Durg that are use for pneumocystis there mechanism of action, uses and adverse effects.

1. Drug for Treatment of pneumocystis
By Bhairavlal Parmar

2. Pneumocystis :
Pneumocystis jirovecii (previously P. carinii) is a yeast-like fungus of the
genus Pneumocystis. The causative organism of Pneumocystis pneumonia,
it is an important human pathogen, particularly among
immunocompromised hosts. Prior to its discovery as a human-specific
pathogen, P. jirovecii was known as P. carinii.

3. LIFECYCLE :
The complete lifecycles of any of the species of Pneumocystis
are not known. It is an extracellular parasite. All stages are found
in lungs and because they cannot be cultured ex vivo, direct
observation of living Pneumocystis is difficult.

4. Drug for Treatment of pneumocystis:
1. ATOVAQUONE(MEPRON)
 Formula: C22H19ClO3
 IUPAC: trans-2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-
naphthalenedione
 Atovaquone has structural similarity to ubiquinone metabolites.

5. Mechanism of Action:
 It mainly Inhibit mitochondrial respiratory chain.
Inhibit UBIQUINONE REDUCTASE
Thus inhibiting cytochrome bc1 complex
Leads to collapse of mitochondrial membrane
potential
Death of parasite

6. Uses :
1. For pneumocystis pneumonia (PCP), it is used in mild cases, although it is not
approved for treatment of severe cases.
2. For toxoplasmosis the medication has antiparasitic and therapeutic effects.
3. For malaria, it is one of the two components (along with proguanil)
Adverse effects :
 coughing, diarrhoea, dizziness, headache, loss of appetite, mouth sores,
nausea, stomach pain, vomiting, or weakness.

7. 2. PENTAMIDINE ISETHIONATE :
 Formula : C23H36N4O10S2
 IUPAC : 4-[5-(4-carbamimidoylphenoxy)pentoxy]benzenecarboximidamide;2-
hydroxyethanesulfonic acid
 Pentamidine is an antimicrobial medication used to treat African trypanosomiasis,
leishmaniasis, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people
with poor immune function.In African trypanosomiasis it is used for early disease before central
nervous system.
 Pentamidine is available as water soluble isethionate salt, which is used both
IV and as aerosol.

8. Mechanism of Action :
 The mechanism seems to vary with different organisms and is not well understood.
However, pentamidine is suspected to work through various methods of interference of
critical functions in DNA, RNA, phospholipid and protein synthesis.
 Pentamidine binds to adenine-thymine-rich regions of the Trypanosoma parasite DNA,
forming a cross-link between two adenines four to five base pairs apart.
 The drug also inhibits topoisomerase enzymes in the mitochondria of Pneumocystis
jirovecii. Similarly, pentamidine inhibits type II topoisomerase in the mitochondria of
the Trypanosoma parasite.
 INSHORT :
Mainy it inhibit topoisomerase in pneumcystics carinii
Makes cell DNA Inactive
CELL DEATH

9. USES :
 Treatment of PCP caused by Pneumocystis jirovecii
 Treatment of leishmaniasis
 Treatment of African trypanosomiasis caused by Trypanosoma brucei gambiense
 Use as an antitumor drug has also been proposed.
Side effects :
 Burning pain, dryness, or sensation of lump in throat
 Chest pain
 Coughing
 Difficulty in breathing
 Difficulty in swallowing
 Skin rash
 Nausea and vomiting
 Pain in upper abdomen
 Severe pain in side of chest
 Shortness of breath

10. 3. Co-trimaxazole :
 Trimethoprim/sulfamethoxazole, also known as co-trimoxazole among other
names, is an antibiotic used to treat a variety of bacterial infections.
 It consists of one part trimethoprim to five parts sulfamethoxazole.
 It is used for urinary tract infections, MRSA skin infections, travelers'
diarrhea, respiratory tract infections, and cholera, among others.[1][2] It may
be used both to treat and prevent pneumocystis pneumonia.
 It can be given by mouth or intravenously.

11. Mechanism of Action:
 Seqential blocking of two enzyme dihydroptreoate synthase & dihydrofolate
reductase leads to inhibition of folic acid synthesis which is essential for
thymidine which require for DNA replication.
 Thus it ultimately leads to cell death

12. 4. Trimetrexate Glucuronate :
 Formula : C25H33N5O10
 IUPAC : 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-
diamine;(2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-6-oxohexanoic acid
 Trimetrexate has been approved for the treatment of Pneumocysis carinii In
patient with ATDs.
 Trimetrexate combined with cytoprotective agent leucovarin is more
effective and better tolerate while treating Pneumocystis.

13. Mechanism of Action :
 Trimetrexate Glucuronate is a lipid soluble methotrexate. Trimetrexate
glucuronate inhibits the enzyme dihydrofolate reductase, thereby preventing the
synthesis of purine nucleotides and thymidylate, with subsequent inhibition of
DNA and RNA synthesis. Trimetrexate glucuronate also exhibits antiviral
activity.
 INSHORT :
Trimetrexate without glutamate moiety, is absorbed by cell via passive diffusion
Once inside cell Trimetrexate inhibit Dihydrofolate reductase of pneumocystis
Inhibition of folate synthesis
DNA Replication cannot take place

14. USES :
 It has been used with leucovorin in treating pneumocystis pneumonia.
 It has been investigated for use in treating leiomyosarcoma
Side effects :
 Fever
 Nausea
 Fatigue
 Rash and itching
 Nausea
 Vomiting
 Confusion, and
 Low white blood cell count (neutropenia)