Drug Action-Pharmaceutic, Pharmcokinetic, and Pharmacodynamic Phases

jasmine's version from 2015-10-17 23:58

Section 1

Question Answer
PharmaceuticThe discipline of pharmacy that deals with the process of turning a new chemical entity (NCE) or old drugs into a medication to be used safely and effectively by patients. It is also called the science of dosage form design: dissolution
PharmacokineticThe process of drug movement to achieve drug action. The 4 processes are absorption, distribution, metabolism (or biotransformation) and excretion (or elimination).
PharmacodynamicThe study of drug concentration and its effects on the body
DisintegrationThe breakdown of a tablet into smaller particles
DissolutionThe dissolving of smaller particles into the GI fluid before absorption
Drug AbsorptionFirst of four processes of pharmacokinetics; The movement of a drug from its site of administration into the blood; The movement of drug particles from the GI tract to body fluid by passive absorption, active absorption or pinocytosis
Passive AbsorptionOccurs mostly by diffusion (movement from higher concentration to lower concentration); energy is not required
Active absorptionRequires a carrier such as an enzyme or protein to move the drug against a concentration gradient; energy is required
Rate LimitingThe time it takes the drug to disintegrate and dissolve to become available to the body to absorb it
Drug DistributionSecond of four processes of pharmacokinetics; The movement of drugs throughout the body; The process by which the drug becomes available to the body fluids and body tissues
ExcretionAlso known as elimination; Fourth of four processes of pharmacokinetics; The removal of drugs from the body; Drugs and their metabolites can exit the body in urine, bile, sweat, saliva, breast milk, and expired air
RememberDrugs that are lipid soluble and non-ionized are absorbed faster than water-soluble and ionized drugs
Metabolism Also known as biotransformation; Third of four processes of pharmacokinetics; Enzymatic alteration of drug structure; Liver is the primary site; Drugs metabolized in GI tract also
KidneyMost important organ for drug excretion, or elimination

Section 2

Question Answer
PinocytosisMost common way drugs cross a cell membrane; It is a process by which cells carry a drug across their membrane by engulfing the drug particles
Channels and Pores Very few drugs cross through by this way due to the membranes being extremely small, specific for certain molecules, and if direct area is right
Transport Systems Selective carriers that can move drugs from one side of the cell membrane to the other, and may or may not require the expenditure of energy; Without these, certain orally administered drugs could not be absorbed; A number of drugs could not reach intracellular sites of action; Renal excretion of many drugs would be extremely slow, as these are in the kidney and pump drugs from the blood into renal tubules
BioavailibilityA subcategory of absorption; It is the percentage of the administered drug dose that reaches the systemic circulation.
Factors That Affect BioavailibilityBioavailibility: the drug form, the route, GI mucosa and motility, food and other drugs and changes in liver metabolism
First-Pass EffectThe process in which the drug passes to the liver first; Example: Wafrarin and morphine
Creatinine ClearanceMost accurate test to determine renal function; It is used to estimate glomerular filtration rate (GFR). GFR is a measure of how well the kidneys are working, especially the kidneys' filtering units. These filtering units are called glomeruli.
Half-LifeThe time it takes for one half of the drug concentration to be eliminated; A drug goes through several of these before 90 percent of the drug is eliminated
Time-Response CurveEvaluates 3 parameters of drug action; the onset of drug action, peak action and duration of action
Onset Of Action The time it takes to reach the minimum effective concentration (MEC) after a drug is administered
Peak ActionOccurs when the drug reaches its highest blood or plasma concentration
Peak Drug LevelThe highest plasma concentration of drug at a specific time; indicates rate of absorption
Duration Of ActionThe length of time of the drug as a pharmacologic effect
Trough Drug LevelThe lowest plasma concentration of a drug and it measures the rate at which the drug has been eliminated
Therapeutic Range (window)The drug concentration that is between the minimum effective concentration in the plasma for obtaining desired drug action and the minimum toxic concentration
Maximal EfficacyPart of the pharmacodynamic phase; The maximum drug effect; Example: Morphine prescribed for pain relief. The maximum efficacy of morphine is greater than that of Tylenol (regardless of how much Tylenol is given)

Section 3

Question Answer
AgonistsDrugs that produce a response
AntagonistsDrugs that inhibit, or block, a response
Non-specific drugsDrugs that affect various sites, have properties of nonspecificity
Non-Specific Drug EffectEffect where one receptor produces a variety of physiologic responses, depending on where in the body that receptor is located; Example: Cholinergic receptors are located in the bladder, heart, blood vessels, lungs, and eyes. a drug that stimulates/inhibits these receptors affects all anatomic sites of location
Non-selective drugsDrugs that affect various receptors; have properties of nonselectivity
Categories Of Drug ActionStimulation or depression, replacement, inhibition or killing of organisms, irritation
Theraputic IndexEstimates the margin of safety of a drug through the use of a ratio that measres the effective dose (ED) in 50% of persons/animals and the lethal dose (LD) in 50% of people/animals; the closer the ratio is to 1, the greater danger of toxicity
Low Theraputic IindexDrugs that have a narrow margin of safety; small safety range between the ED and LD
High Theraputic IndexDrugs that have a wide margin of safety and less danger of producing toxic effects
Placebo EffectA psychologic benefit from a compound that may not hav the chemincal structure of a drug effect
Loading DoseA large initial dose of drug to achieve a rapid minimum effective concentration in the plasma
TachyphylaxisRefers to a rapid decrease in response to the drug; think "acute tolerance"
ToleranceRefers to a decreased responsiveness over the course of therapy
Side EffectsPhysiologic effects not related to desired drug effects
Adverse ReactionsMore severe than side effects; They are a range of untoward effects (unintended/occurring at normal doses) of drugs that cause mild to severe side effects; Always undesirable, and must always be reported and documented
Toxic EffectsCan be identified by monitoring the plasma (serum) therapeutic range of the drug
Drug Action1) stimulation/depression - epinephrine to ↑HR; 2) replacement - insulin; 3) inhibition or killing of organisms - antibx; and 4) irritation - laxatives/GI system
Dose Response Part of the pharmacodynamic phase; It is the relationship between the minimal versus the maximal amount of drug dose needed to produce the desired drug response; Some clients respond to the lower dose, or need a high dose to elicit the desired response
Volume Of Drug DistributionPart of distribution within pharmacokinetics; It is dependent on drug dose and its concentration in the body; The larger the volume dose (Vd), the longer its half-life and its stay in the body
Role To Avoid Possible ToxicityCheck the protein-binding percentage of all drugs administered to a client; Check client's plasma protein and albumin levels depending on the drug, the result could be life-threatening
Partial AgonistsHas only moderate intrinsic activity; As a result, the maximal effect that it can produce is lower; Example: A degree of pain relief from pentazocine is much lower than the pain relief from meperidine; Can act as both antagonists and agonists

Section 4

Question Answer
Ligand-Binding DomainThe site on the receptor in which drugs bind
Receptor FamiliesCell Membrane-Embedded Enzymes, Ligand-Gated Ion Channels, G Protein-Coupled Receptor Systems, and Transcription Factors
Cell Membrane-Embedded EnzymesThe ligand-binding domain for drug binding is on the cell surface, and the enzyme's catalytic site is inside; Binding of an endogenous regulatory molecule or agonist drug (one that mimics the action of the endogenous regulatory molecule) activates the enzyme, thereby increasing its catalytic activity; Insulin is a good example of an endogenous ligand that acts through this type of receptor
Ligand-Gated Ion ChannelsThe ligand-binding domain for drug binding is on the cell surface; The channels span the cell membrane; The function of these receptors is to regulate flow of ions into and out of cells; Each channel is specific for a particular ion (i.e., Na+, K+, Ca++); When an endogenous ligand or agonist drug binds the receptor, the channel opens, allowing ions to flow inward or outward (direction of flow determined by the concentration gradient of the ion across the membrane); Responses to activation occurring in milliseconds; Several neurotransmitters, including acetylcholine and gamma-aminobutyric acid (GABA), act through this type of receptor
G Protein-Coupled Receptor SystemsCoupled with three components: The receptor itself, G protein (so named because it bind GTP), and an effector (typically an ion channel or an enzyme); They work as follows: Binding of an endogenous ligand or agonist drug activates the receptor, which in turn activates G protein, which in turn activates the effector; Responses for activation develop rapidly; Numerous endogenous ligands-including NE, serotonin, histamine, and many peptide hormones-act through G protein-coupled receptor systems; Ligand binding domain is either on the cell surface or located in a pocket accessible from the cell surface
Transcription FactorsDiffer from other cell receptors in two ways: 1) Transcription factors are found within the cell rather than on the surface; and 2) Responses to activation of these receptors are DELAYED; It is situated on DNA in the cell nucleus; Its function is to regulate protein synthesis; Activation by endogenous ligands or by agonist drugs stimulates transcription of messenger RNA molecules, which then act as templates for synthesis of specific proteins; The entire process from activation to completion of protein synthesis may take hours or even days; Because it is intracellular, it can be activated only by ligands that are sufficiently LIPID SOLUBLE to cross the cell membrane; Endogenous ligands include thyroid hormone and all of the steroid hormones (i.e., progesterone, testosterone, cortisol)
Protein-Binding EffectsPart of distribution in pharmacokinetics;The portion of the drug that is bound is INACTIVE because it is not available to receptors; Portion that remains unbound is a free, active drug; Drugs are bound by varying degrees (percentages) to proteins as they are distributed in the plasma
High Protein-Bound DrugsMore than 89 percent
Moderately High Protein-Bound Drugs61-89 percent
Moderate protein-bound Drugs30-69 percent
Low Protein-Bound DrugsLess than 30 percent
Free DrugsDrugs not bound to protein; Part of distribution within pharmacokinetics are active and can cause a pharmacologic response; As the amount in the circulation decreases, more bound drug is released from the protein to maintain the balance of free drug; When two highly protein-bound drugs are given concurrently, they compete for protein-binding sites → causes more free drug to be released into circulation → drug accumulation/ possible toxicity; Patient with a low protein level (liver or kidney disease, or malnourished...lab = hypoalbuminemia) → decreases the protein binding sites → causes an increase in the amount of free drug in the plasma → possible drug overdose
Receptor Theory Part of the pharmacodynamic phase; Most receptors (protein in nature) are found in cell membranes; Drug-binding sites are primarily on proteins/glycoproteins/proteolipids/enzymes; Drugs act through receptors by binding to the receptor to initiate a response or to prevent a response; The activity of many drugs is determined by the ability of the drug to bind to a specific receptor; The better the drug fits at the receptor site, the more biologically active the drug is (key and lock)
Individual VariationDifferences in drug interactions; Physiologic variables (age, gender, weight), pathological variables (diminished function of kidney and liver), genetic variables (metabolism); Drug therapy tailored to patient
Simple Occupancy TheoryOne of two theories of drug-receptor interaction; It states that 1) The intensity of the response to a drug is proportional to the number of receptors occupied by that drug and that 2) A maximal response will occur when ALL available receptors have been occupied; Certain aspects of dose-response relationships can be explained by this theory; It cannot account for the differences between response elicited by one drug being less than a response elicited by another drug at the same receptor, even if doses were high enough to produce; In other words: The ability to bind to the receptor, and the ability to influence receptor function once binding has taken place
Modified Occupancy TheoryOne of two theories of drug-receptor interaction; It proposes two qualities that are 1) Affinity (strength of attraction between a drug and its receptor), and 2) Intrinsic activity (the ability of a drug to activate the receptor following binding)-both are independent properties