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Intro to Pharm

Dose response relationships, pharmacodynamics/kinetics, R's, signal transduction

What is clinical pharmacology? The science of drugs and their clinical use...focus on application of pharm principles in the real world. It has a broad scope, from the discovery of new target molecules to the effects of drug usage in whole populations.
What are pharmacotherapeutics? The use of drugs to diagnose, prevent, & treat disease (or to prevent pregnancy).
What is the definition of drug effectiveness? The drug elicits responses for which it has been administered.
What is the generic name for tylenol + dolane + panadol, etc.? Acetaminophen
What is the average length of time for preclinical testing and what are two characteristics? Average length of time is 2.6 years & characteristics include toxicities/pharmacokinetics/effects explored using animal testing & application to FDA for Investigational New Drug/begin clinical trials.
What is the average length of time for clincal testing? Average length of time is 5.6 years.
What are the characteristics of phase I of clinical testing? Healthy volunteers, 20-80, metabolism & effects
What are the characteristics of phase II of clinical testing? Patients, 200-300, therapy & dosage range
What are the characteristics of phase III of clinical testing? Patients, 100s to 1000s, safety & effectiveness, next apply to FDA for New Drug Application
What are the characteristics of phase IV of clinical testing? General use, large population
What are the limitations of clinical testing procedures? women of child-bearing age not included, children, failure to detect all adverse effects
What are two advantages to OTC drugs? increased access, less expensive
What are two disadvantages to OTC drugs? self-care, drug interactions
What are pharmacokinetics? The branch of pharmacology dedicated to the fate of substances administered externally to living organisms. The study of drug ABSORPTION>DISTRIBUTION>METABOLISM>EXCRETION (absorption, distribution, elimination)
What are pharmacodynamics? The study of a drug at the site of action and the EFFECT ON THE BODY. (Systemic effects & cellular effects)
What is toxicology? The study of harmful effects of chemicals including drugs, environmental toxins, & poisons
Why utilize pharmacokinetics? better care of pt., decreased toxicity of drugs, better judgment of pharmacodynamic effect, define & eliminate drug interactions, individualize therapy (optimal dose-response relationship)
Why utilize pharmacodynamics? to obtain maximal efficacy (individual variation, status change, drug interactions, misdiagnosis, poor compliance, environmental variables)
If there is a net electrical charge, chan drugs cross the membrane? The drug cannot cross the membrane.
Acid ionizes in ______media; base ionizes in _____media. ionizes in bacic media; ionizes in acidic media
What are the characteristics of first order kinetics? Linear, constant PERCENT of drug is removed per unit time, concentration DEPENDENT
What are the characteristics of zero order kinetics (alcohol)? NONlinear; saturable, constant AMOUNT of drug is removed per unit time, concentration INdependent
What is the sequence of pharmacokinetics? Dose-->(absorption, distribution, metabolism, elimination)> concentration in blood)-->concentration at site of action-->effect
Absorption depends on: Product formulation, disease state, drug interactions, first-pass effect, pH
What is the first-pass effect? The phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches systemic circulation. The liver metabolizes much of oral drugs (take 50mg, only 25mg active); reduces bioavailability.
What are alternative routes of drug administration that avoid the first-pass effect? Suppository, intravenous, intramuscular, & sublingual all allow drugs to be absorbed directly into systemic circulation.
What are the three enteral (GI) routes of drug administration? Oral, sublingual, rectal
What are four parenteral routes of drug administration? inhalation, injection, topical, transdermal
What are the disadvantages of oral drug administration (easiest/most common route)? Drugs must be lipid soluble, first-pass effect (significant amt drug absorbed in liver before reaching site of action)
What are advantages/disadvantages of sublingual drug administration? Advantages: bypass first-pass effect; Disadvantages: amount absorbed is limited (drugs must go through oral mucosa)
What are advantages/disadvantages of rectal drug administration? Advantages: treatment of hemorrhoids/local conditions; Disadvantages: absorbed poorly or incompletely
What are the advantages/disadvantages of inhalation drug administration? Advantages: apply medications to bronchial tissue-anesthetics/asthma; Disadvantages: ability to predict concentration that reaches lungs limited
What are the disadvantages for all injected drug administration methods? Possible infection & problems with patient self-administration
What are the advantages/disadvantages of intravenous injection drug administration? Advantages: ER situations; Disadvantage: appearance of large titers of drug
What are the advantages/disadvantages of intra-arterial injection drug administration? Advantage: focuses the administration of drugs; Disadvantage: dangerous & difficult procedure
What are the advantages/disadvantages of subcutaneous injection drug administration? Advantages: local response such as local anesthesia or slow prolonged release of medication; Disadvantage: amount of drug that can be injected is small
What are the advantages/disadvantages of intramuscular injection drug administration? Advantage: rapid effect while avoiding sudden increases in drug concentration; Disadvantage: local pain and prolonged soreness
What are the advantages/disadvantages of intrathecal (direct to spinal cord) injection drug administration? Advantage: Narcotic analgesics to spinal cord; disadvantage: painful and dangerous
What are the advantages/disadvantages of topical (not absorbed through skin) drug administration? Advantages: nasal spray, eye drops, dermatological interventions; Disadvantages: adverse systemic effects if inadvertently absorbed into body
What are the advantages/disadvantages of transdermal (absorbed through dermal layers) drug administration? Advantages: slow, controlled release of drug (patches); Disadvantage: must be able to penetrate skin & must not be degraded by enzymes in skin
What is bioavailability? Extent to which the drug reaches systemic circulation (IV= 100%, oral= first-pass so not 100%)
Distribution of drugs in the body depends on what three things? Drug characteristics (lipid solubility, molecular size, ionized vs unionized), binding to plasma protein, blood flow to tissues absent in abcesses or tumors
What is volume of distribution? body space into which a drug can diffuse; volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration
What is a loading dose? an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose; most useful for drugs eliminated from the body slowly; 70kg man = 42L
Volume and location of asprin/morphine/lithium? Asprin: 8.4L, retained in bloodstream; Morphine: 420L, concentrated in tissue; Lithium: 42L, distributed uniformly
What occurs during phase I of drug metabolism? Must make the drug hydrophilic (make polar for elimination so body does not reabsorb)
What occurs during phase II of drug metabolism? Cytochrome P450 oxidases (genetically different in each person)
What are the three events during elimination? filtration (protein binding & molecular size & charge); passive transport (depend on pH & lipid solubility); active transport
Weak acids are reabsorbed in more ____ urine, weak bases are reabsorbed in more _____ urine (used to treat overdoses) acidic; alkaline
What is clearance (Cl)? amount of blood or other fluids from which all drug is removed per unit time
Define half-life (t1/2) dosing regimen to achieve steady-state concentration of drug in blood; 4-5 half lives to get steady state concentrations
Describe a dose response curve. x: dose (Log scale); y: response; very low dose: no response-->threshold to see response -->reach maximal efficacy where no increase in response occurs; provide information about dose range over which drug is effective
Describe a graded dose response curve. Dose (log) vs. Effect; note EC50, Emax; involves one patient;
What is the EC50? The dose in a patient that will result in half the maximal effect (Emax is maximal efficacy).
What is potency? If this is increased, the drug requires a lower dosage to produce the same effect as a higher dosee of a second drug. It is determined by affinity for its receptor & the ability of a drug to reach its site of action
How is efficacy determined? By the type of interaction with the receptor & limitations on the amount that can be administered
Describe a quantal dose-response curve. biological variability among people -->populations; y-axis ends in -ing; Dose (log)vs. %people responding; normal curve; hyperreactive (low dose) to hyporeactive (high dose)
List some variations in drug response. alteration in drug concentration reaching receptor, tolerance, changes in components of response after drug binds to the receptor
What is idiosyncratic biological variability? Infrequently observed drug effect.
What is hypersensitivity (describing biological variability)? allergic reaction to a drug
What is tolerance (describing biological variability)? time related loss of response to a drug (weeks-->months)
What is tachyphylaxis related to biological variability? tolerance that happens very quickly (minutes-->hours)
Describe the cumulative dose-response curve. Dose vs. % responding; ED50 curve & TD50 curve with limits of beneficial/toxic
What is ED50? Median effective dose, 50% population responds in a specified manner
What is TD50? Median toxic dose; 50% of population exhibits adverse effects
What is LD50? Median lethal dose; 50% animals studied result in death
What is the therapeutic index? TI= TD50/ED50 (in animal studies LD50 can replace TD50); indicates drug safety; greater TI is considered safer
Therapeutic Index examples: acetaminophen (?); asprin (?); meperidine (demerol) (?); methotrexate (chemo agent) (?) acetaminophen (27); asprin (1); meperidine (demerol) (8); methotrexate (chemo agent) (1)
What are some factors that alter pharmacokinetics/pharmacodynamics? age (liver/kidney function, total body water/fat), sex, pregnancy, body size, genetic factors, body size, genetic factors, drug interactions, disease processes, drug characteristics
What are some basic properties of drug receptors? drugs bind to receptors to produce effects; drug + receptor = drug - receptor complex-->response; when a drug binds it mimics or blocks the action of endogenous regulatory molecules
What are some basic functions of receptors (proteins with unique binding sites)? Interact with endogenous and exongenous compounds; interpret a signal from the drug and transfer that information into effect
Can drugs give cells new functions? NO...they alter pre-existing processes by exploiting the fact that compounds can be administered from an external source to achieve receptor interaction & possible cellular effect
List some factors that determine interactions between drug and receptors. size and shape of drug, electrostatic attraction, configuration of the receptor, ability of the drug to reach the receptor
What is affinity? It refers to the attraction between a receptor and a ligand
What does efficacy refer to? The ability of a ligand to bind to the receptor, activate it, and lead to some physiological response
What is an agonist? a drug that binds to the receptor and causes a response, has both efficacy and affinity (partial agonist has affinity but lacks full efficacy)
What is an antagonist? a drug that binds to the receptor without a response, has only affinity, classified as competitive or noncompetitive
What is a competitive antagonist? a drug that competes for the same binding site as the agonist and can be overcome (reversible)
What is a noncompetitive antagonist? a drug that is irreversible, and cannot be displaced by the agonist; effect long lasting; must recycle receptor complex to reactivate
What are three classifications of receptors? intracellular, membrane bound (Ion channel linked), G-protein coupled
In the cell signal cascade, the signals allow the cell to.... recieve a message, translate message through transduction
What are some examples of second messengers? cAMP, cGMP, NO, DAG, IP3
What are the steps in signal transduction? A ligand binds to the receptor--> receptor propagates the signal --> proteins are turned on & mobilize second messenger molecules -->second messengers activate other proteins that carry the signal further --> physiological response --> termination
In terms of receptor regulation, an increase in stimulation does what to receptor function? decreases receptor function (decreased stimuulation= increased receptor numbers and sensitivity)
What are some factors involved in drug interactions? polypharmacy, intensified therapy, intensified side effects, decreased therapy, decreased side effects, unique response
What are some mechanisms of drug-drug interactions? direct chemical/physical interaction, pharmacokinetic interaction, pharmacodynamics, combined toxicity
What are some possible drug-food interactions? decreased absorption, increased absorption, grapefruit juice, increase toxicity (MAO inhibitors & tyramine), meal times, herbal supplements
Created by: mpost51
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