Antimalarial Drugs Flashcards
SE Asia is known for being resistant to _____; what would you give in treating uncomplicated malaria in that area
mefloquine + artesunate
what re some AE of chloroquine?
- causes oxidative stress on RBC’s so check if the patient has G6PD deficiency
- pruritus (africans)
- nausea, vomiting, abdominal pain etc
generally well tolerated
what are the symptoms of malarial paroxysm?
fever, anemia, jaundice, splenomegaly, hepatomegaly and these are associated with lysis of the RBC by the pathogen
which drugs are given for severe malaria caused by P. falciparum?
- quinine/quinidine
- artemisinin
during what trimester is quinidine given to treat severe malaria in pregnant patients
1st trimester
can you give pregnant patients quinine/quinidine?
it is a category C drug so only give if the benefits outweigh the risks
what are the symptoms of cinchonism and what drugs can cause this AE
- tinnitus (ringing in the ear), headache, nausea, dizziness, flushing and visual disturbances
- quinine/quinidine
______ is an antimalarial drug that is teratogenic
halofantrine; do not give it with mefloquine
what is the MOA of artemisinin
binds to iron to break down peroxide bridges → generation of free radicals that damage parasite proteins
clears the parasites the fastest and can also destroy the gametocytes
how does primaquine exacerbate G6PD and lead to ↑ hemolysis
- primaquine oxidizes GSH back to GSSG
G6PD produces more NADPH from NADP and the resultant NADPH is used to reduce GSSG to GSH. GSH is then used to neutralize toxic compounds
G6PD deficiency has ↓ G6PD and thus ↓ GSH; primaquine will ↓ GSH even more
is the combination of proguanil and pyrimethamine safe for use in pregnancy?
YES but not the first drug to be used
P. falciparum’s resistance to chloroquine is due to ______
mutation in the putative transporter PfCRT (plasmodium falciparum chloroquine resistance transporter)
a patient with malaria is given chloroquine but is ineffective. what is the MOA of the next drug that you would prescribe
- destruction of asexual blood forms
pharmacological therapy for treating malaria would be guided by what 3 main factors?
- what Plasmodium species is responsible: if it vivax/ovale, then have to also kill the hypnozoites
- clinical status of the patients: complicated or uncomplicated malaria
- drug susceptibility of the infecting parasites
malaria caused by ______ can result in cerebral malaria
P. falciparum; irritability → seizures → coma
can chloroquine be used for treatment of malaria in young kids and pregnant patients?
YES
a patient complains of photosensitivity and has discoloration and hypoplasia of their teeth. What drug can cause these AE’s?
doxycycline
sulfadoxine inhibits folate synthesis by ________
↓ the activity of dihydropteroate synthase
sulfonamides directly complete with PABA (p-aminobenzoic acid) for binding with dihydropteroate synthase → ↑ PABA
what is the DOC for treatment AND prophylaxis of all P. vivax and P. ovale malaria infections
Chloroquine (use has been recently compromised by drug resistance)
when is primaquine contraindicated?
pregnant patients;
wait until after delivery to give them primaquine because the fetus has low levels of G6PD
what drug would you give to pregnant patient with chloroquine resistant P. vivax
mefloquine
_______ can cause hypoglycemia by stimulating insulin release
quinine/quinidine
metabolites of _____ have less antimalarial activity but more potential for hemolysis
primaquine; hemolysis or methemoglobin in G6PD deficient patients
what is the drug regiment in pregnant patients with severe malaria?
- 1st option: aretsunate
- 2nd option: artemether
what symptoms help classify malaria as complicated
- impaired consciousness, severe anemia, renal failure, pulmonary derma, ARDS, shock, DIC, acidosis, hemoglobinuria
what drug is give for prophylaxis against chloroquine resistant malaria
- mefloquine, doxycycline, or primaquine
same method for pregnant patients but DONT GIVE DOXYCYCLINE
________ drug for malaria works by disrupting the parasites replication and transcription
quinine/quinidine
Malrone is given for ______
treatment and prophylaxis of P. falciparum
what drugs are used to treat chloroquine resistant P. falciparum
- atorvaquone + proguanil (malarone)
- artemether-lumefantrine
- quinine + doxycycline
- mefloquine
hyper/hypoglycemia is seen in malaria caused by P. falciparum
HYPOglycemia
________ is the only drug that can treat the liver form (hypnozoites) of the parasite
primaquine; can also be used for chemoprophylaxis for all strains
when would you give quinine/quinidine
quinine: oral form given for uncomplicated malaria caused by P. falciparum
quinidine: IV form given for severe malaria caused by P. falciparum
what are 3 drugs that are folate synthesis inhibitors that can be used to treat malaria?
- pyrimethamine
- proguanil
- sulfadoxine
used in combination
_______ can be used as an alternative to doxycline in malaria
clindamycin
what are some AE of quinine/quinidine
- cinchonism
- HS: rash, urticaria, bronchospasm, angioedema
- hematological abnormalities: leukopenia, agranulocytosis, thrombocytopenia
- hypoglycemia: due to stimulation of insulin release
- induce uterine contractions
- severe hypotension
- QT prolongation
- black water fever (acute renal failure): severe hemolysis and hemoglobinuria
______ is one of the first line agents for severe falciparum disease
quindine (quinine is the oral form and quinidine is the IV form and in cases of severe disease, want to give the IV form)
when would you give mefloquine?
- as a chemoprophylaxis because it is effective against P. falciparum and P. vivax
- treatment for mild to moderate malaria caused by P. falciparum and P. vivax
pyrimethamine + proguanil inhibit folate synthesis by inhibiting ________
dihydrofolate reductase causing an ↑ in dihydrofolic acid
which drug has the unique ability to reduce the ability of the mosquito to spread malaria
artemisinin because they can also destroy the gametocytes which are taken up by the mosquito again and then infects other people
what is the MOA of malarone
it is a combination of atovaquone and proguanil (inhibits folate synthesis)
disrupts the mitochondrial electron transport
_______ the preferred chemoprophylactic agent in areas without resistant falciparum malaria
chloroquine
resistance to quinine can sometimes have some resistance to _______
mefloquine (they have similar chemical comp);
no mefloquine resistance in those resistant to chloroquine
what kind of pathogens is aztreonam used for?
gram negative rods
_________ is an antimalarial that can increase the plasma levels of warfarin and digoxin
quinine/quinidine
what are some clinical applications of drugs that are folate synthesis inhibitors
- chemoprophylaxis
- intermittent preventative therapy in high risk patients regardless of infection status
- treatment of chloroquine resistant falciparum malaria: w/ pyrimethamine + sulfadoxine but DO NOT USE FOR SEVERE MALARIA
in treating SEVERE malaria in pregnant patients, the drugs that are used depends on what trimester the patient is in.
what is given in the 1st trimester?
quinidine / artesunate
only give quinidine in the 1st trimester because it can cause uterine contraction so can’t give it later
a patient has infection by P. ovale and you want to treat the dormant hypnozoites in the liver. Before prescribing ______ what would you do first?
DOC: primaquine but because it can cause severe hemolysis in G6PD deficient patients, must test for G6PD deficiency first
psychiatric symptoms such as ________ is an AE of what antimalarial drug?
anxiety, depression, hallucinations;
seen as an AE of mefloquine so dont give mefloquine to people with psychiatric disorders
what is the MOA of quinine and quinidine?
- ↓ O2 uptake and carbohydrate metabolism
- intercalates into DNA and disports parasites replication and transcription
what is the MOA of chloroquine
concentrates in the parasite food vacuoles and prevents the plasmodium ability of biocrystallization of Hb breakdown production heme to non toxic hemozoin
parasite ingests host cells Hb for nutrients and the toxic byproduct, heme, is then polymerized to hemozoin by the parasite and stored in the parasites food vacuole
what is the only medication that is recommended for chemoprophylaxis in pregnant women in chloroquine resistant areas
mefloquine
when would you give chloroquine?
- anti malarial DOC for non falciparum and sensitive uncomplicated malaria
- DOC to treat P. vivax and P. ovale infection
what do you give to treat severe malaria that can be caused by all species of plasmodium?
- quinidine + doxycycline
OR - artesunate
quinine/quinidine should not be used concurrently with ______
mefloquine because they both have similar chemical compositions
_____ and _____ species of plasmodium have different resistance patterns to drugs in different geographic areas
P. vivax and P. falciparum
what kind of patients is chloroquine contraindicated with?
- patients with psoriasis or porphyria
- retinal/visual field abnormalities
describe the use of doxycycline in treating malaria
it is NOT active against the liver stage but is active against the erythrocytic schizonts of all malaria parasites
it is used to complete treatment of severe p. falciparum and thus is usually given after treatment with quinine/quinidine/artesunate
what drug would you give to chloroquine resistant strains of plasmodium?
mefloquine
in addition to P. falciparum, what other species tends to show chloroquine resistance?
how would you treat these resistant strains?
- P. vivax
1. quinine + doxycycline + primaquine
2. malarone + primaquine
3. mefloquine + primaquine
what drugs would you give to a pregnant patient with chloroquine resistant P. falciparum?
- mefloquine
2. quinine + clindamycine (usually given with doxycycline but you cant give doxycycline to pregnant patients)
______ is a drug that prevents the polymerization heme to non toxic form hemozoin
chloroquine
a patient is traveling to SE Asia, when prescribing antimalarial drugs, which would you AVOID because of known resistance to it in that area
quinine/quinidine because that area is common for resistance to them
QT prolongation is an AE of what antimalarial drug
quinine/quinidine
