Term
| What do beta blockers target? |
|
Definition
| target Beta Adrenergic receptors (do not stimulate the same function as the normal ligand (epinephrine)) |
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Term
| What do antihistamines target? |
|
Definition
| histamine receptors (looks like histamine-vasodilator-but doesn't act like histamine) |
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Term
| What do ACE inhibitors target? |
|
Definition
| Angiotensin-converting enzyme (blocks action of enzyme) |
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Term
| What do statins target and what does it do? |
|
Definition
| HMG CoA-reductase (blocks cholesterol synthesis) |
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Term
| What do loop diuretic target and what does it do? |
|
Definition
| Renal Na/K/2Cl channel (blocks channel, increases urine output, lowers bp) |
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Term
| What do local anesthetics target? |
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Definition
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Term
When drug concentration increases, what increases?
At very high drug concentrations, the response to the drug reaches _____
The highest response observed, at very high concentrations of the drug, corresponds to the maximal _______ of the drug. |
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Definition
As the drug concentration increases, the number of receptors occupied by the drug increases, and the response to the drug increases.
At very high drug concentrations, the response to the drug reaches a maximum.
The highest response observed, at very high concentrations of the drug, corresponds to the maximal efficacy of the drug. |
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Term
Two drugs with equal _______ produce the same maximal response
Two drugs with equal ________ produce their
half-maximal effects at the same concentration |
|
Definition
efficacy (one drug is more efficacious than another if it produces a greater maximal effect)
potency (one drug is more potent than another if its
half-maximal effect is observed at a lower concentration.) |
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Term
From the following drugs, which one has the most efficacy? Which one is most potent? which drug(s) is/are safest? (see slide 9 in lecture)
A. Ibuprofen
B. Diphenhydramine
C. Aspirin
D. Acetaminophen |
|
Definition
Acetaminophen- most efficacy
Diphenhydramine (benadryl) - most potent
(A, C, and D are all full agonists)
Impossible to know which is safest bc you don't have all the information based on the specific person |
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Term
| What is a drug that produces the maximal response when used at high enough concentrations |
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Definition
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Term
| What is a drug that produces less than the maximal response even when used at high enough concentrations to cause its maximal response |
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Definition
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Term
| What is the partial agonist called when it may reduce the effect of a full agonist if they are both present at the same time |
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Definition
the partial agonist can be called a mixed
agonist/antagonist) |
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Term
| What binds to the same active site as the normal ligand; is reversible, non-covalent binding; Inhibitory effect can be overcome when ligand concentration is raised |
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Definition
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Term
| What binds to a different site than the ligand; inhibitory effect cannot be overcome by increasing the ligand concentration |
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Definition
| non-competitive allosteric antagonists |
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Term
| What binds irreversibly (covalently) to either the same site or a different site than the ligand; Inhibitory effect cannot be overcome by increasing the ligand concentration |
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Definition
| Non-Competitive Irreversible Antagonists |
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Term
Does a noncompetitive antagonist affect the efficacy or potency of the drug?
Competitive antagonist? |
|
Definition
Noncompetitive - doesn't affect potency, does affect efficacy
Competitive- does affect potency, doesn't affect efficacy |
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Term
| What is an indication of the safety of a drug usually determined by the LD50 (lethal dose in 50% animals) or the TD50 (toxic dose in 50% humans) by ED50 (effective dose) |
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Definition
| Therapeutic Index or therapeutic window |
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Term
| A (small or large) therapeutic index means a drug is more likely to cause harm |
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Definition
A small Therapeutic Index means a drug is more
likely to cause harm. (want it to be 100 or 1000) |
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Term
Identify if this is is a lipid soluble drug or water-soluble:
-are not bound to carrier proteins in the blood
-are better able to cross cell membranes
-are better able to enter the brain
-are usually bound to carrier proteins in the blood and not cleared by renal filtration
-often bind to a receptor on the outside surface of a cell
-are generally cleared more quickly by the kidney
-have a longer half-life
-are often metabolized in the liver (to the other soluble form) |
|
Definition
-are not bound to carrier proteins in the blood - water
-are better able to cross cell membranes - lipid
-are better able to enter the brain - lipid
-are usually bound to carrier proteins in the blood and not cleared by renal filtration - lipid
-often bind to a receptor on the outside surface of a cell - water
-are generally cleared more quickly by the kidney - water
-have a longer half-life - lipid
-are often metabolized in the liver (to the other soluble form) - lipid (metabolized to more water-soluble) |
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Term
| How do hormones exert their effects? |
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Definition
Hormones:
Exert their effects through
binding to various types of
receptors. |
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Term
What does the beta gamma subunits of G-protein Coupled Receptor do?
What are the 3 families of the alpha subunits? |
|
Definition
The beta gamma subunits increase potassium channels and decrease calcium channels and increase the activity of PI3 kinases.
alpha:
G-stimulatory (activates adenylyl cyclase); beta1, beta2, dopamine receptors
G-inhibitory (inhibits adenylyl cyclase) M2, alpha2, dopamine2
Gq(activates phospholipase C) M1, M3, alpha1 |
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Term
| What causes variability in drug metabolism? |
|
Definition
Disease states (ex. renal, hepatic failure)
Concomitant drugs
Environmental factors (diets)
Age
Genetic Factors |
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Term
| In an elderly person, you would expect the total body water to go (up/down), lean body mass to go (up/down)? |
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Definition
total body water-down
lean body mass-down
body fat-up
affects on water or fat soluble drugs |
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Term
| In an elderly person, you would expect serum albumin to go (up/down)? how would this affect drugs? |
|
Definition
serum-usually down
some drugs bind to albumin, without it than only free drugs will have activity |
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Term
| In an elderly person, you would expect mycocardial sensitivity to beta-adrenergic stimulation to go (up/down)? |
|
Definition
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|
Term
| In an elderly person, would you expect gastric pH to go (up/down)? How does this affect the type of drug you give them? |
|
Definition
Gastric pH-up
pH becomes alkaline, will absorb weak bases more (weak acids absorbed in an acid environment better) |
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Term
| In an elderly person, would you expect GI blood flow to go (up/down)? how does this affect drug absorption? |
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Definition
GI blood flow-down
less absorption because blood flow takes it to liver and then to systemic circulation |
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Term
In an elderly person, would you expect gastric emptying to (speed up/delay)?
Intestinal transit to (speed up/slow down)?
How does this affect drugs? |
|
Definition
delayed gastric emptying-onset of drugs will be delayed
slowed intestinal transit-more absorption |
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|
Term
In an elderly person, do you expect the hepatic size to (increase/decrease)?
hepatic flow to (increase/decrease)?
How does this affect drugs? |
|
Definition
hepatic size decrease- some drug metabolizing enzymes (phase I enzymes) will be less in elderly liver = lower metabolism
hepatic blood flow decrease |
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|
Term
In an elderly person, do you expect to see the kidney functions increase or decrease? (glomerular filtration rate, renal blood flow, filtration fraction, tubular secretory function, renal mass)
How does this affect drugs? |
|
Definition
everything decreases
problems in getting rid of drug in the body |
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Term
In the GI, when there is decreased active transport, there is (increase/decrease) bioavailability for some drugs?
When there is is decreased first-pass extraction, there is (increase/decrease) bioavailability for some drugs? |
|
Definition
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|
Term
When there is a decrease of volume distribution, there is a (increase/decrease) in plasma concentration of water-soluble drugs
When there is an increase in volume of distribution, there is (increase/decrease) terminal disposition half-life for fat-soluble drugs |
|
Definition
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|
Term
| In the elderly, the hepatic metabolism will cause decreased clearance and increase half-life for what types of drugs? |
|
Definition
some oxidatively metabolized drugs (ex:codeine)
drugs with high hepatic extraction ratios |
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Term
| What adverse effects can Diphenhydramine (benadryl) and other sedating antihistamines cause in the elderly? |
|
Definition
impaired cognition, urinary retention
(elderly are more sensitive at receptor level) |
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Term
| What drugs can cause sedation, confusion, and cardiorespiratory depression in the elderly? |
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Definition
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|
Term
Determine if the following opiods are less tolerated for analgesia or better tolerate with careful dose adjustment:
Fentanyl
meperidine
butorphanol
morphine
oxycodone
codeine
pentazocine
nalbuphine |
|
Definition
Fentanyl-better
meperidine-less (causes anxiety)
butorphanol-less
morphine-better
oxycodone-better
codeine-less
pentazocine-less (anxiety/agitation)
nalbuphine-less |
|
|
Term
| What drug causes the following adverse effects? (tendon inflammation and rupture, hypoglycemia, arrhythmias, C. difficile associated diarrhea) |
|
Definition
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|
Term
| Why should NSAIDs not be used frequently in the elderly? What are the problems they will most likely get? |
|
Definition
| geriatrics are very susceptible to toxicities, especially GI and renal toxicities. Because they are cleared primarily by the kidneys, they accumulate more rapidly in the geriatrics |
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Term
| What are the drugs that increased half-lives in elderly people? Which one causes up to a 60% increase of falls? |
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Definition
Lactam, aminoglycoside, and fluoroquinolones excreted primarily by the renal route, so ↑ in t1/2 expected in geriatrics.
Benzodiazepines – falls (up to 60% increased risk) |
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Term
| Dosing guidelines may indicate need for adjustment for some drugs that are _______ excreted. |
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Definition
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|
Term
| ________ (breakdown product in muscle and excreted in kidneys) is used as an indicator of renal function |
|
Definition
|
|
Term
| What formula is commonly used for adults with stable renal function whose actual weight is within 30% of ideal body weight to estimate creatinine clearance? |
|
Definition
|
|
Term
| What is the Cockroft and Gault formula for creatinine clearance? |
|
Definition
| (140-age) (Body wt) x 0.85 for women / (72) (creatinine) |
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|
Term
Gastric emptying is (slower, slightly slower, increased, or slightly increased) in neonate, infant, and child?
What does this result in? |
|
Definition
Gastric emptying:
Neonate-slower
Infant-slower
child- slightly slower
results in onset of drug action to be slower |
|
|
Term
| Intestinal transit rate is (slower, slightly slower, increased, or slightly increased) in neonate, infant, and child? |
|
Definition
Intestinal transit rate:
neonate-slower
Infant-Increased
Child-slightly increased |
|
|
Term
| What is the Gastric pH in neonate, infant, and child? |
|
Definition
Neonate-6-8 (neutral
Infant-2-4 (acidic)
Child- 1-3 (normal) |
|
|
Term
| What are the 2 proteins that are low in neonates (binds drugs and carry in plasma) that approach adult values ~1 year? |
|
Definition
| albumin and AAG (alpha-acid glycoproteins) |
|
|
Term
| Does total body water increase or decrease as a baby becomes 1 years old? |
|
Definition
| At birth, ECF ~40% body wt, decrease to 25% by 6 months, decrease to 20% (adult level) by 1 year |
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|
Term
Does CYP450 (cytochrome P450) activity (increase or decrease) by age 2-3? Does it (increase or decrease) by puberty?
What does this mean in terms of metabolism? |
|
Definition
CYP450 activity at birth 50-70% of adult levels; increases to greater than adult levels by age 2-3 and then decreases to adult values by puberty
CYP450 makes up majority of oxidative enzyme. Pediatric population will metabolize drugs faster than adult |
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|
Term
| In pediatrics, what are the 2 phases of metabolism? |
|
Definition
oxidative by CYP450
conjugation to water-loving species like glucuronide (or sulfate)-makes it easy to eliminate |
|
|
Term
Is there a (high or low) ability to conjugate drugs with glucuronide (glucuronidates bilirubin) in neonates?
When is it adult levels? |
|
Definition
low ability
reaches adult values ~3-4 years of age |
|
|
Term
| Does renal function for elimination (increase or decrease) as neonates become older? |
|
Definition
| Renal function is ∼25–30% of adult values at birth, increases to 50–75% by 6 months, and reaches full adult levels by age 2–3 years |
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Term
| What are the objectives of pharmacogenetic studies? |
|
Definition
1. Explain the individual’s response to drugs.
2. Predict the response to drugs/toxins.
3. Control variability of response to drugs. |
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|
Term
| What are the pharmacogenetic targets? |
|
Definition
Absorption and excretion: drug transporters
Distribution- binding proteins
Metabolism -phase I and II enzymes
Drug Targets: receptors and enzymes |
|
|
Term
Where can SNPs (single nucleotide polymorphisms) be found in the DNA?
SNPs are ________ if they change the expression of the gene or alter the gene’s protein product |
|
Definition
SNPs can be in DNA coding regions (exons), or non-coding regions such as introns or promoters
SNPs are consequential if they change the expression of the gene or alter the gene’s protein product (most are inconsequential) |
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|
Term
If a patient has no metabolism, they may have _____ genes
If a patient has decreased metabolism by an enzyme, they may have _____ gene.
If a patient has increased metabolism by an enzyme, they may have _____ gene. |
|
Definition
Deleted gene (No enzyme)
Single gene (unstable mRNA)
Duplicated gene (increase enzyme) "ultra-extensive metabolizer" |
|
|
Term
_______ gene - the mutation exists in >1% population
_______ gene - the mutation exists in < 1% population |
|
Definition
Polymorphic gene – the mutation exists in >1% population
Rare gene – the mutation exists in < 1% population |
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|
Term
| If refer to someone as a "fast" or "slow metabolizer", you are referring to their (phenotype or genotype)? |
|
Definition
| phenotype (physical appearance/what is expressed) |
|
|
Term
| What is one of CYP450 enzyme that is involved in the metabolism of a lot of pain medications (ultra-extensive metabolizers, extensive metabolizer, intermediate metabolizer, poor metabolizer) |
|
Definition
|
|
Term
| What is the anticancer drug that is actually activated by CYP2D6? |
|
Definition
|
|
Term
| When codeine is ingested, what enzyme metabolizes it and what does it metabolize to? |
|
Definition
| CYP2D6 metabolizes it morphine |
|
|
Term
| An individual who has poor metabolism activity will experience (more or less) pain relief after ingesting codeine compared to a normal person (extensive metabolizer)? |
|
Definition
| less pain relief (person with ultra-extensive metabolizer would have greater response) |
|
|
Term
| What is reaction that is uncommon, unpredictable, and unexplained? |
|
Definition
|
|
Term
| What are the human versions of the major histocompatibility complex (MHC) that encode proteins that are related to immune system function in humans and include cell-surface antigen-presenting proteins. They may mediate autoimmune diseases and some immune based idiosyncratic reactions to drugs |
|
Definition
|
|
Term
| What presents peptides from from proteins processed inside the cell (including viral peptides) and attract killer T-cells |
|
Definition
|
|
Term
| Patients with HLA-B*1502 allele are at an increased risk of developing ______________ |
|
Definition
| Patients with HLA-B*1502 allele are at an increased risk of developing hypersensitivity reactions including Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN) when given carbamazepine (Tegretol), a drug used for seizures, neuropathic pain and bipolar illness |
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|
Term
The HLA-B*1502 polymorphism is much more common in people of ______ ancestry.
Is it ok to give the drugs if the patient is heterozygous for the gene? |
|
Definition
| Asian (drug not recommended in patients with at least one copy of HLA-B*1502) |
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