Pharmacology Handout PDF

WHAT IS PHARMACOLOGY?  Pharmacology is the study of chemicals and drugs on living tissues and how those chemicals help diagnose, treat, cure, and prevent disease or correct pathophysiology of living tissues. WHAT ARE THE DIFFERENT BRANCHES RELATED TO PHARM...

WHAT IS PHARMACOLOGY?  Pharmacology is the study of chemicals and drugs on living tissues and how those chemicals help diagnose, treat, cure, and prevent disease or correct pathophysiology of living tissues. WHAT ARE THE DIFFERENT BRANCHES RELATED TO PHARMACOLOGY?  PHARMACODYNAMICS  Study of the mechanisms of action of drugs within the body and how drugs produce their effects in the body.  PHARMACOKINETICS  The study drug actions as they move through the body; the way the body absorbs, distributes, metabolizes and excretes drugs.  Mathematical study of drugs based on time and dose.  PHARMACOTHERAPEUTICS  The study of drugs used to prevent, treat or diagnose disease.  PHARMACOGENETICS  The study of drug reactions in the body that are unanticipated or unusual and may have a hereditary basis for the response.  PHARMACOGNOSY  Study of drug derived from herbal and other natural resources.  TOXICOLOGY  The study of harmful or poisonous effects of drugs.  POSOLOGY  Study of dosage of drugs. Pharmacology Page 1 of 18  PHARMACY  Deals with the study of preparation, compounding and dispensing of different drugs. GENERAL PURPOSES FOR WHICH DRUGS ARE USED 1. PROPHYLACTIC/PREVENTIVE  Decreases the severity of diseases or prevent a disease from occurring.  Example: Prophylactic antibiotics maybe used after a bout of rheumatic fever to prevent the development of Rheumatic Heart Disease (RHD). 2. DIAGNOSTIC  Detects the nature of diseases.  Example: Radiopaque agents- contains iodine which absorbs x-rays, they build up in an area of the body like blood vessels, diseases of the heart, kidney diseases. 3. THERAPEUTIC a. Curative - treats disease; example- antibacterial drugs b. Pallative - relieves the distressing manifestations but does not affect the disease itself; example- pain medication for cancer c. Supportive - sustains patient until another measure can be instituted; example- IVF as volume expanders d. Substitutive - takes as a replacement of other substances; example- insulin- DM, Vitamin B12- pernicious anemia e. Restorative - uses to help the body return to its normal healing state; example - vitamins, minerals, antibacterial CLASSIFICATION OF DRUGS 1. According to the body system they affect  Cardiovascular system- anti hypertensives, anticoagulants, thrombolytics  Urinary system - diuretics  Respiratory system- bronchodilators, mucolytics 2. According to the therapeutic use or clinical indication  Paracetamol- can be an antipyretic or an analgesic As an antipyretic- lowers down body temperature As an analgesic- it relieves mild to moderate pain 3. According to drug’s physiologic or chemical action  Example: anti-cholinergics- affect acetylcholine Adrenergic blokers- affect the release of epinephrine 4. Presciption Drugs- ordered by the physician. Pharmacology Page 2 of 18 5. Non- Prescription Drugs/ Over the Counter Drugs (OTC)  Drugs which can be purchased from a pharmacy without the prescription of a doctor. 6. Investigational Drugs  drugs under study, not yet approved in the market 7. Illicit Drugs/ Illegal Drugs  Drugs that are abused  Example: Metamphetamine, heroin DRUG NOMENCLATURE/ NAMING A DRUG 1. OFFICIAL NAME  Listed on official publication as a drug reference.  Example: Nurses’s Drug references (NDR), Philippine Index for Medical Preparations. 2. CHEMICAL NAME  Describes the drug’s chemical structure on it’s precise composition.  Too complex for general use. 3. GENERIC NAME  Commonly used to identify a drug during its useful clinical lifetime.  AKA non propriety name for the drug  It is not owned by any drug company and is universally acceptable 4. PROPRIETY NAME/ BRAND NAME  Chosen by the drug company and usually a trademark owned by the specific manufacturer. Pharmacology Page 3 of 18  DRUG EVALUATION FDA approval is important, because it validates the need for research on how drugs work on children, not just adults. It also allows us the properly determine the appropriate dosage for children, determine the best route of administration, and test for any drug interactions. FDA APPROVAL  It undergoes 3.5 years of laboratory testing before an application is made to USFDA to begin testing the drug in humans. a. PRE-CLINICAL TRIALS - drugs are tested on animals. b. PHASE I- uses 20-80 healthy volunteers to establish a drug’s safety and profile; it takes about 1 year. c. PHASE II- employs 100-300 patient volunteers to assess drug effectiveness; it takes about 2 years. d. PHASE III- involves 1000-3000 patients in clinics and hospitals who are monitored carefully to determine the effectiveness and identify adverse reactions of the drugs; it takes about 3 years. *then the company applies to the FDA for approval and takes about 2.5 years *after final approval, the drug becomes available for physician to prescribe Pharmacology Page 4 of 18 PREGNANCY CATEGORIES  AKA PRE- CATEGORIES  Established in 1979 to indicate the potential risk birth defects of the drug used during pregnancy. a. CATEGORY A  Adequate and well controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in later trimester.  Safe during pregnancy  Examples: Levothyroxine, Folic Acid b. CATEGORY B  Animal used in studies have failed to demonstrate a risk to the fetus and there are no adequate and well controlled studies in pregnant women.  No adverse effect in animals, but no study in humans  Examples: Metformin, Amlodipine c. CATEGORY C  Has an adverse effect on animals and there are no adequate and well- controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.  Examples: Tramadol, amlodipine d. CATEGORY D  Adverse effect in humans but potential benefit may warrant use of the drug in pregnant women despite potential risk.  The benefit outways the risk  Example: Losartan e. CATEGORY X  The risk in pregnancy outways the benefits, can cause teratogenic effect or abortion  Examples: Atorvastatin, Methotrexate *NEW LABELLING SYSTEM PREGNANCY AND LACTATION LABELLING FINAL RULE (PLLR) went into effect on June 30, 2015. Pharmacology Page 5 of 18   Prescription drugs approved after June 30, 2015 will use the new format immediately.  The pregnancy letter category must be removed by June 29, 2018.  Replaced with narrative sections and subsections a. Pregnancy (labor and delivery) Risk summary of the drug Clinical consideration b. Lactation ( includes nursing mother)- same as pregnancy RELEVANT DRUG LAWS 1. GENERIC ACT OF 1988 (RA 6675)  An act to promote, require and ensure production of an adequate supply, distribution, use and acceptance of drugs and medicines identified by their generic names.  It declares policy of the state to ensure the adequate supply of drugs with generic names at the lowest possible cost and endeavor to make them available for free to indigent patients. 2. ADMINISTRATIVE ORDER NO. 62 S. 1989  Rules and regulations to implement prescribing requirements under the GA of 1988  Use of generic names in all prescriptions, generic name written in full and written after the Rx sign in the prescription.  Rx- latin word meaning “recipe” or “to take”; part of the heading of the prescription PARTS OF THE MEDICAL PRESCRIPTION a. SUPERSCRIPTION -  consists of the heading where the symbol Rx is found. b. INSCRIPTION  Body of the prescription  Provides the names and quantities of the drugs being prescribed  Dosage and dosage form c. SUBSCRIPTION  Gives special direction for the pharmacists how to compound the medication. d. SIGNATURA/ TRANSCRIPTION  Gives instruction to the patient on how, how much, when and how long the drug is to be taken Pharmacology Page 6 of 18   Precedes by the symbol “S” or “Sig”- latin word meaning “mark” e. Below the sig is room for special instructions such as number of times the prescription may be refilled. *Example of a Physician’s prescription 3. DANGEROUS DRUG ACT (RA 6425)  monitors narcotics- drugs which produce insensibility, stupor, delusions or dullness of mind which may be habit forming.  Prohibited drugs- opium, cocaine, hallucinogens  Regulated drugs- self- inducing sedatives, amphetamines, hypnotic drugs (Valium, phenobarbital)  Can cause dependence and sedation  Requirements in prescribing regulated drugs- S2 license  S2 license- solely given to any authoritative person who is acknowledge by law that can prescribe dangerous regulated drugs- physician 4. COMPREHENSIVE DANGEROUS DRUGS ACT (RA 9165)  Repealed RA 6425  Dispense- giving away or selling, paraphernalia/lab equipment  Manufacture- production, preparation, processing of any dangerous drugs. Pharmacology Page 7 of 18 FACTORS AFFECTING RESPONSES TO DRUGS 1. GENETIC MAKE-UP  Affect what the body does to a drug, what the drug does to the body.  Some people metabolize drug so quickly, others so slowly- can cause drug toxicity. 2. AGE  As age increases, the functions of tissues and organs in to body gradually decline.  Due to this decline in organ function, drug absorption, distribution, metabolism and excretion in elderly people are worse than those of young people. 3. BODY SIZE/WEIGHT  Largest person generally needs more of a drug than a smaller person needs for the same effect. 4. USE OF OTHER DRUGS AND DIETARY SUPPLEMENTS  Some dietary supplements may increase the effect of medication and other dietary supplements may decrease it.  Certain dietary supplements can change absorption, metabolism or excretion of a medication and therefore affects its potency.  Also, combining dietary supplements and medications could have dangerous and even life-threatening effects.  Example: drugs for HIV/AIDS, heart disease, depression, treatments for organ transplants and birth control pills when taken with St. John’s wort which is a herbal supplement the results can be serious. 5. CONSUMPTION OF FOOD INCLUDING BEVERAGES  Foods can either delay or inhibit absorption of certain drugs.  Consumption of alcoholic beverages together with a CNS depressant can further cause CNS depression. 6. PRESENCE OF DISEASES  Such as kidney disease which can hamper the excretion of a drug or a liver disease which can affect the metabolism of a drug. 7. STORAGE OF THE DRUG  Whether the drug was stored too long or in the wrong environment. Pharmacology Page 8 of 18 8. DEVELOPMENT OF TOLERANCE AND RESISTANCE  Resistance- ability of the microorganism to withstand the effects of the drug  Tolerance- person’s diminished response to a drug EFFECTS OF DRUGS 1. THERAPEUTIC  The desired effect of the drug  What is expected to achieve 2. SIDE EFFECTS  Secondary effects of drug therapy  All drugs have side effect  Common side effects are nausea, vomiting, diarrhea, constipation 3. ANAPHYLACTIC REACTION  Severe allergic reactions which usually occurs immediately following drug administration.  Can cause respiratory distress and laryngospasm 4. DRUG ALLERGY  Immunologic reactions to a drug  Caused by antigen-antibody reaction  Example: presence of rashes, puffiness in the area around the eyes 5. ADVERSE EFFECTS/ ADVERSE DRUG REACTIONS  Unintentional, unexpected reactions to drug therapy that occur at normal drug dosages  Always undesirable and must be reported and documented because they represent variances from plan therapy 6. TOXIC EFFECTS/DRUG TOXICITY  Occurs when drug level exceeds the therapeutic range  Toxicity makes occur secondary to overdose or drug accumulation  Can be identified by monitoring the plasma (serum) therapeutic range of drugs.  Includes hepatotoxicity, nephrotoxicity, ototoxicity 7. TOLERANCE AND TACHYPHYLAXIS TOLERANCE- refers to a decrease responsiveness to a drug over the course of therapy - An individual with drug tolerance require a higher dosage of drug to achieve the same therapeutic response TACHYPHYLAXIS- refers to an acute rapid decrease in response to a drug -It may occur after the first dose or after several doses 8.PLACIBO EFFECT- a drug response not attributed to the chemical properties of the drug.  the response can be positive or negative and may be influenced by the beliefs , attitudes and expectations of the patient. Pharmacology Page 9 of 18 PHARMACODYNAMIC INTERACTION 1. ADDITIVE DRUG EFFECT  When 2 drugs are administered in combination and the response is increased beyond what either could produce alone  1+1=2  Aspirin + codeine= greater effect 2. SYNERGISTIC DRUG EFFECT AND POTENTIATION  When 2 or more drugs are given together, one drug can have a synergetic effect on another  Combining the drugs leads to a larger effect than expected. 3. INTERFERENCE  Drug accelerates, slows down the other drug 4. DISPLACEMENT  Two or more drugs compete at receptor sites 5. ANTAGONISTIC DRUG EFFECTS  The effects of 2 drugs cancel each when drug with antagonistic effects are administered together, one drug reduces or blocks the effect of the other.  Example: Calcium Gluconate antagonizes the effect of Magnesium Sulfate toxicity. PHARMACOKINETICS  Described as what the body does to the drug.  Process of drug movement to achieve drug action. FIVE PROCESSES 1. LIBERATION  Release of the drug from its dosage form.  First phase of drug action  A drug in solid form- must undergo disintegration in order to dissolve into a liquid, a process known as DISSOLUTION.  A drug in liquid form- already in solution.  Drugs disintegrate faster and absorbed faster in acidic fluids that have a pH of 1 or 2 than in alkaline fluids.  Food in the GIT can interfere with the dilution and absorption of certain drugs. 2. ABSORPTION  Movement of drug particles from the GIT to body fluids by passive, active absorption or pinocytosis. Pharmacology Page 10 of 18   Most oral drugs are absorbed in the small intestine through the action of mucosal villi surface area. THREE PROCESSES a. PASSIVE ABSORPTION- occurs mostly by diffusion  Drug does not require energy to move across the membrane. b. ACTIVE ABSORPTION- requires a carrier to move against concentrated gradient.  An enzyme or a protein can carry drugs through membranes. c. PINOCYTOSIS - engulfs that drug to carry it across the membrane * GI membrane is composed mostly of lipid and CHON. * Lipid soluble drugs- can pass rapidly (passive absorption) * Water soluble drugs - need a carrier either an enzyme or CHON to pass through the membrane (active absorption) FACTORS THAT AFFECT DRUG ABSORPTION a. Blood flow  Poor circulation due to shock, vasoconstrictor drugs or disease hampers absorption. b. Pain c. Stress d. Food- solid, hot and fatty  Can slow gastric emptying time, so the drug remains longer in the stomach. e. Exercise  Can decrease blood flow by causing more blood to flow in the muscles decreasing blood circulation. Pharmacology Page 11 of 18  f. Route of Administration  Intradermal- local effect  IM/SC/IV- systemic effect- faster absorption g. First-pass effect/hepatic first pass  The process in which the drug passes to the liver first.  In the liver, most of the drug is metabolized to an inactive form for excretion, reducing the amount of active drug.  Example: Lidocaine and Nitroglycerin- not given orally due to extensive hepatic first pass. BIOAVAILABILITY Sub category of absorption Percentage of the administered drug dose that reaches the systemic circulation. Oral- always less than 100% - have a high 1st pass hepatic metabolism- 20 to 30% on entering the systemic circulation. IV- 100% FACTORS THAT ALTER BIOAVAILABILITY a. Drug form- tablet, capsule, liquid, patch b. Route of administration- oral, rectal, topical, parenteral c. GI mucosa and motility d. Food and other drugs e. Changes in the liver metabolism- caused by liver dysfunction or a decrease in hepatic 3. DISTRIBUTION  Process in which the drug becomes available to body fluids and body tissues.  Influenced by blood flow, its affinity to the tissue and PROTEIN BINDING EFFECT.  As drugs are distributed in the plasma, many are bound to varying percentage with protein (albumin). o Highly protein bound drugs- drugs greater than 80% bound to CHON o Moderately high protein bound- drugs that are 61-89% bound to CHON o Moderately protein bound- drugs that are 30-60% bound to CHON o Low protein bound drugs- less than 30% bound to CHON  The portion of the drug that is bound is INACTIVE and the portion that remains unbound is FREE ACTIVE DRUG.  Only free drugs or drugs not bound to protein are ACTIVE and can cause a PHARMACOLOGIC RESPONSE. Pharmacology Page 12 of 18  CONSIDERATIONS: a. When 2 highly protein bound drugs are given concurrently, they compete for CHON binding sites, causing more free drug to be released into the circulation. b. A low protein level decreases the number of protein binding sites, causing an increase in the amount of free drug in the plasma. NURSING RESPONSIBILITIES: a. Check the protein binding % of all drugs administered to a client to avoid possible drug toxicity b. Check the client’s plasma CHON and albumin levels. 4. METABOLISM/BIOTRANSFORMATION  The chemical conversion or transformation of drugs into compounds which are easier to eliminate.  LIVER- primary site of metabolism  Most drugs are inactivated by liver enzymes and are then converted or transformed by hepatic enzymes to inactive metabolites or water soluble substances for excretion.  A large percentage of drugs are lipid soluble, thus the liver metabolizes the lipid soluble drug to a water soluble substance for renal excretion.  Some drugs are transformed into ACTIVE METABOLITES, causing an increased pharmacologic response. HALF-LIFE (t 1/2)  The time it takes for one half of the drug concentration to be eliminated.  Metabolism and excretion affect the t ½ of a drug.  A drug goes through several half-lives before more than 90% of the drug is eliminated. o Short t ½ - 4-8 hours o Long ½ - 24 hours or longer  Example: Digoxin- t ½ is 36 hours o Example of t ½ of 650 mg of Aspirin is 3 hours # of t ½ Time of Dose Remaining Percentage Elimination Left 1st 3 325 mg 50% 2nd 6 162 mg 25% 3rd 9 81mg 12.5% 4th 12 40 mg 6.25 % 5th 15 20 mg 3% 6th 18 10 mg 1% Pharmacology Page 13 of 18 5. EXCRETION/ ELIMINATION  The elimination of unchanged drug or metabolite from the body.  Main route- KIDNEY- filter free unbound drugs, water soluble drugs and drugs that are unchanged.  Other routes- bile, feces, lungs, saliva, sweat, and breastmilk FACTORS THAT AFFECT DRUG EXCRETION a. Urine pH  Acidic urine promotes elimination of weak base drugs  Alkaline urine promotes elimination of weak acid drugs- aspirin is a weak acid and is excreted rapidly in an alkaline urine c. Pre-renal conditions  Dehydration or hemorrhage reduce blood flow to the kidney result in decreased GFR d. Intrarenal conditions  Such as Glomerulonephritis and CKD affect GFR and tubular secretion and reabsorption e. Post renal conditions that obstruct blood flow  Such as prostatic hypertrophy and stones adversely affect GFR PHARMACODYNAMICS  The study of the effects of drug on the body.  Drug response can cause a primary or secondary physiologic effect or both. o Primary effect- desirable o Secondary effect- desirable/undesirable o Example: Diphenhydramine (Benadryl)- antihistamine  Primary effect- treat the symptoms of allergy  Secondary effect- CAN depression causing drowsiness DOSE RESPONSE RELATIONSHIP  Body’s physiologic response to changes in drug concentration on the site of action  Two concepts further describe the relationship:  POTENCY- the amount of drug needed to elicit a specific physiologic response to a drug  Maximal Efficacy- the point at which increasing a drug’s dosage no longer increases the drug therapeutic response o Example: Non narcotic analgesic- for mild to moderate pain only Narcotic analgesic- for severe pain Pharmacology Page 14 of 18 ONSET, PEAK AND DURATION OF ACTION  Onset of Action- begins when the drug enters the plasma and lasts until it reaches maximum effective concentration (MEC) after drug is administered.  Peak of Action- occurs when the drug reaches its highest blood or plasma concentration.  Duration of Action- length of time the drug has a pharmacologic effect. Pharmacology Page 15 of 18  RECEPTOR THEORY  Most receptor, which are protein in nature are found in the cell membranes.  Ligand-binding domain- the site on the receptor at which drugs bind. a. CELL MEMBRANE EMBEBDED ENZYME  The ligand-binding domain for drug binding is on the cell surface.  The drug activates the enzyme (inside the cell), and a response is initiated. b. LIGAND- GATED ION CHANNELS  The channel crosses the cell membrane, and with this type of receptor, the channel opens, allowing for the flow of ions into and out of the cells.  Ions are primarily sodium and calcium. c. G PROTEIN-COUPLED RECEPTOR SYSTEMS  There are 3 components to this receptor: (1) the receptor, (2) the G protein that binds with Guanosine Triphosphate (GTP), and (3) the effector that is either an enzyme or an ion channel. d. TRANSCRIPTION FACTORS  Found in the cell nucleus on DNA not on the surface.  Activation of receptors is prolonged through transcription factors regulates protein synthesis and is prolonged while the 1st 3 receptors, activation is rapid AGONISTS PARTIAL, AGONISTS AND ANTAGONISTS a. AGONISTS- drugs that activates receptors and produce a response. Pharmacology Page 16 of 18  Example: Epinephrine (Adrenalin)- stimulates the beta1 and beta2 receptors- so it is an agonist b. PARTIAL AGONISTS  Drugs that elicit only moderate activity when binding to receptors  They also prevent receptor activation for other drugs c. ANTAGONISTS- drug that prevent receptor activation and block a response.  Example: Atropine Sulfate- an anticholinergic (blocks the Histamine2 receptor thus preventing excessive gastric acid secretion. NONSPECIFIC AND NONSELECTIVE DRUG EFFECTS a. Nonspecific drugs- are drugs that affect multiplr receptor sites and have properties of non specificity. Example: Bethanechol (Urecholine)- a cholinergic drug that affects several cholinergic receptor sites. b. Nonselective drugs- drugs that affect multiple receptors Example: Chlorpromazine (Thorazine)- an antipsychotic drug that acts on norepinephrine, dopamine, acetylcholine and histamine receptors Epinephrine- an adrenergic agent that acts on the alpha1, beta1 and beta2 receptors MECHANISMS OF DRUG ACTION a. STIMULATION -a drug that stimulates enhances intrinsic activity b.DEPRESSION- depressant drugs decrease neural activity and body functions. c. IIRITATION- drugs that irritate have a noxious effect such astringents d. REPLACEMENT- replacement drugs such as insulins, thyroid drugs and hormones replace essential body compound e. CYTOTOXIC ACTION- cytotoxic drugs selectively kills invading parasites or cancers - Pharmacology Page 17 of 18   Replace essential body compound.  Example: insulin f. ANTI MICROBIAL ACTIONS- this are anti microbial drugs that prevent inhibit or kill infectious organisms g. MODIFICATION OF IMMUNE STATUS- modify, enhance or depress the immune system THERAPEUTIC RANGE (Therapeutic Window)  The level of the drug between the minimum effective concentration (MEC) in the plasma and the minimum toxic concentration (toxic effect).  If the therapeutic range is narrow, the plasma drug level should be monitored periodically to avoid toxicity.  Example: digoxin- 0.5-1.0 ng/ml, valproic acid- 50-150 mcg/ml THERAPUETIC DRUG MONITORING  Peak drug levels- is the highest plasma concentration of drug at a specified time. o It indicates the rate of absorption.  Trough drug level- is the lowest plasma concentration of a drug, and it measures the rate at which the drug is eliminated. Pharmacology Page 18 of 18