Pharmacological Principles Module 2 PDF

Pharmacological Principles Module 2 1  Pharmaceutics The study of how various drug forms influence the way in which the drug affects the body Dissolution dissolving of solid dosage forms and their absorption...

Pharmacological Principles Module 2 1  Pharmaceutics The study of how various drug forms influence the way in which the drug affects the body Dissolution dissolving of solid dosage forms and their absorption 2  Pharmacological Principles  Pharmaceutics  Pharmacokinetics  Pharmacodynamics  Pharmacogenomics (pharmacogenetics)  Pharmacotherapeutics  Pharmacognosy  Pharmacoeconomics  Toxicology 3 Phases of Drug Activity 4  Pharmacokinetics  The study of what the body does to the drug  From the time drug is put into the body until the parent drug and metabolites have left the body:  Absorption  Distribution  Metabolism  Excretion 5 Pharmacokinetics 6  Absorption Movement of drug from site of administration to bloodstream for distribution Must first pass through liver to be metabolized (broken down) Bioavailability- how much drug is available to be absorbed after reaching liver Drugs administered by mouth have reduced bioavailability (First Pass Effect) Only a portion of the drug is active after it has gone through the first pass effect Intravenous drugs are 100% bioavailable 7  Absorption Different dosage forms can determine the rate of dissolution and onset of action ( ONLY ORAL DRUG) Variety of dosage forms for accuracy and convenience Time Release Technology- released in GI tract over time Immediate Release Continuous Release Thin film drug delivery –tongue, buccal 8  Distribution Transport of a drug by the bloodstream to the drug’s site of action Drugs distributed first to areas with extensive blood supply Heart, liver, kidneys and brain Albumin most common blood protein carries majority of protein-bound drug molecules. – designed to attach to albumin to be carried around throughout the blood stream If a given drug binds to albumin “ not active” = only a limited amount of the drug is not bound. Unbound portion is active and is considered “free” drug. 9  Plasma Membranes  Numerous obstacles in reaching target cells  Greatest barriers is crossing the many membranes  Drugs must penetrate these membranes to produce effects  Diffusion, Active transport  Drug taken by mouth must must pass mucosal cells of GI then capillary endothelial cells to enter bloodstream then leave blood stream through interstitial fluid to enter target cells  Subject to many physiological processes during travel  Enzymes may break down, change , be attacked by phagocytes , or trigger an immune response 10 Protein Binding 11 Dosage Forms 12 13  First-pass effect of a drug by the liver before its systemic availability. 14 First Pass/Non-First Pass Routes 15  Enteral Route  Absorbed into the systemic circulation through the mucosa of the stomach, small/large intestine  Rate of absorption affected by many factors  Oral drugs absorbed from intestinal lumen to mesenteric system and transported by portal vein to liver  Hepatic enzymes then metabolize  Enteric coated bypass the stomach and absorption occurs in the small intestine  Many factors affect absorption, PH ,absorption in intestines, presence or absence of food , bowel removal  Sublingual or Buccal absorbed rapidly highly vascularized tissue 16  Parenteral Route  Intravenous  fastest due to direct delivery into the blood circulation  Intramuscular  Subcutaneous  Intradermal  Intra-arterial  Intrathecal – spinal cord  Intra-articular – joints IM or SC injection absorbed more slowly over hours-days-weeks-months 17  Topical Route  Skin (including transdermal patches)  Uniform amount of drug over longer period.  Slower onset and prolonged duration of action  Systemic absorption can be erratic and unpredictable  Often used for local actions only  No first pass effect (except rectal mixed)  Eyes  Ears  Nose  Lungs (inhalation)  Rectum – rectal is mixed ( depending on area and drug)  Vagina 18 19  Pharmacokinetics Metabolism Also referred to as biotransformation Biochemical alteration of a drug into any of the following in the liver : an inactive metabolite a more soluble compound a more potent metabolite (as in the conversion of an inactive prodrug to its active form) a less active metabolite involves a large class of enzymes cytochrome P450 that aid in metabolism Largely target lipid soluble (lipophilic) which are difficult to eliminate (most medications) Water soluble (hydrophylic) are easier to eliminate 20  Pharmacokinetics  Excretion Elimination of drugs from the body Primary organ responsible is kidney Liver and bowel also play a role Drugs that have been metabolized by liver have undergone extensive biotransformation Now less active form excreted Drugs that bypass first-pass may reach kidney in original form 21 Pharmacokinetics 22  Half-life Time required for half (50%) of a given drug to be removed from the body After 5 half lives most drugs are effectively removed 23  Onset of Action  Onset of action –time required to elicit a therapeutic response  Peak level: highest blood level of a drug  Trough level: lowest blood level of a drug  Toxicity: occurs if the peak blood level of the drug is too high  Duration of Action : length of time concentration sufficient (without more doses) to elicit therapeutic response 24 Pharmacokinetics 25  Pharmacodynamics/ Mechanism of Action  Drugs produce actions several ways  Depend on the cells or tissue targeted by the drug.  Once the drug is at the site of action, it can modify (increase or decrease) the rate and strength at which that cell or tissue functions  Cannot cause a cell or tissue to perform a function that is not part of its natural physiology.  3 Basic ways receptors, enzymes, and nonselective interactions.  Not all mechanisms of action have been identified for all drugs. 26 Receptor Interactions  Reactive site on surface or inside a cell  Drug-receptor action is the joining of the drug molecule with the receptor (often a protein structure within the cell membrane)  The degree to which a drug attaches and binds is called affinity  Drugs may elicit (agonist ) or block a physiological response (antagonist) 27  Enzyme Interactions  Enzymes are substances that cause almost every biochemical reaction in a cell  Drugs can produce effects by interaction with these enzymes  May inhibit or enhance called “selective interaction” 28 29 Drug Receptor Interactions 30  Pharmacotherapeutics  Before drug therapy initiated outcome of therapy should be established  Types of Therapy  Acute  Maintenance  Supplemental (or replacement)  Palliative  Supportive  Prophylactic  Empirical 31  Therapeutic Index  Ratio of drugs toxic level to the level that provides therapeutic benefits  Safety is determined by this index  Low therapeutic index means the difference between a therapeutically active dose and toxic dose is small  These drugs require closer monitoring 32  Tolerance and Dependence  Tolerance: decreasing response to repeated drug doses  Dependence: physiological or psychological need for a drug  Physical dependence:  physiological need for a drug to avoid physical withdrawal symptoms  Psychological dependence (addiction):  obsessive desire for a drug 33  Drug interactions  Alteration of the action of one drug by another  May increase or decrease the actions of one/both drugs  May have additive effects, combined effects of the drugs have similar actions if administered at the same time  Synergistic effects-action of one drug enhances another  Antagonistic effects- combination of two drugs results in effects that are less then if given separately 34  Pharmacogenetics and Pharmacogenomics  Pharmacogenetics study of genetic variations in drug response  Pharmacogenomics study how genetics involves the body’s response to drugs  Ability to individualize drug therapy based on patients genetic makeup instead of standard dose  Differences in alleles (1% of pop) known as genetic polymorphisms  Can affect antimalarial drugs, warfarin, codeine phenytoin (poor or rapid metabolizers) 35 Clinical Applications of Pharmacogenomics 36  Patient-Focused Considerations  Human body changes is many ways through lifespan  Dramatic effects on 4 phases of pharmacokinetics  Newborns, children and older adults have special needs  Fetus exposed to all drugs mother takes, first trimester period of greatest danger  Breast fed babies are at potential for drug exposure from mom 37  Pediatrics  Skin thinner and more permeable  Stomach lacks acid to kill bacteria  Lungs have weaker mucous barriers  Body temp less regulated, dehydration occurs  Liver and kidney immature drug metabolism reduced  Use formulas for pediatric dosage calculation involving weight ,age and BSA  Eg West Nomogram 38 Children 39 Pediatape 40 41  Older Adults  Decline in organ function more adverse effects and toxicity  General decrease in body weight  More or less sensitivity to medications. Eg increased sensitivity to central nervous system depressants because of reduced integrity of blood brain barrier  Liver and Kidney function reduced may not metabolize or eliminate drugs 42  Older Adult Changes  Distribution impaired due to less total body water, hydrophilic drugs may have higher concentrations  Protein stores reduced so reduced binding sites for highly bound protein drugs results in more unbound /active drug (free)  Metabolism decreased , liver loses mass and ability to metabolize-prolonged half life  Excretion –Kidney function commonly declines GFR reduced 40-50% delayed excretion and therefore accumulation 43 44 44 45