Antiprotazoals (L23)

Question 1

distributional selectivity

Answer 1

a drug that is equally toxic to a host and parasite can be useful if the parasitising cell is exposed to a higher concentration than the most cell

Question 2

how can you achieve distributional selectivity?

Answer 2

selective accumulation by parasite

selective distribution into limited compartment colonised by parasite

selective administration into limited compartment colonised by parasite

Question 3

leishmania

Answer 3

superficial infection

infects subcutaneous fat and creates lesions on the skin

Question 4

acanthamoeba

Answer 4

comes through contaminated water, can destroy the cornea by digesting it

Question 5

malaria

Answer 5

is curable but we don’t have the healthcare infrastructure to supply the drugs

Question 6

malaria prevention

Answer 6

mosquito nets

indoor spraying

preventative treatment for pregnant women

Question 7

malaria diagnosis

Answer 7

microscopy

rapid tests

Question 8

how many types of malaria can you be infected with?

Answer 8

4

all cause the same symptoms

Question 9

symptoms of malaria

Answer 9

fever 
pain 
covulsions 
coma 
death

Question 10

what are the 4 types of malaria

Answer 10

P. falciparum
P. vivid
P. ovale
P. malarie

P. falciparum is the worst as is malignant whereas the other 3 are benign

Question 11

what causes malaria

Answer 11

plasmodium

Question 12

what spreads plasmodium

Answer 12

mosquitos

requires blood for effective egg production

when mosquito bites human we get a contamination of saliva which contained sporozoite that get transmitted to human host

Question 13

malaria lifecycle in humans

Answer 13

2 step process
• 1 in the liver
• 1 in the RBCs

Question 14

targets of drug therapy to inhibit malarial infection progression

Answer 14

drugs that affect the exoerythocytic cycle bring about radical cure

precent change to erythrocytic cycle using chemoprophylactic or prophylaxis drugs

prevent asexual reproduction in RBCs and the development into gametocytes

prevent transmission between human and mosquito

Question 15

antimalarial drug therapy

Answer 15

clinical cure

radical cure - elimination of exoerythrocytic cycle

prophylaxis

Question 16

examples of antimalarial drugs

Answer 16

4-aminoquinolines

quinoline-methanols

8-aminoquinolines

antifolates

hydroxynaphthoquinone

Question 17

4-aminoquinolines

Answer 17

eg. chloroquine
• accumulates in lysosomes of parasite and inhibits digestion of hose haemoglobin
• oldest antimalarial drug but most species are now developing resistance

Question 18

quinoline-methanols

Answer 18

eg. quinine & mefloquine
• binds to malarial pigement haemozin and may intercalate into DNA
• stops parasite creating energy to replicate
• long half life
• tonic contains quinine

Question 19

8-aminoquinolines

Answer 19

eg. primaquine
• radical sure of exoerythocytic forms and killing of gametocytes
• prodrug metabolised in liver to quinoline which are cytotoxic for host and parasite

Question 20

antifolates

Answer 20

eg. proguanil
• prodrug activated by CYP2C19 to cycloguanil
• widely used in prophylaxis
• dihydrofolate reductase inhibitor - inhibition of DNA synthesis

Question 21

hydroxynaphthoquinone

Answer 21

eg. atovaguone
• inhibits mitochondria electron transport in parasite
•usually co-admnistered with proguanil

Question 22

malaria prophylaxis

Answer 22

start 1 week before travel and continuee for 4 weeks after return

need to take other precautions against being bitten

dependent on geographical region

Question 23

detecting malaria

Answer 23

parasite antigens:
• histidine-rich protein 2 - HRP2
• plasmodium lactate dehydrogenase - pLDH
• aldolose

antibodies to these proteins important to acquired immunity
• high serum prevalence of IgG