Term
| the study of drugs: drug action, origin, source, chemical structure, physical characteristics, drug metabolism and excretion, therapeutic use of drugs. |
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Definition
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Term
| pharmacology is an ____ science |
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Definition
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Term
| neuropharm, immunopharm, cardiovascular pharm, resp pharm, and GI pharm are all types of ___ categories |
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Definition
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Term
___ - active ingredient in medicine
___ - formulation of drug into specific delivery system (tab, capsule, etc) |
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Definition
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Term
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Definition
natural substances - hormones
everyday substances - caffeine
synthetic chemicals - aspirin
recreation substances - alcohol |
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Term
| main source of drugs prior to 1930 |
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Definition
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Term
| synthetic drugs use these two fields to produce drugs |
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Definition
| medicinal chemistry and biotechnology |
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Term
| trangenic animals producing drugs |
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Definition
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Term
| 3 main properties of an ideal drug |
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Definition
| effectiveness, safety, selectivity |
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Term
| what are some common desired properties of the ideal drug |
|
Definition
reversible action
chemical stability
predictability
ease of administration
freedom from drug interactions
possession of simple generic name
low cost |
|
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Term
|
Definition
Chemical (IUPAC) - description of drug using chemical nomenclature
generic name: subgroups/families that have similar nomenclature to make it easier to identify site of action
Trade/brand/manufacturer name - proprietary name created by pharm company |
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|
Term
what are some common examples of nomenclature used for generic names?
____: drugs that end in -olol
____: drugs that end in -mab
___: drugs that end in -cillin |
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Definition
-olol: B-adrenergic antagonist
-mab: antibody based
-cillin: penicillins |
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Term
| what are the 4 categories of administration of a drug and what does method depend on |
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Definition
oral
injection
inhaled
topical |
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Term
| 4 main categories of drug targets and an example of each |
|
Definition
Protein targets (major target): enzymes, carrier molecules, ion channels, receptors
DNA targets: chemo drugs and antimicrobials
RNA targets: antivirals
Lipid membranes: alcoho, amphotericin B |
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Term
| explain the major steps in drug discovery and development from identification to FDA approval |
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Definition
drug discovery --> compound indentification and optimization
drug development --> biological characterization and tox studies |
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Term
___: compounds that pass screen and bind to the target, include compound-based drug design and target-based drug design
___: further biological and chemic characterization shows promise. molecules need to be soluble but not extremely hydrophilic (metabolically active) |
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Definition
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Term
2 strategies to identify "hits"
1. ___: traditional approach. advantages: biological activity high, easier to isolate than synthesize, gives starting point for making derivatives. disadvantages: lots of effort to get enough products (small yield), expensive.
2. ___: more common. advantages: easier, shotgun approach, tailor libraries to receptor classes. disadvantages: low biological activity |
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Definition
compound-based drug design
target-based durg design
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Term
| low absortpion, high metabolism --- is this high or low biological activity |
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Definition
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Term
| the ___ approach to drug design uses a large library and high-seed automated assay (>10,000) to screen thousands of compounds a day. Employs the ___-based method of drug discovery. |
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Definition
shotgun approach
target-based
(You shoot the shotgun at the target) |
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Term
___ is a division of target-based method known as rational drug design that designs a drug candidate from nuclear magnetic resonance (NMR) or crystal structure of target. identify active binding residues and improve the fit to make a more potent agonist or anatgonist (noncompetitive).
what's a disadvantage? |
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Definition
structure-based drug design
disadvantage: harder to synthesize compounds and requires known structure of target |
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Term
___ is characterization and refining of lead drug's pharmacologic properties, try to select the best molecule to move to drug development and clinical testing, imrpove ADME characteristics.
terminating factors: no efficacy in animal model, low bioavailability and metabolism creates dangerous metabolites, low solubility, toxic effects in animals, molecule damages DNA, not cost-effective |
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Definition
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Term
| explain the importance of preclinical drug development |
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Definition
| production of drug for testing: animal toxicology and pharmacokinetics (safe for humans?), detailed planning of clinical trials, submit INDA (investigal new drug application) |
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Term
| what are the clinical phases of drug development and the purpose of each? |
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Definition
Phase I: safety exposure and tolerance
Phase II: efficacy and dose selection, continue safety monitoring
Phase III: survival, improved fxn, and improved comfort
Phase IV: approved by FDA but continued safety and efficacy monitoring, mostly drugs on fast-track model |
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Term
___ - (1906) act that required drugs to meet purity and quality standards
___ - (1930)
___ - (1938) over 100 died from strep elixer so this act required premarket approval of new drugs
___- 1951 gives FDA authority to tell whcih drugs need Rx
___ - 1962 requires proof of safety and efficacy and reporting of adverse effects
___ - 1992 fast track approval but post market surveillance |
|
Definition
pure food and drug act 1906
FDA 1930
Food, drug, and cosmetic act 1938
durham-humphrey amendment 1951
kefauver-harris amendment 1962
expedited drug approval act 1992 |
|
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Term
| what are the names of the documents that need to be submitted for approval by the FDA before and after clinical trials? |
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Definition
IND - investigational new drug
NDA - new drug application |
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Term
| ___ is the quantitative description of the effects of a drug on the body. receptor-target variations |
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Definition
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|
Term
| what characteristics can the pharmacodynamics of a drug provide? |
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Definition
| appropriate dosage, potency, efficacy, and safety |
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Term
| What is Kd and how is it calculated? |
|
Definition
dissociation constant for a drug. concentration of ligand when 50% of receptors are occupied
Calculated: drug amount x receptor amount/amount of drug-receptor binding |
|
|
Term
what is the relationship of Kd to drug-receptor binding?
LR crap |
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Definition
|
|
Term
| what is the relationship to receptor occupancy and patient response? |
|
Definition
pt response is proportional to concentration of receptors occupied
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Term
___: describes the effects of various doses of drug on an individual
___: describes effects of various doses of a drug on a population of individuals |
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Definition
graded dose-response
quantal dose-response |
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Term
| what does the EC50 of a drug tell you from the dose-response curve? |
|
Definition
measure of POTENCY
amount needed to elicit 50% of the maximal effect |
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Term
| What does the TC50 and LC50 tell you about a drug in relation to its EC50? |
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Definition
TD50 - dose at which 50% of the population experience toxic (adverse) effects
LD50 - lethal to 50%
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Term
| What is the maximal response for a drug? |
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Definition
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Term
| ____: are when Emax is 100% with less tahn 100% of receptors bound. |
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Definition
| spare receptors (most commonly G-protein) |
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Term
| What type of drug favors binding the active site of a receptor? |
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Definition
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Term
| what type of drug favors preventing the active state of a receptor? |
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Definition
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Term
| define the different classifications of antagonists and tell which is reversible and irreversible |
|
Definition
competitive - reversible
noncompetitive - irreversible
allosteric - reversible or irreversible |
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Term
| how do noncompetitive antagonsits effect potency and efficacy? |
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Definition
| reduce efficacy, maintain potency |
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Term
| what is a partial agonist and how does it affect response when combined with a full agonist? |
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Definition
partial agonist - binds all active sites (receptors) but does not result in maximum efficacy.
partial agonist + full agonist = less than maximal response |
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Term
| this drug stabilizes both the active and inactive receptor states |
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Definition
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Term
| A drug that results in Emax has to be what kind of agonist? |
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Definition
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Term
| This drug reduces the constituatively active receptor. |
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Definition
| inverse receptor agonists, BCR-abl tyrosine kinase |
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Term
| effect of spare receptors is due to what process in the cell? |
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Definition
| amplification of signal, seen in G protein receptors and tyrosine kinase or when the receptor is still active after agonist leaves |
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Term
| what is it called when the thearpeutic response is compared to the adverse effects? |
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Definition
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Term
| How is therapeutic index calculated? |
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Definition
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Term
| Is it better for a drug to have high or low TI? |
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Definition
| high - more dosing options |
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Term
| this is measuring and mintoring effectiveness for a specific drug... is repressented by ADME |
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Definition
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|
Term
| what are the barriers that affect absorption? |
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Definition
biological membranes (phosopholipid bilayer and cholesterol)
BBB (tight junctions) |
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Term
| What are the 3 mechanisms used for drugs to cross the membranes? |
|
Definition
active transport
passive transport
simple diffusion |
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Term
| What are OAT and OCT and how do they work? |
|
Definition
OAT - organic anion transporter
OCT - organic cation transporter
solute-linked carriers that pass polar drugs across the membrane via facilitated and active diffusion |
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Term
| if a drug crosses a membrane by diffusion, what are the factors that affect its diffusion? |
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Definition
gradient
membrane thickness
area
permeability |
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Term
| What is pH trapping and how does it aid in absorption? |
|
Definition
pH trapping - when low pH is pushed to electrically neutral pronated form, crosses a membrane, and then deprotonates, making it charged and unable to cross back to the other side (stays in gastric mucosal barrier)
helps increase availability of the drug |
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Term
| what are some special limitations to the BBB and how can it be bypassed? |
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Definition
tight jxns prevent diffusion into CNS
overcome by small hydrophobic drugs or by using special transporter proteins
intrathecal injections (injected straight into CSF) bypasses barrier |
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Term
| ___ is the measure of a drug's absopriton |
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Definition
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|
Term
| when is bioavailability 100% versus less? |
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Definition
100% for IV injections immediately, then decrease with time.
All other routes are less |
|
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Term
| 4 mechanisms of drug administration |
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Definition
enteral (oral)
parenteral
mucous membrane
transdermal |
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Term
| which method of administration has first-pass metabolism? |
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Definition
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Term
| which method of drug administration is the simplest by requires GI absorption? |
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Definition
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|
Term
| whch method of drug administration has the highest bioavailability and fastest dlivery? |
|
Definition
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Term
| for parenteral administration, onset rate depends on what characteristics? |
|
Definition
depends on location and vascularization
fastest: IV, intra-arterial, and intrathecal
IM
slowest: subcu |
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Term
| this method of drug administration is rapid, has no first-pass metabolism and has little limitations |
|
Definition
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Term
| this method of drug administration is limited to lipophilic drugs and has slow absorption by no first-pass metabolism |
|
Definition
|
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Term
| what are the two types of transdermal drug administrations and how do they differ? |
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Definition
transcutaneous - absorption across the skin direction into blood stream
topical -acts directly at site of administration |
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Term
| how does local diffusion rate affect absorption? |
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Definition
| highly vascularized faster availability, increased rate of distribution, decreased equilibrium, increased body mass increases distribution |
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Term
| how is drug distribution measured and what are some factors affecting drug distribution? |
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Definition
plasma protein binding preventing diffusion and decreasing volume of distribution
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Term
| what is the relaitonship of the drug distribution phase to the drug elimination phase? |
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Definition
most drugs distribute rapidly in the body
distribution phase (very quick decline), slower rate of decline (elimination phase)
distribtuion and elimination are faster wtih vascularity
diffusion back into blood as eliminated |
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Term
| where does most drug metabolism occur? |
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Definition
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Term
| why are lipophilic and hydrophobic drugs metabolized more? |
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Definition
| they can get past the membranes easier to enter hepatocytes |
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Term
| what is biotransformation and what is its purpoes? |
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Definition
| taking a drug from an active form to an inactive form by chemical modification |
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Term
| what are two forms of biotransformation and what can they do to the drug? |
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Definition
1. redox reactions (phase 1): add a hydroxyl group (-OH) via cytochrome P450
2. conjugation/hydrolysis reactions (phase II): adding either glutocuronate, sulfate, glutathione, or acetate conjugating the drug to a large polar molecule (conjugation) or adds H2O (hydrolysis) |
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Term
| explain the difference between phase I and phase II metabolic rxns |
|
Definition
phase I adds OH
phase II adds large polar group |
|
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Term
| what are the 4 main pathways for excretion of a drug? |
|
Definition
most to least:
renal
biliary
fecal
resp/dermal |
|
|
Term
| renal excretion is dependent on these three factors. how are they regulated? |
|
Definition
filtration rate: prevented by plasma protein binding, increased by increasing blood flow; depends on GFR
secretion rate: OAT and OCT transporters (penicillins)
Reabsorption rate: limited by pH trapping and urine flow |
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Term
| this excretion method allows the drug to undergo enterohepatic circulation |
|
Definition
|
|
Term
| what are the clinical applications of pharmacokinetics? |
|
Definition
maintaining drug concentrations at target
mulitple dosings
pharmacokinetic profile of drug |
|
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Term
| What are three pharmacokinetic characteristics of a drug required to calculate doseing/ |
|
Definition
| clearance, metabolism, half-life |
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Term
___ is the rate of metabolism and elimination relative to the plasma concentration and it limits time course of action of
drug
what affects this rate? |
|
Definition
clearance
metabolism and excretion measured in first order kinetics |
|
|
Term
| what is the difference between first order and zero order kinetics? |
|
Definition
first order - metabolism and secretion of drug is proportional to amount in plasma
second order - receptors are saturated so clearance rate remains constant |
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Term
| ___: term used for the measurement of clearance directly at the organ level? |
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Definition
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Term
| allows for an estimation of frequency of dosing |
|
Definition
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Term
| relationship btwn half life and volume of distribution and clearnace |
|
Definition
| decreased clearance or increased Vd = inccreased half life |
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Term
| 4 major factors affecting half life |
|
Definition
Vd - decreased wtih age
Vd - increased with obestiy
metabolism (clearance) - increased wtih CYP450 induction
metabolism (clearance) - decreased with CYP450 inhibition, cardiac, hepatic, or renal failure |
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Term
| when dosing a drug what are the most important factors to conisder? |
|
Definition
|
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Term
| what are two types of therapeutic drug dosing methods? |
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Definition
| continuous drug delivery and frequent small doses |
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Term
| change to a new steady state of a drug takes how many half-lives |
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Definition
|
|
Term
| what is a method of quickly acheiving a steady state with only 1-2 doses |
|
Definition
| laoding dose higher to compensate for distribution |
|
|
Term
| what is the most important when calculating a loading dose compared to a maintenance dose? |
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Definition
| clearance - you are only replacing the amount lost |
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Term
| What are 3 metabolic outcomes for a drug and the effects that have on the drug? |
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Definition
beneficial (activiation) - inactive prodrug converted to active drug
harmful (toxic) - active drug converted to active or toxic metabolite
ineffective (deactivation) - active drug converted to inactive drug. or to make it excretable. |
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|
Term
| 5 major sites for drug metabolism and which is the location of the most metabolism? |
|
Definition
liver (most)
GI tract
kidney
lungs
skin |
|
|
Term
| how does high first-pass metabolism affect bioavailability? |
|
Definition
| high first pass = low bioavailability |
|
|
Term
| what is the relationship btwn lipophilicity and bioavialability and excretion? |
|
Definition
| lipophilicity = enhanced bioavailability, and decreased excretion |
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Term
| Where do Phase I and Phase II rxns take place in hepatocytes? |
|
Definition
Phase I: ER
Phase II: ER and cytosol |
|
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Term
| What is the outcome of most Phase I reactions and what other molecules does it depend on? |
|
Definition
oxidation
CYP450, Fe3+, NADPH |
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Term
| This is the mechanism responseibly for the majority of phase I metabolism |
|
Definition
|
|
Term
| How can some drugs induce and inhibit the metabolism of other drugs? |
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Definition
| increased transcription, translation, or decreased degredation |
|
|
Term
| WHat is the outcome of inhibition of drug metabolism/ |
|
Definition
| drugs can rise to toxic levels |
|
|
Term
| What are xenobiotic receptors? |
|
Definition
bind foreign substances
Pregane X receptors (PXR)
Constituatively active/adrostane receptors (CAR)
aryl hydrocarbon receptors (AhR) |
|
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Term
| ___: when one drug causes another drug to be metabolized too quickly and thus its therapeutic effect is decreased |
|
Definition
|
|
Term
| Two ways to inhibit drug metabolism |
|
Definition
| competitive and irreversible inhibition |
|
|
Term
| what is an advantage of inhibition of metabolism |
|
Definition
| can allow drugs with high first pass metabolism to rise to therapeutic levels |
|
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Term
| Factors that affect drug metabolism? |
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Definition
pharmacogenomics: race, ethnicity, gender, age
diet and environment - grapefruit juice decreases first pass metabolism (makes drugs more potent)
metabolic drug interactions - slow/fast acetylators
disease affecting metabolism |
|
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Term
| what are different factors affecting drug variability |
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Definition
age, gender, ethnicity, disease state
genetics: drug target, transporter, metabolic enymes |
|
|
Term
| What are 3 main categories of genes that are altered to supply drug variability? |
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Definition
| drug target, transporters, metabolic enzymes |
|
|
Term
____: the study of the role of inheritance in the variation of drug response
___: the use of the knowledge of pts DNA to enhance pharmacotherapy, maximize drug efficacy, and reduce incidence of adverse drug effects |
|
Definition
pharmacogenetics
pharmacogenomics |
|
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Term
| there are about how many base pairs in the human genome? |
|
Definition
|
|
Term
| two main categories of variation in pharmacogenomics |
|
Definition
pharmacokinetics (ADME variation)
pharmacodynamics (target/receptor variation) |
|
|
Term
| what is the main target for genetic variation in pharmacokinetic variation and how does this affect drug activation and metabolism? |
|
Definition
metabolic enzymes - phase I and II.
involved in activating prodrugs and excretion of drugs |
|
|
Term
____: a variant with decreased rate of acetylcholine metabolism. it results in prolonged paralysis after succinylcholine use (used for muscle relaxation during intubation)>
___: causes people to be fast or slow acetylators |
|
Definition
BCHE (butyrylcholinesterase)
NAT2 (N-Acetyltransferase 2) |
|
|
Term
people who are slow acetylators tend to have what drug effect?
fast acetylators? |
|
Definition
slow: drug toxicity
fast: decreased efficacy |
|
|
Term
Pharmacogenomic biomarkers:
____: phase I enzyme that allows for metabolism of drugs and causes people to slow, extensive, or ultra metabolizers
___: phase II enzyme. associated with increased protein degradation and aggregation resulting in a need for decreased doses of drugs metabolized by this enzyme. |
|
Definition
CYP450 2D6
TPMT (thiopurine S-methyltransferase) |
|
|
Term
|
Definition
| slow, extensive, ultra metabolizers |
|
|
Term
CYP450 2D6 metabolizer variations:
____: homozygous recessive. don't metabolize drugs well so they have adverse effects at standard doses.
___: heterozygous/homozygous wild-type
___: have multiple copies of CYP450 2D6. metabolize drugs too quickly - need higher doses |
|
Definition
poor/slow metabolizers
extensive metabolizers
ultrarapid metabolizrers |
|
|
Term
| codein metabolism by poor and ultra metabolizers |
|
Definition
codeine has to be converted to morphine to work
slow metabolizers - codeine is ineffective because they are unable to metabolize to moprhine
ultra - codeine is toxic because it is metabolized to morphine too quickly |
|
|
Term
2 methods of genotyping the metabolic activity of pts:
____: administration of a prob drug and determination of the amount of probe drug metabolized
____: buccal swab or blood sample. PCR-based genotyping. used to determine whether pts are poor, intermediate, extensive, or ultrarapid metabolizers of CYP450 2D6 |
|
Definition
urinary metabolic ratio
amplichip CYP450 array |
|
|
Term
| what does TPMT metabolize? |
|
Definition
| 6-mercaptopurine and azathiopurine |
|
|
Term
| ____: variation not caused by differences in drug metabolism or targets but due to an interaction btween the drug and the unique physiology of the pt |
|
Definition
idiosyncratic rxns
ex: G6PDH dehydrogenase - protects RBCs from oxidative injury. associated with sickle cell |
|
|
Term
| what is the effect of supratherapeutic doses of a drug? |
|
Definition
|
|
Term
___: undesirable effects that are neutral or beneficial but do not cause a pt to stop taking a drug
___: can be a nuisance, cause harm or can be lethal and results in the unwillingness of the pt to take the drug |
|
Definition
side effect -
adverse effect |
|
|
Term
What are the mechanism of toxicity related to drug receptor binding and explain with they cause adverse effects:
____ - going to the right place but it is either turning on too much (agonist) or turning off too much (antagonist)
____: works on a diff area than desired, enantiomers also cause adverse effects by binding differently |
|
Definition
on-target adverse effects
off-target |
|
|
Term
| 4 mechanisms of toxicity related to harmful immune response |
|
Definition
hapten for small molecules
direct stimulation of larger molecules
hypersensitivity response (allergic)
autoimmune reaction |
|
|
Term
| a small molecule that binds a protein and can result in immune response |
|
Definition
|
|
Term
| toxicity for no known reason or with no known mechanism |
|
Definition
|
|
Term
two methods of drug toxicity:
___: supratherapeutic dose leads to toxicity
___: increase in pharmaceutical tx, increase in adverse drug-drug interactions can lead to change in pharmacodynamics or pharmacokinetic effects, increase in herbal remedies leading to change in pharmacodynamic or kinetic effects |
|
Definition
overdose
drug-drug interactions |
|
|
Term
| ____: when one drug changes ADME of another drug either by inhibition or induction of metabolism, alteration of transport mechanisms, or changes in plasma protein levels |
|
Definition
|
|
Term
| ____: when one drug affects the interaction and response of target or non-target receptors in another drug or when two drugs cause the same response by two different pathways |
|
Definition
|
|
Term
different types of cellular toxicity:
____: reduction of oxidized thiol groups on proteins causing denaturation, turns on repsonse in cell "heat shock" to repair the proteins, if not repaired will result in necrosis
____: DNA and drug interact, mostly reversed by repair mechnisms but if too much DNA damage is present can lead to apoptosis |
|
Definition
protein-drug adducts
DNA-drug adducts |
|
|
Term
different types of organ/tissue toxicity:
___: excessive organ damage that leads to deposits of collagen and EM proteins and eventually loss of organ fxn
___: caused by chemical or physical insult to DNA and/or damaged DNA not being repaired and result in neoplasia and clonal expansion
____ |
|
Definition
fibrosis
carcinogenesis
teratogenesis |
|
|
Term
| 3 stages of genetic changes required for carcinogenesis |
|
Definition
1. mutation in DNA repair or replication
2. inhibition of normal cell cycle (tumor suppression) and or induction of proto-oncogene cell cycles causing neoplastic growth
3. gain ability to move into blood stream |
|
|
Term
| FDA classification of teratogens |
|
Definition
class A: safe
Class X: proven teratogen |
|
|
Term
What occurs if a teratogen is given at each stage in fetal development?
week 0-3
week 3-8
week 8 |
|
Definition
week 0-3: embryonic death, spontaneous abortion
week 3-8: birth defect, affects basic body plan
week 8 on: affects growth and maturation of organs, not body plan |
|
|
Term
| study of deleterious effects on substances |
|
Definition
|
|
Term
3 areas of importance to toxicology and their areas of study:
1. FDLiminting exposure: occupational safety and env tox
2. identification and legal: analytic and forensic tox
3. exposure to xenobiotic toxin - acute and chronic tox |
|
Definition
|
|
Term
| 6 major types of acute xenobiotic tox |
|
Definition
gases - CO
acids/bases - Hydrofluoric acid (HF) from concrete
toxic mixtures - ammonia + bleach = pulmonary edema
pesticides = organophostphates, AChE inhibitors, pyrethroids, delay NA channel termination of AP
food contaminants - infective organisms (1-7 days), bacteral or algae (few hours)
toxic plants/fungi - amatoxins in muschrooms, psoralen isomers
|
|
|
Term
| 6 major types of chronic xenobiotic toxicity |
|
Definition
tobacco - benzo[a]pyrene (30% of all ca death)
ethanol
lead - neural toxicity (fetus to 7 y/o), blocks Ca channels, interferes wtih heme synthesis
cadmium - carcinogen, renal damage
dusts - asbestos and coal - carcinogenic, fibrogenic
|
|
|
Term
| 3 methods of tx for acute xenobiotic toxicity |
|
Definition
change toxicokinetic properties (decreased absorption, prevent toxication, increase metabolism or excretion)
inactivation by binding to antibodies or small molecules (antivenoms)
counteracting action at biochemical, cellular, or orgamismal levels (antidotes) |
|
|
Term
| 4 methods in toxicokinetic tx |
|
Definition
prevent absorption - gastric lavage, vomiting, charcoal dsorption
inhibit toxication - alcohol dehydrogenase inhibiton, fomepizole
detox
enhanced metabolism - increase conjugation
enhanced elimination - prevent kidney resoprtion, hemodialysis, hemofiltration, hemoperfusion, plasma exchange |
|
|
Term
heavy metal chelators:
____: bind gold, lead, arsenic, and mercury
___: binds lead
___: binds copper
___: binds iron
___: binds lead, arsenic, mercury, and cadminum |
|
Definition
dimercaprol - gold, lead, arsenic, mercury
edta - lead
penicillamine - copper
deferoxamine - iron
succimer - lead, arsenic, mercury, cadmium
|
|
|
Term
| this drug was originally rejected by the FDA but latera approved for the tx of heart failure in african americans |
|
Definition
|
|
Term
| this chemo drug is an estrogen antagonist used to tx breast ca has adverse effect of causing endometrial cancer due to its estrogen partial agonist activity at resceptors in endometrium |
|
Definition
|
|
Term
| phase 1 metabolic rxn responsible for 75% of drug metabolism and adds a hydroxyl group to drugs to make them more polar |
|
Definition
|
|
Term
| best toxicokinetic tx for ingestion of ehtylene glycol or methanol: ____ of metabolism via ethanol |
|
Definition
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Term
| gene target where most genetic variations arise |
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Definition
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Term
| reasons mutations in metabolic enzymes have a negative outcome on drug efficacy |
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Definition
increase inactivation
decrease activation of a prodrug
increase drug clearance
increase activation of a prodrug |
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Term
| the application of using a person's genetic makeup to maximize a drug tx |
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Definition
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Term
| metabolic pathway responsible for breakdown of neurotransmitters like NE and histamine |
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Definition
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Term
| chronic xenobiotic toxin causing 30% of all cancers |
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Definition
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Term
| chelation is an example of activation/inactivation tx |
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Definition
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Term
| ___ receptors are responsible for the regulation of CYP450 level in hepatocytes |
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Definition
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Term
| the ___ name of a drug is also considered the proprietary name |
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Definition
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Term
| ___: branch of pharmacology that develops methods of producing natural compounds by synthetic means |
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Definition
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Term
Advantages of ___-based drug discovery:
can screen compounds for agonists, antagonists,or modulatory fxn,
can use large libraries to screen for hits |
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Definition
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Term
| gene pharming - biotechnology |
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Definition
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| a natural drug used to treat malaria |
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Definition
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Term
| what is the target for most chemo drugs and some antimicrobials/ |
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Definition
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Term
spare receptors:
low amounts of noncompetitive antagonist = no decreased efficacy, high potency
high amounts - decreased efficacy and potency |
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Definition
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Term
| Gs binds to adenylyl cyclas to activate it and produce this second messenger |
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Definition
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Term
| ___ drugs require a transporter to get into a cell |
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Definition
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Term
| major class of transmembrane receptors with enzymatic cytosolic domains |
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Definition
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Term
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Definition
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Term
| determinant of drug selectivity where the specific receptor subtype is present int he target cell only |
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Definition
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Term
| ____ - inactivates the consitiuative activation of a receptor |
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Definition
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Term
| suicide substrates are usually irreversible due to a ___ bone |
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Definition
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Term
| ____ effect - when the drug selectivity is determined by the receptor-drug interaction only in a select type of ell |
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Definition
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Term
| factors that affect drug distribution directly |
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Definition
absoprtion
binding to plasma proteins
vascularization of target |
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