Term
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Definition
-The component of a cell or organism that interacts with a drug
–Initiates the chain of biochemical events leading to the drug’s observed effect
–Plays a regulatory role in the drug molecule interaction with specific molecules in the biological system |
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Term
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Definition
–Molecule that binds to a receptor
–Involved in chemical signaling
Examples
•Neurotransmitter
•Hormone
•Drug
•Messenger molecule |
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Term
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Definition
| The study of substances that interact with living systems through chemical processes |
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Term
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Definition
| Deals with the undesirable effects of chemicals on living systems |
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Term
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Definition
–Study of the biochemical and physiologic effect of drugs and their mechanism of action
–The actions of the DRUG on the BODY |
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Term
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Definition
–The actions of the body on the drug- how body moves drug thru out itself
–Involves absorption, distribution, metabolism and elimination (ADME)
-the actions of the BODY on DRUG |
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Term
| Pharmacogenomics (pharmacogenetics) |
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Definition
| The study of genetic variations that cause differences in response among individuals or populations |
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Definition
| Insertion of appropriate “healthy” gene into somatic cells |
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Term
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Definition
| bread to have homozygously complete suppression of studied function |
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Definition
| Over expression of proteins of interest |
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Term
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Definition
| Drug that is synthesized within the body |
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Term
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Definition
| Drug that is made of chemicals outside of the body |
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Term
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Definition
| Poisons of biologic origin, Harmful effects |
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Term
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Definition
| Drugs bind to and activate the receptor, Directly or indirectly brings about the effect |
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Term
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Definition
| Binds to the receptor and prevents binding by other molecules- BLOCKER |
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Term
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Definition
the penetration of a permeate (such as a liquid, gas or vapor) through a solid
Types of permeation:
•Aqueous diffusion
•Lipid diffusion
•Transport by special carriers
•Endocytosis and pinocytosis |
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Term
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Definition
–Occurs within the larger aqueous compartments of the body
–Across epithelial membrane junctions
–Through aqueous pores of the endothelial lining of blood vessels (i.e. between the blood and extravascular space)
–Governed by Fick’s Law |
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Term
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Definition
–Most important limiting factor for drug permeation is lipid barriers
–The ability to move from aqueous to lipid (or lipid to aqueous) varies on the pH of the medium
–Governed by Fick’s Law |
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Term
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Definition
–Exist for certain substances that are important for cell function
•Amino acid carriers in the blood-brain barrier
•Weak acid carriers in the renal tubules
–May be too large to diffuse passively through the membrane
–Not governed by Fick’s Law and is capacity-limited
–Multidrug-resistance type 1 (MDR1) transporter
•Also known as P-glycoprotein
•Found in the brain, testes, other tissues and some neoplastic cells
•Cancer drug resistance in GI tract epithelium |
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Term
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Definition
Involves passive diffusion of molecules down a concentration gradient
(equation is not on this card!)
•Quantifies “common sense” relationships
–Drug absorption occurs faster from organs with large surface area (large intestine) vs. organs with small absorbing areas (stomach)
–Drug absorption is faster from organs with thin membrane barriers (lungs) than from those with thick membranes (skin) |
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Term
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Definition
•Weak acids are usually excreted faster in alkaline urine
•Weak bases are usually excreted faster in acidic urine
•Other fluids where pH can cause “trapping” include stomach, small intestine, breast milk, aqueous humor, vaginal and prostatic secretions |
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Term
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Definition
| The component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drug’s observed effect, Largely determine the quantitative relationships between dose or concentration of drug and pharmacologic effects, Are responsible for selectivity of drug action (Size, Shape, Electrical charge) |
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Term
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Definition
May be inhibited or activated by binding to a drug
Example: dihydrofolate reductase is targeted by MTX |
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Term
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Definition
A protein involved in the movement of a chemical across a biological membrane
Example: Na/K ATPase is the membrane receptor for digitalis |
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Term
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Definition
Those proteins with the primary purpose of producing the essential structural components of the cell
Example: tubulin is the receptor for colchicine |
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Term
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Definition
–A receptor antagonists that binds to a receptor, but does NOT activate it
–Progressively inhibit the agonist responses |
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Term
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Definition
| Antagonist’s affinity for the receptor may be such that the receptor is unavailable for binding to agonist, binds forever: ex) asprin |
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Term
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Definition
–Produces a lower response at full receptor occupancy
–Response similar to that when a competitive antagonist irreversibly blocks some of the receptor sites |
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Definition
| Produces a full response at full receptor occupancy |
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Term
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Definition
Ionically binds to drug to make it unavailable for interaction with receptors or other substances
Example: protamine (positively charged) binds to heparin (negatively charged) to reverse/stop anticoagulant effects of heparin |
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Term
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Definition
| fraction of unchanged drug reaching the systemic circulation following administration by any route |
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Term
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Definition
| Reduction in bioavailability of drug in systemic circulation due to drug metabolism in gut wall, liver, and portal blood. Effect of first pass hepatic elimination on bioavailability is expressed as extraction ratio (ER=Clearance of liver/hepatic blood flow) |
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Term
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Definition
| measure of the ability of the body to eliminate the drug; quantifies elimination; single most important factor in determining drug concentrations |
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Term
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Definition
| measure of the apparent space in the body available to contain the drug |
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Term
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Definition
-Clearance is constant over concentration range
-elimination is not saturable
-Rate of drug elimination is directly proportional to concentration |
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Term
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Definition
| Occurs by excretion and metabolism |
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Term
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Definition
| When drugs ionize in solution, setting the preface for absorption |
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Term
| Diseases affecting drug metabolism |
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Definition
-renal
-hepatic
-cardiac
-pulmonary
-endocrine |
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Term
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Definition
| The maximum dose at which a specific toxic effect is not seen |
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Term
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Definition
| The smallest dose that is observed to kill any experimental animal |
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Term
| Median Lethal Dose (LD50) |
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Definition
| The dose that kills approximately 50% of the experimental animals |
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Term
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Definition
| Patients tend to respond positively to any therapeutic intervention |
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Term
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Definition
| Trials are nonblinded or “open” |
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Term
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Definition
| Uses a placebo or dummy medication |
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Term
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Definition
| Identity of medication is controlled by a third party (two identical bottles, different drugs) and not revealed until all clinical data is collected |
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Term
| Phase 1 of clinical trial |
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Definition
-check drug effects in small group (25-50) healthy volunteers
-Nonblinded, open trials
-Find maximal tolerated dose and to avoid severe toxicity
-Pharmacokinetic measurements |
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Term
| Phase 2 of Clinical Trial |
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Definition
-To determine efficacy in modest number of patients (100-200) who have the target disease
-Single-blind design
-Detect a broader range of toxicities |
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Term
| Phase 3 of Clinical Trial |
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Definition
-To further establish safety and efficacy in large number of patients (100s-1000s) with target disease
-Double-blind, crossover technique
-Designed to minimize errors caused by placebo effects, variable course of disease, etc. |
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Term
| New Drug Application (NDA) |
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Definition
| If phase 3 results meet expectations an NDA is submitted to FDA to request permission to market new agent in US |
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Term
| Phase 4 of Clinical Trial |
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Definition
-Monitoring safety of a new drug under actual conditions of use in large number of patients
-Dependent on careful and complete reporting of events by physicians and patients
-Many important drug-induced events have an incidence of 1/10,000, so may not be detected until phase 4 trials |
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Term
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Definition
| Provides exclusive rights to market the drug |
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Term
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Definition
| can legally protect the brand (proprietary/trade) name indefinitely |
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Term
| Adverse Drug Reactions (ADR) |
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Definition
-Harmful or unintended response
-must be reported to FDA before approval |
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Term
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Definition
Notice of Claimed Investigation Exemption for a New Drug
Includes: 1) info on composition and source of drug
2) chemical and manfg info
3)animal study data
4) clinical plans and protocol
5) names/credentials of physicians conducting trials
6) key data relevant for human studies |
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Term
| How do you measure creatinine clearance? Why? |
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Definition
| Compare creatinine levels in urine with levels in blood. Tells if kidneys are functioning properly |
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Term
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Definition
| concentration that will produce the desired therapeutic effect |
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Term
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Definition
| Used to measure estimated Creatinine clearance rate |
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Term
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Definition
| Vd=amount of drug in body/concentration of drug |
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Term
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Definition
| study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes |
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Term
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Definition
Intrinsic ability of the body or its organs of elimination to remove drug from the blood or plasma
CL = rate of elimination/ drug concentration |
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Term
| Organs important in clearance |
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Definition
Kidneys, liver
also lungs, blood, and muscle |
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Term
| Capacity limited elimination |
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Definition
| Clearance varies depending on concentration of drug achieved (saturable elimination) |
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Term
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Definition
| Time required to change the amount of drug in the body by one-half during elimination |
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Term
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Definition
| Occurs if dosing interval of drug is shorter than 4 half-lives |
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Term
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Definition
| Rate is independent of amount of drug remaining in gut (ie: determined by gastric emptying or controlled-release formulation) |
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Term
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Definition
| Rate is proportional to gastrointestinal concentration (more drug there, more it will be absorbed) |
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Term
| IV Administration of drugs |
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Definition
| most rapid onset, 100% bioavailability |
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Term
| Transdermal Administration |
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Definition
| very slow absorption, bypasses first pass mechanism, prolonged effect, 80-<100 bioavailability |
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Term
| Inhalation Administration |
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Definition
| very rapid onset; 5-<100% bioavailability |
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Term
| Which administration techniques bypass 1st pass? |
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Definition
Sublingual
Transdermal
Rectal |
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Term
| Most convenient method of drug administration? |
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Definition
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Term
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Definition
| administrating a drug in such a way to maintain a steady state of drug in the body |
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Term
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Definition
| Point at which no matter how high drug concentration goes, no further increment in response is achieved |
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Term
| Three factors influence clearance? |
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Definition
1) dose
2) organ blood flow
3) intrinsic function of liver or kidneys |
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Term
| 3 factors affecting protein binding? |
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Definition
1) Albumin concentration
2) Alpha-acid glycoprotein concentration
3) capacity-limited protein binding |
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Term
| What type of products are more easily excreted? |
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Definition
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Term
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Definition
-Occurs between absorption and renal elimination
-Some occur in intestinal lumen or intestinal wall
-All reactions assigned to two major categories
1)Phase I reaction
2)Phase II reaction |
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Term
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Definition
| P450 enzyme that metabolizes over 50% of clinically prescribed drugs metabolized by the liver |
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Term
| Individual differences in drug metabolism determined by: |
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Definition
Age
Sex
Liver size
Liver function
Circadian rhythm
Body temperature
Nutritional and environmental factors |
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Term
| Increased susceptibility to pharmacologic or toxic activity of drugs if patient is: |
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Definition
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Term
| Time-plasma concentration curves |
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Definition
| The time course of drug concentration after an instantaneous IV bolus or an oral dose in the one-compartment model |
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Term
| Pharmacokinetics things to keep in mind: |
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Definition
-Renal Clearance
-Volume of Distribution w/respect to age
-Half-life
-Protein Binding
-Bioavailability
-Some instances pH (ex w/Phenytoin), Albumin (ex w/Phenytoin) |
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Term
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Definition
-Tendency to accumulate in the hydrophobic core of the membranes (concept of partition coefficient)
-Important because of CNS penetration |
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Term
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Definition
| Natural or synthetic Antimuscarinic Agents inhibit acetylcholine neurotransmitter action at muscarinic receptors |
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Term
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Definition
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Term
| Cyclooxygenase Inhibitors |
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Definition
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Term
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Definition
| statins that lower cholesterol |
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Term
| Factors affecting drug distribution: |
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Definition
Solubility
Permeability
pH and pKa
Lipophilicity |
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Term
| Examples of natural ligands: |
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Definition
| ACh, Serotonin, GABA, glutamate |
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Term
| Ligand gated channels: ACH mechanism |
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Definition
| ACh causes Nicotinic Acetylcholine receptor (AChR) to open which allows Na+ to flow |
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Term
| Examples of Ion channel blockers: |
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Definition
| calcium channel blockers, sodium channel blockers |
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Term
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Definition
| Excitatory neurotransmitter used by the spinal cord to control muscles and by the brain to control memory |
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Term
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Definition
Usually Inhibitory neurotransmitter that produces feelings of pleasure
Multiple functions |
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Term
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Definition
| Major inhibitory brain neurotransmitter |
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Term
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Definition
| Common brain excitatory neurotransmitter |
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Term
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Definition
| Inhibitory neurotransmitter |
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Term
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Definition
| A hormone and a neurotransmitter, in the PNS it is part of the “fight and flight” response. Usually excitatory but inhibitory in brain areas Causes Vasocntxn to increase bp |
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Term
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Definition
| Receptors that respond to group of peptide ligands including growth hormone, EPO, interfons, etc; Cytokines are small secreted proteins that control many aspects of growth and differentiation of specific types of cells |
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Term
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Definition
| acts as intracellular messanger, mediates hormonal responses such as mobilization of stored energy |
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Term
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Definition
| To derive maximal benefit with minimal toxicity or damage to tissues |
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Term
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Definition
| the maximum effect of a drug |
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Term
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Definition
| Amount of drug (usually expressed in milligrams) needed to produce an effect, such as relief of pain or reduction of blood pressure |
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Term
| Quantal dose-effect curves |
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Definition
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Term
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Definition
| Relates dose of a drug required to produce a desired effect to that which produces an undesired effect |
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Term
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Definition
| Potential maximal therapeutic response a drug can produce |
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Term
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Definition
| measure of the tightness that a drug binds to the receptor |
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Term
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Definition
| measure of the ability of a drug once bound to the receptor to generate an effect activating stimulus and producing a change in cellular activity |
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Term
| Factors influencing concentration of drug: |
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Definition
Age
Weight
Gender
Disease state
G6PD deficiency |
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Term
| Factors influencing drug concentration: |
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Definition
Gastritis, Enteritis
Liver function (Cirrhosis, Hepatitis)
Renal function (BUN, Creatinine, Stenosis)
Cardiac function (HTN, Cardiac failure) |
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Term
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Definition
| No drug causes only a single specific effect |
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