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General Principles of Pharmacology
Module I
81
Pharmacology
Graduate
01/08/2012

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Term
Clinical Pharmacology
Definition
The study of the effect of drugs in man (as compared to animal or comparative pharmacology). The emphasis is on the drug and its uses.
Term
Pharmacotherapeutics
Definition
Deals with use of drugs in prevention & treatment of disease, usually to alleviate symptoms or sometimes to alter the course of the disease. The emphasis is on the disease and the treatment thereof.
Term
Therapeutic index
Definition
The relative toxicity of a drug is expressed as the therapeutic index. Most commonly in pharmacology this is the ratio of the dose capable of killing 50% of animals (LD50) over that required to achieve a beneficial effect in 50% of the animals (ED50). In clinical terms a drug that has a "small therapeutic index" has little differences between the therapeutic dose and the dose that causes toxicity (ex. Digoxin)
Term
Tolerance
Definition
Pharmacodynamic tolerance is hyporeactivity that occurs from chronic exposure to a drug (such as an opiod or alcohol. When tolerance develops, usually increasing doses are needed to provide a therapeutic effect. This is attributed to neuronal adaptation or cellular tolerance.
Term
Cross Tolerance
Definition
Cross Tolerance may develop between drugs within a class (e.g., opioids)or between drugs of different classes that produce similar pharmacologic effects (e.g., alcohol & inhaled anesthetics)
Term
Enzyme Induction
Definition
Stimulates enzymes to metabolize a drug faster.
Term
Down Regulation
Definition
Another reason for a need in increased dose is a decrease in the number or sensitivity of receptor sites after continued dosing (termed down regulation)
Term
Up regulation
Definition
Up regulation occurs in response to constant depression of receptors (as with beta blockers), the body may either increase the number of receptors or increase the sensitivity of receptors.
Term
Idiosyncrasy
Definition
Describes an unusual effect of a drug. A reaction you don't expect. In usually occurs in a very small percentage of patients and may not be related to the dose of the drug.
Term
Side Effect
Definition
Usually describes any action of the drug other than the desired (therapeutic) effect.
Term
Untoward Effect or Adverse Effect
Definition
Any noxious unintended and undesired effect that occurs at normal drug doses. The terms "side effect" and "adverse effect" are often used synonymously.
Term
Toxic Effect
Definition
The effect (usually expected) produced by large (toxic) doses of the drug.
Term
Food, Drug, & Cosmetic Act and Amendments
Definition
Administed by the FDA. This law was initially developed to improve quality and labeling of drugs. It has been updated through the years to test for toxicity, to restrict certain drugs to prescription use, and to prove the drug is safe and effective.
Term
Controlled Substances Act
Definition
Enforced by the Drug Enforcement agency (DEA), classifies potentially addictive substances into schedules (I through V) and sets requirements for documentation and storage of these substances as well as prescriptions orders and filling of such orders. The prescriber must register with DEA and receive a DEA number to prescribe scheduled drugs.
Term
C-I
Definition
Addictive substances with no approved use (ex. heroin)
Term
C-II
Definition
Highly addictive substances (ex. morphine and amphetamine). Prescriptions must be written and cannot be refilled.
Term
C-III & C-IV
Definition
Less addictive; may be prescribed orally and may be refilled up to 5 times in 6 months (ex. ASA with codeine C-III, Diazepam C-IV)
Term
C-V
Definition
Low addictive potential; some drugs may be sold OTC by pharmacists in some states.
Term
Pharmacokinetics
Definition
The quatitative study of the absorption, distribution, metabolism and excretion of drugs and their metabolites. In simple terms, what the body does to the drug.
Term
Passive Diffusion
Definition
The primary method of passage of drugs across plasma membrane. It is directly proportional to magnitude of concentration gradient of the drug across the membrane and lipid solubility of the drug. Polar molecules (ie. soluble in water) and ions cannot penetrate membranes.
Term
Active Transport
Definition
Characterized by selectivity, competitive inhibition by congeners (similar drugs or metabolites), a requirement for energy, saturability, and movement against and electrochemical gradient.
Term
Facilitated diffusion
Definition
Carrier-mediated transport process but there is no input of energy. The substance moves according to electrochemical gradient (some amino acids)
Term
Bioavailability
Definition
Defined as the fraction of unchanged drug reaching the systemic circulation following administration by any route.
Term
First Pass Effect
Definition
Refers to the rapid hepatic inactivation of certain oral drugs on their first pass through the liver.
Term
P-glycoprotein
Definition
A drug efflux system also found in enterocytes (there are a number of "drug transporters" found in the body.) It is not an enzyme but it excretes drugs back into the intestinal lumen and decreases absorption. It is found in the gut, kidney, and brain. It appears to have an important role in decreasing drug absorption from the gut, removing drugs from the brain and transporting drugs from the blood into the kidney tubules.
Term
First pass hepatic elimination
Definition
Destruction of a drug whether in the stomach, intestines, blood, or liver.
Term
Distribution
Definition
The process of a substance leaving the blood stream and moving to cells or tissues.
Term
1st order reaction
Definition
The body handles most drugs by this kind of reaction. The rate of absorption and elimination is proportional to concentration. The higher the blood concentration, the faster it is eliminated.
Term
Zero order
Definition
Few drugs operate according to this. The rate is independent of concentration. Ex. Alcohol, ASA, and phenytoin at therapeutic concentrations, are the best known drugs. Ex. Alcohol is eliminated at a rate of 10 cc/ hour regardless of the amount of alcohol consumed.
Term
What are some conditions that can lower plasma albumin?
Definition
Alcoholism, pregnancy, aging, CHF, malnutition, burns, trauma, large weeping decubitus ulcers, kidney and liver disease and many other conditions.
Term
Half-life
Definition
The time it takes for 50% of the drug in the body to be eliminated from the body. However, when we measure "half -life" we determine the time it takes plasma concentration to be reduced by 50%. This is more correctly termed the plasma elimination half-life.
Term
Clearance
Definition
The measure of the body's ability to eliminate a drug. It can be calculated.
Term
Steady State
Definition
Plateau in plasma concentration. With repeated drug administation it takes about 4-5 doses of drug administered for the half-life of the drug to reach a steady state.
Term
Loading Doses
Definition
A large initial dose that may be used to boost the drug concentration into the therapeutic range more quickly, especially if the drug has a large volume of distribution, a long half-life, or it is important to reach therapeutic concentration quickly.
Term
Cmax
Definition
Peak (maximum) blood level, max serum concentration
Term
tmax
Definition
Time to reach peak, time to reach Cmax
Term
t 1/2

Bt 1/2
Definition
Half life

Elimination half-life
Term
f
Definition
Bioavailability; percent of drug administered that is absorbed and reaches systemic circulation.
Term
Primary purpose of metabolism
Definition
With many exeptions it is to change lipid soluble active compounds (which are not readily eliminated from the body) to water soluble inactive compounds that can easily be excreted.
Term
Prodrugs
Definition
Drugs that are inactive as such and must be metabolized to active compounds (many of the ACE inhibitors, ex. lisinopril, are prodrugs)
Term
Cytochrome P-450 system
Definition
An important oxidizing enzyme system.
Term
Inducible
Definition
Certain compounds will increase enzyme activity.Increased enzyme activity generally will mean increased drug elimination and decreased effectiveness. Smoking is an enzyme inducer.
Term
Enterohepatic cycling
Definition
The liberated drug may be reabsorbed
Term
Excretion
Definition
The kidneys are the most important organs for elimination of drugs and their metabolites.
Term
Pharmacodynamics
Definition
The study of the relationship between the concentration of a drug and the response obtained in a patient. Simplistically, it is what the drug does to the body.
Term
Affinity
Definition
Attraction between a drug and its receptor or the ability of the agonist to combine to a receptor.
Term
Intrinsic activity (efficacy)
Definition
Ability of a drug to activate a receptor.
Term
Agonist
Definition
Binds to the receptor and causes a change in cellular activity. It has both affinity and efficacy.
Term
Antagonist
Definition
Binds to the receptor, causes no change in cellular activity and blocks the ability of endogenous substances or other drugs to bind to the receptor. It lacks efficacy.
Term
Receptors
Definition
Any functional macromoleculres in a cell to which a drug binds to produce its effects. Proteins in cell plasma membranes form the most important class of drug receptors.
Term
Dose-Response Curve
Definition
Typically, there is a direct relationship between:
a. Dose of drug administered
b. Resulting plasma concentration
c. Intensity of drug effect.
Term
Threshold Dose
Definition
When increasing the dose, the response increases. The first noticeable effect is the threshold dose.
Term
Potency
Definition
Refers to the position along the dose axis.
Term
Maximal efficacy
Definition
Reflects the limit of the dose-response relation on the response axis.
Term
Variability
Definition
Denotes appearance of differences in the magnitude of response among individuals in the same population given the same dose of drug.
Term
Median effective dose
Definition
The dose of drug to produce a specified intensity of effect in 50% of individuals
Term
Median lethal dose
Definition
The dose that is lethal to 50% of animals
Term
Placebo effect
Definition
Drugs are generally more effective when the patient has a poitive attitude. Exaggeration or antagonism of a drug effect can result from the placebo effect.
Term
Compliance
Definition
Probably the most common cause of drug failures or toxicity is lack of compliance. Noncompliance may be the result of a misunderstanding, a failure of communication, the cost of the drug, or due to a pt's concern about the seriousness of the disease and their belief in the medication. The terms adherence and compliance are often used synonymously.
Term
Category A
Definition
No fetal harm in studies in women
Term
Category B
Definition
No fetal harm in animals; no studies in women
Term
Categoy C
Definition
Fetal harm in animals; no studies in women
Term
Category D
Definition
Fetal harm in studies in women; weigh risk vs. benefit
Term
Category X
Definition
Definite fetal harm in studies in women. Contraindicated.
Term
Drugs with definite teratogenic potential
Definition
Alcohol, androgens, antineoplastics, oral anticoagulants, diethrylstilbestrol, smoking and thalidomide. Category X include aminopterin, dienestrol, diethrylstilbestrol, dihydrostreptomycin, disulfiram, ergotamine, estrogen, halothane, iodine, isotrentinoin, methyltestosterone, progestins, quinine, thalidomide, and trimethadone. Teratogenic drugs include phenytoin, carbamazepine, valproic acid, lithium, warfarin, retinoids, and danzol.
Term
Adverse reaction
Definition
Any response (to a drug) that is noxious and untended, that occurs within a reasonable time of administration, and that occurs at doses used in man for prophylaxis, diagnosis, or therapy, excluding failure to accomplish the intended purpose.
Term
Type A or mechanism based adverse reaction
Definition
Undesired effects closely related to pharmacological action of drug and may be termed side effects.
Term
Type B or off-target reactions
Definition
Undesired effects unrelated to known pharmacological action of drug. These reactions are usually unpredictable, not always dose dependent, have low incidence but are sometimes severe. These include allergic reactions.
Term
Drug-drug interaction
Definition
A drug interaction is the phenomenon that occurs when the effects or kinetics of one drug are altered by the prior or concomitant administration of another drug. Although drug interactions are usually thought of as detrimental some are beneficial.
Term
Object drug
Definition
Drug whose action or kinetics are altered. Main characteristic is a narrow therapeutic window.
Term
Precipitant drug
Definition
Drug causing altered action
Term
Important Object drugs
Definition
Aminoglycoside antibiotics
Antiarrhythmics
Carbamazepine
Cyclospoine
Digoxin
Hypoglycemics
Lithium
Phenytoin
Theophylline
Warfarin
Term
Precipitant Drugs
(Absorption)
Definition
Antacids
Cholestyramine
Term
Precipitant drugs
(Enzyme Inducers)
Definition
Carbamazepine
Phenobarbital
Phenytoin
Rifampin
Term
Precipitant Drugs (Enzyme inhibitors)
Definition
Cimetidine Erythromycin Isoniazid Azole antifungals Verapamil Ciprofloxacin Grapefruit juice Ritonavir +
Term
Drug Abuse
Definition
Any use of a drug for nonmedical purposes, usually for altering consciousness but also for bodybuilding
Term
Drug Misuse
Definition
A drug might be to take it for the wrong indication, in the wrong dosage, or for too long a period.
Term
Drug
Definition
A drug is any substance which, when introduced into the body, produces a physiological change, a biological change, a decrease in population of resident or invading microorganisms, or a decrease in abnormal tissue development.
Term
Orphan drugs
Definition
The Orphan Drug act of 1983 provides incentives for the development of drugs for treatment of diseases affecting fewer than 200,000 patients in the US, or for research using commonly available (nonpatentable) chemicals for treatment of specific diseases. The incentives (usually tax breaks) are to encourage companies to do research for which they are unlikely to recoup their costs.
Term
Metabolic tolerance
Definition
Defined as decreased response to a dose of a drug which develops because of an increease in rate of elimination of the drug (enzyme induction is an example) The opposite can also occur, that is enzyme inhibition and you can develop toxicity. With enzyme induction the enzymes are stimulated to metabolize the drug faster so that the usual dose is no longer effective. Need to increase the dose.
Term
Tachyphylaxis
Definition
Rapid tolerance to the effect of some drugs
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