Week 3 drugs

Question 1

Primaquine

Answer 1

used in radical cure of plasmodium.
Use only after everything is cleared out
goes after hypnozoite in liver
vivax and ovale

Question 2

what forms of plasmodium are comon to drug resistance

Answer 2

falciparum and vivax

Question 3

atovaquone / proguinil

When good to use?

Answer 3

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

Question 4

chloroquine

Answer 4

drug of choice to PREVENT

Question 5

doxycyline

Answer 5

alternative prophylaxis in chloroquine resistant areas

give AFTER infection if resistant to chloroquine (with quinine in FALCIPARUM and VIVAX resistant)

Question 6

mefloquine and toxic?

Answer 6

alternative prophylaxis in chloroquine resistant areas of FALCIPARUM
NEUROPSYCHIATRIC REACTIONS. hence why chloroquine is preferred

Question 7

primaquine mech and problems

Answer 7

unknown mech. maybe make ROS

HEMOLYTIC ANEMIA IF G6PD defient

Question 8

quinine

Answer 8

give AFTER infection if resistant to chloroquine (falciparum and vivax resistance)
+doxy

Question 9

quinidine

Answer 9

Used with doxy for treating SEVERE DISEASE OF ALL PLASMODIUM

Question 10

artemisinin based combo therapy (ACT)

Answer 10

always used in combo therapy

Question 11

aretesunate

Answer 11

given with mefloquine. ALWAYS GIVE IN COMBO

Question 12

radical cure

Answer 12

use primaquine to take out vivax and ovale in liver. last resort

Question 13

best treatment for acute attack of plasmodium

Answer 13

Chloroquine unless falci and vivax resistant!

Question 14

prophylatic dosing of anti malria

Answer 14

lower doses

Question 15

mechanism of chloroquine

Answer 15

inhibits heme polymerase (normally converts FPIX to hemozoin). Result is high levels of FPIX which are toxic to parasite

Question 16

toxicity of chloroquine

Answer 16

none in low dose

if given for acute attack: can cause blindness if large doses over long period of time

Question 17

mech and toxic of quinine and quinidine

Unique toxic to quinidine?

Answer 17

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

Question 18

atovaquone and proguinil mechanism and problems

Answer 18

Ato - depolarized parasite mito
pro - inhibits parasite DHFR
Not good if severe malaria
GI PROLEMS are common

Question 19

artemisinins mech and toxicity

Answer 19

produce free radicals
VERY RAPID activity
DO NO USE ALONE to avoid resistance

Question 20

CCS examples

Answer 20

plant alkaloid

dna synthesis inhibitors

Question 21

CCNS examples

Answer 21

crosslinking agents
anthracycline antibiotics (rubicin)

Question 22

leucovorin

Answer 22

methylated folate. given with methotrexate.
leucovorin rescue
CAN NOT GIVE INTRATHECAL

Question 23

allopurinol

Answer 23

xanthine oxidase inhibitor

prevents uric acid build up when giving 6-mercaptapurine or 6-tu

Question 24

6 mercaptopurine and 6 thioguinine

Answer 24

activate by HGPRT and inhibits guanylyl kinase

Question 25

f - fluorouracil

Answer 25

inhibits thymidylate synthase

Question 26

pemetrexed

Answer 26

folic acid analogue that inhibits thymidylate synthase more than DHFR

Question 27

hydroxyurea

Answer 27

inhibits ribonucleotide reductase | prevents making deoxynucleotides

Question 28

cytarabine and gemcitabine

Answer 28

pyrimidine analogues | inhibits DNA synthesizing enzymes

Question 29

pyrimidine monophosphate kinase

Answer 29

converts ump to udp | important in resistance to 5-FU

Question 30

dihidropyrimidine dehydrogenase

Answer 30

degrades thymidine nucleotides | defiency leads to sensitivity to 5-fu

Question 31

cyclophosphamide\ | steps of activation / degrade

Answer 31

first step activated by cyp450 induction of cyp2b6 increases drug activity final step makes phosphoramide mustard and acrolein

Question 32

crosslinking agents | pharmacokinetics

Answer 32

need to convert to electrophile

Question 33

mechlorethamine

Answer 33

instantaneous activation | given IV to avoid GI problems

Question 34

acrolein

Answer 34

byproduct of cyclophosphamide toxic: hemorrhagic cystitis (bladder epithelium) GIVE MESNA to treat

Question 35

ifosfamide

Answer 35

Acts slowly MOST NEUROTOXIC alkylating agent -causes mental problems

Question 36

crosslinking toxicities

Answer 36

1. myelosuppression 2. severe nausease and vomiting 3. vesicant (blistering), avoid oral - bad if escapes IV

Question 37

anthryacycline antibiotic toxicities:

Answer 37

``` unusual cardiomyopathy extravasation necrosis myelosuppression radiation recall reaction handfoot syndrome RED urine ```

Question 38

bleomycin unique mechanism

Answer 38

binds to DNA and generates free radicals that cut DNA | causes pile up of cells in g2 with chromosome problems

Question 39

hydrolase

Answer 39

found in lungs and skin Degrades bleomycin increased activity increases drug resistance along with increased DNA repair (bleomycin resistance)

Question 40

crosslinking agents examples

Answer 40

cyclophosphamide busulfan melphalan (activated in diff tissues) mechlorethamine must be given IV

Question 41

intercalating agent examples

Answer 41

doxorubicin

Question 42

drugs that cause strand break

Answer 42

etoposide | bleomysin

Question 43

etoposide

Answer 43

binds with topo2 and dna that results in strand breaks. stays bound to enzyme to prevent repair S and G2 phase

Question 44

glutathione peroxidase

Answer 44

increases resistance to intercalating agents | so does increased p-glycoprotein and change in target

Question 45

etoposide

Answer 45

ccs g2 and 2 | binds topo2 and causes double strand break

Question 46

TECANS

Answer 46

ironotecan and topotecan | cause single strand dna breaks binding topo1

Question 47

ddrugs that cause strand breaks

Answer 47

etoposide and bleomycin

Question 48

bleomycin toxicity

Answer 48

lungs and skin dont have hydrolase so causes damage

Question 49

most neurotoxic alkylating agent

Answer 49

IFOSFAMIDE. causes mental problems

Question 50

hemorrhagic cystis

Answer 50

side affect from cyclophosphamide

Question 51

extravasation necrosis (vesciant)

Answer 51

can be from anthracyclines (intercelating agents) or from mechlorethamine

Question 52

MESNA

Answer 52

given to treat for hemorrhagic cystis from cyclo and byprodu of acrolein

Question 53

capecitabine

Answer 53

3 step activation with first 2 in liver | last step by thmidine phosphorylase which is higher in some tumors making better than 5-fu