General Principles of Pharmacology Flashcards
What are the steps involved in the marketing of drugs?
Preclinical testing, clinical testing phases I, II & III, and Phase IV or post marketing surveillance
What does a drug need to be approved for marketing by the Food and Drug Administration (FDA)?
Drug must be shown by studies to be “safe and effective”
What is “indications?”
Conditions for the drugs use
What is “unlabeled” uses for drugs?
Therapeutic utility for different purposes or in populations other than those described in the package insert
Which group of people are considered “therapeutic orphans?”
Pregnant women, women of child bearing age, infants, and children
What is Bioavailability?
is the percentage of the dose of the drug administered by any route reaches the systemic circulation
What is bioequivalence?
equivalent release of the same drug substance from 2 or more drug products or formulations
Are drugs with the same same active ingredient bioequivalent?
No; to be bioequivalent when they produce AUC, Cmax and Tmax values that are neither clinically nor statistically different
What is Pharmacology?
The total knowledge of drugs including history, chemistry, source, biochemical & physical effects, pharmacodynamics (what the drug does to the body), pharmacokinetics (what the body does to the drug), therapeutics, site of action, interactions, distinctive features, etc.
What is a Drug?
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
What are Orphan drugs?
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
What is Clinical pharmacology?
The study of the effect of drugs in man
What is Pharmacotherapeutics?
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
What is therapeutic index and how is it calculated?
The relative toxicity of a drug 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)
What constitutes a “small therapeutic index?”
little difference between the therapeutic dose and the dose that causes toxicity
What is Tolerance?
is hyporeactivity that occurs from chronic exposure to a drug
What is CROSS TOLERANCE?
tolerance between drugs within a class; or between drugs of different classes that produce similar pharmacologic effects
What is enzyme induction?
stimulate production of drug-metabolizing enzymes resulting in increased rate of metabolism and usually decreased blood level of the drug
What is down regulation?
is a decrease in the number or sensitivity of receptor sites after continued dosing
What is up regulation?
the body may either increase the number of receptors or increase the sensitivity of receptors
What is Idiosyncrasy?
describes an unusual effect of a drug
What is Side effect?
describes any action of the drug other than the desired (therapeutic) effect
What is Adverse Effect?
is any noxious, unintended, and undesired effect that occurs at normal drug doses
According to the Controlled Substances Act, addictive substances are categorized into?
schedules (I through V)`
What drugs are Schedule I?
(Written C-i): Addictive substances with no approved use (e.g., heroin)
What drugs are Schedule II?
C-ii: Highly addictive substances (e.g., morphine; amphetamine). Prescriptions must be written in ink or typed or submitted using electronic prescribing procedures and cannot be refilled. A DEA rule in 2007 allows a prescriber to write multiple prescriptions on the same day for the same patient and same drug to be filled sequentially for up a 90 day supply. (I did not see this but I assume C-ii prescriptions are limited to a 30 day supply.)
What drugs are Schedule III and Schedule IV?
C-iii & C-iv: Less addictive; may be prescribed orally and may be refilled up to 5 times in 6 months (e.g., aspirin with codeine C-iii; diazepam C-iv)
What drugs are Schedule V?
C-v: Low addictive potential. Texas law requires a prescription for C-v drugs so essentially, in Texas, there is no difference in prescribing or how schedules iii, iv & v are handled. See Lehne p. 434 for more comprehensive description of the various DEA schedules.
What is Pharmacokinetics?
is the quantitative study of the absorption, distribution, metabolism and excretion of drugs and their metabolites. In simple terms, pharmacokinetics (often simply called “kinetics”) is what the body does to the drug.
What factors affect Plasma membranes?
molecular size and shape, solubility at the site of absorption, the degree of differences in pH across the membrane, the electrochemical gradient for the lipid form of the drug, degree of ionization, vascularity of the tissue, and relative solubility of ionized and nonionized forms
What substances cannot penetrate Plasma membranes?
Polar molecules (e.g., soluble in water) and ions cannot penetrate membranes and require transport systems.
What substances are ionized or partially ionized?
Strong acids (e.g., HCl) and bases (e.g., NaOH) are completely ionized On the other hand, many drugs are weak acids or weak bases and are present in solution as both nonionized and ionized species
What substances can penetrate Plasma membranes?
The nonionized is usually lipid soluble and able to penetrate the lipid membrane while the ionized moiety cannot. With a few drugs, the ratio of ionized to nonionized molecules is affected by change in pH
What happens to salicylic acid in an acid environment?
a weak acid (such as salicylic acid, the active metabolite of aspirin), in an acid medium (such as the stomach or acid urine,) is predominantly in the nonionized state (hence lipid soluble and can be absorbed)
What happens to morphine in an acid environment?
a weak base in an acid medium is predominantly in the ionized state; hence gets “trapped” in the more acidic fetus if morphine is given to a woman at term
What is “ion trapping?”
A change in pH causing a change in a weak acid/base to a strong acid/base causing the medication to not be excreted
What is the blood-brain barrier?
Tight junctions are characteristic of capillaries of the CNS, which, along with surrounding lipid glial cells
What is Active transport?
characterized by selectivity, competitive inhibition by congeners (similar drugs or metabolites), a requirement for energy, saturability, and movement against an electrochemical gradient (usually polar or water soluble: e.g., levodopa)
What is p-glycoprotein?
transporter; move chemicals out of cells.
is a drug efflux system also found in enterocytes, the kidney and brain
What is Absorption?
is the transfer of a substance from the site of application to the blood stream (usually the systemic circulation)
What is First pass effect?
refers to the rapid hepatic inactivation of certain oral drugs on their first pass through the liver
What activates prodrugs?
prodrugs are inactive as such and are activated by metabolism in the liver
What is Distribution?
is the process of a substance leaving the blood stream and moving to cells or tissues.
What is volume of distribution (Vd)?
is a mathematical expression of the sum of the apparent volumes of the compartments that constitute the body. Vd relates the amount of drug in the body to the concentration of drug in the blood (or plasma).
What is 1st order reactions?
rate of absorption and elimination is proportional to concentration
What is zero order reactions?
rate of elimination is independent of concentration
What is Half-life? How to calculate?
is the time it takes for 50% of the drug in the body to be eliminated from the body
What is Clearance?
is the measure of the body’s ability to eliminate a drug
What is steady state?
reach a plateau in plasma concentration takes about four or five doses
What are loading doses and what are they used for?
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
What is Cmax, Tmax, and t 1/2?
peak (maximum) blood level; time to reach peak; half-life. βt½: elimination half-life
What is the purpose of metabolism?
the primary purpose of metabolism is to change lipid soluble active compounds
What is phase I metabolism and what occurs?
Phase I (termed “asynthetic”) usually converts the parent drug to more polar metabolites by oxidation, reduction, hydrolysis, dealkylation, etc
What is phase II metabolism and what occurs?
Phase II (“synthetic”) involves coupling the drug or its phase I metabolite to endogenous water-soluble substrates, such as glucuronic acid, sulfuric acid, mercapturic acid, acetic acid, or an amino acid.
What is cytochrome P-450 system (CYP 450)?
oxidizing enzyme system
What does it mean if an enzyme is “inducible?”
certain compounds will increase enzyme activity
What does it mean if an enzyme is “inhibited?”
certain compounds will decrease enzyme activity
What is enterohepatic cycling?
drug may be reabsorbed
What is he classical explanation of drug-receptor coupling?
is that the intensity of response produced by a drug is related to the number of receptors occupied thus is proportional to the dose of the drug
What is Affinity?
attraction between a drug and its receptor
What is Efficacy or Intrinsic activity?
ability of a drug to activate a receptor and produce an effect
What is a drug agonist?
agonist binds to the receptor and cause a change in cellular activity. It has both affinity and efficacy.
What is an antagonist?
An antagonist 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.
What is a partial agonist?
A partial agonist binds to the receptor, causes a low level of change in cellular activity, but blocks endogenous substances or other drugs from binding to the receptor.
What is the cause of non-compliance?
the result of a misunderstanding, a failure of communication, the cost of the drug (I couldn’t afford it), or due to a patient’s concern about the seriousness of the disease and their belief in the medication
How does the FDA categorizes drug safety in pregnancy ?
A. No fetal harm in studies in women
B. No fetal harm in animals; no studies in women
C. Fetal harm in animals; no studies in women
D. Fetal harm in studies in women; Weigh risk vs. benefit
X. Definite fetal harm in studies in women. Contraindicated
What is an Object drug?
drug whose action or kinetics is altered
What is a Precipitant drug?
drug causing altered action
What are important object drugs?
aminoglycoside antibiotics hypoglycemics antiarrhythmics lithium carbamazepine phenytoin cyclosporine theophylline digoxin warfarin
What are characteristics of object drugs?
Narrow therapeutic index.
Used chronically.
Metabolized by hepatic microsomal enzymes
What are Important precipitant drugs:
Absorption
antacids, cholestyramine
Enzyme Inducers
carbamazepine, phenobarbital, phenytoin, rifampin, NNRTs
Enzyme Inhibitors
cimetidine, ciprofloxacin, erythromycin, isoniazid, azole antifungals, clarithromycin, verapamil, grapefruit juice, ritonavir +
Transport inhibitors
diltiazem, amiodarone, quinidine, ketoconazole
How is grape fruit juice an enzyme inhibitor?
Grapefruit juice inhibits CYP 3A4
What is the difference between drug misuse and abuse?
Abuse of a drug might be construed as any use of a drug for nonmedical purposes
To misuse a drug might be to take it for the wrong indication, in the wrong dosage, or for too long a period
What are the physiological factors on neonates when prescribing medication?
Small body mass Low body fat Low albumin Immature kidney and liver High body water Greater membrane permeability
What physiological considerations are there for elderly?
Increase in body fat
Decrease in most physiologic functions
Multiple diseases
Multiple medications
Which drugs are Teratogenic?
Teratogenic drugs include phenytoin, carbamazepine, valproic acid, lithium, warfarin, retinoids, and danazol
How does smoking affect theophyline?
decreasing the effectiveness of theophylline
What does smoking and drinking do to enzymes?
enzyme inducer
