Introduction to Pharmacology Pharmacology the study of science of drugs Drug any chemical that affects the processes of a living organism
I. Drug sources: a. b. c. d. II. Drug uses:
plants animals minerals chemical synthesis/ biogenetic engineering
prevent diseases treat diseases diagnose diseases prevent pregnancy maintain health III. Drug names Chemical name o the drug’s chemical composition and molecular structure o ex.( +/- ) – 2 – ( p-isobutylphenyl ) proponic acid Generic Name ( Nonproprietary name ) o name given by the United States Adopted Name Council o universally accepted o ex.ibuprofen Trade Name ( Brand name/ Proprietary name) o the drug has a registered trademark ; use of the name restricted by the drug’s owner o ex. Motrin IV. Drug Standards: same drug name must have same strength, quality & purity based on United States Pharmacopeia and National Formulary (USP-NF)
V. Drug references: American Hospital Formulary Service (AHFS) Drug Information Physicians’ Desk Reference (PDR) Package inserts Drug Facts and Comparisons Saunders/ Lipincott’s Nursing Drug Guide Journals Internet
VI. Phases of Drug Development 1. Preclinical trial 2. Phase 1 3. Phase 2 4. Phase 3 5. Phase 4
VII. Legal Regulation A. Food and Drug Administration (FDA) Pregnancy Categories: Category A Category B Category C Category D Category X no risk to fetus no risk in animal fetus; no human studies available adverse effects to animal fetus; no human studies available possible fetal risk in humans reported fetal abnormalities reported; + evidence of fetal risk in animal/& human studies.
B. Controlled Substances: controlled substances OTC drugs prescription drugs orphan drugs dependence
Drug Enforcement Agency (DEA) Schedules of Controlled Substances: Schedule I Drugs high potential for abuse used for research only ex. heroin, marijuana, lysergic acid diethylamide (LSD) Schedule II Drugs high abuse potential severe physical & psychologic dependence acceptable medical use, with restrictions ex. amphetamines, cocaine, mepiridine (Demerol) , morphine, anabolic steroids Schedule III Drugs moderate potential for abuse psychological dependence , low physical dependence acceptable medical use, by prescription only ex. secobarbital (Seconal), Tylenol with codeine Schedule IV low potential for abuse limited physical & psychological dependence ex. diazepam (Valium), phenobarbital, chlordiazepoxide (Librium) Schedule V low potential for abuse acceptable medical use OTC narcotic drugs, sold only by registered pharmacists: buyer must be 18yo Ex. cough syrups with codeine eg. Guaifenesin, diphenoxylate HCL with atropine ( Lomotil)
Pharmacologic Principles I. Drug Action: Pharmaceutics Pharmacokinetics Pharmacodynamics II. Drug Effect: Pharmacotherapeutics
Pharmaceutics the study of how various drug forms influence pharmacokinetic and pharmacodynamic activities. o disintegration o dissolution Pharmacokinetics the study of what the body does to the drug: o Absorption o Distribution o Metabolism or biotransformation o Excretion or elimination Pharmacodynamics the study of what the drug does to the body : o the mechanism of drug action in living tissues. Pharmacotherapeutics the use of drugs and the clinical indications for drugs to prevent and treat diseases. Pharmacognosy the study of natural ( plant and animal ) drug sources.
I. The 3 Phases of Drug Action: A. Pharmaceutic Phase 1. disintegration 2. dissolution Rate limiting – time it takes for drug to disintegrate & dissolve to be absorbed by the body B. Pharmacokinetic Phase 1. Absorption: passage of a drug into the bloodstream from site of administration Processes of drug absorption: passive absorption active absorption pinocytosis
Drug absorption of Oral Preparations: Liquids, elixirs, syrups Fastest Suspension solutions Powders Capsules Tablets Coated tablets Enteric-coated tablets Slowest The rate at which the drug leaves its site of administration, and the extent to which absorption occurs. Bioavailability Factors that affect absorption : solubility of drug food or fluids administered with the drug dosage formulation status of the absorptive surface rate of blood flow to the small intestine acidity of the stomach status of GI motility administration route of drug Routes : a drug’s route of administration affects the rate and extent of absorption of the drug. o Enteral o Parenteral o Topical Enteral Route drug is absorbed into the systemic circulation through the oral or gastric mucosa, the small intestine, or rectum. o oral o sublingual* o buccal o rectal Parenteral Route Intravenous * Intramuscular Subcutaneous Intradermal Intrathecal Intraarticular Topical Route skin ( including transdermal patches ) eyes, ears & nose lungs ( inhalation )* vagina
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 ). The same drug – given IV – bypasses the liver, preventing the first – pass effect from taking place, the more drug reaches the circulation. Routes that bypass the liver : o sublingual o buccal o rectal* o intravenous o intranasal
transdermal vaginal intramuscular subcutaneous inhalation
2. Distribution transport of a drug by the bloodstream to its site of action Factors affecting drug distribution: protein-binding water soluble vs fat soluble areas of rapid distribution o heart, liver, kidneys, brain areas of slow distribution o muscle, skin, fat 3. Metabolism or biotransformation the transformation of a drug into an inactive metabolite, a more soluble compound or a more potent metabolite liver* others: kidneys, lungs, plasma ,intestinal mucosa Factors that decrease metabolism: cardiovascular problem renal problem starvation liver problem erythromycin or ketoconazole drug therapy Factors that increase metabolism: nicotine alcohol barbiturates & glucocorticoids rifampin therapy Half-life o time it takes for one half of the original amount of a drug in the body to be removed. o a measure the rate at which drugs are removed from the body
4. Excretion elimination of drugs from the body kidneys* others: lungs, exocrine glands (sweat, salivary or mammary glands), skin & intestinal tract
C. Pharmacodynamics Phase Onset of Action time it takes for the drug to elicit a therapeutic response minimum effective concentration (MEC) Peak Action time it takes for drug to reach its maximum therapeutic response Duration of Action the time a drug concentration is sufficient to produce its therapeutic response Receptor Theory most receptors are found on cell membrane drug binding occurs on receptors lock & key interaction : Agonist & antagonist: Agonists drugs that attracts to receptors stimulate/ enhance a response ex. Insulin, isoproterenol – stimulate beta 1 receptor Antagonists drugs that attracts to receptors block a response ex. cimetidine – blocks H2 receptor Nonspecific & Nonselective Drugs Nonspecific Drugs affect various sites of the body ex. Bethanecol stim. cholinergic receptor strengthen bladder contraction,increases HR, decreases BP, bronchiole & pupil constriction Nonselective Drugs affect various receptors ex. Epinephrine acts on alpha1, beta 1 & 2 receptors
Categories of drug action: a. depress cellular activities b. stimulates cellular activities c. inhibit or kill organisms d. act as substitute for missing chemicals
Therapeutic Index & therapeutic Range: Therapeutic Index (TI) relationship bw the drug’s therapeutic effects & its adverse effects TI= LD50 ED50 High TI wide margin of safety Low TI narrow margin of safety
Therapeutic Range (therapeutic window) drug concentration bw therapeutic effect & toxic effect Ex. Digoxin = 0.5 to 2 ng/ml Peak & Trough Level Peak drug level highest plasma concentration of drug at a specific time indicate rate of absorption Trough level lowest plasma concentration indicate rate of elimination Loading dose large initial dose given for immediate response. given to achieve a rapid minimum effective concentration. Ex. Digoxin (digitalization)
II. Pharmacotherapeutics use of drugs to treat disease. A. Types of Therapies: 1. acute therapy px is critically ill & requires immediate intensive therapy 2. empiric therapy based on practical experience rather than on pure scientific data 3. maintenance therapy chronic conditions that don’t resolve 4. supplemental or replacement therapy replenish or substitute missing substances in the body 5. supportive therapy doesn’t treat the cause of disease but maintains other threatened body systems until the patient’s condition resolve. 6. palliative therapy used for end-stage or terminal diseases to make the patient as comfortable as possible
Drug Effects: Main effect desired therapeutic effect reason drug is administered Side effects physiologic effects that are not related to desired drug effects expected, well-known reactions that result in little or no change in patient intervention Adverse Reactions more severe than side effects undesirable & unexpected effects occurring even at normal dose Local vs Systemic drug effect Placebo Effect a therapeutic effect that results from a patient’s belief in the benefits of a medication
Factors affecting Drug Effects: Age Size Sex Genetic factors Disease conditions Emotional conditions Route of administration Time of day Drug taking history Environmental conditions Drug-interactions
Drug Interactions Drug interactions occur bw drugs or bw drugs & foods I. Drug – Drug Interactions: 1. additive drug effect 2 drugs produce equivalent effects when either drug is given alone in higher doses. ex. diuretic & beta blocker aspirin & codeine 2. synergistic/potentiation – 2 drugs produce same effects but one drug enhances the effect of the other drug greater effect ex. meperidine (Demerol) & promethazine alcohol & sedatives 3. antagonistic – combined effects of 2 drugs are less than the effect produced by the 2 individual drugs ex. tetracycline & antacid morphine & naloxone 4. Incompatibility – 2 drugs mixed together chemically incompatible ex. ampicillin & gentamicin II. Drug – Food Interactions: tetracycline & dairy products levodopa & high protein meals monoamine oxidase inhibitor (MAO) inhibitor & tyramine-rich foods nitrofurantoin Metoprolol & food lovastatin
Adverse Drug Reactions I. Dose- related adverse reactions: Secondary effects Hypersensitivity or hypersusceptibility Overdose Iatrogenic Tolerance Dependence Patient sensitivity-related adverse reactions Allergic reaction Idiosyncrasy I. Dose-related adverse reactions: a. Secondary effects ex. morphine antihistamine b. Hypersensitivity or hypersusceptibility excessive therapeutic response even with usual therapeutic dose ex. anticholinergics dry mouth, blurring of vision, urinary retention & constipation narcotic analgesic oral contraceptives digitalis aspirin c. Overdose & toxicity excessive dose exaggerated response pediatric & elderly ex. CNS depressants digoxin d. Iatrogenic effects adverse reactions that caused by drugs that are part of medical tx. drug-induced diseases ex. antineoplastics, aspirin, corticosteroids GI irritation & bleeding propanolol gentamicin e. tolerance decrease response to drug over time ex. psychoactive drugs (e.g. benzodiazepines) propanolol cocaine morphine
II.
f. dependence strong physical & psychological need for a certain drug habituation addiction
g. cumulation body cannot metabolize & excrete one dose of a drug completely before the next dose. II. Patient sensitivity-related adverse reactions: result from unusual & extreme sensitivity to a drug a. Allergic reaction abnormal response due to antibodies against a certain drug ex. antibiotics (penicillin) , aspirin, sulfonamides Types: 1. Immediate allergic reaction : Urticaria sxs: skin rash with severe itching swelling Anaphylaxis sxs: dyspnea extreme weakness nausea & vomiting cyanosis hypotension circulatory collapse 2. Delayed allergic reaction Serum sickness Sxs. itchy rash fever swollen & stiff joints Interventions: notify prescriber & discontinue drugs emergency tx for anaphylactic shock Epinephrine Antihistamines or topical corticosteroids Cool environment
b. Idiosyncratic reactions: unique or strange responses to certain drugs thought to be caused by genetic factors ex. succinylcholine primaquine
III.
Other drug- related effects: a. Teratogenic produce organ defects in developing fetus ex. marijuana/ cocaine alcohol aminoglycoside
b. Carcinogenic induce malignant changes in cells ex. estrogen therapy antineoplastics for pediatric leukemias
c. Mutagenic produce genetic mutations
IV.
Drug-induced tissue & organ damage: A. Dermatological reactions: Sxs: hives/ urticaria rash exfoliative dermatitis Stevens- Johnson syndrome Ex. procainamide - butterfly- rash sulfonamide - Stevens-Johnson syndrome Tx: frequent skin care notify prescriber & discontinue drug topical corticosteroids, antihistamine & emollients
B. Stomatitis S/sxs: swollen gums & tongue. difficulty swallowing bad breath pain in mouth & throat ex. antineoplastic agents (eg fluorouracil) Tx: frequent mouth care frequent, small meals D. Gingival hyperplasia S/sxs: red, & enlarged gums ex. phenytoin (anticonvulsant) E. Superinfections S/sxs: fever diarrhea hairy tongue mucous membrane lesions vaginal discharge ex. antibiotics F. Blood dyscrasias agranulocytosis* anemia thrombocytopenia s/sxs: fever & chills extreme weakness sore throat high risk to infection high risk for bleeding/hemorrhage ex. antineoplastics & antipsychotics antibiotics (eg. chloramphenicol, sulfonamides) anti-inflammatory (eg non-steroidal anti-inflammatory drugs (NSAID) tx. monitor blood counts protect from exposure to infection avoid activities that result in injury or bleeding
G. Hepatotoxicity s/sxs: jaundice* fever nausea & vomiting increase in liver enzymes (AST & ALT) altered bilirubin ex. isoniazid (INH) acetaminophen H. Nephrotoxicity s/sxs edema increase Crea & BUN decrease hematocrit electrolyte imbalances ex. aminoglycosides (eg gentamicin) sulfonamide I. Ototoxicity s/sxs dzziness ringing in ears loss of balance hearing problem ex. aminoglycoside (eg. Gentamicin) azithromycin, erythromycin aspirin quinidine J. Ocular toxicity s/sxs burring of vision color vision changes blindness ex. chloroquine (anti-malarial ) K. Hypoglycemia s/sxs headache tremors drowsiness cold clammy skin seizures/coma ex. antidiabetic agents (eg. Insulin, glipizide)
L. Hyperglycemia s/sxs polyphagia polyuria polydipsia kussmaul’s respiration fruity breath ex. ephedrine ( bronchodilator) M. Hypokalemia s/sxs serum K irregular, weak pulse weakness & numbness of extremities paralytic ileus o absent bowel sounds o abdominal distention ex. loop diuretics (eg, furosemide) N. Hyperkalemia s/sxs same as hypokalemia ex. potassium-sparing diuretics (eg. Spironolactone) antineoplastic drugs O. General CNS effects s/sx anxiety insomnia nightmares ex. beta-blockers (eg. Metoprolol) P. Atropine- like (Cholinergic) effects s/sxs dry mouth constipation urinary retention decrease sweating, hot dry skin ex. antidepressants (eg. TCA)
Q. Extrapyramidal reactions/ parkinson- like syndrome s/sxs immobility (akinesia) rigidity muscular tremors violent movement of head & arms (dystonia) restlessness (akathisia) ex. antipsychotic drugs R. Neuroleptic Malignant syndrome s/sxs extrapyramidal symptoms hyperthermia ex. general anesthetics
S. Photosensitivity s/sxs itching scaling reddening of skin Ex. sulfonamides, tetracycline
T. Cough - ACE inhibitors U. Gray Baby Syndrome - chloramphenicol V. Osteoporosis – corticosteroids, heparin W. Pseudomembranous colitis – clindamycin X. Discolors teeth – tetracycline Y. Nasal stuffiness – reserpine Z. cervical cancer – estrogen hemorrhage – oral anticoagulants, heparin
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