Pharmacology 1-6.pdf

 NURS 3020: Pharmacology Module 1 (1-6) Learning Objectives ❑ Define four basic terms essential to pharmacology ❑ Discuss properties of an ideal drug ❑ Provide information about drug development including legislative issues ❑ Examine the concepts of pharmacokinetics and pha...

 NURS 3020: Pharmacology Module 1 (1-6) Learning Objectives ❑ Define four basic terms essential to pharmacology ❑ Discuss properties of an ideal drug ❑ Provide information about drug development including legislative issues ❑ Examine the concepts of pharmacokinetics and pharmacodynamics ❑ Review the relationship between pharmacology and nursing practice LO1: Define four basic terms essential to pharmacology 4 Basic Terms C-Clinical Pharmacology D-Drug P-Pharmacology T-Therapeutics Clinical Pharmacology: Study of drug humans, discipline includes PT and in healthy volunteers. Drug: Any chemical that can affect living processes. Pharmacology: The study of drugs and their interactions with living systems. Therapeutics: Use of drugs to diagnose, prevent or treat disease, or to prevent pregnancy. LO2: Discuss properties of an ideal drug An ideal drug has the properties of being Effective, Safe, Selective, and Best Drug. More properties are Reversible, Predictable, Easy to administer, Inexpensive. More properties are being Stable, Simple name, free from drug interactions. Ways to remember (E)everyone. (S)sucks. (S)some. (B)balls- Effective, Safe (Most important), Selective, Best Drug ever (R)Rebecca (P)prepares (E)eggrolls (F)for (I)Isabel (S)Sarah and (S) Suzzie- Reversible, Predictable, Easy to administer, Free from drug interactions, Inexpensive, Simple name, Stable LO3: Provide information about drug development including legislative issues Stage 1 of Drug Development: Preclinical Testing Most be done on animals The drug is evaluated on three things: T.P.B- Toxicities, Pharmacokinetics, Biological effects. May take 1-5 years Becomes investigational new drug if approved by FDA Stage 2 of Drug Development: Clinical Testing Clinical testing has four phases I, II, III, IV Phase I- Healthy volunteers, evaluations of drug metabolism (process by which body chemically alters drugs to make them easier to eliminate), effects in humans Phase II & III- Patients, determine therapeutic effects, dosage range and safety. Under New Drug Application. Phase IV- Released for general use, has a post marketing surveillance, observation of effects in large, population, new unintended, harmful events attributed to the use of medication (adverse) effects commonly arise. Drug Legislation To start with a new drug there needs to be minimal to extensive governmental control. FDA (Federal Pure Food and Drug Act of 1906) check quality and purity but nothing about drug safety or effectiveness. FDCA (Food, Drug, and Cosmetic Act of 1938) has mandated drug safety testing and needs FDA approval. LO4: Examine the concepts of pharmacokinetics and pharmacodynamics Two main branches of pharmacology are Pharmaco kinetics and dynamics Kinetics- What the Body does to the Drug. Dynamic-What the Drug does to the Body. Simple thinking- Medication help the body help itself Pharmacokinetics: What the body does to the drug, has four sections Minimum effective concentration: Lowest blood level to cause intended action Steady state: Balance between drug entry and elimination Duration of action: How long drug remains at minimum effective concentration Potency: Strength of the drug Pg 3: Pharmacology 8/15/2024 LO5: Review the relationship between pharmacology and nursing practice Pharmacology 8/16/2024 Lecture Notes Drugs can prevent, correct, or reduce health problems Can be used to treat and diagnose health problems Drug: Any small molecules that change a body function by working at the chemical and cell levels. Drug therapy: When a plan to improve a problem includes drugs Identifying specific health problems Determining what drug or drugs would best help the problem Deciding the best delivery method and schedule Ensuring that the proper amount of the drug is given Helping the patient become an active participant in their drug therapy. Drug Therapy and Body Intrinsic drugs: Chemicals the body makes Extrinsic drugs: Must be taken into the body to change cell, organ or body action Pharmacology: Study of drugs Therapeutic Objective: “The object of drug therapy is to provide maximum benefit with minimum harm. Primary concern: Intensity of response Drug Regulation Drug Enforcement Administration (DEA): All prescribers must register with DEA/ have DEA number. Food and Drug Administration (FDA): Enforces standards set by USP United States Pharmacopeia (USP): Develops manufacturing standards, purity, strength, packaging, and labeling. New Drug Development  10–15-year completion 2.558 billion for each approved drug Randomized Controlled Trials: Use of controls, Randomization Blinding Drug Names Chemical Names: Uses the nomenclature of chemistry Generic Name: Established by US Adopted Names Council Every drug has only generic name acetaminophen Brand name (proprietary/trade names) Created by drug companies Multiple trade names can exist for same drug Tylenol, Tempra, Bromo Seltzer Drug Categories Over the counter (OTC) drugs considered safe for self-medication; may interact with prescription drugs. Ex: Tylenol Prescription drugs: Available only from a pharmacy with a drug order from prescriber Ex: Antibiotics High-alert drugs- Increased risk for harm if used in error Herbal products: Made from plants Ex: Ginger tea Source of Drug Information Newsletters Reference Books The Internet P-Glycoprotein P-Glycoprotein: Transmembrane protein that protein that transports a wide variety of drugs out of cells. Liver: Transports drugs into the bile for elimination Kidney: Pumps drugs into the urine for excretion Placenta: Transports drugs back into the maternal blood Brain: Pumps drugs into the blood to limit drug’s access to the brain Passage of Drugs Across the Membrane  Channel and Pores- Very few drugs cross this way Transport Systems- Important mean of drug transit Direct penetration of membrane- Most Common Some drugs movement is dependent on ability to penetrate membranes directly - D- Distribution Extent that a drug spreads into three specific compartments: Blood stream or blood volume, Interstitial space, Intracellular space, Intracellular space Distribution determined by size and chemical nature Essentially: Movement of Drugs throughout the body Blood Flow to Tissues Drugs are carried by blood to tissues and organs The rate of delivery is determined by blood flow Abscesses are pus-filled pockets rather than internal blood vessels, both tumors and abscesses have low regional blood flow that affects therapy. And solid tumors have a limited blood supply. Exiting the Vascular System Capillary beds are where drugs typically leave. Blood- Brain Barrier Capillary walls in the central nervous system have tight junctions between cells. Drugs need to pass through these cells to enter the body. Only drugs that are lipid-soluble or have special transport systems can cross the blood-brain barrier effectively. This barrier can make it difficult for antibiotics to reach infections in the central nervous system. Entering Cells To reach the site of action some drugs must enter cells To undergo metabolism and excretion most drugs must enter the cells. Binding with receptors on the external surface of the cell membrane is how many drugs produce their effects. * These don’t need to cross the cell membrane to act Metabolism The liver, kidneys, lungs, and white blood cells are some organs/living cells that can metabolize drugs Drugs metabolized mostly in the liver. The liver’s hepatic microsomal enzyme system(P450) is what performs the metabolism Metabolism doesn’t always result in a smaller molecule Therapeutic Consequences of Drug Metabolism “A DIAL” Accelerated renal drug excretion Drug inactivation  Increased therapeutic action Activation of prodrugs Levels of toxicity either increased or decreased Special Considerations in Drug Metabolism Age Induction of drug-metabolizing enzymes First-pass effect Nutritional status Competition among drugs First-Pass effect Certain oral drugs have an rapid hepatic inactivation Drugs w/h rapid hepatic metabolism(how the liver processes and gets rid of chemicals) generally aren’t given orally but parenterally (administering drugs other than digestive tract). Ex: Nitroglycerin= Given under tongue (sublingual) Elimination/Excretion Intestinal tract, kidney, lungs are main organs that help inactivate/remove drugs from body. Metabolized drugs from the liver are sent to either intestinal tract or blood then to kidneys. Dissolved drugs in the blood leave by through urine. Liver metabolizes to make ready for elimination by kidney. Renal Excretion 1. Glomerular Filtration: Drugs pushed out of capillary into urine 2. Passive Reabsorption: Lipid soluble drugs move back into capillary through passive reabsorption 3. Active Transport: Drugs pumped back into urine for excretion Influence on Drug Activity Half-time: Time needed for half a dose to be eliminated Loading dose: Larger first dose of drugs with longer half-life Peak: The maximum/highest drug blood level Trough: Lowest/minimal blood drug level  Toxicity: Occurs if the peak blood level of the drug is too high Half-Life Time required for 50% of the drug to leave the body. It’s the percentage not the actual amount Amount depends on how much is in the body. Some drugs half-time can be days, some can be weeks. Half-life is important because it determines dosing interval for drugs with repeated dosing. Drug Levels with Repeated Dosing Accumulation of a drug in the body can be caused by multiple dosing. Plateau (steady state) is where a nurse should reach. Occurs when amount of drug eliminated between doses equals dose administered. Plateau will be reached in- 4 half-lives independent of the dose. Drug Level Fluctuation Peak: Highest drug level Trough: Lowest drug level Depending on the situation it’s okay to have fluctuating levels but you want to stay in therapeutic range. Mechanisms to decrease fluctuations: Continuous infusion, Depot preparations, Decrease size of dose and dosing interval. Life Span Considerations: Organ Health Cardiopulmonary health Adults older than 70 have some degree of heart failure and poor blood flow to the liver and other body areas Older adults often have fewer red and white blood cells than younger adults Pharmacodynamics- What the drug does to the body Meachanism of action: Exactly how a drug changes cell activity Target tissues: Actual cells or tissues affected by mechanism of action To control activity a drug attaches to a receptor A receptor will not activate if the wrong drugs tries to bind with it. Dose-Response Relationships Relationship btw size of administered dose and intensity of of response produced.  This relationship determines the following: (1) Minimum amount of drug to be used. (2) Maximum response a drug can elicit. (3) How much to increase the dosage to produce the desired increase in response The response becomes progressively larger as the dosage increases The desired intensity of response is achieved by tailoring the treatment either increasing or decreasing dosage. Maximal Efficacy and Relative Potency Dose-response curves reveal two characteristic properties of drugs. Maximal Efficacy: Largest effect that a drug can produce (Height of curve) Match the intensity of the response with the pt’s need Very high maximal efficacy isn’t always more desirable Relative potency: Amount of drug that must be given to elicit an effect Rarely an important characteristic of the drug. Be important if a lack of potency forces inconveniently large doses Implies nothing about maximal efficacy; refers to dosage needed to produce effects Receptor Functional macromolecule in cells to which a drug binds to produce effects. Enzymes, ribosomes, and tubulin are all receptors Term receptor is generally reserved for the body’s own receptors for hormones, neurotransmitters, and other regulatory molecules. Types of Receptors Agonists: An agonist drug is a substance that binds to a specific receptor in the body and activates it, mimicking the effects of a natural chemical or substance. Has the right key to turn on cell’s ignition Agonist drugs must interact with CORRECT RECEPTOR to change cell activity. Antagonists: An antagonist drug is a substance that binds to a receptor in the body but does not activate it. Instead, it blocks or dampens the effects of other substances BLOCK RECEPTORS so intrinsic drug can’t bind with it Receptors: Sites of direct action for many drugs Partial Agonist: Can act as both agonist and antagonist Important Properties of Receptors Receptors naturally control the body’s processes Normally, the body regulates receptors w/h own molecule Drugs can either mimic or block natural molecules Drugs can’t create new functions for cells Drugs work by enhancing body’s existing abilities Receptors and Selectivity of Drug Action Fewer side effects= More selective Drug Selectivity is possible because of receptors Each type of receptor controls only a few specific processes. Safety isn’t guarantee by selectivity Therapeutic Index Measure of a drug’s safety LD-Lethal Dose ED-Effective Dose The larger/higher the therapeutic index= safer the drug Smaller/lower the therapeutic index= less safe the drug Ratio of LD50 to ED50 Life Span Considerations: Children Body Size: Children are smaller than adults, prescribed in mg/kg or body surface area (BAS) Pediatric Dosages Always compare the drug dose prescribed for an infant or child w/h the recommended dose Question any drug prescription for a child in which prescribed dose isn’t recommended dose. Double check drug dose calculation w/h a colleague or a pharmacist Life Span Considerations: Organ Health Liver Metabolism may be slower or faster in children  Older adults may have serious liver damage Kidney Kidneys in infants don’t concentrate fluids well There is a reduced kidney size and function in adults Drug Interactions Drugs can interact with: Dashing, Foxes, Visit, Hills Other Drugs Food Vitamins Herbal Compounds Drug-Drug Interactions Interactions can occur whenever a patient takes more than one drug Interactions can be intended/desired or unintended/undesired Patient freq. Take more than one drug: Mult. Drugs to treat one disorder Multi. disorder requiring diff. Drugs Over- the counter medications, caffeine, nicotine and alcohol Consequences of Drug-Drug Interactions Intensification of effects: (1) increased therapeutic effects, (2) increased adverse effects Reduction of effects: (1) reduced therapeutic effects, (2) Reduced adverse effects Creation of a unique response Interactions occur through 4 basic mechanisms 1. Direct contact(Physical or chemical): Usually render drugs inactive, * DO NOT COMBINE DRUGS unless SAFETY is ESTABLISHED!!!! 2. Pharmacokinetic Interactions 3. Pharmacodynamic Interactions 4. Combined toxicity Pharmacokinetic Interactions Absorption: Can be blocked or enhanced/ ph, GI tract, regional blood flow Distribution: Competition for protein binding, increase in free drug Metabolism: Altered metabolism Induction of CYP- Increases metabolism of drugs=lower drug levels Inhibition of CYP- Decreases metabolism of drugs= increase drug levels=toxicity Basic Mechanisms of Drug-Drug Interactions Pharmacodynamic interactions, that have the same receptor, almost always inhibitory (antagonist/ agonist) Pharmacodynamic that have separate sites, may be potentiative (morphine and diazepam) or inhibitory (hydrochlorothiazide and spironolactone) Pharmacodynamic can have combined toxicity: Drugs w/h overlapping toxicities should not be used together Minimizing Drug-Drug Interaction Minimize multi-drug therapy Complete drug history Adjust timing r/t absorption Be careful with drugs w/h low therapeutic indexes Drug-Food Interactions Absorption Food decreases absorption of drugs in 2 ways: (1) rate of absorption, (2) extent of absorption. Food can also increase the extent of absorption of some drugs Drug-Food Interactions: Drug Metabolism Grapefruit juice effect: Inhibits metabolism of certain drugs, raise drug’s blood level, increase in felodipine Drug-Food Interaction: Toxicity Monoamine oxidase inhibitors and tyramine contain foods Theophylline and caffeine Potassium-sparing diuretics and salt substitutes Aluminum-containing antacids and citrus beverages Drug-Supplement Interactions Conventional drugs can interact w/h herbal preparations Interaction w/h herbal medicine are just as likely as they are w/h prescription medications Reliable information about drug-herb interactions lacking