BSN Pharmacology Drug Action PDF

PHARMACOLOGY NCM 106 MIKHAIL NESS M. BUHAY, RN, MD Objectives Briefly discuss Define the common pharmacokinetics, List the five phases of terms used in pharmacodynamics...

PHARMACOLOGY NCM 106 MIKHAIL NESS M. BUHAY, RN, MD Objectives Briefly discuss Define the common pharmacokinetics, List the five phases of terms used in pharmacodynamics the nursing process. pharmacology. and pharmacotherapeutics. Distinguish among a Outline the major drug’s chemical name, differences between generic name, and prescription and over- trade name. the-counter drugs. HISTORY of PHARMACOLOGY ▪ began when humans first used plants to relieve symptoms of disease ▪ “prescriptions” Babylonians’ clay tablets in 3000 B.C ▪ “Materia Medica” the study of herbal remedies Pen Tsao (Great Herbal) in 2700 B.C HISTORY of PHARMACOLOGY ▪ pharmacology “Pharmacologia sen Manuductio and Materiam Medicum,” by Samuel Dale, in 1693 ▪ 18th and 19th century – Francois Magendie and later student Egyptians’ Eber’s Papyrus in 1500 B.C. Claude Bernard developed experimental physiology and pharmacology ▪ 20th century - synthesize drugs in the laboratory Francois Magendie Claude Bernard HISTORY of PHARMACOLOGY Oswald Schmiedeberg Father of Pharmacology Born in 1838, Latvia A professor of pharmacology at the University of Strasburg Studied Chloroform- an anesthetic, Chloral hydrate, a sedative hypnotic, and muscarine- stimulates PNS and treats glaucoma and various diseases Pharmacology the study or science of drugs and their actions on living organisms pharmakon (drug/medicine); logos (science) DRUG any chemical that affects the physiologic processes of a living organism medicines: therapeutic drugs PHARMACOLOGY Drug names: a. Chemical name –chemical constitution and molecular structure b. Generic name – common name; universally accepted c. Brand name/ trade name – proprietary name; trademark Ex. N-(4-hydroxyphenyl) acetaminophen Tylenol acetamide N-(4-hydroxyphenyl) acetaminophen/ Tylenol/ acetamide paracetamol Biogesic PHARMACOLOGY Classifications: a. Body system that is affected (respi, CV) b. Therapeutic use/ clinical indications (anti HPN, OHA) c. Physiologic or chemical action (anticholinergic) d. Prescription/ non-prescription drugs e. Illegal drugs (recreational drugs) Based on Chemical Nature i) Inorganic Drugs Metals and their salts: Ferrous Sulphate, Zinc Sulphate, Magnesium Sulphate Non-Metals: Includes Sulphur ii) Organic Drugs Alkaloids: Atropine, Morphine Glycosides: Digitoxin, Digoxin Protein: Insulin, Oxytocin Esters, Amide, Alcohol, Glycerides.  Classification based on source 🠶 i) Natural Source 🠶 Plants: Morphine, Atropine, Digitoxin 🠶 Animals: Insulin 🠶 Microorganism: Penicillin 🠶 Mineral: Sodium chloride 🠶 ii) Synthetic source E.g. Sulfonamides (synthetic antimicrobials)  Classification based on target organ: 🠶 Drugs acting on CNS: Phenobarbitone; Barbiturates 🠶 Drugs acting on Respiratory system: Bromhexine; Mucolytics 🠶 Drugs acting on Cardio-vascular System: Digitoxin, Digoxin; Glycosides 🠶 Drugs acting on Gastro-intestinal tract: Sulphadimidine; Antibacterial 🠶 Drugs acting on Urinary system: Magnesium Sulphate; Tocolytic 🠶 Drugs acting on reproductive system: Oxytocin, Estrogen; Oxytocic Hormones  Classification based on mode of action: 🠶 Inhibitor of bacterial cell wall synthesis: Penicillin 🠶 Inhibitor of bacterial synthesis: Tetracycline 🠶 Calcium channel blocker: Verapamil, Nifedipine  Classification based on physical effects: 🠶 Emollients (substances that soften and moisturize the skin and decrease itching and flaking) Lanolin, Vaseline 🠶 Caustics (substance that burns or destroys organic tissue by chemical action, generally a strong corrosive alkali): Silver nitrates 🠶 Demulcents (substance that relieves irritation of the mucous membranes by forming a protective film): Zinc oxide, Tannic Acid PHARMACOLOGY Drug Information/ Drug Resources: ▪ medication information, or drug informatics ▪ discovery, use, and management of information in the use of medications ▪ covers from identification, cost, and pharmacokinetics to dosage and adverse effects PHARMACOLOGY Classification of Information Sources: PRIMARY SOURCES - consists of clinical research studies and reports, both published and unpublished SECONDARY SOURCES - references that either index or abstract the primary literature, with the goal of directing the user to relevant primary literature TERTIARY SOURCES - provide information that has been summarized and filtered by the author or editor to provide a quick easy summary of a topic (e.g textbooks, compendia, review articles in journals) PHARMACOLOGY Black box warnings - notifications within a prescription drug’s package inserts provided by the FDA to call attention to an extreme adverse drug effect - primary alerts for identifying extreme adverse drug reactions Drug Action: pharmacokinetic and Pharmacodynamic Process 2 Phases of medicine: PharmacoKinetic – movement of drug throughout the body to achieve drug action. a. pharmacokinetic “What the Katawan does to the drug” i. LIBERATION PharmacoDynamic – involves receptor bindings, post-receptor effects, chemical reactions. ii. absorption “What the Drug does to the body” iii. Distribution iv. Metabolism or biotransformation v. Excretion or elimination b. pharmacodynamics – biologic or physiologic response results Pharmacokinetic Phase - first phase of drug action is the release of drug from its dosage form (LIBERATION) a. Disintegration – breakdown of tablet into smaller particles b. Dissolution – dissolving of the smaller particles in the GI fluid before absorption Excipients – fillers and inert substances that allows drug to take on a particular size and shape and to enhance drug dissolution * Drugs are disintegrated and absorbed faster in acidic fluids (pH of 1 or 2). Pharmacokinetic Phase (ADME) Pharmacokinetic Phase (ADME) Absorption - movement of drug particles from GI tract to body fluids by passive absorption, active absorption, pinocytosis passive absorption – occurs by diffusion (higher to lower); no energy needed active absorption - requires a carrier (enzyme or protein); needs energy pinocytosis – engulfing the drug particles Pinocytosis Pharmacokinetic Phase (ADME) Nsg Mngt: Administer with adequate amount of fluid Give parenteral drugs properly Reconstitute and dilute with recommended diluent Pharmacokinetic Phase (ADME) Drugs that are lipid soluble and nonionized are absorbed faster than water-soluble and ionized drugs First-pass effect (hepatic first pass) – process which the drug passes to the liver first Bioavailability – percentage of the administered drug dose that reaches the systemic circulation 100% for IV Pharmacokinetic Phase (ADME) Pharmacokinetic Phase (ADME) Factors that affect bioavailability: a. drug form b. route of administration c. GI mucosa and motility d. food and other drugs e. changes in liver metabolism Pharmacokinetic Phase (ADME) Distribution – transportation of drugs throughout the body by body fluids to the sites of action or to the receptors Factors: a. rate of blood flow b. drug’s affinity to the tissue c. protein-binding effect Pharmacokinetic Phase (ADME) Protein-binding effect – inactive - drugs are bound to varying degrees with protein (albumin) Free drugs – active that can cause pharmacologic response Nsg Resp: To avoid possible drug toxicity, check the protein- binding percentage of drugs administered. Check also plasma protein and albumin levels. Highly Protein bound drugs- 90% binds to protein Weak Protein bound drugs- 10% binds to protein Pharmacokinetic Phase (ADME) - General or selective ✔Blood-brain barrier ✔Placental barrier Pharmacokinetic Phase (ADME) Metabolism or biotransformation – process by which the body chemically changes drugs into a form that can be excreted - liver and liver enzymes (cytochrome P450 system) Pharmacokinetic Phase (ADME) Half-life – t1/2 - time it takes for one half of the drug concentration to be eliminated - affected by metabolism and excretion - short half-life (4 to 8 hours); long half-life (24 hours or longer) Steady state –the amount of drug administered is the same as the amount of drug being eliminated - after four to five half-lives Pharmacokinetic Phase (ADME) Loading Dose – large initial dose given to achieve a rapid minimum effective concentration in the plasma ex. Digoxin (Digitek, Lanoxin) Phenytoin Pharmacokinetic Phase (ADME) Excretion - elimination of drugs from the body - lungs eliminate volatile drug substances and products metabolized to CO2 and H2O - kidney filter free unbound drugs, water-soluble drugs, unchanged drugs - intestines (biliary excretion); taken by the liver, released into the bile, eliminated in the feces Pharmacodynamic Phase Pharmacodynamics – study of the way drugs affect the body - primary effect (desirable) and secondary effect (undesirable) ex. Benadryl Pharmacodynamic Phase Dose Response Relationship - Magnitude of the drug effect depending on the drug concentration at the receptor site Graded-Dose Response Relationship - As the concentration of a drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied - Graded effect (response is continuous and gradual) Pharmacodynamic Phase Graded-Dose Response Relationship 1. Potency – amount of drug necessary to produce an effect of a given magnitude 2. Efficacy - magnitude of response a drug causes when it interacts with a receptor Maximal efficacy – point at which increasing a drug’s dosage no longer increases the desired therapeutic response Pharmacodynamic Phase Therapeutic Index and Therapeutic Range (Therapeutic Window) Therapeutic index (TI) – estimates the margin of safety of a drug - relationship between a drug’s desired therapeutic effects (ED50) and its toxic dose (TD50) Therapeutic range – level of drug between the minimum effective concentration in the ED50 - dose of a drug that produces a therapeutic response in 50% of the plasma for obtaining desired drug action and population TD50 - dose of a drug that produces a the minimum toxic concentration toxic response in 50% of the population Pharmacodynamic Phase Pharmacodynamic Phase Onset, Peak and Duration of Action onset of action – time it takes to reach the minimum effective concentration (MEC) after drug administration peak action – highest blood or plasma concentration duration of action – length of time the drug has a pharmacological effect time-response curve - Pharmacodynamic Phase Pharmacodynamic Phase THERAPEUTIC DRUG MONITORING Peak drug levels – highest plasma concentration of drug at a specific time - indicate the rate of absorption of the drug Trough drug levels – lowest plasma concentration of the drug - indicate the rate of elimination of the drug - drawn immediately before the next dose Pharmacodynamic Phase Peak and Trough Drug Levels – for drugs with narrow therapeutic index and considered toxic ex. Aminoglycoside antibiotics (amikacin, gentamycin, tobramycin) Anticonvulsants (carbamazepine, phenytoin, valproic acid) Pharmacodynamic Phase Pharmacodynamic Phase TARGET PROTEINS AND LIGANDS 1. target protein - protein molecule which permits another molecule to bind to it e.g. receptor 2. ligand - general term for a substance which binds to a target protein e.g. hormone, a neurotransmitter or a drug Pharmacodynamic Phase RECEPTOR THEORY: - drugs act by binding to receptors FOUR (4) RECEPTOR FAMILIES: a. Cell membrane-embedded enzymes b. Ligand-gated ion channels c. G-protein coupled receptor systems d. Transcription factors Pharmacodynamic Phase RECEPTOR FAMILIES Cell membrane-embedded enzymes - ligand-binding domain is on the cell surface Ligand-gated ion channels - channel crosses the cell membrane; ions flow into and out of the cells Pharmacodynamic Phase RECEPTOR FAMILIES G-protein coupled receptor systems - With 3 components: receptor, G protein and effector Transcription factors - Found in the cell nucleus on DNA Pharmacodynamic Phase Agonists and Antagonists Agonists – drugs that produce a response ex. Epinephrine Antagonists – drugs that block a response ex. Atropine AGONIST Example: Epinephrine What it does: An agonist is a substance that binds to a receptor and activates it, mimicking the effect of a natural substance in the body. How it works: When epinephrine (a natural hormone) binds to its receptors, it triggers a response in the body, such as increasing heart rate or opening up the airways. In simple terms, an agonist turns the "on" switch for a specific bodily function. ANTAGONIST Example: Atropine What it does: An antagonist is a substance that binds to a receptor but does not activate it. Instead, it blocks or dampens the action of an agonist or natural substance. How it works: Atropine binds to the same receptors as certain natural substances but prevents them from triggering their usual effects. For instance, atropine can block the effects of acetylcholine (a neurotransmitter), which slows down the heart rate. By doing so, atropine can increase the heart rate. In simple terms, an antagonist turns the "off" switch or blocks the "on" switch from being activated. Pharmacodynamic Phase Nonspecific and Nonselective Drug Effects Nonspecific drugs – drugs that affect various sites; evoke a variety of responses throughout the body ex: Betanechol (Urecholine) affects multiple receptor sites Nonselective drugs – drugs that affect various receptors ex: Epinephrine (anaphylaxis, severe asthma) alpha1, beta1, beta2 Widespread Effects: Since Bethanechol isn’t specific to just one type of muscarinic receptor, it can affect multiple systems in the body. This can lead to both the desired therapeutic effects (like helping with urination) and potential side effects (like increased salivation or gastrointestinal cramping). Pharmacodynamic Phase Categories of Drug Action 1. Stimulation (increases activity) 2. Depression (reduces function) 3. Irritation (ex. Laxatives) 4. Replacement (ex. Insulin) 5. Cytotoxic action 6. Antimicrobial action (ex. Penicillin) 7. Modification of immune status Pharmacodynamic Phase Side Effects, Adverse Reactions, and Drug Toxicity Side effects – physiologic effects not related to drug effects; nearly unavoidable - desirable and undesirable - expected Nurse’s role: patient teaching of side effects encouraging to report occurrence of S/E Pharmacodynamic Phase Adverse reactions – more severe; undesirable - range of untoward effects (unintended and occurring at normal doses) that cause mild to severe side effects - reported and documented - “Right drug, right dose, right patient, bad effect” Drug toxicity – when drug levels exceed therapeutic range - overdosing or accumulation - identified by monitoring the plasma therapeutic range Ex. Morphine – coma insulin – hypoglycemia Pharmacodynamic Phase Pharmacodynamic Phase Allergic reaction – immune response; prior sensitization of the immune system - mild itching or severe rash to anaphylaxis (bronchospasm, laryngeal edema, drop in BP) Ex. Penicillin, anti-inflammatory drugs Idiosyncratic effect – uncommon drug response resulting from a genetic predisposition Ex. succinylcholine Iatrogenic disease – iatros (physician); genic (to produce) - a disease produced by a physician; a disease produced by drugs Pharmacodynamic Phase Physical dependence – long-term use of certain drugs (opioids, barbiturates, amphetamines) - abstinence syndrome Nsg. Resp. warn patients against abrupt discontinuation Carcinogenic effect – ability of certain medications and environmental chemicals to cause cancers Teratogenic effect – drug-induced birth defect teratogens – medicines and other chemicals capable of causing birth defects Pharmacodynamic Phase Pharmacogenetics – scientific discipline studying how the effect of a drug action varies from a predicted drug response because of genetic factors Pharmacogenomics – refers to the study of how genetics play a role in a person’s response to drugs (ADME) - to develop precision medicine Pharmacodynamic Phase Tolerance – decreased responsiveness over the course of therapy Tachyphylaxis – acute tolerance; rapid decrease in response to the drug ex. Narcotics, barbiturates, laxatives, psychotropic agents Placebo effect – psychological benefit from a compound that may not have the chemical structure of a drug effect Drug Interactions - altered or modified action or effect of a drug as a result of interaction with one or multiple drugs 2 categories: a. pharmacokinetic interactions b. pharmacodynamics interactions Drug incompatibility: chemical or physical reaction that occurs among two or more drugs in vitro (syringe, IV bag); environment outside the body Drug Interactions - Pharmacokinetic Absorption – block, decrease, increase Ways: 1. by decreasing or increasing gastric emptying time ex. Laxatives – increase gastric and intestinal motility; decrease drug absorption 2. by changing the gastric pH ex. pH absorbs weakly acidic drug like aspirin rapidly Magnesium hydroxide (Maalox) raises gastric pH and slows absorption of weakly acidic Drug Interactions - Pharmacokinetic 3. by forming drug complexes – Ex. activated charcoal after toxic ingestion decreased absorption and diminish untoward effects Distribution – affected by its binding to protein or plasma - 2 drugs that are highly bound to protein or albumin can result in drug displacements Drug Interactions - Pharmacokinetic Metabolism – controlled by hepatic microsomal system Enzyme inducers – drugs that promote induction of enzymes ex. Barbiturates (phenobarbital) - metabolism of antipsychotics and methylxanthine (theophylline) * metabolism promotes elimination & plasma concentration = decreased therapeutic drug action Drug Interactions - Pharmacokinetic Enzyme inhibitors – decreases metabolism ex. Antiulcer drug (cimetidine) - Use of tobacco and alcohol Polycyclic aromatic hydrocarbons – induce production of the specific family of enzymes (use of theophylline) Alcohol use: chronic – hepatic enzyme activities acute – inhibited metabolism Drug Interactions - Pharmacokinetic Grape-fruit products – contains flavonoids; inhibitors - inhibits metabolism of carbamazepine, diazepam, statins, calcium channel blockers or erectile dysfunction drugs Drug Interactions - Pharmacokinetic Drug Interactions - Pharmacokinetic Excretion – glomeruli (urine) - interstinal tract (bile) Factor: Decreased cardiac output Drugs with same route of elimination Changing urine pH Decreased renal or hepatic function Drug Interactions - Pharmacodynamic A.Additive effect B.Synergistic effect and Potentiation C.Antagonistic effect Drug Interactions - Pharmacodynamic Additive Drug Effect - Sum effects of 2 drugs administered in combination - Desirable effect ex. Diuretic + beta-blocker = blood pressure lowering effect aspirin + codeine = increased pain relief Drug Interactions - Pharmacodynamic Undesirable effect - Hydralazine for hypertension + Nitroglycerin for angina = severe hypotensive response - Aspirin + alcohol = prolong bleeding time Drug Interactions - Pharmacodynamic Synergistic effect/ Potentiation - 2 or more drugs are given; one drug can potentiate the other drug - Effect is greater than the combined effect Ex. desirable cytotoxic + cytotoxic = decreased S/E - undesirable: alcohol + sedative-hypnotic = increased CNS depression Drug Interactions - Pharmacodynamic Antagonistic Drug Effect - 2 drugs have opposite effects; each drug cancels/blocks the effect of the other Ex.isoproterenol – adrenergic beta stimulant propranolol – adrenergic beta blocker antidotes morphine overdose - naloxone Drug Food Interactions Food – can increase, decrease or delay absorption - can bind with drugs causing less or slower absorption ex. Tetracycline and dairy products - 1 hour before or 2 hours after; no dairy products (interferes) grape-fruit juice (flavonoids) Drug Food Interactions MAOI (monoamine oxidase inhibitor) – should not be taken with tyramine-rich food (aged cheese, wine, organ meats, beer, yogurt, sour cream, bananas) *hypertensive crisis Protein energy malnutrition (PEM) - toxicity Drug Food Interactions Administer with food – administer with or shortly after a meal Administer on empty stomach – administer 1 hour before or 2 hours after a meal Drug Laboratory Interactions Drugs interfere by: Cross reaction with antibodies Interference with enzyme reactions Alteration in chemical reactions Results: Misinterpretation or invalidation of results Additional testing Erroneous clinical diagnosis Drug-Induced Photosensitivity Photosensitivity - Skin reaction caused by exposure to sunlight - caused by interaction of drug and exposure to UVA (cellular damage) 2 types: photoallergic reaction phototoxic reaction Drug-Induced Photosensitivity Photoallergy – drug undergoes activation in the skin by ultraviolet light to a compound more allergenic than the parent compound - delayed hypersensitivity reaction Drug-Induced Photosensitivity Phototoxicity – photosensitive drug undergoes chemical reactions within the skin to cause damage - rapid onset; 2 to 6 hours of sunlight exposure * Can be avoided by using sunscreen with SPF greater than 15, avoiding excessive sunlight, wearing protective clothing; decreasing dose or if necessary, treatment PHARMACOLOGY New Drug Development Stages: a. pre-clinical research and development b. Clinical research and development stage c. New drug application review d. Postmarketing surveillance stage PHARMACOLOGY Pharmacotherapeutics - clinical purpose or indication of giving a drug - patient-specific (cure, reducing/ eliminating symptoms, slowing disease process, preventing disease, improving quality of life) Contraindication – any patient condition (ex. Disease state) that makes the use of medication dangerous for the patient Type of therapies: 1. Acute therapy – intensive drug treatment in the acutely ill or critically ill - to sustain life or treat disease ex. Volume expanders for shock patients Pharmacotherapeutics 2. Maintenance therapy – prevent progression of a disease or condition ex. hypertension 3. Supplemental therapy – replacement therapy ex. Iron to px with iron-deficiency anemia 4. Palliative therapy – providing relief from symptoms, pain and stress - improve quality of life for both patient and family ex. high dose opioid analgesics 5. Supportive therapy – maintains integrity of body fxns while recovering from trauma or illness ex. Fluids and electrolytes Pharmacotherapeutics 6. Prophylactic therapy and empiric therapy – prophylactic: prevent illness during planned events (ex. Antibiotics) empiric: based on clinical probabilities - drug administration when a certain pathologic condition has an uncertain but high likelihood of occurrence based on presenting symptoms (ex. Antibiotics before CS reports) Pharmacognosy – study of natural sources of drugs (plants and animals) 4 main sources of drugs: a. Plants b. Animals c. Minerals d. Laboratory synthesis Toxicology - the study of poisons and unwanted responses to both drugs and other chemicals - the science of adverse effects of chemicals on living organisms Clinical toxicology – deals with poisoned patients (drug overdose, ingestion of household cleaning agents, snakebite) Tx: ABC prevent absorption and speed elimination Toxicology Substance Antidote acetaminophen Acetylcysteine tricyclic antidepressants, quinidine Sodium bicarbonate calcium channel blockers IV calcium iron salts Deferoxamine digoxin Digoxin antibodies beta blockers Glucagon opiates, opioid drugs Naloxone Toxicology Substance Antidote benzodiazepine Flumazenil Magnesium sulfate Calcium Gluconate anticholinesterase Atropine sulfate anticholinergic Neostigmine heparin Protamine sulfate warfarin Vitamin K OTC – over-the-counter drugs - Safe and appropriate to use without the supervision of a health care provider - Can be accessed without a prescription - Nsg. Resp. - Emphasize that these drugs can cause side effects OTC – over-the-counter drugs Cautions: Delay in professional dx and tx of serious conditions Masked symptoms Labels and instructions should be followed HCP or pharmacist should be consulted first OTC may interact with meds prescribed by HCP Potential overdosing Risk for adverse rxns and drug-drug interactions OTC – over-the-counter drugs Common OTC drugs: Ibuprofen – increases fluid retention - long-term use decreases anti HPN effect Aspirin – trigger asthma Aspirin, acetaminophen, ibuprofen – decrease renal function OTC – over-the-counter drugs - Cough and Cold Remedies Guaifenesin Dextromethorpan Pseudoephedrine Analgesic antihistamine OTC – over-the-counter drugs - Cough and Cold Remedies Nasal congestion: Phenylephrine Pseudoephedrine Phenylpropanolamine – increased risk for hemorrhagic stroke in young women - causes psychosis, hypertension, renal failure, cardiac dysrrhythmias OTC – over-the-counter drugs - Cough and Cold Remedies -safe for >6years old - 2 to 6 yrs old consult HCP -