C3

Question 1

Antiprotozoal and antihelminthic drugs

Answer 1

• Antiprotozoal agents:
  
  • Antimalarials
    
    • chloroquine
    • mefloquine
    • primaquine
    • quinine
    • artemether
    • atovaquone
    • proguanil
  • Anti-amebic:
    
    • metronidazole, tinidazole
    • paromomycin
• Anti-helminthic agents:
  
  • mebendazole
  • ivermectin
  • niclosamide

Question 2

DRUGS FOR MALARIA?

Answer 2

Chloroquine
Artemether
Quinine
Mefloquine
Primaquine

atovaquone

proguanil

lumefantrine , minimal cardiotoxicity, is now used in fixed combination with artemether

(Coartem) for uncomplicated falciparum malaria.

Question 3

Chloroquine MOA?

Answer 3

prevents polymerization of the hemoglobin breakdown product heme into hemozoin

blood schizonticide

• Intracellular accumulation
  of heme is toxic to the parasite

Question 4

Chloroquine PharmacoKinetix?

Answer 4

orally

large volume of distribution ( needs a loading dose in lifethreatening infection)

• Antacids may decrease oral absorption
  of the drug
• Elimination: unchanged in the urine.

Question 5

Chloroquine Clinical use?

Answer 5

Blood schizonticide

ALL non-resistant malarias

• autoimmune disorders (rheumatoid arthritis)

Question 6

Chloroquine Toxicity?

Answer 6

1. GI irritation
2. skin rash
3. headaches

Question 7

what about Artemether?

Answer 7

• metabolized in the food vacuole of the parasite –> toxic free radicals
• blood schizonticides active against P.falciparum (also MDRs)
• Adverse effects are mild : GI upset

Question 8

Quinine MOA?

Answer 8

• form complexes with double-stranded DNA to prevent strand separation –> block of DNA replication and transcription to RNA
• it is blood schizonticide

Question 9

Quinine PharmacoKinetix?

Answer 9

orally
- metabolized before renal excretion

• I.V. administration is possible in severe infections

Question 10

Quinine Clinical use?

Answer 10

• in P.falciparum infections resistant to chloroquine (for those who tolerate oral treatment)
• should not be used routinely for prophylaxis

Question 11

Quinine Toxicity?

Answer 11

• cinchonism (GI distress, headache, vertigo, blurred vision, and tinnitus)
• Severe overdose: disturbances in cardiac conduction
• Hematotoxic effects: G6PD-deficient
• Blackwater fever (intravascular hemolysis) is a rare and sometimes fatal complication in quinine-sensitized persons
• it is contraindicated in pregnancy

Question 12

Mefloquine, primaquin MOA?

Answer 12

unknown :)

Question 13

Mefloquine PharmacoKinetix?

Answer 13

orally because of local irritation

Question 14

Mefloquine clinical use?

Answer 14

• first-line drug (taken weekly) for prophylaxis
• daily for infection

Question 15

Mefloquine Toxicity?

Answer 15

• GI upset
• skin rash, headache, and dizziness
• At high doses:
  cardiac conduction abnormality, psychiatric disorders, and seizures

Question 16

Primaquine MOA?

Answer 16

• unknown mech
• it is a tissue schizonticide
• limits malaria transmission by acting as a gametocide

Question 17

Primaquine PharmacoKinetix?

Answer 17

Absorption is complete after oral administration

Question 18

Primaquine Clinical use?

Answer 18

• against liver stages of P.Vivax and P.Ovale
• PCP ( P.jiroveci pneumonia)
• should be used in conjunction with a blood schizonticide

Question 19

Primaquine Toxicity?

Answer 19

• well tolerated but may cause:
  1. GI distress
  2. headaches
  3. . Blood cytopenias
• More serious toxicity:
  hemolysis (G6PD-deficients)

*contraindicated in pregnancy*

Question 20

what about Atovaquone ?

Answer 20

• disrupt mitochondrial metabolism ( electron transport in protozoa)

Malarone (Atova + Proguanil) for both chemoprophylaxis (taken daily) and treatment of falciparum malaria

• rash , fever, GI effects occur at the higher doses

Question 21

DRUGS FOR AMEBIASIS?

Answer 21

Metronidazole, tinidazole

Paromomycin

Question 22

Antihelminthic drugs

Answer 22

• Round worms (Nematodes):
  
  • Mebendazole
  • Ivermectin
  • Albendazole
  • Diethylcarbamazine
• FLUKES (Trematodes)
  
  • Praziquantel
• Tape worm (Cestodes)
  
  • Albendazole
  • Mebendazole
  • Niclosamide
  • Praziquantel

Question 23

Proguanil MOA, administration

Answer 23

Antifolate

-inhibits folate synthesis

oral

Question 24

Proguanil effects

Answer 24

Mostly blood schizonticide

Question 25

Proguanil toxicity

Answer 25

GI upset rash (sometimes severe) cytopenia

Question 26

metronidazole MOA

Answer 26

reactive metabolic products Anti-amebic agents

Question 27

metronidazole clinical uses

Answer 27

* Luminal amebiasis * Extra-intestinal amebiasis * giardiasis * trichomoniasis

Question 28

metronidazole pharmacokinetic

Answer 28

* oral * rapid diffusion into all tissues

Question 29

metronidazole toxicity

Answer 29

* Nausea * headache * paresthesia * disulfiram effect

Question 30

Mebendazole MOA

Answer 30

**Selective inhibiton** of _microtubule synthesis_ and _glucose uptake_ in round worms

Question 31

Mebendazole clinical uses

Answer 31

* Ascariasis * pinworm * whipworm infections

Question 32

mebendazole pharmacokinetics

Answer 32

* less than 10% is absorbed systematically after oral use * metabolised by hepatic enzymes plasma levels can be increased by cimetidine decreased by carbamazepine or phenytoin

Question 33

mebendazole toxicity

Answer 33

* GI irritation * granulocytopenia (high dose) * alopecia (high dose) * teratogenic ; CI in pregnancy

Question 34

Ivermectin MOA

Answer 34

* intensifies GABA-mediated neurotranmission in round worms * causes immobilization of parasite; facilitate their removal by reticuloendothelial system. * DOESNT cross BBB

Question 35

Ivermectin clinical use

Answer 35

* Onchocerciasis * cutaneous larva migrans * stronglodiasis against round worms

Question 36

Ivermectin SE

Answer 36

* reactions due to dying worms : * fever * headache, dizziness * rash * pruritis * tachycardia * hypotension * joint pain * muscle pain * lymph gland pain * controlled with NSAID, Antihistamines * CI in pregnancy

Question 37

Niclosamide MOA

Answer 37

* Uncoupling oxidative phosphorylations * OR by activating ATPases.

Question 38

Niclosamide Clinical uses

Answer 38

* Beef, pork, fish tapeworm * small, large intestinal flukes

Question 39

Niclosamide toxicity

Answer 39

* GI distress * headache * rash * fever Avoid ethanol consumption 24-48 hres