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 |
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|
Term
hoq is the success of a drug measured (3) |
|
Definition
insturments (BP cuff), lab tests on fluid or tissue, observation of pt symptoms |
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|
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 |
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|
Term
what biological differences may alter choice in drug (4) |
|
Definition
body size, personal response to drug, patient preferences, age |
|
|
Term
|
Definition
substance that acts on libing systems at a chemical or molecular level |
|
|
Term
|
Definition
molecular component a drug interacts with |
|
|
Term
define medical pharmacology |
|
Definition
study of drugs for diagnosis, prevention, and treatment of disease |
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|
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 |
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|
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 |
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|
Term
define pharmacokinetics: what processes does this involve |
|
Definition
actions of the body on a drug
absorption, distribution, biodisposition (metabolism and excretion) |
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|
Term
define therapeutic inxex: what is a aka |
|
Definition
margin of safety
measure of how safe a drug is |
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|
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 |
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|
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 |
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|
Term
when is a pharmological response the greatest |
|
Definition
when the concentration of the drug at the point of action is the highest |
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|
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) |
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Term
what qualifies drug pregnacy category A |
|
Definition
safe, no risk to fetus in any trimester |
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|
Term
what qualifies drug pregnacy category B |
|
Definition
mostly safe, animal studies may show risk but human studies dont |
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|
Term
what qualifies drug pregnacy category C |
|
Definition
unsure if safe, benifit may outweigh risk, there were no studies |
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|
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 |
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|
Term
what are examples of drugs in category d |
|
Definition
ACEI, ARBs, anticonvulsants |
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|
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
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|
Term
when prescribing a drug in category X at any time, what needs to be done |
|
Definition
inform female patient not to get pregnant |
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|
Term
what is another way to say a drug harms the fetus |
|
Definition
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|
Term
what is the purpose of the controlled substance act |
|
Definition
regulate manufacture, distribution, dispensing, and use of all CNS drugs |
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|
Term
which drugs are an exception to the controlled substance act |
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Definition
alcohol, tobacco, and states can make more strict laws |
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Term
schedule C-I: abuse potential, when allowed and warnings, when it can be used, examples |
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Definition
highest abuse potential
no medical use allowrd, only experimental
heroin, LSD, marijuna, PCP |
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|
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 |
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|
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 |
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|
Term
what are the 4 categories of drug characteristics |
|
Definition
physical, size, reactivity/bonding, shape |
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|
Term
what are the possible physical characterisics of drugs |
|
Definition
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|
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) |
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|
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 |
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|
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 |
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|
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 |
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|
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 |
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|
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 |
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|
Term
what is a viral capsule composed of |
|
Definition
lipid envelope with antigenic glycoproteins |
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|
Term
where do viruses replicate |
|
Definition
in the cytoplasm except influenza which replicates in the nucleus |
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|
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 |
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|
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 |
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|
Term
two examples of retroviruses |
|
Definition
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|
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 |
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|
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 |
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|
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 |
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|
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) |
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|
Term
what is a antimetabolite, what drug is an example of this |
|
Definition
drug that looks like something in the body
NRTI |
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|
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 |
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|
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 |
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|
Term
what are the elimination methods of the NRTIs |
|
Definition
• AZT, ABV: eliminated by liver metabolism (glucuronidation) • D4T, 3TC, ddC, ddI: eliminated by kidney |
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|
Term
what are the adverse effects of AZT, what type of drug is this |
|
Definition
bone marrow supression NTRI |
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|
Term
what are the adverse effects of ddl, what type of drug is this |
|
Definition
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|
Term
what are the adverse effects of ABV, what type of drug is this |
|
Definition
|
|
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 |
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|
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
|
Definition
in combination with other antiretroviral agents (like a NRTI) |
|
|
Term
what are the adverse effects of tenofovir |
|
Definition
|
|
Term
what is a NNRTI
what drugs do we need to know |
|
Definition
non-nucleoside reverse transcriptase inhibitor
efacirenz, nevirapine, rillpivirine, etarvirine |
|
|
Term
|
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
|
|
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
|
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
|
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
|
|
Term
drug that is a CCR5 receptor antagonist |
|
Definition
|
|
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
|
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
|
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
|
|
Term
how is mycobacterium TV isoniazid resistant treated |
|
Definition
rifampin 600 mg PO qd x 10 mo |
|
|
Term
how is toxoplasmosis gondii treated |
|
Definition
|
|
Term
|
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
|
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
|
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
|
|
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
|
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
|
|
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
|
Definition
|
|
Term
|
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
|
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
|
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
|
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
|
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
|
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
|
|
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
|
Definition
efects of large single dose up to lethal dose. max tolerated dose |
|
|
Term
|
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
|
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
|
|
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
|
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
|
Definition
drug produces lesser response than ligand and competes for ligand sites competetivly |
|
|
Term
|
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
|
Definition
|
|
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
|
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
|
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
|
|
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
|
|
Term
if there are 11 receptors and 4 receptors how many spare receptors are there, what is the relationship of EC50 to Kd |
|
Definition
|
|
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
|
|
Term
|
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
|
|
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
|
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
|
|
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
|
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
|
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
|
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 |
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Definition
drugs with very large doses saturate metaboling enzymes
constant amount of drug metabolized per unit time |
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Term
phase 1 metabolism: location, main driving reaction / mechanism |
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Definition
on surface of SER
conversion of lipophillic molecules into polar molecules by adding or unmasking a polar functional group (NH2, OH) |
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Term
in phase 1 metabolism, once the molecule is polar what happens to it (5) |
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Definition
cytochrome P450 dependent oxidation cytochrome P450 independent oxidation reduction hydrolysis of esters hydrolysis of amides |
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Term
cytochrome p450 dependent oxidation: 4 types and their examples |
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Definition
hydroxylation: ibprofin, phenytoin
N or O dealkylation: morphine, codeine, caffiene
N or S oxidation: tylenol, nicotine, ametidine
deamination: diazepam, amphetamines |
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Term
cytochrome p450 independent oxidation: 2 types and their examples. just checking... what does this even have to do with |
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Definition
amine oxidation: epinepherine
dehydrogenation: ethanol
phase 1 metabolism reaction after conversion into a polar molecule |
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Term
in phase 1 metabolism give example of a drug that is reduced |
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Definition
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Term
in phase 1 metabolism give example of a drug thats ester is hydrolyzed |
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Definition
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Term
in phase 1 metabolism give example of a drug thats amide is hydrolyzed |
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Definition
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Term
where does phase 2 metabolism take place, what is the initial reaction that takes place, what is the goal here |
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Definition
cytoplasm
endogenous substrate is conjugated to the drug increasing the size and decreasing lipophilicity size keeps it in the kidney tubule helping elimination |
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Term
what is different in phase 2 metabolism in neonates |
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Definition
they dont have transferase enzyme so drugs accumulate fast and can be toxic |
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Term
what reactions occur in phase 2 metabolism (6) |
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Definition
glucuronidation sulfation acetylation glycine conjugation glutathione conjugation methylation |
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Term
phase 2 metabolism glucuronidation MOA |
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Definition
addition of glucuronic acid to the drug vua glucuronosyl transferase |
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Term
phase 2 metabolism sulfation MOA |
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Definition
adding sulfate to the drug via sulfotransferase |
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Term
phase 2 metabolism acetylation MOA, why is this reaction different than the others |
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Definition
add acetyl group to the drug
some people are slow or fast acetylators. slow acetylators are a genotypic variation that can cause lupus) |
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Term
phase 2 metabolism glycine conjugation MOA and examples |
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Definition
add glycine to the drug
asprin and niacin |
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Term
phase 2 metabolism glutathione conjugation MOA and example |
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Definition
add acetylcysteine to the drug
acetaminophen (toxic metabolite) |
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Term
phase 2 metabolism methylation MOA |
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Definition
add methyl group to the drug |
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Term
name the sites of metabolism (9) intracellular and system levels |
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Definition
liver, kidney, GI, skin, lungs, SER, cytoplas, mitochondria, cell membrane |
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Term
where are most drugs metabolized |
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Definition
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Term
what is a drug metabolizing initiator isoenzyme, what does this mean for the drug in the body |
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Definition
makes you less able to metabolize drugs. adding drug will give side effects stopping drug from being broken down |
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Term
drug metabolizing initiator examples |
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Definition
cimetidine, erythromycin, ketonasole, grape fruit |
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Term
what is a drug metabolizing inducer isoenzyme, what does this mean clinically |
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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 |
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Term
give examples of drug metabolizing indicers and their MOA |
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Definition
bensopyrine: p460 1As family in the liver
chronic ethanol: p450 2E1 family
phenytoin, carbamepine, rifampin, barbituates: p450 3A4 family |
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Term
what are the drugs that follow zero order kinetics, under what conditions |
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Definition
asprin, ethanol, penytoin
when in high dose, except ethanol |
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Term
what determines the interaction of a drug |
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Definition
rate of elimination and dosage |
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Term
what is the relationship between elmination and excretion |
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Definition
there is none, drug can be eliminated by metabolism before excretion |
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Term
how is a drug eliminated if it is not metabolized |
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Definition
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Term
where are the areas in the kidney excretion occur |
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Definition
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Term
what types of drugs are filtered in the glomerulus |
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Definition
free unbound filter by size, not by pH or solubility |
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Term
what drugs are filtered in the PCT, how |
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Definition
drugs not filtered in the glomerulus that pass into capillary plexus
active transport for specific anions (deprotinated WA) and cations (protinated WB) |
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Term
how does PCT drug excretion cause hypernatremia |
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Definition
drug is WA and competes for uric acid in PCT causing side effects |
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Term
what is the down side of PCT filtration |
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Definition
low specificity, drugs can compete for carriers
incompletely developed in infants and neonates can cause toxicity due to inability to eliminate |
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Term
explain how DCT reabsorption works |
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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 |
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Term
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Definition
acidify urine traps protonated weak bases increasing their clearance |
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Term
how is clearance calculated |
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Definition
rate of elimination of te drug / plasma drug concentration |
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Term
how is rate of elimination calculated |
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Definition
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Term
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Definition
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Term
what is excreted in the GI |
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Definition
poo
drugs orally administered and not absorbed
MW > 300 |
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Term
what is excreted in the pulmonary |
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Definition
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Term
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Definition
highly lipid soluble drugs |
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Term
give 5 examples of drugs secreted in milk |
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Definition
barbituates, salicylates, morphine, steroids, radioactive substances |
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Term
what is half life not affected by |
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Definition
constant infusion, injection, or oral if the drug is eliminated by 1st order kinetics |
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Term
what is half life affected by |
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Definition
clearance which is easily changed too |
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Term
how os half live calculated |
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Definition
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Term
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Definition
diminished renal plasma flow renal disease decreased metabolism |
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Term
what causes deminished plasma renal flow |
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Definition
cardiogenic shock, heart failure, hemorrhage |
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Term
what causes decreased metabolism |
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Definition
cytochrome p45o inhibitor hepatic insufficiency cirrhosis |
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