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Catherine Luksic BSN, RN Level I DRUG Any chemical that affects the physiologic processes of a living organism PHARMACOLOGY Study (science) of drugs Includes: Absorption Distribution Metabolism Excretion Mechanism of Action Therapeutic effects Adverse effects Subspecialty Areas of Pharmacology Pharmaceutics Pharmacokinetics Pharmacodynamics Pharmacotherapeutics Pharmacognosy Toxicology NURSES MUST UNDERSTAND BASIC PRINCIPLES OF PHARMACOLOGY Therapeutic and Toxic SAFETY ! Drugs will acquire 3 names CHEMICAL (N-4 hydroxyphenyl acetamide) Drugs chemical composition, molecular structure GENERIC Shorter than chemical name Used as official listing of drugs TRADE (acetaminophen) (Tylenol) Registered trademark, “brand” name Name is restricted to “owner” (company, ie, Merck) **Patent lasts 17 years - 10 years for research and development - 7 years of marketability Process of turning chemicals into safe medications Science of dosage form & design ie – tablet, capsule, liquid, powder, etc. Study of how various dosage forms/designs influence a drugs metabolism and use in the body Design that will allow drug molecules to bind to a target site Drug Oral Intramuscular, Subcutaneous, Intravenous, Topical Via intestine Via NG tube, feeding tube (or rectal) Rectal Parenteral Via mouth Includes sublingual, buccal Enteral routes Directly applied to skin Mucosal **Forms/designs of drugs: Oral Tablets, capsules, powder, liquid, elixir, suspension EC, ER, SR Enteral Meds given via NG or feeding tube (solid or liquid) Crushed meds – must be dissolved Rectal Suppositories, creams, enema Also considered as ENTERAL route Parenteral Injections (solutions, powder) Topical Ointments, creams, pastes, powders, patches Mucosal eye, ear, nasal, vaginal Inhaled Drug Dissolution & Absorption **Drugs must dissolve 1st (before absorbed) Oral Preparations Liquids, elixirs, syrups Suspension solutions Powders Capsules Tablets Enteric coated tablets Extended release tablets Fastest Slowest *Extended Release (forms) = SR (slow release), CR (controlled release), XL (extended length) Drug Dissolution & Absorption Parenteral Preparations Do NOT have to dissolve 1st Subcutaneous, Intramuscular Intravenous *directly into bloodstream *immediate absorption Study of what happens to a drug from entrance into body until it leaves the body 4 phases Absorption Distribution Metabolism Excretion Absorption Occurs after dissolution of drug Drug → GI tract → blood/body fluids → tissue Affected by form of drug Affected by ROUTE of administration (oral, parenteral,etc.) Factors That Affect Absorption Administration route Dosage formulation Food or fluids administered with the drug Grapefruit, fruit juices, antacids, fat soluble vitamins, iron Rate of blood flow to the small intestine Acidity of the stomach Status of GI motility Bioavailability Extent of drug absorption Amount of drug actually available to circulation Depends upon “first pass effect” Example: Aspirin Has high “first pass effect” First Drugs must dissolve & be absorbed by GI tract Must pass through LIVER before reaching circulation (bloodstream) Pass effect Drug GI system Portal vein Liver Hepatic vein Circulation (distribution) Liver may metabolize drug into smaller metabolites Therefore, less amount of drug will pass into circulation Intravenous drugs = no “first pass” in liver Oral/Enteral Route Drug is absorbed into the systemic circulation through the oral or gastric mucosa, the small intestine, or rectum Oral – high “first pass” effect Sublingual – dissolve under tongue, highly vascular area, these drugs bypass liver, no “first pass” effect Buccal – same as sublingual Rectal (suppository or topical) – rectal drugs have SOME “first pass” effect Routes that bypass the liver: Sublingual Buccal Rectal* Intravenous Intranasal Transdermal Vaginal Intramuscular Subcutaneous Inhalation *Rectal drugs may have some degree of first-pass effect Parenteral Route *No “first pass” effect Intravenous* Intramuscular Subcutaneous Intradermal Intraarticular (physician) *Fastest delivery into the blood circulation Topical/Mucosal Route Skin Includes transdermal route, patches Eyes Ears Nose Vagina Topicals = slower onset, longer duration No “first pass” effect, bypass liver Exception = rectal Transport of drug by bloodstream to site of action Areas of “rapid” distribution Heart Liver Kidneys Brain Areas of Muscle Skin Fat “slower” distribution Areas “difficult” to reach Bone Blood brain barrier ** BLOOD BRAIN BARRIER Restricts passage of various chemicals between the bloodstream and the central nervous system CNS = brain, spinal cord BBB allows may oxygen to pass restrict certain bacteria & viruses Not all meds can pass through Distribution depends upon protein-binding Albumin = most common blood protein, carries protein-bound drug molecules “bound” portion of drug = pharmacologically inactive “unbound” portion = pharmacologically active Easily distribute to body tissues (outside of blood vessels) and reach site of action Lasix, Coumadin, Aspirin, Digoxin aka “Biotransformation” Process by which a drug is biochemically altered inactive metabolite (compound) more potent, active metabolite Less potent, active metabolite LIVER – most responsible for metabolism of drugs Also involved = kidneys, lungs, skeletal muscle, intestines Factors that decrease metabolism: Cardiovascular dysfunction Kidney failure Liver failure Genetics Starvation Factors that increase metabolism: Certain drugs (dilantin, barbiturates, rifampin) Delayed drug metabolism results in: Accumulation Prolonged of drugs (toxicity) action of the effects of drugs Elimination of drugs from the body All drugs must eventually be excreted Kidney = organ most responsible for excretion of drugs (urine) Also, liver (bile), bowel (feces), sweat glands Liver metabolizes most drugs, kidney excretes what is “left behind” Kidneys can also metabolize certain drugs insulin Time required to eliminate (½) 50% of a drug Example: Digoxin - 36 hr. half-life Takes 7.5 (up to 9) days to clear Takes 5–6 half-lives to eliminate ~ 98% of a drug Liver or kidney disease Can prolong half-life Increases risk of toxicity # of half lives remainder of drug 1 50 % 2 25 % 3 12.5 % 4 6.25 % 5 3.125 % Onset The time it takes for the drug to elicit a therapeutic response Insulin: 10-20 min Peak The time it takes for a drug to reach its maximum therapeutic response 30-60 min Duration The time a drug concentration is sufficient to elicit a therapeutic response 2-4 hours Peak Peak effect, maximum therapeutic response Highest blood level of the drug If too high = toxicity of drug Trough Lowest blood level of the drug If too low, then may not be therapeutic Furosemide (LASIX) Pharmaceutics: Tablet, Oral solution, Injection Pharmacokinetics: Absorption: Bioavailability = 64% tablet, 60% oral soln, 100% IV Tablet, oral soln – 60 min. delay if taken w/ food Distribution: highly protein bound to albumin, 91-99% Metabolism: metabolized in liver Elimination: excreted by kidneys Onset: 1 hr. (oral) 5 minutes (IV) *store Peak: 1-2 hr. (oral) ½ hr. (IV) room Duration: 6-8 hrs. (oral) 2 hrs. (IV) temp Mechanism of drug action - how drugs act at sites of activity Involves receptors and enzymes Not all drugs have a known mechanism of action Most drugs produce more than one effect Therapeutic effect – desired or primary effect Secondary effect – may be desirable or not 1. Drug-receptor interaction: drug binds to a receptor site on cell surface, causes or blocks an action 2. Enzyme interaction: drug binds to enzyme molecule & either enhances or inhibits its action 3. Nonselective interactions: do not bind to enzyme or receptor, act on cell membrane or cell wall Drug-Receptor Drug binds to specific receptor Alters cell function Produces desired effect Can bind completely or partially Agonists Interaction Drugs that bind and produce desired effect example, Morphine Antagonist Drugs that block agonist effect at binding site example, Narcan, reverses effect of narcotic Example, Toprol, beta-blocker, lowers HR Enzyme Interaction Drug interacts with enzyme system Inhibits the action of the enzyme The action of the cell is changed or altered Example: ACE inhibitor (Lisinopril) Inhibits conversion of angiotensin I to angiotensin II The treatment of pathologic conditions through the use of drugs “drug therapy” Desired therapeutic outcome Should be established before drug started What is expected ? Must be measurable and realistic Progress must be monitored (example = antibiotics) Types of therapy Acute Maintenance Supplemental Palliative Supportive Prophylactic Empiric Acute Involves more intensive drug therapy Used in the acutely or critically ill therapy Example: to maintain heart rate or BP Usually needed to maintain life ie – dopamine (vasopressor to maintain BP) Maintenance May not cure but prevents progression of disease therapy May prevent progression Used in chronic illnesses (example: hypertension, diabetes) ie – lisinopril, oral contraceptives Supplemental Replaces body substances needed to maintain normal functioning May not be produced by the body Produced in insufficient amounts Example: Insulin Palliative therapy therapy Goal is to provide comfort Used in end stage illnesses Usually all other therapy has failed Example: Morphine for pain Supportive therapy Maintains integrity of body functions while patient recovering from illness Examples Providing fluids/electrolytes to prevent dehydration In vomiting or diarrhea Blood products or blood volume expanders Blood loss during surgery Prophylactic Used to prevent illness Example: pre-op antibiotics, vaccines Empiric therapy therapy Use of a drug based on probability, certain illness/disease has likelihood of occurrence Example: Antibiotic for UTI before actual diagnosis Adverse effects – unintended effects Side Effects Therapeutic index – ratio of toxic level to therapeutic level Low therapeutic index: difference between toxic and therapeutic dose is low – dangerous ! Example: coumadin (anticoagulant) Tolerance – Pts. decreasing response to repeated doses ie – valium, pain meds Dependence for drug addiction – Physiologic or psychologic need Patient’s condition - Physiological Age Infants & children need ↓ dose Immature organ function Elderly may require ↓ dose Decreased gastric acidity Dry mouth/decreased saliva Decreased liver blood flow/mass Increased body fat, decreased muscle mass Decreased kidney function Patient’s condition - Physiological Weight Average = 150lb Dosage adjustments Large weight differences Gender Women Smaller Different fat/water ratio May need dosage adjustments Patient’s condition - Pathological Liver/kidney disease Inability to metabolize/excrete one normal dose before next drug given Leads to drug toxicity Lower doses are frequently given Liver disease Kidney disease Allergic Reactions (hypersensitivity) Usually begins after 2nd dose or more May occur within minutes or delay for hours or even days Immune system views “drug” as foreign substance Histamine is released S/S = skin rashes, hives, itching (urticaria or pruritis), facial swelling, difficulty breathing, sudden LOC, throat swelling (angioedema), wheezing Anaphylactic Shock Severe allergic rx, severe respiratory distress, life threatening Mr. Carter has a rash and pruritis. You suspect an allergic reaction and immediately assess him for other more serious symptoms. What question would be most imortant to ask Mr. Carter ? A 78 y.o. man who has been diagnosed with a URI tells the nurse that he is allergic to Penicillin (PCN). Which is the most appropriate response by the nurse ? 1. “that’s to be expected, lots of people are allergic to penicillin” 2. “this allergy is not a big concern right now” 3. “what type of reaction did you have when you took penicillin ?” 4. “drug allergies don’t usually occur in older individuals” Idiosyncratic reaction: unexpected reaction in a particular patient, not common reaction Pharmacogenetics: study of genetic traits that result in abnormal metabolism of drugs ie: coumadin, codeine, psych drugs (chap. 5) Teratogenic effects: result in structural defects of in fetus FDA – 5 categories (A,B,C,D,X) of teratogens Category A – studies show NO risk (multivitamin) Category X – Completely contraindicated in pregnancy, HIGH fetal risk Category A No risk to fetus in first, second or third trimesters Category B Studies have not shown fetal risk in animals, but no controlled studies in pregnant women Considered safe in all trimesters (benadryl,tylenol,PCN) Category C Animal studies have revealed adverse effects on fetus Drugs should be given only if benefit outweighs risk Category D Positive evidence of harm to fetus Use may be acceptable absolutely necessary (life threatening situations) Category X Studies have shown fetal abnormalities, drug is completely contraindicated (acutane, coumadin) The study of natural drug sources Plants Animals Four Plants Animals main sources of drugs Source of many hormone drugs (premarin – urine of pregnant mares; insulin – pigs & humans; heparin – pigs) Minerals (salicylic acid, sodium chloride) Laboratory synthesis Place drugs in similar categories Similar general use Similar mechanisms of actions Similar contraindications Similar precautions Similar nursing implications Examples: Antibiotics Antihypertensives Antiepileptics Sedatives Anesthetics Decongestants Antineoplastics Etc. Physicians Desk Reference (PDR) U.S. Pharmacopia National Formulary Various Nursing Drug Handbooks/References Davis Drug Guide