Chloroquine | Primaquine
| Quinine | Pyrimethamine/Sulfadoxine
| Tetracyclines | Mefloquine
| Artemisinin | Halofantrine
| Atovaquone/Proguanil | Other
In Cardiovascular
disease | In C.N.S.
Disease | In epilepsy | In Diabetes Mellitus | In Renal Disease | In Liver Disease |
In Myasthenia Gravis | Antimalarials and
Anaesthesia | In dermatitis
"Mother Nature gave
us the cinchona alkaloids and qinghaosu. World War II led to the introduction of
chloroquine, chloroguanide (proguanil), and eventually amodiaquine and pyrimethamine. The
war in Vietnam brought mefloquine and halofantrine. These drugs are all we have available
now to treat malaria. It is difficult to see where the next generation of antimalarial
drugs will come from....there is little pharmaceutical industry interest in developing new
antimalarial drugs; the risks are great, but the returns on investment are low....If drug
resistance in P. falciparum continues to increase at the current rate, malaria may become
untreatable in parts of Southeast Asia by the beginning of the next millennium."
White
NJ. The treatment of malaria. NEJM. 12.9.1996;335:11:800-806
|
The effectiveness of
early diagnosis and prompt treatment as the principal technical components of the global
strategy to control malaria is highly dependent on the efficacy, safety, availability,
affordability and acceptability of antimalarial drugs. The effective antimalarial therapy
not only reduces the mortality and morbidity of malaria, but also reduces the risk of
resistance to antimalarial drugs. Therefore, antimalaria chemotherapy is the KEYSTONE of
malaria control efforts. On the other hand, not many new drugs have been developed to
tackle malaria; (Nature, Oct 3, 2002; 419:426) of the 1223 new drugs registered
between 1975 and 1996, only 3 were antimalarials! Hence the need for a rational
antimalaria treatment policy. |
Classification
Anti malarial drugs can be
classified according to anti malarial activity and structure.
1. According to anti malarial
activity:
-
Tissue schizonticides for causal
prophylaxis: These drugs act on the primary tissue forms of the plasmodia which after
growth within the liver, initiate the erythrocytic stage. By blocking this stage, further
development of the infection can be theoretically prevented. Pyrimethamine and Primaquine
have this activity. However since it is impossible to predict the infection before
clinical symptoms begin, this mode of therapy is more theoretical than practical.
-
Tissue schizonticides for preventing
relapse: These drugs act on the hypnozoites of P. vivax and P. ovale in the liver that
cause relapse of symptoms on reactivation. Primaquine is the prototype drug; pyrimethamine
also has such activity.
-
Blood schizonticides: These drugs act
on the blood forms of the parasite and thereby terminate clinical attacks of malaria.
These are the most important drugs in anti malarial chemotherapy. These include
chloroquine, quinine, mefloquine, halofantrine, pyrimethamine, sulfadoxine, sulfones,
tetracyclines etc.
-
Gametocytocides: These drugs destroy
the sexual forms of the parasite in the blood and thereby prevent transmission of the
infection to the mosquito. Chloroquine and quinine have gametocytocidal activity against
P. vivax and P. malariae, but not against P. falciparum. Primaquine has gametocytocidal
activity against all plasmodia, including P. falciparum.
-
Sporontocides: These drugs prevent the
development of oocysts in the mosquito and thus ablate the transmission. Primaquine and
chloroguanide have this action.
Thus in effect, treatment of malaria
would include a blood schizonticide, a gametocytocide and a tissue schizonticide (in case
of P. vivax and P. ovale). A combination of chloroquine and primaquine
is thus needed in ALL cases of malaria.
2. According to the structure:
| Aryl
amino alcohols: |
Quinine,
quinidine (cinchona alkaloids), mefloquine, halofantrine. |
| 4-aminoquinolines:
|
Chloroquine,
amodiaquine. |
| Folate
synthesis inhibitors: |
Type
1 - competitive inhibitors of dihydropteroate synthase - sulphones, sulphonamides
Type 2 - inhibit dihydrofolate reductase - biguanides like proguanil and chloroproguanil;
diaminopyrimidine like pyrimethamine |
| 8-aminoquinolines:
|
Primaquine,
WR238, 605 |
| Antimicrobials:
|
Tetracycline,
doxycycline, clindamycin, azithromycin, fluoroquinolones |
| Peroxides:
|
Artemisinin
(Qinghaosu) derivatives and analogues - artemether, arteether, artesunate, artelinic acid |
| Naphthoquinones:
|
Atovaquone |
| Iron
chelating agents: |
Desferrioxamine
|
|
|
Quick comparison between blood schizonticidal drugs
|
Chloroquine |
Pyr./Sulpha. |
Quinine |
Mefloquine |
Qinghaosu |
Efficacy |
++++ |
++ |
+++ |
+++ |
+++++ |
Onset of action |
Rapid |
Slow |
Rapid |
Rapid |
Fastest |
Use |
Prototype drug, first choice for all cases |
Only for uncomplicated, resistant
P. falciparum |
Only for resistant
P. falciparum |
Only for uncomplicated, multi drug resistant
P. falciparum |
Reserved for drug resistant
P. falciparum. However, it may be considered in life threatening complications of
P. falciparum due to its rapid action |
Use in severe
P. falciparum
malaria |
Parenteral preparation can be used in areas with sensitive strains |
Not useful in acute illness; can be co- prescribed with other parenteral
antimalarials |
Drug of choice for severe malaria; it was the only parenteral drug
available for a long time until parenteral chloroquine and artemisinin arrived |
Not to be used in acute illness; can be co-prescribed with artemisinin
after acute phase is over. |
Useful in severe malaria; may be more effective and better tolerated than
quinine. |
Toxicity |
++ |
+++ |
+++ |
+++ |
+ |
Contra indications |
Almost none, only advanced liver disease |
Allergy to sulpha |
Prior hypersensitive reactions |
Epilepsy, psychosis, heart block, ß blocker use |
None |
Use in pregnancy |
Yes |
Only in 2nd trimester if warranted |
Only if warranted, watch for hypoglycemia |
Not in first trimester |
Yes, if the situation demands |
Cost |
Cheapest |
Cheap |
Moderate |
Expensive |
Expensive |
The Salt-Base Table |
Drug |
Salt |
Base |
Chloroquine sulphate |
136 mg |
100 mg |
Chloroquine diphosphate |
250 mg |
150 mg |
Quinine sulphate |
362 mg |
300 mg |
Quinine bisulphate |
508 mg |
300 mg |
Quinine hydrochloride |
405 mg |
300 mg |
Mefloquine hydrochloride |
274 mg |
250 mg |
Primaquine |
26.3 mg |
15 mg |
|
