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Pharm Block 9
KYCOM Block 9
351
Pharmacology
Graduate
08/31/2013

Additional Pharmacology Flashcards

 


 

Cards

Term
pharmacology: definition, what subjects is it composed of
Definition
study of interaction of chemicals with living systems

combines biochemistry, pathophysiology, molecular biology, microbiology, and organic chemistry
Term
hoq is the success of a drug measured (3)
Definition
insturments (BP cuff), lab tests on fluid or tissue, observation of pt symptoms
Term
how does a doc choose a drug? 9 criteria
Definition
patient population of the specility (knowledge of drugs), decide if the new drug is really bettwe, experimentation, experience, variability of the patient, lab results, emergent or non emergent results needed, patient status changes, drug interactions/multiple illnesses
Term
what biological differences may alter choice in drug (4)
Definition
body size, personal response to drug, patient preferences, age
Term
define drug
Definition
substance that acts on libing systems at a chemical or molecular level
Term
define drug receptor
Definition
molecular component a drug interacts with
Term
define medical pharmacology
Definition
study of drugs for diagnosis, prevention, and treatment of disease
Term
define toxicology: what is its root subject, what substances does it include
Definition
study of undersiable effects of chemicals on living systems

part of pharmacology

deals with industrial pollutants, organice and inorganic poisons, and other chemicals
Term
define pharmacodynamics: what are three types of examples of subjects within this topic
Definition
action of a drug in the body

receptor interactions, dose response (side effects), mechanism of theraputic and toxic action
Term
define pharmacokinetics: what processes does this involve
Definition
actions of the body on a drug

absorption, distribution, biodisposition (metabolism and excretion)
Term
define therapeutic inxex: what is a aka
Definition
margin of safety

measure of how safe a drug is
Term
how is the TI calculated: give equation and word definition
Definition
ratio of dose that causes toxicity in 50% of the population to dose that causes clinical response in 50% of the population

TI=TD50/ED50
Term
explain how the number given for TI is interperteted
Definition
small TI is bad. if very small it could mean even putting doses too close together could cause overdose

example: TI of 10 means 10xED becomes toxic
Term
when is a pharmological response the greatest
Definition
when the concentration of the drug at the point of action is the highest
Term
what are the three ways to name drugs, how is each determined, which do we care about
Definition
chemical: molecular structure (dont care)
generic: US adopted name council (comlex cares)
trade: drug company (we care sometimes)
Term
what qualifies drug pregnacy category A
Definition
safe, no risk to fetus in any trimester
Term
what qualifies drug pregnacy category B
Definition
mostly safe, animal studies may show risk but human studies dont
Term
what qualifies drug pregnacy category C
Definition
unsure if safe, benifit may outweigh risk, there were no studies
Term
what qualifies drug pregnacy category D
Definition
will harm fetus, positive evidence of fetal risk, only use if benifit to mom > risk to fetus
Term
what are examples of drugs in category d
Definition
ACEI, ARBs, anticonvulsants
Term
what qualifies drug pregnacy category X
Definition
never use will harm fetus, animal or human studies show fetal abnormalities, risk always > benifit
Term
what are examples of drugs in category X
Definition
OCs, statins
Term
when prescribing a drug in category X at any time, what needs to be done
Definition
inform female patient not to get pregnant
Term
what is another way to say a drug harms the fetus
Definition
termatogenic
Term
what is the purpose of the controlled substance act
Definition
regulate manufacture, distribution, dispensing, and use of all CNS drugs
Term
which drugs are an exception to the controlled substance act
Definition
alcohol, tobacco, and states can make more strict laws
Term
schedule C-I: abuse potential, when allowed and warnings, when it can be used, examples
Definition
highest abuse potential

no medical use allowrd, only experimental

heroin, LSD, marijuna, PCP
Term
schedule C-II: abuse potential, when allowed and warnings, when it can be used, examples
Definition
high abuse potential

may cause dependence, accepted for medical use, no refills allowed, perscription must be signed

morphine, amphetamine, fentaynl
Term
schedule C-III: abuse potential, when allowed and warnings, when it can be used, examples
Definition
moderate abuse potential

may cause moderate dependence, accepted medical use, perscription may be phoned in, no more than 5-6 refills

codine for pain, steroids, sedatives, stimulants
Term
schedule C-IV: abuse potential, when allowed and warnings, when it can be used, examples
Definition
less abuse potential

no restrictions for medical use, perscription can be phoned in, no more than 5-6 refills

benzodiazepine
Term
schedule C-V: abuse potential, when allowed and warnings, when it can be used, examples
Definition
least abuse potential

no medical restrictions, can be bought OTC sometimes

codine for cough
Term
what are the 4 categories of drug characteristics
Definition
physical, size, reactivity/bonding, shape
Term
what are the possible physical characterisics of drugs
Definition
solid, liquid, gas
Term
how does the size of a drug affect its function
Definition
related to specific receptor

related to ability to move within the body, smaller can cross more selective barriers (BBB, placenta)
Term
what types of bonds to drugs use to bind to their receptors from strongest to weakest
Definition
covalent, ionic, hydrogen, dipole dipole, hydrophobic interactions
Term
covalent bond: strength, effect on drug, proportion of drugs with them
Definition
strong irreversible bond

not common

drug that binds covalently is long lasting because it is hard to remove
Term
what is the major difference in the function of strong vs weak bonds in drugs
Definition
strong bonds only have one bond making it more likley that they will bind something else that isnt the receptor

weak bonds have multiple bonds to the receptor, making it less likley something other than the intended receptor will have the exact configuration to accomodate all those bonds
Term
why is drug shape important, what is the main thing about shape we are concerned about
Definition
important for proper binding, chirality or steriosmerism is the most important part of shape
Term
what does it mean for a drug when it has multiple enatiomer possabilities
Definition
one will fit the receptor and will work the best, the others may be toxic, useless, too susceptible to metabolism
Term
what is a viral capsule composed of
Definition
lipid envelope with antigenic glycoproteins
Term
where do viruses replicate
Definition
in the cytoplasm except influenza which replicates in the nucleus
Term
how do DNA viruses replicate there genetic materia, give 5 examples
Definition
DNA transcribed into mRNA by host polymerase

herpes: chicken pox, shingles, CMV
HepB
Term
RNA viruses: how do they replicate their genetic materia, give 5 examples
Definition
mRNA is translated directly into viral proteins via viral RNA polymerase

rubella, HepC, polio, rhinovirus, influenza
Term
two examples of retroviruses
Definition
HIV
HTLV
Term
what is the prefered way for anitvirals to work
Definition
stop virus rather than host cell directed synthesis
Term
what type of virus is HIV classified as (4 ways)
Definition
lentivirus
mammalian, retro, or enveloped virus
Term
what are the three major parts to the HIV genome, what is their general function
Definition
gag: major structural proteins
pol: reverse transcriptase and viral integrase
env: envelope protein for cell binding and entry
Term
what 3 proteins does env make, what do they do
Definition
env protein (GP160) binds CD4 receptor on lymphocytes and macrophages

Gp41 domain: part of env that controls fusion of the virus lipid bilayer with host cell

CCr5: co-receptor required for binding on macrophages
Term
what are the common clinical presentations of HIV
Definition
mononucleosis like
fever
pharyngitis
adenopathi
erythmatous macular or maculopapular rash
primary infection associated with high viral load
persistant decrease in CD4
Term
what are the aids interventions
Definition
no cure

administer perscribed medications
treat opportunistic infections
maintain standard percautions
psychosocial, financial, or occupational support
Term
what is a NRTI, which 5 do we need to know, what are their abrevirations
Definition
nucleoside reverse transcriptase inhibitor

Zidovudin (AZT, ZDV), didanosine (DDI), lamivudine (3TC), abacavir (ABV), emtricitabine (FTC)
Term
what is a antimetabolite, what drug is an example of this
Definition
drug that looks like something in the body

NRTI
Term
what is the MOA of a NRTI
Definition
• Must be phosphorylated to the 5-triphosphate moiety to be active
• HIV does not encode viral kinases so phorphorlyation is by host kinases and phospotransferases
• 5-triphosphate-DRUG prematurely terminates DNA elongation and competes with natural deoxynucleotides for reverse transcriptases
Term
what are the base analogs involved with each of the NRTI drugs, why do we care
Definition
• Thymidine: AZT, d4T
• Cytosine: 3TC, ddC, FTC
• Adenosine: ABV
• Inosine: ddI

because you cant use to of the same base analogs together
Term
what resistance concerns do we have with NRTIs
Definition
develops due to mutation of reverse transcriptase
Term
what are the elimination methods of the NRTIs
Definition
• AZT, ABV: eliminated by liver metabolism (glucuronidation)
• D4T, 3TC, ddC, ddI: eliminated by kidney
Term
what are the adverse effects of AZT, what type of drug is this
Definition
bone marrow supression
NTRI
Term
what are the adverse effects of ddl, what type of drug is this
Definition
pancreatitis
NTRI
Term
what are the adverse effects of ABV, what type of drug is this
Definition
hypernsensitivity
NHRI
Term
what side effects do most NTRIs have, what predispositions
Definition
lactic acidosis especially in renal issues

peripherial neuropathy is very common
Term
what are the two safest NTRIs, what is wrong with this
Definition
3TC and FTC, they are both cytosine analogs and cannot be used together
Term
what is a NtRTI what drg do we need to know, what is the naming warning
Definition
nucleotide reverse transcriptase inhibitor

tenofovir

has an -ovir but isnt a herpes drug
Term
what is the composition of tenofovir
Definition
conformulated with entricitabine (truvada), combivir, or enzicon
Term
what is the function of a conformulation
Definition
perferred nucleoside analog combination due to overall efficacy, favorable toxicity, and convenience of dosing

reduce pull burdon and increase pt compliace
Term
what is the MOA of tenofovir
Definition
single phosphate on surfar nucleotide residue must be phosphorlyated to the active form (tenofovir triphosphate) by the host
Term
how is tenofovir used
Definition
in combination with other antiretroviral agents (like a NRTI)
Term
what are the adverse effects of tenofovir
Definition
none
Term
what is a NNRTI

what drugs do we need to know
Definition
non-nucleoside reverse transcriptase inhibitor

efacirenz, nevirapine, rillpivirine, etarvirine
Term
what is the MOA of NNRTI
Definition
bind to reverse transcriptase below catalytic site (allosteric inhibition) causing enzyme inactivation

does not require phosphorlyation to become active
Term
what are the resistance issues with NNRTIs
Definition
major issue
develops rapidly and can cause cross resistance with other agents
resolved by combination therapy
Term
what are the pharmacokinetics of the NNRTIs
Definition
nevirapine and efavirenz have good CNS presentation
some P450 effects
Term
what are the adverse effects of NNRTIs
Definition
maculopapular rash
CNS effects with efavirenz
Term
what are the function of proteases in viruses
Definition
help virus mature
Term
what are the protease inhibitor drugs we need to know
Definition
Ritonavir, lopinavir, atazanavir, darunavir
Term
what is the MOA of a protease inhibitor
Definition
HIV-1 proteast inhibited. it normal cleaves viral precurose proteins so this stops mature virons
Term
what are the resistance issues with PIs
Definition
mutation of protease causes some
Term
what are the pharmacokinetics
Definition
take with food
indinavir and amprenavir noo need for food
Term
adverse effects of PIs
Definition
• sulfonamide allergy with darunavir (sulfa drugs)
• GI upset, nausea, vomiting, diarrhea (esp nelfinavir)
• Disordered lipid and carb metabolism: central adiposy and insulin release (fat deposition). The longer the use of the drug the more likely to happen
Term
what interactions are there with PIs
Definition
• All protease inhibitiors inhibit P450 enzymes (esp ritonavir which is most potent)
• Rifampin (TB druf): Reduced dose of rifabutin (indinavir and nelfinavir require lesser adjustment) will work for TB
Term
what are some tips on how to use PIs
Definition
use ritonavir with other PIs to take advantage of its ability to increase plasma levels of other drugs
Term
how does ritonavir increase plasma levels of other drugs
Definition
potent P450 inhibitor
well tolerated at a low dose
can make some additional PI dose lower and less frequent
Term
lopinavir: how is it perscribed, what is the function
Definition
only comes =with ritonavir

boosted due to P450 effects, strong, has few side effects, preferred
Term
MOA fusion inhibitor
Definition
blocks gp41 protein on T cell surface ot prevent viral entry
Term
how is a fusion inhibitor used
Definition
in combo with other HIV drugs when they have failed
Term
drug that is an infusion inhibitor
Definition
fuzeon
Term
drug that is a CCR5 receptor antagonist
Definition
maraviroc (selzentry)
Term
CC5R receptor antagonist MOA
Definition
CCR5 protein on macrophage (or T cell) surface to prevent viral entry
Term
CCRF receptor antagonist: use
Definition
in combination with other HIV drugs in treatment experiencded patients
Term
drug that is an intigrase inhibitor, naming issue?
Definition
reltegravin (isentress)
watch out -avir and not a protease inhibitor
Term
integrase inhibitor MOA
Definition
inhibits HIV enzyme integrase which integrates viral genetic material into host chromosomes
Term
what is the use of an integrase inhibitor
Definition
in combination with other HIV drugs in treatment experinced pt who has failed other methods
Term
what are the combination cocktails used in HIV treatment
Definition
2 NRTI + 1-2 PT (one is ritonavir)
OR
2 NRTI + NNRTI
OR
2NRTI + raltegravir
Term
what is the HIV treatment during pregnacy
Definition
zidovudine: prior to labor and during for mom. six weeks after birth for baby
Term
what qualifications suggest you should start treating AIDs
Definition
severe symptoms, any CD4 count, any HIV RNA count
OR
asymptomatic, CD4 between 200-350 cells/mm
OR
asymptomatic, >35 CD4 cells, >100,000 HIV RNA: sometimes treat
Term
how is a HIV treatment evaluated for success
Definition
monitor viral load, VD4, and clinical symptoms every 3 months
if two or more indicatoes show change (toxicity or treatment failure) change therapy
Term
what are the reasons for HIV therapy failure
Definition
non-adherance
advsere drug reactions
development of reiestance
Term
order of perdicted infections in a HIV pt over time
Definition
bacterial skin infections
varicella zoster, kaposi's sarcoma
oral candidias
pneumocstitis jiroveci pneumona
non-hodgkins lymphoma

Once CD4 halved
cryptococcal meningitis, herpes simplex
CMV, mycobacterium avium
Term
what are 8 common infections associated with HIV
Definition
mycobacterium avium
mucocutaneous herpes zimplex
varicella zoster
CMV
pneumoystis jurioveci
mycobacterium TB isoniazid sensitive
mycobacterium TB isoniazid resstannt
toxoplasma gondii
Term
how is mycobacterium avium treated
Definition
clathromycin 500 mg PO 2x/d
azithromycin 1200 mg PO 1x/wk
Term
how is mucocutaneous herpes simplex treated
Definition
acyclovir 1-2 g/d PO in 3-5 doses for 7-10d
Term
how is varicella zoster treated
Definition
acyclovir 30 mg mg/kg/d IV in doses
OR
4 g/d PO for 7-10d
Term
how is CMV treated
Definition
ganciclovir 7.5-10 mg/kg/d in 2-3 doses for 14d
OR
foscarnet 180 mg/kg/d in 2-3 doses for 14 days
Term
how is pneumocystis jiroveci treated
Definition
trimethoprim sulfmexthoxazole 1 tab/d
Term
how is mycobacterium TV isoniazid sensitive treated
Definition
isoniazid 300 mg
Term
how is mycobacterium TV isoniazid resistant treated
Definition
rifampin 600 mg PO qd x 10 mo
Term
how is toxoplasmosis gondii treated
Definition
TmP-SMX 1 tab PO qd
Term
HSV1 symptoms 14
Definition
HSV1: cold sores, oral transmission, respiratory secretions, fever, sore, red, swollen throat, vesicles on tongue in 2-12d, cheeks, lips, lymphadenopathy, increased salivation, halitosis, anorexia
Term
HSV2 symptoms 8
Definition
HSV2: genital herpies, sexual transmission, malase, tingling, burning, itching, malaize, fluid vesicle that ruptue and become painful
Term
what is the intervention for herpes simplex 7
Definition
NSAIDs for pain and fever
anesthetic mouth wash
cool compress
topical anesthetics
drying agents
antiherpetics
good hygiene
Term
herpes zoster (shingles) pathophysiology
Definition
herpes virus varicella-zoster is reactivated and causes acute inflammation of dorsal root ganglion of each spinal nerve.
virus multiples and antibodies form chicken pox infection to neutralize it
Term
signs and symptoms of herpes zoster 6
Definition
pain (post herpatic neurlgia)
fever
malaise
small red vesicular lesions errupt and spread in 48-72 hours
10-21 says afrer rash vesicles dry and scab
trigeminal nerve symptoms if there
Term
acyclovir MOA
Definition
thymidne kinase phosphorlyates acyclovir (faster than host can), host adds additional 2 phosphate

product (acyclo-GTP) is incorporated into the viral DNA and terminates chain growth because it dosent have a 3'hydroxyl to continue the chain
Term
what is acyclovir triphosphate a competitive inhibitor to
Definition
DNA polymerase
Term
what is the acyclovir MOA simillar to, except
Definition
NRTA MOA with different target
Term
what is the antiviral spectrum of acyclovir: what is the method of administration
Definition
orally for mucocutaneous and genital herpes and prophylaxis of AIDS

IV for severe herpes (encephalitis and neonatal HSV)
Term
what ar the resistance concerns with acyclovir
Definition
mutation in DNA polymerases
lack of thymidine kinase can cross transfer resistance to famciclovir, ganciclovir, and valacyclovit
Term
what are the pharmacokinetics of acyclovir
Definition
topical or oral 5x/d or IV
excreted by kidney
Term
what are the adverse effects of acyclovir
Definition
Gi upset
delerium
tremor
seisures
hypotension
nephrotoxicity (crystal urea: keep well hydrated)
Term
what is the MOA of valacyclovir like, how is the drug used differently
Definition
prodrug of acyclovir and acts like it is used like it

doses less frequently
oral only
Term
what is the MOA of penciclovir like, what is the difference
Definition
it acts alike acyclovir but is used topically for cold sores
Term
what drug is famciclovir like, how is it different
Definition
it is a prodrug of penciclovir and acts like it.
used like acyclovir but dosed less frequently
Term
what are the three antiherpes drugs for the eye, what is the MOA
Definition
vadarabine, idoxuridine, trifluridine

blocks viral DNA synthesis stopping keratoconjunctivitis and epithelial keratitis due to the viral actions
Term
what are the resistance concerns, pharmacokinetics, and adverse effects with vidarabine, idoxuridine, trifluridine,
Definition
concerned about altered DNA polymerase

given as opthalamic solution

may cause burning, photophobia, visual haze
Term
cidofovir: ganciclovir: MOA, antiviral spectrum, resistance, pharmacokinetics, adverse effects
Definition
chain terminator

antiviral spectrum is same as acyclovir but used only for CMV retinitis

TK- strains are resistant

given via IV

glanciclovir causes marrow supression which is dose limiting
cidofovir causes nephrotoxicity
Term
foscarnet MOA
Definition
selective inhibitor of pyrophosphate building sote on virus DNA polymerase and reverse transcriptase

not an antimetabolite, no TK or kinase activation needed
Term
foscarnet antiviral spectrum
Definition
CMV retinitis, acylovir-resistant HSV, herpes zoster
used when resistant to acyclovir
Term
foscarnet: resistance concerns, pharmacokinetics, adverse effects
Definition
concerned for mutated DNA polymerase

given via IV

can cause nephrotoxocity and altered electrolyte balance (Ca and P)
Term
what are the different types of influenza, what are their differences
Definition
A: seasonal epidemics, has hemagglutin 1-3 and neuraminidase 1-2 antigens that affect humans

B: sporatic outbreaks, especially iin long term care facilities
Term
what is the most common antigen configuration for influenza
Definition
H3N2 and H1N1
Term
signs and symptoms of linfluenza
Definition
rapid onset fver, myalgia, headache, malaise, nonproductive cough, sore throat, rhinitis
Term
what lavs should you get to diagnose inflenze
Definition
CBC, chem pannels, viral culture (best but longest)
Term
what drugs are used to teat influenza
Definition
amantadine and rimantidine
zanamivir and osteltamivir
Term
amantidine and rimantidine MOA
Definition
inhibit uncoating of influenza A, rase endosomal pH (need acidic for enzyme function). target M2 protein
Term
amantidine and rimantidine antiviral spectrum
Definition
influenza A prophylaxis and treatment within 40 hours of contact (except it is 92% resistant)
amantidine has some usefelness in parkinsinism (increases dopaine)
used in oselatamivit resistant areas (combined with zanamavir)
Term
amantidine and rimantidine pharmacokinetics
Definition
oral amantadine: penetrates CNS, not metabolized

rimantidine: does not penetrate CNS, very metabolized (water solube0
Term
amantidine and rimantidine adverse effects
Definition
amatadone: CNS effects )insomnia, dizzyness, seizures, hallucinations)

ramantadine: GI upset
Term
zanamivir and osteltamivir (tamaflu) MOA
Definition
inhibit budding, neuraminidase inhibitor
Term
zanamivir and osteltamivir (tamaflu) antiviral spectrum
Definition
influenza A and B prophylaxis and treatment
commonly used
Term
zanamivir and osteltamivir (tamaflu) pharmacokinetics:
Definition
zanamivir: disc inhaled
ozeltamivit: oral, give within 12 h of onset
Term
zanamivir and osteltamivir (tamaflu) adverse effects
Definition
GI upset, headache, bronchitis
Term
respiratory synctial virus (RSV): organism, infection process, common infected, clinical appearance, normal care
Definition
paramycovirus
infection of respiratory tract and prominent rhinorrhea
common in kids 0-2yo in winter
looks like common cold to pneumonaw
usually treated with bronchodilators and supportive care
Term
RSV drugs
Definition
ribavirin
palivisuamb
Term
ribavirin MOA
Definition
converted to ribavirin-triphosphate and inhibits viral mRNA synthesis
antimetabolite
Term
ribavirin antiviral spectrum
Definition
not recommened in children with bronchiolitis or pneeumonia
laslas fever, hantavirus associated hemorrhagic fever, RSV
Term
ribavirin pharmacokinetics
Definition
aerosol for inhalation, IV or viral hemorrhagic fever, RSV
Term
ribavirin adverse effects
Definition
bronchial irritation, myelosupression when systemic
Term
palivisuamb MOA
Definition
humanized monoclonial antobidy against RSV F glycoprotein
Term
palivisuamb antiviral spectrum
Definition
for select infants and kids under 24 mo
used to prevent RSV
Term
where do herpes infect, what do they cause
Definition
infect and damage liver
jaundice, release of liver enzymes
Term
what are the three herpes viruses
Definition
picornovirus
serum hepatitis
flavivirus
Term
picornovirus: type, aka, type of infection, tx
Definition
RNA virus
causes HepA
fecal-oral route
no drugs needed
Term
serum hepatitis; aka, type of virus, spread by
Definition
hepadenvirus
DNA virus
causes HepB
spread by blood or sex
Term
glavivirus: type, aka, spread by
Definition
RNA virus
causes HepC
spread by blood or sex
Term
antihepatitic drugs
Definition
interferon-a
adefovir
lamivudine
Term
interferon a: what does it treat, MOA, pharmacokinetics, adverse effects
Definition
treats HepB and HepC (Hep C also needs ribavirin)

inhibits viral RNA translation

giben IV, penetrates cns

lethargy, marrow supression, ChF, acute hypersensitivity reaction
Term
adefovir: treats, pharmacokinetics, MOA, adverse reactiopns
Definition
treats HepB

take for 1 year

nucleotide is converted to triphosphate form to inhibit DNA polymerase

low nephrotoxicity
Term
lamivudine; treats, take for how long
Definition
treas HepB, take for 1 year
Term
define regimen
Definition
plan for administration over a period of time

achievement of therapeutic level of the drug in blood without exceeding the minimum toxic concentration
Term
define target plasma level
Definition
guide dosage, able to determine if we can measure effect of the drug
Term
how can you evaluate the effect of a drug that can't be measured
Definition
pick a desired target (steady state) plasma level

compute dose to achieve that level

measure plasma levels of the drug

adjust dose as needed to get that level
Term
define maintience dose
Definition
adjust dose so rate of input equals rate of loss, keeps plasma level at target
Term
calculation of maintience dose
Definition
Dosing rate Ro = Css x CL/F
F= bioavailability
Term
define loading dose
Definition
initial dose to get drug to target level, can be a series
Term
calculation of loading dose
Definition
loading dose = Css x Vd/F
Term
what is the steady state, what is the function
Definition
ensures appropirate response to a drug given for long term therapy
Term
how is steady state effected
Definition
elimination
Term
how can you improve steady state
Definition
give the drug more frequently
Term
how is steady state related to half life
Definition
double dose has higher steady state so the half life is the same as a lower dose

time to steady state is determine by half life

dose and how often dont help steady state

for every 1/2 life you get 1/2 the way to the goal of steady state

clinical steady state is 4-5 1.2 lives which is close enough to 100%
Term
define therapeutic window and are the parts, define themm too
Definition
useful opening between min theraputic concentration and min toxic concentration

through levels: determined by min effective concentration

peak plasma concentration: determine by min toxic concentration
Term
what does a bad kidney do the clearance how do we adjust this
Definition
renal disease or reduced CO reduces clearance
Term
how is clearance calculated
Definition
corrected dose = average dose x (creatine clearance / (100mL/min))
Term
equation for clearance not inthe kidney
Definition
corrected dose = amt by non renal - amt by kidney x (creatine clearance / (100mL/min))
Term
what are the general steps in new drug synthesis
Definition
discovery and synthesis of new molecule

in vitro studies determine effective dose

animal testing

IND

clinical trials (3 phases)

data gathering phase

approval
Term
what is the information gathered for pre-clinical safety and toxicity (8)
Definition
acute toxicity
subacute toxicity
chronic toxicity
effects on reproduction: cellular and behavorial
carcinogenicity: 2 years looking into prolonged use
mutagenicity: effect on genetically stable bacteria or mammal cell culture
investigaive toxicology: determine MOA of toxic actions
quantative estimates
Term
define acute toxicity
Definition
efects of large single dose up to lethal dose. max tolerated dose
Term
define subacute toxicity
Definition
effects of multiple doses over time in ratio to the expected clinical duration
Term
what are the wuantative estimates in teh pre-clinical safety and toxicity assessment
Definition
no-effect dose: max dose at which toxic effect is not seen

minimal leathl dose: smallest dose that is observed to kill any animal

median lethal dose (LD50): dose tha tkills approx 50% of animals
Term
what are limitations during the pre-clinical safety and toxicity testing
Definition
toxicity testing is time consuming and expensive
large numbers of animals are used which is mean
extrapolation of toxicity from all species tested has a high perdictive value to statistical reasons, rare adverse effects are unlikley to be detected
Term
what drug testing design must be used for human approval, explain it
Definition
crossover: alternating periods of administration of test drug, placebo, and standard treatment
Term
how must human test subjects be chosen
Definition
large enough population over sufficient period of time

presence of other diseases and lifetyle choices can affect the study so you have to randomize

minimize subject and observer bias and weed out placebo effect results. double blind can help this out
Term
what does the FDA mandate about drugs, what is concerning about this
Definition
drugs must be safe and effective

safe means different things to doc, patient, and society. complete absence of risk is impossible

public assumes FDA approval means free of serious or all side effects
Term
what is IND, when does it happen, what must be done by this point
Definition
new drug is ready for trial in humans and must be filed with the FDA

need acute and subacute animal toxicity studies

chronic safety testing can be done in animals and humans at the same time

volunteers and patients informed of status of drugs and risk and be allowed to decline at any time
Term
what happens in clinical trial phase 1, what is the goal
Definition
effect of drug dose in a small number of healthy volunteers unless drug has a toxic risk (then use sick volunteers) non-blind

determine if humans and animals have the same response, show perdictable toxicities
Term
what are the chances of getting past clinical trial phase 1
Definition
you can usually find a non toxic dose so pretty good
Term
what happens in phase 2, how is it done, what is the goal
Definition
drug is studied in a small number of patients with the disease to determine EFFICACy

single bind with placebo or older active drug usually in a university hospital

find a broader range of toxicities
Term
what are the chances of getting past clinical trial phase 2
Definition
not so much most drugs fail here
Term
what happens in clinical trial phase 3, how is it done
Definition
evaluation of a large population to judge safety and efficacy

double blind cross over study performed in the natural setting for the drug future use

goal is to have success and get permission to market in a controlled setting
Term
what happens in clinical trial phase 4, what is the goal
Definition
begins after marketing approval
postmarking surveillance program
important side effects at incidence f 1:10,000 or less are formed
Term
what are the considerations when evaluating a clinical drug study
Definition
ethical considerations: adequate safegaurds, proper concent

statement of objectives: what are they? are they clear?

experimental methods: were they ok? were they sensitive?

statistical methods: how were patients selected? were placebo positive controls used?

conclusions: does the data justify them? does the drug have a cost, efficacy, or safety advantage over the old drug?

look at peer reviews
Term
define an orphan drug, what is the problem, how was it fixed
Definition
drugs for rare diseasees

difficult to research, develop, and market

kids diseases, not as cost effective, less people buying the drug, pathology gets little attention

orphan act is incentive to develope these drugs
Term
define chronic toxicity
Definition
required when drug is intened for prolonged use. tested for 2 years
Term
what is the qualification of a drug that binds to a receptor
Definition
it must induce a biological response
Term
what drugs dont use receptors
Definition
diuretics and anesthetics
Term
where are drug receptors located
Definition
membrane proteins, cytoplasmic enzymes, extracellular enzymes, nucleic acids
Term
why are drugs/receptors specific
Definition
differnet tissues have receptors with different conformations that will only accept certian drugs
Term
what is the purpose of innert binding sites
Definition
drug binds a non-regulatory molecule (most commonly plasma membrane) and causes no changes but hitches a ride because it is lipid soluble and cannot travel in the blood
Term
how does innert binding sites affect drug effects
Definition
they ability or need of a drug to bind to them effects distribution and amount of the drug availiable
Term
explain the role of ionization in drug binding to receptor, what is the down side of needing to be ionized for bonding
Definition
when drug nears receptor various ionic bonds form but to participate the drug needs to be ionized first.

some drugs are already ionized

pH will alter non-ionized drugs
Term
what is the down side of a pre-ionized drug, what is the up side
Definition
it is water solube and will not distribute as well in the body because it cant get through membranes well (so no BBB or placenta crossing)

pH will not alter these as much
Term
where are nicotinic ACh receptors located
Definition
neuromuscular junction muscle end plate

autonomic ganglic

CNS
Term
what type of receptors are nicotinic ACh receptors
Definition
ligand gated ion channels
Term
what is the general function of a nicotinic ACh receptor, how does it work
Definition
depolarization of a cell

2ACh bind to 2 alpha subunts on recpetor and electrically open Na or K channels causing depolarization
Term
what is the down side of using nicotinic ACh receptors as a drug target, why
Definition
they can become desensitized if they have prolonged ACh exposure because the conformation of the receptor is altered so even if ACh binds there is no depolarization
Term
where are sodium channels located
Definition
excitable tisses like nerve, cardiac, skeletal muscle
Term
what type of channel are sodium channels, how do they work
Definition
voltage gated ion channels

resting state channel is closed and intracellular Na is low due to Na/K pump. depolarization of the membrane opens the channel allowing Na into the cell
Term
what drugs target Na channels, why
Definition
anesthetics to block nerve transmission by stopping Na influx
Term
where are g-protein coupled receptors located, describe their general structure
Definition
on almost all cells

heterotrimetric receptor with 7 transmembrane domains
Term
explain the process of a Gs or Gi protein once a ligand binds them
Definition
alpha subunit catalizes exchange of GDP to GTP and releases from beta and gamma creating alpha-GTP

alpha-GTP activates adenylyl cyclase then hydrolyzes GTP back to GDP

adenylyl cyclase converts ATP to cAMP

cAMP activates protein kinase A
Term
explain the process of a Gq protein once a ligand binds them
Definition
alpha subunit catalizes exchange of GDP to GTP and releases from beta and gamma creating alpha-GTP

alpha-GTP activates phospholipase C then hydrolyzes GTP back to GDP

phospholipase C releases IP3 and DAG from the phosphatidylinositol in the plasma membrane

IP3 activates Ca and calmodulin dependent kinase

DAG activates protein kinase C
Term
give examples of receptors Gs proteins are on
Definition
b-adrenergic

H2 histamine
Term
give examples of receptors Gi proteins are on
Definition
M2 muscrinic
a2 adrenergic
D2 dopamine
Term
give examples of receptors Gq proteins are on
Definition
a2 adrenergic
M2 and M3 muscerinic
5HT2 serotonin
Term
what agonists can activate a tyrosine kinase receptor
Definition
insulin, EGF, PDGF, HGF, ANF, TGF-beta
Term
describe the structure of a tyrosine kinase receptor
Definition
extracellular ligand binding domain

single transmembrane domain

intracellular binding domain with an INTRINSIC tyrosine kinase (means it is not activated by the receptor, it is ON the receptor)
Term
explain how a tyrosine kinase receptor works
Definition
ligand binds the extracellular domain, receptor dimerizes, tyrosine kinase signals within the cell
Term
what agonists can activate a cytokine receptor
Definition
growth hormone, erythropoetin, interferons
Term
explain how a cytokine receptor works
Definition
ligand binds, receptor dimerizes

JAK activates STATs

STATs signal transcription of genes
Term
agonists to intracellular receptors (6)
Definition
corticosteroids, mineralcorticoids, sex steroids, thyroid hormones, vitamin D, NO
Term
how does a steroid agonist activate a receptor
Definition
agonist goes through cell membrane to intracellular cytoplasmic receptor, receptor ligand complex travels to nucleus and signals transcription of genes
Term
explain how NO activates the receptor and changes within the cell
Definition
NO is generated in endothelial cells and diffuses into smooth muscle cells and reacts with gyanylyl cyclase which stimulates cGMP which activates protein kinase G which phosphorlyates to relax smooth muscle
Term
define agonist
Definition
drug that binds to same site as ligand and creates same signal
Term
define allosteric agonist
Definition
drug binds to different site than ligand creating no signal but causing ligand to be more effective
Term
define partial agonist
Definition
drug produces lesser response than ligand and competes for ligand sites competetivly
Term
define antagonist
Definition
drug binds to ligands receptor and inhibits it leading to no signal within the cell
Term
define competitive agonist
Definition
drug binds irreversibly to the receptor and prevents agonist from binding and producing max effect
Term
define chemical antagonist
Definition
drug binds to another drug to antagonize its action. no receptor involved
Term
define physiological antagonist
Definition
antagonist makes physiological action that is opposite of agonist and by separate mechanism

opposing drugs compete effects but go for different receptors
Term
compared to the agonist, what receptor and signal does an allosteric agonist have, what response does it ilict
Definition
receptor: different
signal: same
response: increased (assuming agonist present)
Term
compared to the agonist, what receptor and signal does an partial agonist have, what response does it ilict
Definition
receptor: same
signal: same
response: less than agonist
Term
compared to the agonist, what receptor and signal does an antagonist have, what response does it ilict
Definition
receptor: same
signal: none
response: less than agonist
Term
how can the drug dose relationship, in a general statement, serve as a guidline for perscribing
Definition
dont perscribe over the minimum dose it takes to produce the maximum response

increase in dose generally means an increase in response, at some point the response will max out though
Term
how is the drug dose relationship calculated
Definition
E=(Emax x C) / (C + EC50)
E = effect
C = concentration
Emax = max response
EC50 = concentration that produces 50% of max effect
Term
what is a similar theory that the drug dose relationship equation can be used for, what is the equation
Definition
B = (Bmax x C) / (C + Kd)
B = number of receptors
Kd = concentration of free drug producing half max binding to receptors
Term
what does a low Kd mean
Definition
high binding affinity
Term
what does it mean if Kd = EC50
Definition
nothing much,

at 50% of drug binding, you get 50% of drug max effect
Term
where are Kd and EC50 found on a percent bound/max effect vs drug concentration graph
Definition
on the x axis at 50% binding or 50% max effect
Term
explain where an agonist + allosteric agonist, a partial agonist, a non-competitive agonist, and an agonist + antagonist are on a graph in comparison to just an agonist
Definition
agonist + allosteric agonist: shift left
partial agonist: shorter
non-competitive agonist: much like partial agonist, progressivly decreases
agonist + antagonist: shift right
Term
define pharmacological antagonism, what antagonists fit into this category, which dont
Definition
2 drugs with opposite effects go for the same receptor

pharmacological antagonists: competitive and non-competitive agonists

not: chemical and physiological agonists
Term
potency definition
Definition
concentration needed to produce 50% of the drug max response

the dose, how much you need to take, the size of the pill
Term
how is potency determined on a graph
Definition
by looking at the Y axis, the more left the more potent

if curve on the left is taller than the right every dose is more potent
Term
define efficacy
Definition
upper limit of the dose response curve

the higher the more effective the drug
Term
what is the most important thing about a drug
Definition
efficacy
Term
how is efficacy determine on a graph
Definition
look at the X axis, the higher the curve the more effective
Term
what is clinical effectiveness dependent on
Definition
potency, max efficacy, ability to reach receptors
Term
why are there spare receptors
Definition
max effect was achieved without filling all the receptors because there are more receptors than effectors to signal within the cell

OR

receptors, although without ligand, are still occupied with the signaling process so are empty until finished
Term
what can spare receptors tell us about drug sensitivity
Definition
if max effect is achieve with few receptors occupied, the drug is more sensitive
Term
on a graph, where is the drug response curve depicting spare receptors
Definition
to the left of receptor binding
Term
what can indicate to you that at the time there are no spare receptors
Definition
EC50 = Kd
Term
if there are 11 receptors and 4 receptors how many spare receptors are there, what is the relationship of EC50 to Kd
Definition
7 spare receptors

EC50
Term
what information does a quantal dose effect plot give us
Definition
EC50, LD50 (leathal dose in 50% of popultation), TD50 (toxic dose in 50% of the population)
Term
what do we want our drugs to show on a quantal effective dose plot
Definition
ED50 far away from TD50 and REALLY far from LD50
Term
what are the reasons for drug response variations (3)
Definition
pharmakinetics: alterations in the drug concentrations that reach the receptor

variation in receptors due to physiological differences (obease, genetics, athletic)

altered number of receptors due to up or down regulation due to body status
Term
when choosing a dose of a drug, what is our goal. what if we need a higher dose how can we achieve that and avoid side effects
Definition
use lowest dose needed to produce desired effects and minimise undesired effects

if you need a higher dose use two different drugs with different mechanisms to lower chance of undesired effects

alter the method of delivery
Term
what are the two types of non-competitive inhibition, explain them
Definition
irreversible: more common, same receptor as drug

allosteric: different receptor than drug
Term
what are the methods of drug input (10)
Definition
oral
buccal
sublingual
rectal
intramuscular
subcutaneous
IV
inhalation
topical
transdermal
Term
oral drugs: benifits (3), downfalls (5)
Definition
benfitis: most common, safest, economical

downfalls: slow, less complete, first pass effect, absorption affected by stomach contants, most absorbed in intestines
Term
buccal drugs: benifits (2), downfalls (1)
Definition
benifits: direct absorption into venous circulation, no first pass

downfalls: fast or slow depending on the drug
Term
sublingual drugs: benifits (2), downfalls (1)
Definition
benifits: direct absorption into venous circulation, no first pass

downfalls: fast or slow depending on the drug
Term
what drugs are commonly siblingual, what are they for
Definition
nitryglocerin: angina
Term
define first pass effect
Definition
drug must first pass through the liver where some is metabolized or less active when it leaves
Term
rectal drugs: benifits (3), downfalls (1)
Definition
benifits: partial escape from first pass, can give higher dose, good for vomiting or nausea

downfalls: can cause irritation
Term
intramuscular drugs: benifits (3)
Definition
fast, complete, can give large volumes
Term
subcutaneous drugs: benifit and downfall
Definition
benefit: large doses ok

downfall: slow absorption
Term
IV drugs: benifits and downfalls
Definition
benifits: bioavaility 100%

downfalls: dangerous because if administration is too rapid, blood levels can become too high
Term
topical drugs: locations, effect radius, downfulls
Definition
skin or mucous membranes
local effects
rate of absorption depends on area but is usually slow
Term
transdermal drugs: benifits (2), downfalls (3)
Definition
benifits: systemic effect, first pass avoidance

downfalls: apply to skin, slow absorption, drug must be potent or the patch has to be huge
Term
what are the three different types of absorption
Definition
passive diffusion
facilitated diffusion
active transport
Term
passive diffusion: power source, MOA, saturatble, specificity
Definition
driven by concentration gradient
ions flow down concentration gradient without a carrier
unable to saturate
low specificity
Term
facilitated diffusion: power source, MOA, saturatble, specificity
Definition
driven by concentration gradient
involves a carrier protein
able to saturate
specific
Term
active transport: power source, MOA, saturatble, specificity
Definition
moves against concentration gradient via ATP
needs carrier proteins
able to saturate
specific
Term
define pKa, what does the number mean if it is high or low
Definition
strength of the acid/base
higher is basic
lower is acidic
Term
how is pKa and pH related mathmatically
Definition
log (A-)/(HA) = pH - pKa for acids

log (B)/(BH+) = pH - pKa for bases
Term
in a sentence relate pH to pKa
Definition
if drug is in pH equal to its pKa, it will be 50% ionized
Term
what type of molecules are most drugs
Definition
weak acids and bases
Term
how is the concentration of a drug that will be ionized on each side of a membrane determined
Definition
pH and pKa which change wether the drug is charged or uncharged
Term
how can drug movement be determined, what is the best mode for a drug to be in for movement
Definition
wether the drug is charged or uncharged, and thus the pH/pKa

uncharged
Term
write the weak acid / weak base ionization equations and explain why they would shift left or right
Definition
BH+ -> B + H+ HA -> A- + H+ shift left when pHpKa equlibrium when pH=pKa
Term
why is a weak base better absorbed in the intestines rather than the stomach
Definition
the intestines are more basic so it will be non-ionized and thus uncharged, allowing bettwer movement and thus absorption
Term
what are physical factors that affect absorption
Definition
blood flow to the absorption site: different in each tissue and body situations

SA for absorption

contact time at the absorption site: during travel drug will get stuck in some areas and go fast through others
Term
define bioavailbility
Definition
fraction that reaches systemic circulation
Term
what is bioavilavility influenced by
Definition
first pass metabolism

solubility of the drug: hydrophillic drugs have less

chemical instability
Term
what are the 4 areas of the plasma curve, explain their boundries and significance
Definition
lag time: time from drug administration to appearance in the blood

onset of activity: time from administration to minimin effective concentration

duration of action: time plasma concentration remains above MEC

elimination: changing elimination of the drug changes its duration of action
Term
if you take an antacid what happens to absorption on the plasma curve for a weak acid and weak base
Definition
donno yet, go look it up
Term
what is distribution of a drug determined by
Definition
size of organ
blood flow
capillay permeability
hydrophobic or hydrophillic drugs (lipid soluble can go more places like CNS)
size of drug: smaller can go through BBB
Term
what is the relationship between drugs and protein binding, why do they do this, what situations, what does it mean for the drug
Definition
most drugs bind to albumin in the blood to hitch a ride because they are lipid soluble

if the drug binds proteins in the tissue compartment it can increase concentration in that compartment
Term
define Vd
Definition
volume distribution

volume of fluid a drug is put into

the volume it would require to contain all the drug in the body at the same concentration in the plasma

relates amount of drug in the body to the plasma concentrations
Term
what is Vd dependent on, give values
Definition
water compartments in the body

plasma 6%
ECF 20% (plasma and IF)
TBW 60%
Term
what does it mean if Vd is larger than TBW
Definition
it rapidly leaves the vascular compartment
Term
how is Vd calculated
Definition
Vd = amount in the body / amount in the blood
Term
what happens to Vd if the drug was not eliminated? if the drug is eliminated? what about graphically
Definition
if not eliminated: the plasma concentration stays the same

if eliminated; the curve is extrpolated to ge the plasma concentration of the drug you need the calculation
Term
how is Vd used, what does it mean if it is big, what other factors is it related to
Definition
tells the amount of drug needed to achieve a desired plasma concentration

large Vd means most of the drug isnt in the extraplasmic space

Vd is related to half life and can extend duration
Term
what are the drug reservoirs (4)
Definition
bound to plasma protein
cellular reserviors
fat
bone
Term
when a drug is bound to a plasma protein that mean the drug structure is like what, what protein is it bound to
Definition
acidic bind albumin and basic bind 1-a-glycoprotein

not hydrophillic or neutral
Term
what does it do to the drug when it binds to a plasma protein
Definition
inactive, cannot cross membranes

dont worry its reversible
Term
what qualifies a tissue to be a cellular reserve, give examples
Definition
if binding of the drug within the cell is reversible, the tissue can be a drug reservior

muscle, ECF, etc
Term
what is cellular reserve in fat not awesome, what types of drugs do this
Definition
it can be a toxin risk in obease people

lipid soluble ones
Term
what drugs accumulate in bones, why is this in particular bad
Definition
tetracyclines, heavy meatals

can cause slow release of toxins like lead over time
Term
what types of drugs enter fetal circulation, by what method
Definition
lipid soluble, non-ionized

simple diffusion
Term
define drug metabolism
Definition
disppearance of a drug by chemically changing it another compound
Term
what normally happens to lipid soluble drugs in metabolism
Definition
absorbed well but removed slow from the body because they are reabsorbed in the renal tubule

drugs are metabolized to a less lipid soluble form to help elimination
Term
metabolism can inactivate drugs: explain this
Definition
drug is metabolized to be biologically inactive, becoming more polar and less lipid soluble

less lipid soluble means less renal reabsorption and more excretion
Term
define prodrug, give two examples, what is an exception that still fits into the prodrug category
Definition
inactive drugs that must be metabolized to activate agents

levodopa
methyldopa

some drugs are active when administered but other parts become active through metabolism (sometimes toxic parts)
Term
some drugs dont need to be metablized, why, what is happening to them
Definition
lithium isnt modified in the body
these drugs act up until the time they are excreted
Term
1st order kinetics of metabolism: laws, definition
Definition
follows michalis-Menten kinetics

rate of drug metabolism is proportional to concentration of free drug

a constant fraction of the drug is metabolized per unit time

enzymes not saturated
Term
zero order kinetics of metabolism: when is it used, what is the law
Definition
drugs with very large doses saturate metaboling enzymes

constant amount of drug metabolized per unit time
Term
phase 1 metabolism: location, main driving reaction / mechanism
Definition
on surface of SER

conversion of lipophillic molecules into polar molecules by adding or unmasking a polar functional group (NH2, OH)
Term
in phase 1 metabolism, once the molecule is polar what happens to it (5)
Definition
cytochrome P450 dependent oxidation
cytochrome P450 independent oxidation
reduction
hydrolysis of esters
hydrolysis of amides
Term
cytochrome p450 dependent oxidation: 4 types and their examples
Definition
hydroxylation: ibprofin, phenytoin

N or O dealkylation: morphine, codeine, caffiene

N or S oxidation: tylenol, nicotine, ametidine

deamination: diazepam, amphetamines
Term
cytochrome p450 independent oxidation: 2 types and their examples. just checking... what does this even have to do with
Definition
amine oxidation: epinepherine

dehydrogenation: ethanol

phase 1 metabolism reaction after conversion into a polar molecule
Term
in phase 1 metabolism give example of a drug that is reduced
Definition
warfarin
Term
in phase 1 metabolism give example of a drug thats ester is hydrolyzed
Definition
asprin, procaine
Term
in phase 1 metabolism give example of a drug thats amide is hydrolyzed
Definition
lidocaine, procalnamide
Term
where does phase 2 metabolism take place, what is the initial reaction that takes place, what is the goal here
Definition
cytoplasm

endogenous substrate is conjugated to the drug increasing the size and decreasing lipophilicity
size keeps it in the kidney tubule helping elimination
Term
what is different in phase 2 metabolism in neonates
Definition
they dont have transferase enzyme so drugs accumulate fast and can be toxic
Term
what reactions occur in phase 2 metabolism (6)
Definition
glucuronidation
sulfation
acetylation
glycine conjugation
glutathione conjugation
methylation
Term
phase 2 metabolism glucuronidation MOA
Definition
addition of glucuronic acid to the drug vua glucuronosyl transferase
Term
phase 2 metabolism sulfation MOA
Definition
adding sulfate to the drug via sulfotransferase
Term
phase 2 metabolism acetylation MOA, why is this reaction different than the others
Definition
add acetyl group to the drug

some people are slow or fast acetylators. slow acetylators are a genotypic variation that can cause lupus)
Term
phase 2 metabolism glycine conjugation MOA and examples
Definition
add glycine to the drug

asprin and niacin
Term
phase 2 metabolism glutathione conjugation MOA and example
Definition
add acetylcysteine to the drug

acetaminophen (toxic metabolite)
Term
phase 2 metabolism methylation MOA
Definition
add methyl group to the drug
Term
name the sites of metabolism (9) intracellular and system levels
Definition
liver, kidney, GI, skin, lungs, SER, cytoplas, mitochondria, cell membrane
Term
where are most drugs metabolized
Definition
the liver
Term
what is a drug metabolizing initiator isoenzyme, what does this mean for the drug in the body
Definition
makes you less able to metabolize drugs. adding drug will give side effects stopping drug from being broken down
Term
drug metabolizing initiator examples
Definition
cimetidine, erythromycin, ketonasole, grape fruit
Term
what is a drug metabolizing inducer isoenzyme, what does this mean clinically
Definition
increase production of enzymes via gene expression
make plasma levels lower via more enzymes
you may need to increase dose if they are on an inducer
Term
give examples of drug metabolizing indicers and their MOA
Definition
bensopyrine: p460 1As family in the liver

chronic ethanol: p450 2E1 family

phenytoin, carbamepine, rifampin, barbituates: p450 3A4 family
Term
what are the drugs that follow zero order kinetics, under what conditions
Definition
asprin, ethanol, penytoin

when in high dose, except ethanol
Term
what determines the interaction of a drug
Definition
rate of elimination and dosage
Term
what is the relationship between elmination and excretion
Definition
there is none, drug can be eliminated by metabolism before excretion
Term
how is a drug eliminated if it is not metabolized
Definition
excretion
Term
where are the areas in the kidney excretion occur
Definition
glomerulus, PCT, DCT
Term
what types of drugs are filtered in the glomerulus
Definition
free unbound
filter by size, not by pH or solubility
Term
what drugs are filtered in the PCT, how
Definition
drugs not filtered in the glomerulus that pass into capillary plexus

active transport for specific anions (deprotinated WA) and cations (protinated WB)
Term
how does PCT drug excretion cause hypernatremia
Definition
drug is WA and competes for uric acid in PCT causing side effects
Term
what is the down side of PCT filtration
Definition
low specificity, drugs can compete for carriers

incompletely developed in infants and neonates can cause toxicity due to inability to eliminate
Term
explain how DCT reabsorption works
Definition
drug concentration now increases that of the perivascular space

if uncharged the drug back diffuse back into circulation

you can manipulate pH of urine do decrease reabsorption and increase elimination. increase percent of drug ionizationed form
Term
define ion trapping
Definition
acidify urine traps protonated weak bases increasing their clearance
Term
how is clearance calculated
Definition
rate of elimination of te drug / plasma drug concentration
Term
how is rate of elimination calculated
Definition
CL x Cp
Term
how is clearence altered
Definition
disease, age, other
Term
what is excreted in the GI
Definition
poo

drugs orally administered and not absorbed

MW > 300
Term
what is excreted in the pulmonary
Definition
anesthetics
alcohol
Term
what is excreted in milk
Definition
highly lipid soluble drugs
Term
give 5 examples of drugs secreted in milk
Definition
barbituates, salicylates, morphine, steroids, radioactive substances
Term
what is half life not affected by
Definition
constant infusion, injection, or oral if the drug is eliminated by 1st order kinetics
Term
what is half life affected by
Definition
clearance which is easily changed too
Term
how os half live calculated
Definition
t1/2 = (0.7 x Vd) /CL
Term
increased half life
Definition
diminished renal plasma flow
renal disease
decreased metabolism
Term
what causes deminished plasma renal flow
Definition
cardiogenic shock, heart failure, hemorrhage
Term
what causes decreased metabolism
Definition
cytochrome p45o inhibitor
hepatic insufficiency
cirrhosis
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