PharmacoTherapeutics. Exam 1 Flashcards
What are three factors that influence drug effects?
- Pharmacokinetic differences
- Pharmacodynamic differences
- Secondary Factors
A _______ difference exists if a drug is given at a specific dose but reaches a difference concentration in different people.
pharmacokinetic
A ________ difference exists if a drug present at a given concentration produces difference responses in different people.
pharmacodynamic
________ is a very important concept in pharmacokinetics that determines dosage differences within a specific drug that will produce either a therapeutic effect or a toxic side effect.
Therapeutic Index
What is more dangerous, a low TI or a high TI?
a low TI is dangerous (there is only a slight difference between the dosage that has effect and the dosage that is deadly)
True or False: Both pharmacokinetic and pharmacodynamic differences exist in children.
True.
In general, dosing in children is based on ______ because complexities and uncertainties make prediction difficult.
clinical data
True or False: Geriatric patients tend to be hyporeactive to drugs.
False. More often they are hyper-reactive
Dosage for women tends to be _____, but much data is missing to base dose on sex alone.
lower
What is a drug induced arrhythemia?
an alteration in cardiac rhythm due to influence on the conduction system or physiological changes
True or False: In lactating women, drugs may be excreted through breast milk.
True
What are four environmental factors that can have influences on drug effects?
- Temperature
- Sunlight
- Altitude
- Diet
Nitrous oxide is _____ effective at high altitude.
less
True or False: Eating cheese or drinking red wine with antidepressant medications could cause a hypertensive crisis.
True
How could cheese or red wine cause hypertensive crisis?
If taking antidepressants, the MAO enzymes are blocked from breaking down norepinephrine and serotonin. Tyramines in cheese/wine release norepinephrine which is not metabolized as it should be.
_______ is responsible for metabolism of 60% of all drugs.
CYP3A4
How does grapefruit juice effect drug metabolism?
Grapefruit juice reduces the expression of CYP3A4
The ________ has a significant effect on metabolism of drugs and changes the pharmacokinetics of a drug when the patient is taking antibiotics.
bacteria in the gut
_______ is a decreased responsiveness to drug upon repeated or continuous administration.
Tolerance
What effect does pharmacokinetic tolerance have on the drug?
the effective drug concentration is diminished
In pharmacodynamic tolerance, the _____ is diminished.
response
kinetic = concentration, dynamic = response
Tachyphylaxis is a _____ loss of response after repeated drug administration in short intervals. For example, it may occur with ______ because norepi. stores are depleted.
rapid
tyramine
What are two mechanisms of pharmacodynamic tolerance?
- Down regulation of receptors
2. impairment in signal transduction
Drugs can induce changes in ________ such as the over-expression of proteins that pump drugs out of cells.
cellular distribution
What are extension effects?
adverse drug effects in which the drug does too much of what you expected it to do. For example, Warfarin = inhibits clotting…extension = hemorrhaging
When you see side effects from an overdose, the drug is acting at _______ targets.
Unintended
What are idiosyncratic reactions?
effects that occur rarely and unpredictably among the population; unusual metabolism, distribution, binding affinity for receptor
What drug interaction account for 10% of all adverse effects?
drug allergies (IgE = immediate reaction, IgG = cytotoxic)
Drugs taken orally are ____ allergenic; Drugs taken topically are _____ allergenic.
less
more
What is a pseudo-allergy?
a reaction produced by the direct release of mediators from mast cells and basophils that shows a downstream effect that mimics that of an allergy
True or False: Drugs can cause cancer.
True
How many categories exist for the labeling of drugs based on fetal risk?
five: A, B, C, D, X
Sodium Fluoride is labeled as drug class ____.
A
If the potential risk of a drug to a fetus clearly outweighs the potential benefit, the drug is labeled as class ____.
X (ex. warfarin, estradiol)
What is pharmacogenetics?
field of study that attempts to understand the genetic basis for differences in how patients respond to drugs
By using pharmacogenomics, patients can be _______ for a drug in order to identify who will benefit and who will suffer adverse effects.
pre-screened
What is a monogenic phenotype?
variation in a single gene
What is a polygenic phenotype?
variation in multiple genes that complicates its predictive value
Pharmacokinetic (concentration) variations usually result from differences in ________ and are ________ understood.
metabolism better understood (many examples)
Pharmacodynamic (response) variations usually result from differences in _______ or ______ and are not well understood (few examples).
targets
downstream elements
Polymorphisms of drug-metabolizing enzymes can effect ______.
plasma concentration (homozygote wild type vs homozygote variant)
Phase II conjugation by N-acetyltransferase effects drug metabolism by acting on drugs that contain aromatic _____, _______, and hydroxylamines. Slow acetylator phenotype is most common in which population?
amines
alcohols
Egyptian (85%)
True or False: Some consequences of slow acetylation include neurophathy, systemic lupus, and cancer predisposition.
True
Oxidation of many drugs occurs through which enzyme?
Cytochrome P450 enzymes (many alleles)
Which four alleles of Cytochrome P450 are most important?
CYP3A4
CYP2D6
CYP2C9
CYP2C19
What does CYP2D6 do?
about 25% of drugs are metabolized by this particular allele of CYP.
it removes methyl groups from oxygen*
_______ is a muscarinic agonist that is used to treat dry mouth and is metabolized by CYP2D6. Poor metabolizers of CYP2D6 could experience nausea and vomiting because of _____poisoning.
Cevimeline
muscarinic
Why would poor metabolizers have generally poorer outcomes when treated for breast cancer with tamoxifen?
Tamoxifen is the prodrug for the active form (Endoxifen). CYP2D6 is required to create the functional antagonist to estrogen.
Codeine is an _______ that is converted to morphine by CYP2D6.
Opioid Agonist
For 10% of the population, codeine is ineffective as an analgesic. Why?
poor metabolizers cannot convert codeine to morphine
Ultra metabolizers of CYP2D6 experience ______ in response to codeine.
severe abdominal pain
CYP2C9 poor metabolizers may have serious _______ complications with drugs such as Warfarin.
bleeding
Succinylcholine is a muscle relaxant that can induce prolonged _____ in poor metabolizers.
apnea
The ________ receptor mediates calcium-mediated calcium release from the sarcoplasmic reticulum in muscle and a mutant allele for this receptor could cause _________.
Ryanodine
malignant hyperthermia
Malignant Hyperthermia (ryanodine receptor) is an example of a ________ polymorphism in drug targets.
pharmacodynamic (response from target is different not the metabolism)
