Term
| What are the three ways cells may change genetic composition? |
|
Definition
| mutation, gene transfer, gene amplification |
|
|
Term
| How are Gram positive cells intrinsically resistant? |
|
Definition
| with their thick cell walls protecting it from many antimicrobials |
|
|
Term
| Describe the effect of growing acholeplasma laidlawii in cholesterol containing medium. |
|
Definition
| It becomes easily killed by polyene antibiotics where as normally grown in a sterol-free medium it is insensitive to the drug. |
|
|
Term
| What can be added to rifampin to make it effective against fungi? |
|
Definition
| a small amount of polyene antibiotic |
|
|
Term
| Differentiate beta lactamase in gram positive and negative bacteria. |
|
Definition
| Gram positive secretes it while it is localized between the membranes in gram negative |
|
|
Term
| What are the three mechanisms of resistance to the beta lactam antibiotics (penicillin and cephalosporins)? |
|
Definition
| binding protein mutations, porin mutations, and beta lactamases |
|
|
Term
| Describe the binding protein mutation used as a resistance to beta lactam drugs. |
|
Definition
| mutations at the active site where the drugs bind. considered highly intrinsically resistant. |
|
|
Term
| Describe porin mutations used as a resistance to beta lactam drugs. |
|
Definition
| common in gram negative bacteria to decrease outer membrane permeability so that only a small amount of drug can get in which is neutralized by transpeptidases |
|
|
Term
| Describe how beta lactamases (transpeptidases) provide resistance to beta lactam drugs. |
|
Definition
they open up the beta lactam ring in the drug which inactivates it permanently
specifically cleave c-n bond and have genes that code them on both chromosomes and plasmids |
|
|
Term
| What is the main compound given in conjunction with antibiotics to eliminate transpeptidases so the antibiotic can be effective? |
|
Definition
clavulanic acid
penicillin and clavulanic acid=augmentin |
|
|
Term
| What are the three genetic mechanisms of drug resistance? |
|
Definition
mutation and selection
gene transfer
gene amplificaion |
|
|
Term
| How do drugs increase both mutations and selection? |
|
Definition
drugs that affect dna can cause it to mess up and mutate
drugs not given in enough quantity kill off susceptible cells while leaving resistant ones to proliferate |
|
|
Term
| What is combination chemotherapy? |
|
Definition
| giving two different drugs with different mechanisms simultaneously because the the odds of the cell being resistant to both is very unlikely |
|
|
Term
| What are the three mechanisms of resistance via gene transfer? |
|
Definition
transformation- uptake by competent cells
transduction- transfer by bacteriophages
Conjugation- cell-cell contact transfer using transfer units(transposons) |
|
|
Term
| What is an example of a drug that had problems with resistance via gene transfer? |
|
Definition
|
|
Term
| What is gene amplification resistance? |
|
Definition
spontaneous amplification of gene coding for a specific cell function that promotes cell survival
most common is over production of DHFR |
|
|
Term
| Other than the three genetic mechanisms of resistance (mutation, gene transfer, gene amplification) what is another group of resistances? |
|
Definition
| biochemical mechanisms of drug resistance |
|
|
Term
What are two general ways of decreasing intracellular drug concentrations?
*biochemical resistance* |
|
Definition
efflux
decreased permeability |
|
|
Term
| Describe the tetracycline resistance. |
|
Definition
efflux mechanism
tetracycline binds to inhibitor protein which allows more TET protein to be made which increases the efflux of tetracycline. |
|
|
Term
| Describe how methotrexate can be used on resistant cells without damaging normal cells. |
|
Definition
| By giving it in high conc you can force diffusion into cell. Because the resistant cells have developed poor permeability you can give a small quantity of leucovorin which will "rescue" normal cells but not be taken up by the resistant ones. |
|
|
Term
Aminoglycosides (streptomycin, gentamycin, etc) are antibiotics commonly resisted by increased inactivation of drug mechanisms, what are these three mechanisms?
*biochemical resistance* |
|
Definition
1)receptor mutations on 30s
2)decrease drug uptake
3)modifying enzymes (-transferases) |
|
|
Term
What are three drug examples that are resisted by increased inactivation of drug mechanisms?
*biochemical resistance* |
|
Definition
penicillin- beta lactamase
aminoglycosides- transferases
chlorophenicol- acetylation |
|
|
Term
Some drugs must be converted to active form once they are in the cell, decreasing this conversion to active is a resistance mechanism commonly found in what groups? 2 examples also
*biochemical resistance* |
|
Definition
purine and pyrimidine analogs that must be converted to nucleotides
5-FU is an anticancer drug example
6-mercaptopurine must be activated by |
|
|
Term
Cells can also increase the amount of antagonizing metabolites to prevent drug action, what is increased to resist sulfonamides?
*biochemical resistance* |
|
Definition
| para-aminobenzoic acid x100 |
|
|
Term
What is an example of overproduction of a target enzyme for resistance?
*biochemical resistance* |
|
Definition
| increasing DHFR for trimethoprim resistance |
|
|
Term
What is an example of decreasing target enzyme receptors and function as a resistance mechanism?
*biochemical resistance* |
|
Definition
| decreasing glucocorticoid receptors |
|
|
Term
| Why would a cell increase target enzymes instead of just reducing its function with less receptors? |
|
Definition
| if that enzyme is needed for cell growth the bacteria is not going to reduce its function |
|
|
Term
Give two examples of drugs resisted by decreased affinity of receptor for drug.
*biochemical resistance* |
|
Definition
Rifampin not being able to bind rna polymerase of resistant bacteria
Antifolate drugs having different affinity for DHFR of different species( bacteria, protozoa, mammals) |
|
|
Term
What kind of resistance can be developed against drugs that alter dna or dna strands?
*biochemical resistance* |
|
Definition
Repairing the drug-sensitive damage
"repairs damage caused by drugs with the standard dna repair mechanisms" |
|
|
Term
| Differentiate short-patch repair and long-patch repair. |
|
Definition
short- 3-4 nucleotides repairs from alkylating agents and xrays
long- up to 120 nucleotides repairs bulky groups substituted in from UV irradation |
|
|
Term
| What are the characteristics of average population? |
|
Definition
18-65 yo
150lbs (70kgs)
normal body function |
|
|
Term
| What is a primary underlying cause of altered response to drugs between patients? |
|
Definition
|
|
Term
| What is pharmacokinetic variability? |
|
Definition
| variability in the delivery to or removal of the drug from the active site due to alterations in drug transporters or metabolizing enzymes |
|
|
Term
| What are the effects of pharmacokinetic variability? |
|
Definition
| varied drug concentration at site which causes varied intensity of drug effect |
|
|
Term
| Drugs with what characteristic make pharmacokinetic variability very important? |
|
Definition
| drugs with small therapeutic windows |
|
|
Term
| What is the formula for dosing based on weight? |
|
Definition
| dose= (regular dose/70kg)*(weight of pt.) |
|
|
Term
| What physiological characteristics are different for infants? |
|
Definition
increased permeability
increased body water %
Decreased biotransformation
Decreased renal clearance
Lower rate of blood flow |
|
|
Term
| What physiological characteristics are different for Elderly? |
|
Definition
decline in organ function
Decreased hepatic blood flow
decreased excretion and metabolism
concentrations of drugs are higher |
|
|
Term
| What are gender-related differences in physiological characteristics? |
|
Definition
fetus sensitive to drugs
lipophilic transfer into milk |
|
|
Term
| What is pharmacodynamic variability? |
|
Definition
| variation in drug effects despite equal drug delivery |
|
|
Term
| What causes pharmacodynamic variability? |
|
Definition
| receptor differences, altered signal transduction, altered membrane TRANSPORTERS |
|
|
Term
| What is the difference between ABC (atp binding cassets) and SLC (solute carrier tranporters) transporters? |
|
Definition
ABC is effux only
also known as p glycoproteins |
|
|
Term
| What are circadian rhythms? |
|
Definition
Regular recurrence of a biological process in cycles of
about 24 hours |
|
|
Term
| When are cortisol, catecholamines, angiotensisn, and aldesterone secreted most? |
|
Definition
|
|
Term
| When are gastric acid, growth hormone, and follicle-stimulating hormone secreted most? |
|
Definition
|
|
Term
| Why do asthma symptoms increase at night? |
|
Definition
decreased cortisol(anitiinflammatory)
increased levels of histamine (bronchoconstrictor) |
|
|
Term
| Differentiate partial and noncompliance. |
|
Definition
| partial is not full dose non is missing doses entirely |
|
|
Term
| Differentiate quantitative and qualitative ADRs. |
|
Definition
| Quantitative are dose related(95%) |
|
|
Term
| How are chelating agents used in regards to pharmaceutical drug interactions? |
|
Definition
| used as antidotes for heavy metal poisoning to form poorly soluble complexes |
|
|
Term
| What do divalent ions chelate with in pharmaceutical drug interactions? |
|
Definition
| tetracyclines, cipro, and antacids |
|
|
Term
Why can you not take antacids, histamine blockers, or PPI's with ampicillin in ester form?
*pharmaceutical drug interaction* |
|
Definition
| they increase stomach pH and ampicillin needs a low pH for absorption. |
|
|
Term
What happens if you put phenytoin in glucose solution?
*pharmaceutical drug interaction* |
|
Definition
|
|
Term
| What are *pharmaceutical* drug interactions? |
|
Definition
| interactions that interfere with absorption due to physical or chemical interactions between drugs |
|
|
Term
| What are *pharmacokinetic* drug interactions? |
|
Definition
alter ADME that results in
abnormally high or low plasma or tissue
levels |
|
|
Term
| How do phenytoin, morphine, and erythromycin affect gastric emptying time in pharmacokinetic drug interactions? |
|
Definition
phenytoin and morphine increase(slows down)
erythromycin decrease time(speeds up which is better for absorption) |
|
|
Term
| What are the three mechanisms of pharmacokinetic interactions affecting absorption? |
|
Definition
| Change in GI motility, altering intestinal flora, and saturation of carrier-mediated absorption. |
|
|
Term
| What alters normal flora in intestines and what is affected by it? |
|
Definition
| antibiotics affect it, digoxin and oral contraceptives absorption is affected |
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving distribution? |
|
Definition
| plasma protien binding and displacement |
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving excretion? |
|
Definition
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving biotransformation? |
|
Definition
| CYP 450 inhibition and induction |
|
|
Term
| How do phenytoin, morphine, and erythromycin affect gastric emptying time in pharmacokinetic drug interactions? |
|
Definition
phenytoin and morphine increase(slows down)
erythromycin decrease time(speeds up which is better for absorption) |
|
|
Term
| What are the three mechanisms of pharmacokinetic interactions affecting absorption? |
|
Definition
| Change in GI motility, altering intestinal flora, and saturation of carrier-mediated absorption. |
|
|
Term
| What alters normal flora in intestines and what is affected by it? |
|
Definition
| antibiotics affect it, digoxin and oral contraceptives absorption is affected |
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving distribution? |
|
Definition
| plasma protien binding and displacement |
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving excretion? |
|
Definition
|
|
Term
| What is the main factor involved in pharmacokinetic interactions involving biotransformation? |
|
Definition
| CYP 450 inhibition and induction |
|
|
Term
| What are pharmacodynamic drug interactions? |
|
Definition
| when one drug alters sensitivity to another drug. Addditive or subtractive |
|
|
Term
| Differentiate additive, potentiation, and antagonism in pharmacodynamic drug interactions. |
|
Definition
additive- most common, effects added, same receptor
potentiation- different receptors, >sum of effects
antagonism- one diminshes other(competitive and noncompetitive) |
|
|
Term
*Drug Food Interactions*
Why take drugs with meals? |
|
Definition
| increase or decrease GI residence time |
|
|
Term
*Drug Food Interactions*
What does alcohol affect? What is affected by this? |
|
Definition
cns depressant and increase oxidases
acetaminophen toxic metabolites |
|
|
Term
*Drug Food Interactions*
What does Grapefruit affect? |
|
Definition
CYP3A4 down regualation which enhances absorption and bioavailability
can also enhance p glycoprotein mediated effluxes which decrease absorption (digoxin, cylcosporin) |
|
|
Term
*Drug Food Interactions*
What is tyramine? What can affect it and what does this cause? |
|
Definition
component of cheese and drinks and is metabolized by MAO
MAOI's decrease its metabolism and increased levels of tyramine increase NE and can cause hypertensive crisis |
|
|
Term
| Describe drug side effects |
|
Definition
unrelated to therapeutic action
expected response and not life threatening
ex-1st gen antibiotics cause drowsiness
ex- gentamycin caused hearing loss |
|
|
Term
| Describe the idiosyncratic response. |
|
Definition
unusual and unpredictable
genetic based
ex- G6P deficiency after oxidant drug |
|
|
Term
|
Definition
immunological reaction
drug acts as antigen
ex- penicillin allergy of the free carboxyl on it |
|
|
Term
| Differentiate pharmcogenetics and pharmacogenomics. |
|
Definition
| pharmcogenetics is single genes where pharmacogenomics is the study of the whole genome |
|
|
Term
| Do genetic factors affect pharmacokinetics or pharmacodynamics? |
|
Definition
|
|
Term
~~~Succinylcholine apnea~~~
What is it? What is the genetic disorder of it? |
|
Definition
a short duration muscle relaxer used in surgeries
people with abnormal cholinesterase with reduced affinity for the drug do not metabolize it quickly and they have a prolonged effect |
|
|
Term
| How can you test for abnormal cholinesterases? |
|
Definition
using dibucaine(anesthetic) in the presence of cholinesterase
normal=80
abnormal= 20-40 (not limited by enzyme) |
|
|
Term
~~~Acetylation polymorphism~~~
What is it? What enzymes are involved? |
|
Definition
metabolism involving the formation of amides from acetyl CoA and amines
N-acetyltransferases are involved in the metabolism of drugs and carcinogens |
|
|
Term
| What the two types of N-acetyltransferases (NAT)? |
|
Definition
NAT-1- metabolizes p-aminosalicylate and p-aminobenzoic acid
NAT-2-metabolizes isoniazid and other anti infectives. Caffeine too |
|
|
Term
| What are the two varients of NAT-2? |
|
Definition
i-slow acetylators
ii- rapid acetylators |
|
|
Term
CYP3A4
what is family, subfamily, gene in family |
|
Definition
family-3
subfamily-a
gene in subfamily- 4 |
|
|
Term
| What are cytochrome p-450 polymorphisms? |
|
Definition
| polymorphisms of CYP 450 enzymes. this is the most common variation of pharmacokinetic metabolism |
|
|
Term
|
Definition
most polymorphic (70 variants)
~25% of drugs metabolized by it(beta blockers, antidepressants, opiods, etc)
-lower activity in whites and asians |
|
|
Term
| What drug can inhibit CYP2D6? |
|
Definition
prozac(fluoxetine)
this can cause increased levels of drugs metabolized by it such as tricyclic antidepressants |
|
|
Term
| What drug is associated with CYP2C9? |
|
Definition
warfarin
screening for CYP2C9 variants allows better dosing |
|
|
Term
| Which CYP2C9 variants are associated with excessive anti-coagulation? |
|
Definition
|
|
Term
~~~Thiopurine biotransformation~~~
What are the two drugs associated with it? What is the genetic disorder? |
|
Definition
azathioprine and mercaptopurine
HPRT converts it to toxic derivative
TPMT converts it to inactive form
TPMT alterations leave more thiopurines available to be metabolized to toxic form thus toxicity |
|
|
Term
| What is the difference of giving drugs based on phenotype vs genotype? |
|
Definition
phenotype- works with the genetic disorder
genotype- works to try and fix the disorder |
|
|
Term
| What is chronic myeloid leukemia(CML)? |
|
Definition
blood disorder characterized by myeloid cells in blood and marrow
it has the unique philadelphia chromosome structure of BCR-ABL fusion gene
cells with this gene continue to divide even after genotoxic drugs |
|
|
Term
| How do you treat CML? Both phenotype and genotype ways. |
|
Definition
Phenotype- allogenic stem cells
genotype- imatinib(gleevac), inhibits CML cells but not regular |
|
|
Term
| What is Cystic Fibrosis(CF)? |
|
Definition
autosomal disorder with thick mucous
symptomatically treated with bronchodialators, mucous thinners, antiinflammatory |
|
|
Term
| What is the most common cause of CF? |
|
Definition
| CFTR mutation of improper folding of the the protein which cause abnormal transport |
|
|
Term
| What is the new treatment for CF? Genotype treatment |
|
Definition
| small molecule chaperones stabalize misfolded protiens |
|
|
Term
| Does pharmacogenomic therapy replace genes? |
|
Definition
|
|
Term
| What is restriction fragment length polymorphism? |
|
Definition
| mutation at site where restriction enzyme cuts dna. changes sizes of fragments |
|
|
Term
| What is single nucleotide polymorphism(SNP)? |
|
Definition
point mutation at 1 per 1000 bases. 10mil in genome
used to track mutations although they dont cause the disease |
|
|
Term
|
Definition
| collaboration of identifying SNPs |
|
|
Term
|
Definition
sections of dna that are passed down
used SNPs based around the haplotypes 300k |
|
|
Term
| What are gene chips(microarrays)? |
|
Definition
| chip with genes in it allowing for identifying genes in patient |
|
|
Term
| What is expression profiling? |
|
Definition
| determining mRNA levels at certain times during the day |
|
|
Term
| Iressa is used for lung cancer, what recpetor does it act on? |
|
Definition
EGFR
only 10-25% of patients will benefit from it |
|
|
Term
| What are susceptibility markers BRCA1 and BRCA2 associated with? |
|
Definition
|
|
