effects. The higher the affinity and efficacy of a given drug, the smaller the amount of drug necessary to activate a critical mass of drug receptors to effect a tissue response, and the lower the potential for nonselective actions. As the concentration of a drug increases, the drug will combine with receptors for which it has lower affinity and may generate off-target effects. Thus selectivity of a drug to a specific receptor is obtained at low to moderate doses. STEP 3: Types of Receptor 45Minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are the types of receptors? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below There are four receptor types or superfamilies namely: Type 1-Ligand-gated ion channels (ionotropic receptors) Type 2- G-protein-coupled receptors (GPCRs) [metabotropic receptors or seven-transmembrane-spanning (heptahelical) receptors Type 3-Kinase (Enzyme) linked and related receptors PST 05104 Pharmacology & Therapeutics 36 NTA Level 5 Semester 1 Facilitator Guide Type 4-Nuclear receptorsIntranuclear/intracellular receptors (e.g. gonadal and glucocorticosteroids hormones) Type 1-Ligand-gated ion channels/Trans membrane ion channel (ionotropic receptors) Conduct ions across membrane in response to ligand binding, voltage gradient or second messenger; e.g., H+/K+-ATP‘ase Transmembrane ion channels allow the passage of ions from one side of a membrane to

NTA Level 5 • Semester 1 • PST05104 Drug Excretion Total Session Time: 120 minutes Pharmacology and Therapeutics • Source Session/Topic 4 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 4: Drug Excretion Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe routes of drug elimination Describe factors affecting renal drug excretion Calculate clearance Describe clinical importance of elimination half life Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD Projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 25 minutes 25 minutes Presentation/ Routes of Drug Excretion Routes of Drug Excretion 2 2 25 minutes 25 minutes Buzzing Routes of Drug Excretion Routes of Drug Excretion Buzzing 3 3 40 minutes 40 minutes Presentation/ Factors Affecting Renal Drug Excretion Factors Affecting Renal Drug Excretion 3 3 40 minutes 40 minutes brainstorming Factors Affecting Renal Drug Excretion Factors Affecting Renal Drug Excretion brainstorming 4 4 20 minutes 20 minutes Presentation Calculation of Clearance Calculation of Clearance 5 5 20 minutes 20 minutes Presentation/ Description of Clinical Importance of Description of Clinical Importance of 5 5 20 minutes 20 minutes Brainstorming Elimination Half Life Elimination Half Life Brainstorming Elimination Half Life Elimination Half Life 6 6 05 minutes 05 minutes Presentation Key Points Key Points 7 7 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 26 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Routes of Drug Elimination (25 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes What routes are involved in the excretion of drugs? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Removal of a drug from the body may occur via a number of routes, the most important being through the kidney into the urine. Other routes include o the bile, o intestine, o sweat o lung, o Milk in breastfeeding mothers. Renal excretion: Most drugs are renally cleared and differ greatly in the rate at which they are excreted by the kidney Some drugs are almost completely cleared renally such as penicillin and others are slowly cleared, eg diazepam Three fundamental processes account for renal drug excretion: o glomerular filtration o active tubular secretion o passive diffusion across tubular epithelium Excretion via Breast Milk Breast milk is a quantitatively relatively minor route of drug excretion. PST 05104 Pharmacology & Therapeutics 27 NTA Level 5 Semester 1 Facilitator Guide Nevertheless, it is clinically important for breastfeeding mothers and their infants. The baby will ingest drugs excreted in the breast milk. Moreover, breast milk has a lower pH than plasma. Accordingly, basic drugs will be concentrated in the breast milk through the phenomenon of ion (pH) trapping. A number of drugs can reach clinically significant concentrations in the breast milk and thereby affect nursing babies. Pulmonary excretion Is important for gaseous lipophilic substances. The gaseous general anaesthetics are the most common example. Drug diffuses from the plasma into the alveolar space and is excreted during expiration. Biliary Excretion: Biliary excretion involves active secretion of drug molecules or their metabolites from hepatocytes into the bile. The bile then transports the drugs to the gut, where the drugs are excreted. The transport process is similar to those described for renal tubular secretion. The efficiency of biliary excretion is quite variable. Enterohepatic cycling. Although many drugs may reach the gut through Biliary Excretion, deconjugating enzymes in the gut and the gut pH causes many drugs to assume nonpolar lipophilic forms that then are promptly reabsorbed by diffusion into the plasma. Drugs that undergo extensive enterohepatic cycling generally have long durations of action e.g Rifampicin STEP 3: Factors Affecting Renal Drug Excretion (40 Minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are the factors affecting renal drug clearance? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below PST 05104 Pharmacology & Therapeutics 28 NTA Level 5 Semester 1 Facilitator Guide Renal excretion of a drug is affected by the following factors depending on the mechanism: Glomerular filtration: Molecular weight of a drug Glomerular capillaries allow drug molecules of molecular weight below about 20 000 to pass into the glomerular filtrate. Plasma albumin (molecular weight approximately 68 000) is almost completely impermeant, but most drugs-with the exception of macromolecules such as heparin or biological products can cross the barrier freely. Protein binding If a drug binds to plasma albumin, only free drug is filtered. If, like warfarin, a drug is approximately 98% bound to albumin, the concentration in the filtrate is only 2% of that in plasma, and clearance by filtration is correspondingly reduced. Disease or age Glomerular filtration rate decreases approximately 1% per year and may be significantly compromised in elderly patients. The decline in glomerular filtration rate is accelerated by disease states such as diabetes. For drugs that are eliminated by glomerular filtration, dosages are often adjusted based on the patient‘s glomerular filtration rate. Tubular secretion Secretory mechanisms in the renal tubules actively transport endogenous substances and drug molecules from the plasma in peritubular capillaries to the tubular lumen. Although quite diverse in some characteristics, the tubular transporters can be classified into two major groups: the organic anion transporter (OAT) and the organic cation transporter (OCT) families. Tubular

NTA Level 5 • Semester 1 • PST05104 Metabolism of Drugs Pharmacology and Therapeutics • Source Session/Topic 3 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 3: Metabolism of Drugs Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe reactions involved in drug metabolism Describe factors affecting drug metabolism Describe first pass effect Describe kinetics of metabolism Explain clinical importance of drug metabolism Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD Projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 10 minutes 10 minutes Presentation/ Reactions Involved in Metabolism Reactions Involved in Metabolism 2 2 10 minutes 10 minutes Buzzing Reactions Involved in Metabolism Reactions Involved in Metabolism Buzzing Presentation/ 3 3 45 minutes 45 minutes Small Group Factors Affecting Metabolism Factors Affecting Metabolism Discussion 4 4 20 minutes 20 minutes Presentation First Pass Metabolism First Pass Metabolism 5 5 20 munites 20 munites Presentation Kinetics of Metabolism Kinetics of Metabolism 6 6 10 minutes 10 minutes Presentation Clinical Importance of Metabolism Clinical Importance of Metabolism 7 7 05 minutes 05 minutes Presentation Key Points Key Points 8 8 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 19 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Reactions Involved in Drug Metabolism (10 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes What are thereactions involved in drug biotransformation? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below There are several reactions involved in drug biotransformation. These reactions are grouped into two major groups called Phase 1 and Phase 2. Phase 1 Reaction Phase 1 reactions are catabolic (e.g. oxidation, reduction or hydrolysis), and the products are often more chemically reactive and hence, paradoxically, sometimes more toxic or carcinogenic than the parent drug. Phase 1 reactions often introduce a reactive group, such as hydroxyl, into the molecule, a process known as 'functionalisation'. This group then serves as the point of attack for the conjugating system to attach a substituent such as glucuronide explaining why phase 1 reactions so often precede phase 2 reactions. Phase 1 reactions take place mainly in the liver whereby many hepatic drug-metabolising enzymes, including CYP enzymes are involved. In general phase 1 reactions include hydroxylation, dealkylation, deamination, desulfuration, dechlorination, hydrolysis and reductions reactions PST 05104 Pharmacology & Therapeutics 20 NTA Level 5 Semester 1 Facilitator Guide Phase 2 reactions Most of phase 1 metabolites are more polar hence expected to be readily excreted. However some drugs are not eliminated rapidly require a further reaction involving an addition of an endogenous glucuronic acid, sulfuric acid, amino acid or acetic acid to form a highly polar conjugate for elimination. In general Phase 2 conjugation reactions involves glucuronidation, acetylation, conjugation, sulphation and methylation. Rang and Dale pharmacology seventh edition STEP 3: Factors Affecting Metabolism of Drugs (45Minutes) Activity: Small Group Discussion ( 30 minutes) DIVIDE students into small manageable groups ASK students to discuss on the following question What are factors affecting metabolism of drugs? ALLOW students to discuss for 15 minutes ALLOW few groups to present and the rest to add points not mentioned CLARIFY and SUMMARIZE by using the contents below Drug metabolism is affected by the followings: Genetic factors o Genetic factors influence enzyme levels and expression of activity. There is a great variation in the population how individuals metabolize drugs. o The greater part of this effect is due to Cytochrome P450 polymorphism. PST 05104 Pharmacology & Therapeutics 21 NTA Level 5 Semester 1 Facilitator Guide A few examples of variation on metabolism due to genetics include acetylation of isoniazid and hydroxylation where there are slow and fast metabolizers in the population for the drugs. Diet and environmental factors Cigarette smokers metabolize some drug faster than non-smokers because of enzyme induction Some foods and drinks also affect drug metabolism. For example grape juice decrease metabolism of some drugs because of enzyme inhibition Age and Sex A decreased metabolism of drugs is observed in clinical practice in very young patients due to immature enzymes and very old patients due to deterioration of liver function A variation in metabolism basing on sex difference in human is reported for ethanol, salicylates, some benzodiazepines, oestrogens and propranolol Drug drug interactions Drugs known to be enzyme inducers or enzyme inhibitors can affect metabolism of other drugs when administered concomitantly Diseases Some acute or chronic diseases/conditions decrease greatly hepatic metabolism. Such conditions include alcoholic hepatitis, alcoholic cirrhosis and drug or viral induced hepatitis STEP 4: First Pass Effect (20minutes) Some drugs are extracted so efficiently by the liver or gut wall that the amount reaching the systemic circulation is considerably less than the amount absorbed. This is known as first-pass or presystemic metabolism and reduces bioavailability even when a drug is well absorbed. Presystemic metabolism is important for many therapeutic drugs and is a problem because: o A much larger dose of the drug is needed when it is given orally than when it is given parenterally o Marked individual variations occur in the extent of first-pass metabolism Examples of drugs that undergoes first pass metabolism are as follows; o Aspirin o Metoprolol o Glyceryl trinitrate o Morphine o Isosorbide dinitrate o Propranolol o Levodopa o Salbutamol PST 05104 Pharmacology & Therapeutics 22 NTA Level 5 Semester

NTA Level 5 • Semester 1 • PST05104 Drug Distribution Total Session Time: 120 minutes Pharmacology and Therapeutics • Source Session/Topic 2 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 2: Drug Distribution Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe the distribution of drugs in various compartments of the body Describe factors affecting/determining distribution of drugs Describe Volume of distribution Calculate Volume of distribution Explain clinical applications of volume of distribution Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers Computer and LCD Projector SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 10 minutes 10 minutes Presentation/ Distribution of Drugs in Various Distribution of Drugs in Various 2 2 10 minutes 10 minutes Buzzing Compartments of the Body Compartments of the Body Buzzing Compartments of the Body Compartments of the Body 3 3 30 minutes 30 minutes Presentation/ Factors Affecting Distribution of Drugs Factors Affecting Distribution of Drugs 3 3 30 minutes 30 minutes Brainstorming Factors Affecting Distribution of Drugs Factors Affecting Distribution of Drugs Brainstorming 4 4 20 minutes 20 minutes Presentation Volume of Distribution Volume of Distribution 4 4 20 minutes 20 minutes Presentation Presentation/ 5 5 30 minutes 30 minutes Small Group Calculation of Volume of Distribution Calculation of Volume of Distribution Discussion 6 6 15minutes 15minutes Presentation Clinical Application of Volume of Clinical Application of Volume of 6 6 15minutes 15minutes Presentation Distribution Distribution Distribution Distribution 7 7 05 minutes 05 minutes Presentation Key Points Key Points 8 8 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics 11 NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning objectives and clarify ASK students if they have any questions before continuing. STEP 2: Distribution of Drugs in various Compartments of the Body (10 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes What is distribution process of drugs in the body? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Once in the systemic circulation drugs will distribute into sections/units called compartments. The following are the compartments for governing drug distribution: o Plasma compartment (Vascular compartment) Drugs with very large molecular weight or those binding extensively to plasma proteins are effectively trapped within the plasma (vascular) compartment because such drugs are too large to move out through the endothelial slit junctions of the capillaries. Extracellular fluid o Observed in drugs with low molecular weights but also hydrophilic, such drugs can move through the endothelial slit junctions of the capillaries into the interstitial fluid. However, these hydrophilic drugs cannot move across the membranes of cells to enter the water phase inside the cell. Total Body Water o Observed in drugs with low molecular weight and are hydrophobic, such drugs can not only move into the interstitium through the slit junctions, but can also move ,through the cell membranes into the intracellular fluid. Other sites o In pregnancy, the foetus may take up drugs and thus increase the volume of distribution. PST 05104 Pharmacology & Therapeutics 12 NTA Level 5 Semester 1 Facilitator Guide STEP 3: Factors Affecting Distribution of Drugs (30Minutes) Activity: Brainstorming (5 minutes) Ask students to brainstorm on the following question: What are the factors determining distribution of drugs? ALLOW few students to respond WRITE their responses on the flip chart/ board CLARIFY and SUMMARISE by using the content below Distribution of drugs in the body is dependent on the following factors: Organ Blood Flow o Organs with high blood flow will have larger amounts of drug delivered to them per unit time. o Organs with high blood flow will experience initial high concentrations of drug, but these high concentrations will diminish as the drug is redistributed throughout the body to sites with lower blood flow. Barriers to diffusion o There are special barriers which restrict drug entry to some organs o Blood Brain Barrier ―BBB‖ is a special case o In general, the BBB restricts the movement of hydrophilic drugs into brain; however, the BBB is ―broken‖ by ischemia and inflammation. o The BBB can be exploited to develop drugs with reduced CNS adverse effects Adipose tissue o Lipophilic drugs will distribute into adipose (fat) tissue. o Distribution of lipophilic drugs into fat may necessitate a larger initial bolus of drug to achieve the desired effect. o Large depots of drug in fat may necessitate a longer period of time for drug to be removed from the body. o The distribution of lipophilic drugs will be different in thin versus obese patients Plasma protein Binding o Drugs bound to protein are pharmacologically inactive. o Only when the protein molecules release the drug can the drug diffuse into the tissues, interact with receptors, and produce a therapeutic effect. o Some drugs are highly bound (> 90%) to plasma proteins. o Acid drugs bind to albumin and basic drugs bind to alpha1-acid glycoprotein. o Binding of drugs by plasma proteins limits the distribution of drugs out of the vascular compartment, necessitating more drug initially to achieve the desired effect PST 05104 Pharmacology & Therapeutics 13 NTA Level 5 Semester 1 Facilitator Guide Displacement of a highly plasma-protein bound drug by another drug may lead to drug-drug interactions because of a rapid increase in the availability of ―free‖ (unbound) drug. Tissue protein binding Some drugs are highly bound to tissue proteins. Binding of drugs by tissue may necessitate a larger initial

NTA Level 5 • Semester 1 • PST05104 Drug Absorption Total Session Time: 120 minutes Pharmacology and Therapeutics • Source Session/Topic 1 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. Session 1: Drug Absorption Total Session Time: 120 minutes Prerequisites None Learning Tasks By the end of this session students are expected to be able to: Describe absorption Describe factors affecting/determining absorption Differentiate between Absolute and relative bioavailability Calculate bioavailability Explain clinical application of bioavailability Resources Needed: Flip charts, marker pens, and masking tape Black/white board and chalk/whiteboard markers LCD projector and computer SESSION OVERVIEW Step Time Activity/ Content Step Time Activity/ Content Step Time Method Content Method Method 1 1 05 minutes 05 minutes Presentation Introduction, Learning Tasks Introduction, Learning Tasks 2 2 10 minutes 10 minutes Presentation/ Definition of Absorption Definition of Absorption 2 2 10 minutes 10 minutes Buzzing Definition of Absorption Definition of Absorption Buzzing Presentation/ 3 3 45 minutes 45 minutes Small Group Factors Affecting Absorption Factors Affecting Absorption Discussion 4 4 20 minutes 20 minutes Presentation Absolute and Relative Bioavailability Absolute and Relative Bioavailability 5 5 20 minutes 20 minutes Presentation/ Calculation of Bioavailability Calculation of Bioavailability 5 5 20 minutes 20 minutes Brainstorming Calculation of Bioavailability Calculation of Bioavailability Brainstorming 6 6 10minutes 10minutes Presentation Clinical Application of Bioavailability Clinical Application of Bioavailability 7 7 05 minutes 05 minutes Presentation Key Points Key Points 8 8 05 minutes 05 minutes Presentation Evaluation Evaluation PST 05104 Pharmacology & Therapeutics NTA Level 5 Semester 1 Facilitator Guide SESSION CONTENTS STEP 1: Presentation of Session Title and Learning Tasks (5 minutes) READ or ASK students to read the learning tasks and clarify ASK students if they have any questions before continuing. STEP 2: Description of Absorption (10 minutes) Activity: Buzzing (5 minutes) ASK students to pair up and buzz on the following question for 2 minutes What is absorption? ALLOW few pairs to respond and let other pairs add on points not mentioned WRITE their response on the flip chart/board CLARIFY and SUMMARIZE by using the content below Absorption follows administration and is the process by which a drug is made available for use in the body. It is the transfer of a drug from its site of administration to the Blood stream. It occurs after dissolution of a solid form of the drug or after the administration of a liquid or parenteral drug. In this process the drug particles within the gastrointestinal tract are moved into the body fluids. • Transport of drug from the GIT involves passive diffusion, active transport and pinocytosis. In active absorption a carrier molecule such as a protein or enzyme actively moves the drug across the membrane. Passive absorption occurs by diffusion (movement from a higher concentration to a lower concentration). In pinocytosis cells engulf the drug particle causing movement across the cell STEP 3: Describe Factors Affecting Absorption (45 Minutes) Activity: Small Group Discussion ( 20 minutes) DIVIDE students into small manageable groups ASK students to discuss on the following question What are factors affecting drug absorption? ALLOW students to discuss for 15 minutes ALLOW few groups to present and the rest to add points not mentioned CLARIFY and SUMMARIZE by using the contents below: PST 05104 Pharmacology & Therapeutics 2 NTA Level 5 Semester 1 Facilitator Guide Absorption Absorption is the movement of a drug from its site of administration into the blood. Most drugs are absorbed by passive absorption but some drugs need carrier mediated transport. Small molecules diffuse more rapidly than large molecules. Lipid soluble non – ionized drugs are absorbed faster. Factors determining absorption include; route of administration, Blood flow to the absorption site Surface area available for drug absorption GI motility Physiochemical properties of drugs Particle size of the formulation Route of administration Drugs are most rapidly absorbed when given by the intravenous route, followed by the intramuscular route, the subcutaneous route, and lastly, the oral route. Typically, about 75% of a drug given orally is absorbed in 1-3 h, but numerous factors alter this, some physiological and some to do with the formulation of the drug. The main factors are: o gastrointestinal motility o splanchnic blood flow o particle size and formulation o Physicochemical factors. Blood flows faster through the deltoid muscle (in the upper arm) than through the gluteal muscle (in the buttocks). o The gluteal muscle, however, can accommodate a larger volume of drug than the deltoid muscle Fig 1.1 Main routes of drug administration PST 05104 Pharmacology & Therapeutics 3 NTA Level 5 Semester 1 Facilitator Guide Blood flow to the absorption site o Blood flow to the intestine is much greater than the flow to the stomach resulting to a favored absorption from the intestine over that from stomach. Total surface area available for absorption o Absorption of a drug across the GI tract is much efficient in the small intestine than the stomach due to a higher surface area resulting from presence of microvilli: o Other bodily conditions such as the development of lipodystrophy (atrophy of the subcutaneous tissue) from repeated subcutaneous injections inhibit absorption of a drug given in the site of lipodystrophy. Enzyme activity o Drugs such as insulin and other proteins may be degraded by gastric enzyme resulting to poor absorption. o The presence of food in the stomach both dilutes the drug and slows gastric emptying thus taking a drug together with food results to a generally slow absorption. GI tract motility Gastrointestinal motility has a large effect. Many disorders (e.g. migraine, diabetic neuropathy) cause gastric stasis and slow drug absorption. Drug treatment can also affect motility, either reducing (e.g. drugs that block muscarinic receptors) or increasing it (e.g. metoclopramide, which is used in migraine to facilitate absorption of analgesic). Excessively rapid movement of gut contents can impair absorption. A drug taken after a meal is often more slowly absorbed because its progress to