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131 Cards in this Set

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therapy duration depends on?
pathogen

site of infection

host factors
what diseases have precise data on duration of therapy?
"STaGS"
strep pharyngitis

TB

gonorrhea

syphilis
bactericidal drugs?
aminoglycosides
metronidazole
quinolones
quinupristin/dalfopristin
polymixin
vancomycin
rifampin
pyrazinamide
bacitracin
beta-lactams
isoniazid
what types of drugs are indicated in immunosuppressed pts?
bacteriocidal
concentration dependent drugs

1) what are they
2) how do you dose them
3) are they bacteriostatic or bacteriocidal?
[ ] dependent drugs

1) aminoglycosides - inhibit protein synthesis
quinolones - inhibit DNA gyrase/topoisomerase

2) once daily dosing

3) bacteriocidal
therapy duration depends on?
pathogen

site of infection

host factors
what diseases have precise data on duration of therapy?
"STaGS"
strep pharyngitis

TB

gonorrhea

syphilis
bactericidal drugs?
aminoglycosides
metronidazole
quinolones
quinupristin/dalfopristin
polymixin
vancomycin
rifampin
pyrazinamide
bacitracin
beta-lactams
isoniazid
what types of drugs are indicated in immunosuppressed pts?
bacteriocidal
concentration dependent drugs

1) what are they
2) how do you dose them
3) are they bacteriostatic or bacteriocidal?
[ ] dependent drugs

1) aminoglycosides - inhibit protein synthesis
quinolones - inhibit DNA gyrase/topoisomerase

2) once daily dosing

3) bacteriocidal
time dependent drugs

1) what are they
2) how do you dose them
3) are they bacteriostatic or bacteriocidal?
time dependent drugs

1) beta lactams - inhibit cell wall synthesis
vancomycin - inhibit cell wall synthesis

2) serum [ ] must remain > MBC

3) bacteriocidal
antimicrobials are preferred to be administered how?
orally
in what pt populations would you give IV antimicrobials?
critically ill

N/V/gastrectomy

bacterial meningitis/endocarditis
what drug combos would you use to rx enterococcal endocarditis?
penicillins/vancomycin + aminoglycosides

combo makes it bactericidal
what prophylactic drugs would you use for emergency colorectal surgery/colorectal obstruction/appendectomy?
cefoxitin

cefotetan
what prophyllactic drugs would you use in elective colorectal surgery?
oral erythromycin

neomycin

cephalosporin
what are the mechanisms of antimicrobial synergism
1) block sequential steps in metabolic sequence

2) inhibit enzymatic inactivation

3) enhance antimicrobial agent uptake
what is the DOC for surgical prophyllaxis
cefazolin
what is the requirement of antimicrobial drugs in surgical prophylaxis?
[ ] of agent > MIC @ time of incision
nonsurgical prophyllaxis of suspected exposure of anthrax
ciprofloxacin, doxycycline
nonsurgical prophylaxis of close contact w/ cholera
tetracycline
nonsurgical prophylaxis of dental procedures in @ risk pt for endocarditis
amoxicillin

clindamycin
nonsurgical prophylaxis of HIV blood exposure by needle stick
zidovudine

lamivudine
nonsurgical prophylaxis of recurrent otitis media infection
amoxicillin
what antiprotozoal drugs are used for malaria prophylaxis
chloroquine

mefloquine

pyrazinamide

proguanil

doxycycline
which species is responsible for most disease and death of malaria worldwide
Plasmodium falciparum
what anti-protozoal drug rx tissue schizonticides in malaria?
primaquine
what anti-protozoal drug rx blood schizonticides in malaria?
chloroquine
mefloquine
quinine
pyrimethanine
proguanil
antibiotics
what anti-protozoal drug rx gametocides in malaria?
primaquine

quinine (P.vivax, ovale)
what drugs disrupt polymerization of heme -> hemozoan to lyse RBC's and the bug?
chloroquine
mefloquine
quinine
contraindications to chloroquine
psoriasis/porphyria
retinal abnormalities
kaolin / antacids reduce absorption
myopathy
SAFE IN PREGNANCY AND CHILDREN
against what does quinine eradicate?
all 4 species blood schizo

ovale+vivax gametocytes

NOT ACTIVE AGAINST LIVER STAGE PARASITES
quinine is effective against what species?

how do you administer
P. falciparum

give with doxycycline to reduce duration of use to 3 days (toxicity)
AE of quinine
tinnitus
headache
nausea
deafness
dizziness
flushing
visual disturbances
contraindication quinine
cardiac abnormalities - QT prolongation

taking with or recently taken mefloquine - cardiac arrest/convulsions
what do you give chloroquine resistant strains of P. falciparum
mefloquine
what do you give to rx severe infections.. why
quinine

rapid activity, less likely resistance
AE mefloquine
nausea
vomiting
dizziness
sleep, behavioral disturbances
contra mefloquine
epilepsy
psychiatric disorders
quinine/quinidine
cardiac conditions - arrythmias
G6PD deficiency (decreased NADPH/GSH levels)
primaquine is effective against what species
P. ovale, vivax

liver forms

gametocides
AE primaquine
hemolysis in G6PD def

intestinal distress

methemoglobinemia
contra primaquine
pregnancy

myelosuppression
pyrimethamine MOA
inhibit folate metabolism in parasite (dihydrofolate reductase)
proguanil MOA
inhibit folate metabolism in parasite (dihydrofolate reductase)
ab effective against all 4 species of erythrocytic schizonts
tetracycline
doxycycline
clindamycin
azithromycin
what ab do you give in chloroquine resistance malaria
clindamycin
what antiprotozoal drugs are effective against all 4 species of erythocytic schizonts
quinine

pyrimethamine

proguanil

antibiotics
what are the 4 stages of amebiasis
asymptomatic intestinal infection

mild to moderate intestinal colitis

severe intestinal infection (colitis)

liver abcess
what drugs to you give to rx asymptomatic intestinal infection of amebiasis
luminal amebicide

iodoquinol

paromomycin
what drugs to you give to rx amoebic colitis of amebiasis
metronidazole + luminal amoebocide (iodoquinol, paromomycin)
what drugs to you give to rx extraintestinal infections of amebiasis
metronidazole + luminal amoebocide (iodoquinol, paromomycin)
metronidazole is the DOC 4?
amebiasis

trichomoniasis

giardiasis
metronidazole MOA
protozoal enzymes reduce the nitro grp to produce toxic, nitro-free radicals that damage DNA and protein
metronidazole caution?
H2 blockers (cimetidine)

peptic ulcers

toxic b/c block metabolic pathway of liver *need to lower dose*
paromomycin contra?
renal problem - accumulates with renal insufficiency leading to toxicity

ulcers - increases amt in circulation - *reduce dosage*
what drug do you use to rx giardiasis in kids?
nitazoxanide
what drug do you use to rx giardiasis in adults
metronidazole
MOA nitazoxanide
active metabolite : tizoxanide

inhibits pyruvate: ferredoxin oxidoreductase pathway (needed in anaerobic energy metab in protozoa)
american trypanosomiasis

symptoms and rx
cardiomyopathy

common in infants

transmitted by feces

rx: nifurtimox
african trypanosomiasis - gambiense

symptoms and rx
slow to enter CNS

transmitted by tsetse fly

causes sleeping sickness

rx: suramin (IV), petamidine in early stages
african trypanosomiasis - rhodensiense

symptoms and rx
early invasion CNS

fatal if not rx

Rx: eflornithine (less toxic than melarsoprol), melarsoprol
melarsoprol MOA
react with trypanothione *reducing agent inside parasite* --> makes parasite susceptible to oxidative stress

affect parasite replication
why is melarsoprol not given prophylactically
contains arsenic -> toxic

readily [ ] in parasite and eliminated rapidly
eflornithine MOA
selective irreversible inhibitor of ornithine decarboxylase

inhibits replication
nifurtimox MOA
generates oxygen radicals which are toxic to parasite (lacks catalase)
leishmaniasis

1) transmitted by?
2) 2 forms of infection?
3) geographic area?
1) sandfly

2) mucosal, visceral

3) seen around mexican border
rx leishmaniasis
sodium stibogluconate - inhibit glycolysis/FA metab
reduces production ATP/GTP

miltefosine - inhibit RNA synthesis
AE nifurtimox
anorexia
vomiting
neuropathy
pancytopenia
AE sodium stilbogluconate
bone marrow suppression
chemical pancreatitis
prolonged QT
rash
AE metronidazole
headache,
nausea,
metallic taste,
neuropathy
AE suramin
nausea
vomiting
shock
AE melarsoprol
fever
phlebitis
neuropathy
reactive encephalopathy
what is the helminth that accounts for most of the infections of the world's population
nematode

MCC=ascaris
albendazole

1) DOC

2) MOA
1)nematodes:
ascariasis, trichuriasis, hookworm, pinworm

2) inhibits beta tubulin microtubule synthesis in worm
Diethylcarbamazine

1) rx for?

2) half life longer in acidic/alkaline urine?

3) MOA
1) filariasis, loiasis, tropical eosinophilia

2) alkaline

3) immobilizes microfilaria, displacing them from tissue so cleared by host defenses
*alters arachidonic acid pathway in worm *if knock out INOS/COX2 in human host not protected*
Ivermectin

1) rx?

2) MOA?

3) drug has __affinity for worm ___
1) strongloidiasis, onchocerciasis, lymphatic filariasis (elephant leg), cutaneous larva migrans

2) activates glutamate-gated Cl channels in worm, enhances GABA signals in peripheral nerves - CAUSE WORM FLACCID PARALYSIS

3) 100x, GABA
what is the Mazzotti rxn?

symptoms?

DOC??
hypersensitivity response from microfilariae (parasitic antigens) targeted by rx drug

fever, pruitis, arthralgia, headache

DOC=corticosteroids
Mebendazole

1) rx?

2) MOA?

3) contra?
1) nematode infections
ascariasis, trichuriasis, hookworm, pinworm

2) inhibits microtubule synthesis

3) pregnancy
praziquantel

1) rx for?

2) MOA?
1) schistosome,
TREMATODES (paragonimiasis, clonorchiasis, schistosomiasis)
cestodes

2) increases Ca permeability leading to SPASTIC PARALYSIS - dispels worm
pyrantel pamoate

1) rx for?

2) active against?

3) MOA?
1) pinworm, ascaris, hookworm (NO TRICHURIASIS / STRONGYLOIDIASIS)

2) active against luminal organisms

3) neuromuscular blocking agent - produces depolarization of NMJ blockade - SPASTIC PARALYSIS AND EXPULSION - Ach release, cholinesterase inhibition
how do you reverse drug resistance?
verapamil inhibits Ca channel transporter
alkylating agents

1) MOA

2) drug resistance
1) transfer alkyl grp to N7 position of guanine within DNA

2) increased DNA repair
decreased permeability to drug
increased glutathione production
Cyclophosphamide

1) MOA

2) contra
1) must be converted to active metabolite by liver P450

in non-hepatic tissue, nonenzymatic conversion to other cytotoxic forms

2) liver problems
carmustine

1) MOA

2) DOC for?

3) unique pharmacokinetics
1) requires nonenzymatic conversion to active form

2) glioma

3) highly soluble, crosses BBB
procarbazine

1) MOA

2) doc for?
1) inhibit DNA, RNA, protein synthesis via alkylation - generates azoprocarbazine and H2O2--> cause strand breaks

2) hodgkin's dz
Cisplatin

1) MOA

2) AE

3) rx for?
1) crosslinks DNA @ N7 guanine

2) nephrotoxicity (need aggressive IV hydration/diuretics) and severe nausea

3) rx testicular, ovarian, bladder cancer
name 6 antimetabolites
MERCAP CLAD METH in a FLUORO-CYTA CAPE

mercaptopurine
cladribine
methotrexate
fluorouracil
cytarabine
capecitabine
Methotrexate

1) MOA

2) AE

3) drug resistance mech
bind to dihydrofolate reductase catalytic site

interferes with DNA, RNA, protein synthesis

polyglutamates of methotrexate are [ ] inside the tumor cells

2) toxic to normal and abnormal cells - requires leucovorin rescue

3) decrease drug transport
mutation/change formation polyglutamate
overexpress DHFR
reduced affinity of MTX DHFR
what is leucovorin rescue
give folinic acid to bypass the inhibited dihydrofolate reductase so cell can recover from methotrexate
what are 2 purine antagonists
mercaptopurine

cladribine
mercaptopurine (6-MP)

1) MOA

2) drug resistance

3) caution when given with allopurinol?
1) decrease purine synthesis by being converted to HGPRT

2) drug resistance - decreased HGPRT activity

3) need to reduce dose by 75% when given with allopurinol
Cladribine

1) MOA
prodrug converted to CDAMP which is resistant to adenosine deaminase - toxic [ ] buildup in cell -> interfere with elongation of strand - strand breaks.
Fluorouracil

1) MOA

2) AE

3) where metabolized

4) indicated for?
1) FdUMP - forms complex with thymidylate synthase... thymidylate is not synthesized... inhibits DNA synthesis
FUTP - incorporated to RNA - interfere with RNA processing and prevent mRNA translation
FdUTP - incorporated into DNA - inhibits DNA synthesis

2) severe oral/GI ulceration, bone marrow suppression, anorexia

3) liver, lung, kidney

4) colorectal cancer, solid tumors
Capecitabine

1) MOA

2) AE

3) where metabolized?

4) indicated for?

5) contraindications?

6) caution?
1) prodrug for 5-FU
thymidine phosphorylase convert to 5-FU

2) GI distress

3) liver

4) metastatic breast cancer resistant to 1st line therapy and other solid tumors

5) pregnant, lactating mothers, 5-FU hypersensitivity

6) hepatic/renal
Cytarabine

1) MOA?

2) indicated for?

3) admin?

4) AE?
1) metabolized to Ara-CTP... S-phase specific.... competitively inhibits DNAP... incorporates into DNA/RNA and interfere with chain elongation

2) AML

3) IV

4) severe myuelosuppression, hepatic dysfxn
Vinblastine

1) MOA

2) indicated for

3) AE
1) depolymerizes microtuble - binds tubulin and terminates microtubule assembly
MITOTIC ARREST IN METAPHASE

2) Hodgkins, non-Hodgkins, breast cancer

3) myelosuppression
Vincristine

1) MOA

2) indicated for

3) AE
1) depolymerizes microtubules - binds to tubulin and terminates assembly

2) ALL, hematologic malignancies (Hodgkins, non-Hodgkins), pediatric tumors (Ewing's and Wilm's)

3) peripheral neuropathy, constipation, inappropriate secretion ADH
Etoposide

1) MOA

2) indicated for?

3) caution? when should dose be reduced?
1) block cell division in late S-G2 phase.... inhibits topoisomerase II - breaks DNA strand

2) germ cell cancer, lung cancer, hematologic malignancies, gastric cancer

3) renal dysfxn - dose needs to be reduced
Topotecan

1) MOA

2) indicated for?

3) caution? dose needs to be reduced with?
1) inhibit topoisomerase I

2) advanced ovarian cancer (when 1st line CISPLATIN, CARBOPLATIN, OXALIPLATIN doesn't work)

3) renal insufficiency - dose needs to be reduced
Paclitaxel

1) MOA

2) indication

3) AE?

4) need to know before give drug?
1) bind microtubule, enhance and stabilize tubulin polymerization - render it nonfxnal

2) solid tumors - ovarian/breast

3) neutropenia, transient asymptomatic bradycardia

4) premedicate - dexamethasone/diphenhydramine and H2 blocker to prevent serious hypersensitivity rxn
Doxorubicin

1) MOA

2) indicated for?

3) AE?
1) inhibit topoisomerase II - affect S and G2
DNA binding and inhibit DNA synmthesis
bind cell membrane and alter fluidity and ion transport
generate Reactive Oxygen Species (tumor and heart cells low in superoxide dismutase)

2) BROAD SPECTRUM
hematologic malignancies, solid tumors, sarcomas

3) irreversible dose dependent heart toxicity, increase skin pigment, bone marrow suppression
Daunorubicin

1) MOA

2) indicated for?

3) AE?
1) inhibit topo II
DNA binding and inhibit DNA synthesis
bind cell membrane and alter fluidity and ion transport
generate ROS

2) AML

3) irreversible dose dependent heart toxicity, increased skin pigment, bone marrow suppression
Dactinomycin

1) MOA

2) indicated for
1) bind btw G-C pair of DNA - interferes with DNA dependent RNAP.. inhibits RNA synthesis

2) pediatric tumors
Dactinomycin

1) MOA

2) indicated for?

3) AE?
1) binds DNA btw G-C base pairs... interfere with DNA dependent RNAP... inhibit RNA synthesis

2) Ped tumor - Wilms, etc

3) bone marrow suppression, sensitizes to radiation - inflamm @ radiation sites
Mitomycin

1) MOA

2) indication?
1) metabolized to alkylating agent that cross-links DNA

2) hypoxic tumor cells of solid tumors that are usu resistant to alot of chemo drugs
Bleomycin

1) MOA

2) indication

3) attack where in cell cycle?

4) caution?

5) AE?
1) peptide with DNA binding region + Fe binding domain... when bind DNA, Fe oxidizes and chromosome abnormailities form

2) broad spectrum - testicular tumors

3) G2

4) dose needs to be reduced in renal insufficiency

5) pulmonary toxicity, myelosuppression
Tamoxifen

1) MOA

2) indicated for?
1) binds estrogen receptor of estrogen dependent tumors - endogenous estrogen must be ablated

2) breast cancer
Flutamide

1) MOA

2) indicated for?

3) AE
1) competitively binds and blocks androgen receptor with testosterone - androgen antagonist

2) prostate cancer

3) liver failure, gynecogmastia, GI distress
Leuprolide

1) MOA

2) indicated for
1) analog of GnRH... initial binding leads to a increase in FSH/LH ->desensitization and reduced FSH/LH + decreased testosterone synthesis

2) androgen-receptor positive tumors (prostate cancer)
Anastrolzole

1) MOA

2) indicated for
1) nonsteroidal aromatase inhibitor

2) postmenopausal metastatic breast cancer
Exemestane

1) MOA

2) indicated for

3) metabolism?
1) irreversible steroidal aromatase inhibitor

2) postmenopausal metastatic breast cancer

3) CYP3A4 but no cross resistance
Imatinib

1) MOA

2) indicated for
1) inhibits oncoprotein tyrosine kinases (inhibit cell proliferation, promote abn proliferation and anti-apoptotic pathways)

2) Bcr-Abl (CML)
c-kit (GI stromal tumors)
Asparaginase

1) MOA

2)indicated for
1) deprive tumor of asparagine (tumor cells lack asparagine synthetase).. prevents protein synthesis

2) ALL
Sorafenib

1) MOA

2) indicated for
1) inhibits many kinases involved in angiogenesis and intraceullar signalling - inhibits tumor growth

2) renal cell carcinoma
Nelarabine

1) MOA

2) indicated for
1) LIKE CYTABINE
prodrug of ara-G.... ara-GTP disrupts DNA synthesis and induces apoptosis

2) lymphoblastic leukemia
Lenalidomide

1) MOA

2) indicated for
1) thalidomide analog... anti-angiogenic, anti-inflamm axns and enhances anti-cancer activity of T cells and NK cells

2) myelodysplastic syndromes, skin disorders
immunosuppressive agents?
SITAGAC

sirolimus
interferons
tacrolimus
azathioprine
glucocorticoids
antibodies
cyclosporine
glucocorticoids

1) MOA

2) ex?

3) caution?

4) when want to terminate - what should you do?
1) inhibit leukocyte migration... interfere with cell cycle of activated lymphoid cells.... inhibit production of proinflammatory mediators (LT, PG, histamine, bradykinin)

2) prednisone

3) adrenal suppression if > 7 days... body reduced amt corticosteroids produced

4) reduce dosage gradually
Cyclosporine

1) MOA

2) indication?
1) bind to cyclophilin, block NF-AT

2) prevent tissue rejection following transplant
Tacrolimus

1) MOA

2) indication?
1) complex with FK-Binding protein... inhibit calcineurin - block IL-2

2) organ transplants
Sirolimus

1) MOA

2) indication
1) bind FK-BP..inhibits mTOR - inhibits cell cycle progression from G1->S phase... inhibits lymphocyte proliferation
Interferon alpha

1) MOA

2) indication
1) inhibit cell proliferation and activate NK cells to kill tumor

2) melanoma, renal cell carcinoma, CML.... ANTIVIRAL TO RX HEP C
Interferon beta

1)MOA

2)indication
1) inhibit cell proliferation and activate NK cells to kill tumor cells

2) melanoma, renal cell carcinoma, CML.........MULTIPLE SCLEROSIS
Azathioprine

1) MOA

2) AE
1) antimetabolite that inhibits de novo purine synthesis -> lymphoid cell proliferation.... DERIVATIVE OF MERCAPTOPURINE

2) myeloid suppression
Mycophenolate mofetil

1) MOA

2) indication
2) what is it replacing?
1) reversible inhibitor of inosine monophosphate dehydrogenase - blocks de novo formation of guanosine phosphate....rapidly hydrolyzed in GI tract to mycophenolic acid... DEPRIVES RAPIDLY PROLIFERATING LYMPHOCYTES KEY COMPONENTS OF NUCLEIC ACIDS....

2) graft survival

3) azathioprine b/c more safe and efficacious in graft survival
Rh ab

1) MOA

2) indication
1) deliver w/in 72hr after delivery

2) Rh - mom
Trastuzumab

1) MOA

2) indication
1) bind and downregulate epidermal growth factor receptor HER-2/neu

2) breast cancer
Rituximab

1) MOA

2) indication?
1) bind CD20 on normal and malignant B cells, activates antibody dependent cell cytotoxicity + complement-mediated lysis

2) follicular B cell non-Hodgkin's lymphoma
Daclizumab

1) MOA

2) indication?

3) what other mAb has a higher affinity
1) IL-2 antagonist - bind CD25 - suppress lymphocyte activation

2) organ transplant - give with glucocorticoids and cyclosporine

3) basiliximab
Palivizumab

1) MOA

2) who give to?
1) binds fusion protein of RSV - prevents infection of cell

2) neonates @ risk
Abatacept

1) MOA

2) indication?
1) bind CD80 and CD86 on APC - blocks interaction with CD 28 on T cell - prevent autoimmune T cell activation

2) rheumatoid arthritis