Pharmacology in DSW PDF

PHRM-3019 Pharmacology in DSW Instructor: Mujtaba Badr, MScPharmSc Pharmacology Pharmacology is the Drug sources. Study of drugs. Plants. Animals. Drug (French: Drogue—a dry herb) is the single Micro...

PHRM-3019 Pharmacology in DSW Instructor: Mujtaba Badr, MScPharmSc Pharmacology Pharmacology is the Drug sources. Study of drugs. Plants. Animals. Drug (French: Drogue—a dry herb) is the single Microorganisms. active chemical entity Chemical synthesis. present in a medicine that Biotechnology. is used for diagnosis, prevention, treatment/cure of a disease. Major Areas of Pharmacology Katzung, Basic and Clinical Pharmacology, 14th edition, 2018 Major Areas of Pharmacology Area Description Pharmacodynamics Study of the action of drugs on living tissue Pharmacokinetics Study of the processes of drug absorption, distribution, metabolism, and excretion Pharmacotherapeutics Study of the use of drugs in treating disease Pharmacy Science of preparing and dispensing medicines Posology Study of the amount of drug that is required to produce therapeutic effects Toxicology Study of the harmful effects of drugs on living tissue Terminology Related To Drug Effects Desired Effects Side effects. Therapeutic Effect. Causes slight discomfort. Undesired Effects Not harmful. Side Effect. Adverse effects. Adverse Effect. Potentially harmful. Toxic Effect. Toxic effects. Extremely harmful. Concepts in Pharmacology 1 Site of action. Agonists and antagonists: Location where a drug exerts its effect. Agonists produce drug action. Mechanism of action. Antagonists inhibit drug action. How a drug produces its effects. Receptor site. Site on a cell where a drug exerts its effects. Agonism, Antagonism, & Allosteric Modulation Dose Response and Time-Plasma Drug Concentration Curves Dose response curve. Time-plasma drug concentration curve. Response of a drug proportional to dose. Shows the relationship between time and plasma Dose: Exact amount of a drug drug concentration. administered in order to produce a specific effect. A Typical Dose-Response Curve A Typical Time-Plasma Drug Concentration Curve Drug Safety Medications must be proven Adverse drug effects: safe and effective. May or may not depend on the Therapeutic index (TI). dose. Ratio of lethal dose 50 (LD50) Dose dependent effects can be to effective dose (ED50). caused by teratogens and carcinogens. Gives an estimate of a drug’s relative safety. Examples of dose independent effects - Drug idiosyncrasy and TI = LD50/E D50. drug allergy. Drug Legislation Drug References https://health-products.canada.ca/dpd-bdpp/ Drug Forms Physical and chemical properties of Capsules. a drug determine its most effective form. Delayed-release products. Aqueous preparations. Enteric-coated products. Alcoholic preparations. Suppositories. Solid and semisolid preparations. Ointments. Powders. Transdermal products. Tablets. Parenteral injections. Troches and lozenges. Routes of Administration Route Approximate Indications Examples onset of action Oral (P O) 30 to 60 minutes Whenever possible, the safest and most Most medications-aspirin, convenient route sedatives, hypnotics, antibiotics Sublingual Several minutes When rapid effects are needed Nitroglycerin in angina pectoris Buccal Several minutes Convenient dosage form for certain drugs Androgenic drugs Rectal 15 to 30 minutes When patient cannot take oral medications and Analgesics, laxatives parenteral is not indicated, also for local effects Transdermal 30 to 60 minutes Convenient dosage form that provides Nitroglycerin, estrogen continuous absorption and systemic effects over many hours Subcutaneous Several minutes For drugs that are inactivated by the G I tract Insulin (S C) Intramuscular Several minutes For drugs that have poor oral absorption, when Narcotic analgesics, antibiotics (I M) high blood levels are required, and when rapid effects are desired Routes of Administration Route Approximate Indications Examples onset of action Intravenous (I V) Within 1 minute In emergency situations, where immediate I V fluids (dextrose), nutrient effects are required, also when supplementation, antibiotics medications are administered by infusion Intraarterial Within 1 minute For local effects within an internal organ Cancer drugs Intrathecal Several minutes For local effects within the spinal cord Spinal anesthesia with lidocaine Inhalation Within 1 minute For local effects within the respiratory tract Antiasthmatic medications such as epinephrine Topical Within 1 hour For local effects on the skin. eye. or ear Creams and ointments Vaginal 15 to 30 minutes For local effects Creams, foams, and suppositories A Drug Journey Through The Body Pharmacokinetic Phases Absorption: Distribution: Transport mechanisms - Plasma protein binding. Filtration, active transport, and Blood flow. passive transport. Blood-brain barrier. Determined by: Lipid solubility. Drug ionization and formulation. Pharmacokinetic Phases Metabolism: Excretion: Drug microsomal metabolizing Renal. system. GI. Enzymes within the cells of the Respiratory. liver that function to metabolize foreign substances. Sweat, saliva, and lactation. Clinical Factors That Determine the Intensity of Drug Response Half-life: Blood drug levels: Amount of time it takes for the Intensity of a drug effect is blood concentration to drop determined by the by half of its original level. concentration of drug in the blood. Bioavailability: Percentage of drug that is absorbed into the bloodstream. Factors of Individual Variation Age. Emotional state. Weight. Placebo effect. Sex and percent body fat. Disease state. Genetic variation. Patient compliance. Pharmacokinetic Considerations for Pediatrics Medications taken by Drug absorption differs. pregnant women can pass to Infants have a small skeletal the fetus. muscle mass and limited movement. Drugs can pass through breast milk to infants. Distribution of drugs differ. Pharmacokinetic and pharmacodynamic differences Infants have a higher exist between pediatric and percentage of body water adult patients. and a lower percentage of body fat. Drug metabolism and excretion is slower in infants. Description of FDA Pregnancy Categories Category Description Pregnancy category A Drug studies in pregnant women have not yet demonstrated risk to the fetus Pregnancy category B Drug studies have not been performed in pregnant women; animal studies have not demonstrated fetal risk Pregnancy category C Drug studies have not been performed in pregnant women or in animals, or animal studies have revealed some teratogenic potential but the risk to the fetus is unknown Pregnancy category D Drug studies have revealed adverse risk to the fetus. The benefit-to-risk ratio of the drug must be established before use during pregnancy Pregnancy category X Drug studies have revealed teratogenic effects in women and/or animals. Fetal risk clearly outweighs benefit. Drug is contraindicated in pregnancy Pregnancy category N R Drug has not yet been rated by F DA Terminology Associated with Chronic Drug Use and Abuse Tolerance. Dependence: Decreased drug effect with Reliance on a drug becomes repeated administration. vital to the well-being of the patient. Cross-tolerance - Tolerance that exists between drugs of Can impact a person the same class. physically and/or psychologically. Types: Leads to drug abuse or drug Metabolic tolerance. addiction. Pharmacodynamic tolerance. Drug Use in the Elderly Geriatric: Individuals over 65 years of age. Progress of medical technology has improved health and quality of life. Aging affects drug absorption, distribution, metabolism, and excretion and the size of organs. © McGraw Hill 25 Age-Related Changes in Pharmacokinetic Processes Pharmacokineti Age-related change c process Drug absorption Decreased intestinal blood flow, surface area, and motility delay drug absorption and slow onset of drug action Drug distribution Decreased body water, lean body mass, and plasma proteins along with increased fat content increase plasma drug concentrations and pharmacologic effects Drug Decreased liver blood flow, liver organ size, and metabolism enzyme concentrations decrease the rate of drug metabolism and increase the duration and intensity of drug Action Drug excretion Age-related decreases in renal function and blood flow slow the rate of drug excretion and increase the duration and intensity of drug action © McGraw Hill 26 Effects of Age on Drug Response Factors: Nutritional status. Presence of disease. Changes in pharmacodynamic response. © McGraw Hill 27 Drug Compliance/Adherence in the Elderly Elderly patients face difficulty in understanding and remembering their medications. Polypharmacy is a concern. Patients may need a change in dosage form to allow for easier administration. © McGraw Hill 28 Pharmacodynamics Concerned with pharmacologic actions of drugs Therapeutic effects To treat a disease or disorder Adverse effects Harmful effects continued on next slide Pharmacodynamics How a medication causes changes in the body Biochemical, physiologic effects of drugs Molecular mechanisms producing these effects Pharmacodynamics is essential for: Safe prescribing, use, evaluation of responses continued on next slide Pharmacodynamics Dose-Effect Relationship Drugs must dissolve before being absorbed Some absorbed, metabolized before reaching site of action Drug effects are influenced by: Absorption Reabsorption Site of action Metabolism Excretion Observed response continued on next slide Pharmacodynamics Dose-Effect Relationship Pharmacokinetics, pharmacodynamics determine dose-effect relationship: Relationship between dose that produces harmful effects and severity of effects Response to drug or toxic agent increases as overall exposure increases continued on next slide Pharmacodynamics Dose-Effect Relationship Relative potency Amount of drug required to cause an effect Maximal efficacy Largest effect a drug can produce Figure 2-1 The dose–effect relationship, showing (A) drug potency and (B) drug efficacy (or effectiveness). Copyright © 2018, 2013, 2008 Pearson Education, Inc. All Rights Reserved Pharmacodynamics Frequency Distribution Curve Number of patients that respond to a drug’s action at different doses Median effective dose (ED 50) Amount needed to produce a specific response in 50% of patients Figure 2-2 The frequency distribution curve of a drug. Source: Adams, Michael Patrick; Holland, Leland; Urban, Carol, Pharmacology for Nurses: A Pathophysiologic Approach, 4th Ed., ©2014. Reprinted and Electronically reproduced by permission of Pearson Education, Inc., New York, NY Copyright © 2018, 2013, 2008 Pearson Education, Inc. All Rights Reserved Pharmacodynamics Therapeutic Index and Drug Safety Therapeutic index (TI) Predicts if a certain dosage is safe for a specific patient Median lethal dose (LD50) Dose that is lethal in 50% of a group of test animals continued on next slide Pharmacodynamics Therapeutic Index and Drug Safety Calculating the therapeutic index Median lethal dose (LD50) divided by the Median effective dose (ED50) continued on next slide Pharmacodynamics Therapeutic Index and Drug Safety Larger therapeutic index Difference between the two doses is larger. The higher its value, the safer it is to use. Since LD50 cannot be tested in humans: Median toxicity dose (TD50) is used. The dose producing a given toxicity in 50% of patients Figure 2-3 The therapeutic indexes for two drugs. Source: Adams, Michael Patrick; Holland, Leland; Urban, Carol, Pharmacology for Nurses: A Pathophysiologic Approach, 4th Ed., ©2014. Reprinted and Electronically reproduced by permission of Pearson Education, Inc., New York, NY Copyright © 2018, 2013, 2008 Pearson Education, Inc. All Rights Reserved Pharmacodynamics Cellular Receptors and Drug Action Drugs alter cell function, body tissues, structures of microorganisms. Each drug has specific affinity (attractive force) for a target receptor: Cell recipient Receptor (usually a specific protein, in cell membranes) Intracellular receptors Located in cellular cytoplasm continued on next slide Pharmacodynamics Cellular Receptors and Drug Action Receptor theory How most drugs produce their effects Most receptors are proteins May be any type of macromolecule Consist of protein subunits around a central channel A drug may trigger second messenger events in cells. continued on next slide Figure 2-4 Drug action through channels, via voltage changes or chemicals. Source: Adams, Michael Patrick; Holland, Leland; Urban, Carol, Pharmacology for Nurses: A Pathophysiologic Approach, 4th Ed., ©2014. Reprinted and Electronically reproduced by permission of Pearson Education, Inc., New York, NY Copyright © 2018, 2013, 2008 Pearson Education, Inc. All Rights Reserved Pharmacodynamics Cellular Receptors and Drug Action Types of drug receptors Enzymes embedded in cell membranes Ligand-gated ion channels G protein-coupled receptor systems Transcription factors Figure 2-5 The four primary drug-receptor families. Copyright © 2018, 2013, 2008 Pearson Education, Inc. All Rights Reserved Pharmacodynamics Drug-Receptor Interactions Drugs interact with other chemicals (receptors). Receptors Macromolecules inside cells Including neurotransmitters and hormones Target molecules (not true receptors) Enzymes Ribosomes Other macromolecules continued on next slide Pharmacodynamics Drug-Receptor Interactions Equation for drug-receptor interactions D + R → D–R Complex → Response continued on next slide Pharmacodynamics Drug-Receptor Interactions Agonists, Partial Agonist-Antagonists, and Antagonists Agonists Bind to a receptor Produce stimulatory responses similar to that produced by endogenous chemicals Antagonists Prevent agonists from binding to receptors, Blocking their effects continued on next slide Type of Agonist Drugs The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy and an inverse agonist has < 0% (i.e., negative) efficacy