Transcript Lecture 8
Cardiovascular Anatomy, Physiology and Pharmacology BS913 Lecture 8: General Pharmacology, Pharmacokinetics and –dynamics, Introduction to cardiovascular drugs … Mücke Leithauser 1) What is Pharmacology? 2) What do you want to know / learn about pharmacology? 3) Why is some knowledge in pharmacology important to you? Learning objectives „Pharmacology“ - Describe the prescribed usage, alternative nomenclature, dosages, adverse reactions, cautions and common routes of administration - Describe the pharmacological interventions commonly used in the treatment of cardiac disorders - Discuss the effect of common cardiac drugs on the body and their cellular and physiological actions. - Understand the effect of common cardiac drugs on physical activity, and the special considerations related to these drugs. What is pharmacology? - Pharmacology is the study of drugs and their actions on living organisms - A sound knowledge of basic pharmaceutical principles is essential for professionals who interact with patients who receive medications 1) What is Pharmacology? 2) What do you want to know / learn about pharmacology? 3) Why is some knowledge in pharmacology important to you? 4) Where do we start? General principles of pharmacology - Drug development - Drug names - Drug categories - Drug actions within the body - Drug reactions - Drug interactions - Factors influencing drug response Drug development - Long and arduous process 7 to 12 years or longer - New drugs need to be approved (FDA = Food and Drug Administration and / or similar national organisations) - Development of a new drug is a multiphase process pre-FDA phase FDA phase Drug development - pre-FDA phase: - - in-vitro testing using animal and human cells studies in live animals FDA-phase: clinical testing phase I: 4 - 6 weeks; 20 - 100 individuals (“normal” volunteers or in intended treatment population) Drug development - FDA-phase: clinical testing phase II: more people compared to phase I - phase III: more people compared to phase II; generates more info on dosing and safety - Phases I-III last 2-10 years (average 5) Decision of (dis)approval approx. 2 yr Phases of drug development Drug names Drugs are referred to in a number of ways: - By the class or group of drugs Anti-Histamins - By generic names Loratadine By proprietary (or brand) names Claritin - Drug names GROUP Ca-channel blockers ß-blockers Generic name Verapamil Proprietary name Cordilox Verapamil Securon Propanolol Inderal Atenolol Tenormin Drug categories - Prespription drugs: - - Non-prescription drugs: - - Largest category of drugs Must be prescribed by licensed health care provider most drugs taken by cardiac patients need to be prescribed can be obtained without prescription are drugs; may cause adverse effects Controlled substances: - high potential for abuse; may cause physical or psych. dependence Drug actions within the body: - Pharmaceutical phase - Pharmacokinetic phase - Pharmacodynamic phase Drug actions within the body: - Drugs act in various ways in the body - Solid drugs taken by mouth go through all three phases - Liquid drugs and parenteral drugs (given by injection) go through the latter two phases Drug actions within the body: - Who has ever taken medication because of horrible headache? Pharmaceutical phase: - Dissolution of the drug - Drugs must be in solution to be absorbed - Tablets or capsules: disintegrate into small particles and dissolve into body fluids within the gastrointestinal tract - Enteric-coated tablets do not disintegrate until reaching an alkaline environment (small intestine) Pharmacokinetic phase: Pharmacokinetic phase: - Refers to activities involving the drug after it is administered - - Absorption Distribution Metabolism Excretion Half-life of a drug: measure of rate at which drug is removed from the body Absorption - Follows administration - Process by which drug becomes available for use in the body - Occurs after dissolution of solid drug or after administration of a liquid or parenteral drug Absorption - Drug particles in GIT are moved into body fluids active absorption (carrier moves drug through membrane) passive absorption (diffusion) pinocytosis (cells engulf drug particle causing movement across the cell) - Drug transfer to tissue sites – absorption into body tissues Absorption - Factors influencing rate of absorption - route of administration solubility of drug certain body conditions (e.g. Lipodystrophy) Absorption - Drugs most rapidly absorbed - intravenous application - intramuscular application - subcutaneous application - oral application Distribution - - Systemic circulation distributes drugs to various body tissues / target sites There, drugs interact with specific receptors - Some drugs travel by binding to protein (albumin) - Drugs bound to protein are pharmacologically inactive Distribution - Needs to be released by protein molecules to diffuse into tissue, interact with receptors, produce a therapeutic effect - Certain blood level must be maintained for drug to be effective - If level too low: drug will not produce desired effect - If level too high: toxic symptoms may develop Metabolism - Sometimes called biotransformation - Process of chemical reactions by which the liver converts the drug to inactive compounds - Important: patients with liver disease may require lower dosage; frequent liver function tests are necessary - Kidneys, lungs, plasma and intestinal mucosa aid in metabolism of drugs Excretion - Elimination of drugs from the body - After liver renders a drug inactive, kidneys excrete inactive compounds from the body in the urine - Some drugs are excreted unchanged by the kidney without liver involvement Excretion - Important: Patients with kidney disease may require a lower dosage; careful monitoring of kidney function - Special case “children”: immature kidney function Special case “older adults”: reduced kidney function Other ways of elimination: breast milk, breathing, faeces - Half life - Time required for the body to eliminate 50% of the drug - It takes five to six half-lives to eliminate approximately 98% of a drug Half-life of a drug is the same in most people - Reduced liver and kidney function can increase half-life and by this the risk of toxicity Pharmacodynamic phase - The drug’s action and effects within the body - After administration most drugs enter the systemic circulation and expose almost all body tissue to their potential effects - All drugs produce more than one effect in the body - The primary effect is the desired or therapeutic effect Pharmacodynamic phase - - Secondary effects are all other effects (desirable or undesirable) produced by the drug Most drugs have an affinity for certain organs or tissues - They exert greatest action at the cellular level in those specific areas - Main mechanisms of action: alteration in cellular environment alteration in cellular function Pharmacodynamic phase - Physical alterations in cellular environment, e.g. Changes in osmotic pressure Absorption (activ. charcoal) Conditions on surface of cell membrane (stool softener) - Chemical alterations in cellular environment, e.g. alteration of chemical components of body fluid (ph-change; antacids) Pharmacodynamic phase - Most drugs act on body by altering cellular function increase or decrease of certain physiologic function, e.g. heart rate blood pressure urine output Pharmacodynamic phase - Receptor-mediated drug action Cell function alters when drug interacts with receptor - Agonists: drugs bind with receptor to produce a therapeutic response - Antagonists: drugs bind with receptor and thereby prevent the action of an agonist Pharmacodynamic phase - Receptor-mediated drug effects - Number of available receptor sites influences effects of a drug - If drug occupies only few receptors when many are available: small effect Drugs : a variety of reactions - Adverse drug reactions - Allergic drug reactions - Drug idiosyncrasy - Drug tolerance - Cumulative drug effect - Toxic reactions Adverse Drug reactions: - Adverse drug reactions - Undesirable drug effects - May be mild, severe, life-threatening - Occur after first dose, several doses, many doses - Sometimes predictable - In many cases without warning Adverse effects: Allergic Drug reactions: - Hypersensivity - Occurs usually after more than one dose has been given - Immune system views drug as a foreign substance (antigen) Initiates antibody production - Allergic reaction must be reported to health care provider Allergic Drug reactions: - Symptoms - Itching skin Rash Breathing difficulties Wheezing swelling of the eyes, lips Anaphylactic Shock: Drug idiosyncrasy: - Unusual or abnormal reaction to a drug Drug tolerance - Decreased response to a drug After taking the drug for long time increase in dosage to maintain effect Cumulative Drug effect: - In patients with liver / kidney problems Can lead to toxic reactions Toxic reaction - If administered in large dosages When blood concentration level exceeds therapeutic level sometimes antidote available Drug interactions: - Drug-drug interactions - Drug-food interactions Drug interactions: - Drug-drug interactions - Additive drug reaction: 1+1=2 - Synergistic drug reaction: 1 + 1 = (>2) - Antagonistic drug reaction: Drug interactions: - Drug-Food interactions - Drug taken on empty stomach: Faster absorbed - Full stomach: Slower absorbed Drug-food complex (tetracycline) food as “antagonist” (vit. K and warfarin) - Factors influencing drug response: - Age - Weight - Gender - Disease - Route of administration Factors influencing drug response: - Age: immature organ function in kids reduced function in elderly - Weight: reference weight 75 lb - Gender: higher fat/water ratio in F - Disease: liver, kidney; - Route of administration Factors influencing drug response: - Route of administration some drugs can onlygiven by one route differences in appearance of drug action Factors influencing drug response: Drugs used to treat cardiac conditions: