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
|
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 |
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 |
|
|
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 |
|
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
|
|
Term
| in phase 1 metabolism give example of a drug thats ester is hydrolyzed |
|
Definition
|
|
Term
| in phase 1 metabolism give example of a drug thats amide is hydrolyzed |
|
Definition
|
|
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
|
|
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
|
|
Term
| where are the areas in the kidney excretion occur |
|
Definition
|
|
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
|
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
|
|
Term
|
Definition
|
|
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
|
|
Term
|
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
|
|
Term
|
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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|
