Module 1 - General Principles of Pharmacology Flashcards
What is the half-life of a drug?
- It is the time it takes for 50% of the drug to be eliminated from the body.
- A drug’s half-life can vary greatly from patient to patient (usually associated with impairment of the liver or kidneys but also by genetic variations in metabolizing enzymes).
What is the steady state of a drug?
Refers to a state that occurs when there is repeated administration of a drug, usually 4-5 doses, that results in a drug’s concentration in the body being equal with its elimination
What does Tmax mean?
It is a term used to describe the time it takes a drug to reach peak concentrations in plasma
What does Cmax mean?
Refers to when peak concentrations of a drug are reached in the blood
What is creatinine clearance?
- It is an indirect measure of renal function
- An age-related decline in creatinine clearance occurs in about 2/3 of the population. Note, this decline may not be reflected in an equivalent rise in serum creatinine because the production of creatinine is reduced as muscle mass declines with age (hence the use of creatinine clearance in the elderly).
What are teratogenic drugs?
For a drug to be considered teratogenic the drug should:
- Result in a characteristic set of malformations, indicating selectivity for certain target organs
- Exert its effects at a particular stage of fetal development
- Show a dose-dependent incidence.
What are some drugs with definite teratogenic potential?
alcohol, androgens, antineoplastics, oral anticoagulants, diethylstilbestrol, smoking and thalidomide
What are some examples of teratogenic drugs?
phenytoin, carbamazepine, valproic acid, lithium, warfarin, retinoids, and danazol
Describe the FDA categories for drug safety in pregnancy
Pregnancy Category
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 the MOA of theophylline?
Theophylline produces bronchodilation by relaxing the smooth muscle of the bronchi by blocking the receptors for adenosine.
What is theophylline used for?
Asthma:
- Oral theophylline is used for maintenance therapy for chronic stable asthma. With regular use, it can decrease the frequency and severity of asthma attacks
What are some drug/food interactions with theophylline?
- Taking caffeine with theophylline can cause a competition for drug-metabolizing enzymes for both substances, causing theophylline levels to rise. It can also lead to more intense CNS and heart adverse effects
- Smoking while taking theophylline causes an increased drug clearance of the theophylline leading to lower theophylline levels in the body.
What is bioavailability?
It is the percentage of the dose of the drug administered by any route that reaches the systemic circulation
What is bioequivalence?
- Occurs when there is equivalent release of the same drug substance from 2 or more drug products or formulations
- Ex: the generic drug must produce AUC, Cmax and Tmax values that are neither clinically nor statistically different from a brand name drug to be termed bioequivalent
What are first-order reactions?
- A reaction in which the rate of absorption and elimination is proportional to concentration
- The higher the blood concentration of a drug, the faster it is eliminated from the body
What is meant when a drug operates at zero order?
- Occurs when the rate of drug absorption is independent of its concentration (sometimes called saturation kinetics, capacity-limited elimination, or Michaelis Menten kinetics).
- Ex: of zero order drugs: Alcohol; aspirin at high concentrations, & phenytoin at therapeutic concentrations are the best known drugs with zero order elimination
What is a loading dose?
It is a large dose of a medication that may be used to boost the drug’s 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 are some important physiologic changes seen with aging?
The aged subject will likely have:
- decreased gastric acidity
- increased body fat
- decreased body water
- decreased serum albumin,
- decreased cardiac output
- lean body mass
- decreased renal blood flow, splanchnic blood flow, and hepatic blood flow.
What are some changes in drug elimination seen with the elderly?
- Decreased 1st pass elimination and hepatic function result in increased amount of drug entering the systemic circulation and prolonged half-life.
- Decrease serum albumin may result in increased concentration of unbound drugs and more intense effects.
- An age-related decline in creatinine clearance occurs in about 2/3 of the population.
What is an adverse reaction?
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 humans for prophylaxis, diagnosis, or therapy, excluding failure to accomplish the intended purpose
What is the Cytochroe p-450 and what is its importance?
- Cytochrome P-450 is a term that describes a group of hepatic enzymes that metabolize drugs.
- Depending on how some drugs interact/affect these hepatic enzymes results in different drug effects for the person:
- Some drugs are P450 substrates (they are metabolized by these hepatic enzymes)
- Some drugs are P450 inducers (they act on the liver to increase drug metabolism, leading to subtherapeutic responses)
- Some drugs are P450 inhibitors (they decrease the rate of drug metabolism, leading to higher blood concentrations of a drug)
What is the first pass effect?
- Refers to the rapid hepatic inactivation of certain oral drugs on their first pass through the liver.
- To prevent this effect from happening the drug would be given via another route, mostly likely intravenously
What are the effects of age on drug metabolism?
- The drug-metabolizing capacity of infants is limited because their liver is not fully developed to metabolize drugs until about 1 year of age.
- With older adults, their ability to metabolize drugs is commonly decreased, and dosages should be reduced to avoid toxicity.
How are drugs primarily eliminated from the body?
- The kidneys are the most important organs for the elimination of drugs and their metabolites.
- Excretion of drugs & metabolites in the urine involves three processes: glomerular filtration, active tubular secretion, and active or passive tubular reabsorption.
- The amount of drug entering the tubular lumen by filtration is dependent on its fractional plasma protein binding, glomerular filtration rate (GFR), and cardiac output.
Describe glomerular filtration and its effect on drug elimination
- Involves the process of moving drugs from the blood into the tubular urine.
- Since large molecules (such as proteins) are too big to pass through the capillaries in the glomerulus they cannot be filtered and remain in the blood.
What is pharmacology?
It is 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 are orphan drugs?
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.
What is clinical pharmacology?
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.)
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 the “therapeutic index” of a drug?
- It 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 difference between the therapeutic dose and the dose that causes toxicity (e.g., digoxin).
What is drug tolerance?
- It is hyporeactivity that occurs from chronic exposure to a drug (such as an opioid or alcohol).
- When tolerance develops, usually increasing doses are needed to provide a therapeutic effect.
- This is attributed to neuronal adaptation or cellular tolerance.
What is a “side effect” of a drug?
It usually describes any action of the drug other than the desired (therapeutic) effect.
What is an “adverse effect” of a drug?
It is any noxious, unintended, and undesired effect that occurs at normal drug doses
Describe the DEA schedule of drugs
Schedule:
- Addictive substances with no approved use (e.g., heroin)
- 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.
- 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)
- “same as 3”
- 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. 411 for a more comprehensive description of the various DEA schedules.
What is down regulation?
Occurs when there is a decrease in the number or sensitivity of receptor sites after continued dosing of a drug
What is upregulation?
Occurs when the body increases the number of receptors or increase the sensitivity of receptors to a drug
What are drug receptors?
They are any functional macromolecules 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. These proteins can be selective and recognized by selective ligands (e.g., drugs, hormones, neurotransmitters).
What are agonists?
An agonist (drug) binds to the receptor and causes a change in cellular activity. It has both affinity and efficacy.
What is an antagonist?
An antagonist (drug) 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 Ion-Trapping?
- The process whereby a drug accumulates on the side of the membrane where the pH most favors ionization is referred to as ion trapping or pH partitioning.
Example:
- 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).
- A weak base (e.g., morphine sulfate) 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 (“ion trapping”)
How can acidosis affect the drug action of salicylic acid or aspirin
. Development of acidosis drives the drug to its nonionized form, which can go into tissues (i.e., brain) and cause toxicity. On the other hand, treat salicylate toxicity by alkalinizing the urine to increase the ionized form that cannot be reabsorbed though the kidney tubules. Cases of aspirin toxicity are treated with “forced alkaline diuresis,” i.e. giving sodium bicarbonate IV along with furosemide.
How is aspirin at high concentrations eliminated?
Some few drugs operate at zero order, where rate is independent of concentration Alcohol; aspirin at high concentrations, & phenytoin at therapeutic concentrations are the best known drugs with zero order elimination. For example, alcohol is eliminated at a rate of 10 cc/hour regardless of the amount of alcohol consumed.
