Week 3 drugs Flashcards
Primaquine
used in radical cure of plasmodium.
Use only after everything is cleared out
goes after hypnozoite in liver
vivax and ovale
what forms of plasmodium are comon to drug resistance
falciparum and vivax
atovaquone / proguinil
When good to use?
drug of choice to PREVENT if chloroquine resistant. used alternative to prevent in areas non chloroquine resistant
not good if acute attack. Takes awhile to work
chloroquine
drug of choice to PREVENT
doxycyline
alternative prophylaxis in chloroquine resistant areas
give AFTER infection if resistant to chloroquine (with quinine in FALCIPARUM and VIVAX resistant)
mefloquine and toxic?
alternative prophylaxis in chloroquine resistant areas of FALCIPARUM
NEUROPSYCHIATRIC REACTIONS. hence why chloroquine is preferred
primaquine mech and problems
unknown mech. maybe make ROS
HEMOLYTIC ANEMIA IF G6PD defient
quinine
give AFTER infection if resistant to chloroquine (falciparum and vivax resistance)
+doxy
quinidine
Used with doxy for treating SEVERE DISEASE OF ALL PLASMODIUM
artemisinin based combo therapy (ACT)
always used in combo therapy
aretesunate
given with mefloquine. ALWAYS GIVE IN COMBO
radical cure
use primaquine to take out vivax and ovale in liver. last resort
best treatment for acute attack of plasmodium
Chloroquine unless falci and vivax resistant!
prophylatic dosing of anti malria
lower doses
mechanism of chloroquine
inhibits heme polymerase (normally converts FPIX to hemozoin). Result is high levels of FPIX which are toxic to parasite
toxicity of chloroquine
none in low dose
if given for acute attack: can cause blindness if large doses over long period of time
mech and toxic of quinine and quinidine
Unique toxic to quinidine?
more toxic than chloroquine
same mech and chloroquine
Adverse if acute attack doses: CINCHONISM which is hearing loss, tinnitus, nausea, etc
Quinidine blocks na and k current - CARDIAC PROBLEMS
atovaquone and proguinil mechanism and problems
Ato - depolarized parasite mito
pro - inhibits parasite DHFR
Not good if severe malaria
GI PROLEMS are common
artemisinins mech and toxicity
produce free radicals
VERY RAPID activity
DO NO USE ALONE to avoid resistance
CCS examples
plant alkaloid
dna synthesis inhibitors
CCNS examples
crosslinking agents anthracycline antibiotics (rubicin)
leucovorin
methylated folate. given with methotrexate.
leucovorin rescue
CAN NOT GIVE INTRATHECAL
allopurinol
xanthine oxidase inhibitor
prevents uric acid build up when giving 6-mercaptapurine or 6-tu
6 mercaptopurine and 6 thioguinine
activate by HGPRT and inhibits guanylyl kinase
f - fluorouracil
inhibits thymidylate synthase
pemetrexed
folic acid analogue that inhibits thymidylate synthase more than DHFR
hydroxyurea
inhibits ribonucleotide reductase
prevents making deoxynucleotides
cytarabine and gemcitabine
pyrimidine analogues
inhibits DNA synthesizing enzymes
pyrimidine monophosphate kinase
converts ump to udp
important in resistance to 5-FU
dihidropyrimidine dehydrogenase
degrades thymidine nucleotides
defiency leads to sensitivity to 5-fu
cyclophosphamide\
steps of activation / degrade
first step activated by cyp450
induction of cyp2b6 increases drug activity
final step makes phosphoramide mustard and acrolein
crosslinking agents
pharmacokinetics
need to convert to electrophile
mechlorethamine
instantaneous activation
given IV to avoid GI problems
acrolein
byproduct of cyclophosphamide
toxic: hemorrhagic cystitis (bladder epithelium)
GIVE MESNA to treat
ifosfamide
Acts slowly
MOST NEUROTOXIC alkylating agent
-causes mental problems
crosslinking toxicities
- myelosuppression
- severe nausease and vomiting
- vesicant (blistering), avoid oral
- bad if escapes IV
anthryacycline antibiotic toxicities:
unusual cardiomyopathy extravasation necrosis myelosuppression radiation recall reaction handfoot syndrome RED urine
bleomycin unique mechanism
binds to DNA and generates free radicals that cut DNA
causes pile up of cells in g2 with chromosome problems
hydrolase
found in lungs and skin
Degrades bleomycin
increased activity increases drug resistance along with increased DNA repair (bleomycin resistance)
crosslinking agents examples
cyclophosphamide
busulfan
melphalan (activated in diff tissues)
mechlorethamine must be given IV
intercalating agent examples
doxorubicin
drugs that cause strand break
etoposide
bleomysin
etoposide
binds with topo2 and dna that results in strand breaks. stays bound to enzyme to prevent repair
S and G2 phase
glutathione peroxidase
increases resistance to intercalating agents
so does increased p-glycoprotein and change in target
etoposide
ccs g2 and 2
binds topo2 and causes double strand break
TECANS
ironotecan and topotecan
cause single strand dna breaks binding topo1
ddrugs that cause strand breaks
etoposide and bleomycin
bleomycin toxicity
lungs and skin dont have hydrolase so causes damage
most neurotoxic alkylating agent
IFOSFAMIDE. causes mental problems
hemorrhagic cystis
side affect from cyclophosphamide
extravasation necrosis (vesciant)
can be from anthracyclines (intercelating agents) or from mechlorethamine
MESNA
given to treat for hemorrhagic cystis from cyclo and byprodu of acrolein
capecitabine
3 step activation with first 2 in liver
last step by thmidine phosphorylase which is higher in some tumors making better than 5-fu
