Navirapine drug

It is an effective antiretroviral drug which is medically used in various HIV/AIDS therapies, the trade name is Viramune

1. NEVIRAPINE Madish Chemistry Department

2. TABLE OF CONTENT Introduction History Structure Preparation Mechanism of action Applications/Medical uses Adverse effects

3. CLASSIFICATION OF ANTI-RETROVIRAL DRUGS (ANTI-HIV DRUGS):

4. ITRODUCTION OF NEVIRAPINE:

5. HISTORY:

6. IMPORTANT INFORMATION:

7. MECHANISM OF ACTION: NNRTIs attach to and block an HIV enzyme called reverse transcriptase, (an enzyme that controls the replication of the genetic material of HIV). By blocking reverse transcriptase (NON-COMPETITIVELY), NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body BY preventing the conversion of RNA to DNA

8. GENERAL REPRESENTATION: Blue color -------RT active domain Red atoms -------- active site Pink---------- DNA Yellow -------------- NNRTI drug

9. ROLE OF NEVIRAPINE: HIV medicines can’t cure HIV/AIDS, but taking a combination of HIV medicines (called an HIV treatment regimen) every day helps people with HIV Live longer, Healthier lives. Reduce the risk of HIV transmission

10. STRUCTURE: Molecular Formula C 15 H 14 N 4 O Average mass 266.298 Da Monoisotopic mass 266.116760 Da It is of Synthetic origin. The chemical name : 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido [3,2-b:2', 3'-e][1,4] diazepin-6-one. Nevirapine is a white to off-white crystalline powder

11. STRUCTURE: belongs to the dipyridodiazepinone chemical class According to Single crystal X-ray diffraction it has Butterfly shape

12. STRUCTURE: The butterfly structure has a hydrophilic centre as a ‘body’ and two hydrophobic moieties representing the wings.  Wing I is heteroaromatic ring Wing II is phenyl or allyl substituent. Functional group Wing I has a  functional group  at one side of the ring which is capable of accepting and/or donating hydrogen bonds with the main chain of the amino acids Wing II interacts through π-π interactions with a hydrophobic pocket, formed in most part by the side chains of aromatic amino acids. Through this interaction side chains formed

13. FIRST METHOD OF PREPARATION: produces 2-chloro-N-(2-chloro-4methyl-3-pyridinyl)-3-pyridine carboxamide Which is then, reacts with cyclopropylamine in a sealed reactor to give N-(2-chloro-4-methyl-3-pyridyl)-2( cyclopropylamino )-3-pyridine carboxamide Followed by cyclization in presence of sodium hydride to produce nevirapine

14. MATERIALS AND METHODS: SECOND METHOD OF PREPARATION:

15. Preparation of Nanosuspensions:   Nano-suspensions were prepared using nanoedge method Initially nevirapine solubility studies in various solvents were performed to select a suitable solvent to be used in the formulation The solvents used were To dissolve nevirapine ( a cyclo mixture and a sonicator ) were used Dichloromethane chosen as the solvent (showed good solubility of 10 mg/ml)

16. TWO STEP MECHANISM:

17. MECHANISM:

18. MECHANISM:

19. TABLE:

20. MECHANISM OF ACTION: Nevirapine falls in the non-nucleoside reverse transcriptase inhibitor ( NNRTI ) class of antiretrovirals. Both nucleoside and non-nucleoside RTIs inhibit the same target. The reverse transcriptase enzyme, (an essential viral enzyme which transcribes viral RNA into DNA) Unlike nucleoside RTIs, which bind at the polymerase active site,  NNRT.Is bind to a hydrophobic pocket in the subdomain of p66 which is about 10 angstrom away from the active site.

21. MECHANISM OF ACTION: Nevirapine is not effective against HIV-2 , as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class Esistance to nevirapine develops rapidly if viral replication is not completely suppressed The most common mutations observed after nevirapine treatment are Y181C and K103N, which are also observed with other NNRTIs

22. MECHANISM OF ACTION: All NNRTIs bind within the same pocket, viral strains which are resistant to nevirapine are usually also resistant to the other NNRTIs,  efavirenz  and  delavirdine Second generation NNRTIs like  rilpivirine  and  etravirine  are effective in treatment for HIV strains resistant to nevirapine and other first generation drugs in that same class

23. cART Treatment that uses a combination of three or more drugs to treat HIV infection. Combination antiretroviral therapy stops the virus from making copies of itself in the body

24. HAART HAART stops the virus from making copies of itself in the body. This may lessen the damage to the immune system caused by HIV and may slow down the development of AIDS. It may also help prevent transmission of HIV to others, including from mother to child during birth.

25. Antiretroviral therapy

26. MEDICAL USES: To help control HIV infection Decrease the amount of HIV so immune system can work better Decrease the risk of spreading HIV disease to others Used in (ART) Used in cART Used in HAART

27. MEDICAL USES: Nevirapine is used if the CD4 cell count in the body is very low It is also useful component of salvage Chemothraphy (when all of theraphy   fails  ) used in combination with one or more PIs as well as  nucleotide reverse transcriptase inhibitor  (NRTIs), especially in those who have not previously taken an NNRTI.

28. Preventing mother-to-child transmission A single dose of nevirapine given to both mother and child reduced the rate of HIV transmission by almost 50% compared with a very short course of   zidovudine (AZT) prophylaxis A subsequent study in  Thailand  showed that prophylaxis with single-dose nevirapine in addition to zidovudine is more effective than zidovudine alone

29. SIDE EFFECTS:

30. SIGNS OF ALLERGY: Joint or muscle pain Fever and Cough Mouth sores, Facial swelling, Blistering skin rash, Flu symptoms, Swollen glands, Feeling weak or tired, Severe tingling or numbness Pain or burning when you urinate, Swelling in your legs feet, lips, tongue, or throat Chest pain, Trouble breathing

31. LIFE-THRETNING EFFECT ON LIVER: ( Cause Especially in women ) Nausea Loss of appetite Upper stomach pain Tiredness Fever Unexplained muscle pain or weakness Dark urine Clay- colored stools Jaundice (yellowing of the skin or eyes)

32. LIFE-THREATNING SKIN REACTIONS: Fever Sore throat Swelling in your face or tongue Burning in your eyes Skin pain Red or purple skin rash that spreads and causes blistering and peeling NOTE:  This type of reaction is a medical emergency.

33. AUTOIMMUNE DISORDER: May cause by changing the way your immune system works. TIME PEROID: Symptoms may occur within the weeks or months

34. AUTOIMMUNE DISORDER (SYMPTOMS) signs of a new infection— fever  night sweats swollen glands mouth sores   diarrhea stomach pain  weight loss

35. AUTOIMMUNE DISORDER (SYMPTOMS) NORMAL SYMPTOMS: Chest pain (especially when you breathe) Dry cough and Wheezing Feeling short of breath Cold sores including Sores on your genital or anal area Rapid heart rate Feeling anxious or irritable Weakness or prickly feeling Problems with balance or eye movement Trouble speaking or swallowing Severe lower back pain loss of bladder or bowel control Swelling in your neck or throat (enlarged thyroid) menstrual changes, Impotence Loss of interest in sex

36. WHAT OTHER DRUGS WILL AFFECT NEVIRAPINE:

37. WHAT OTHER DRUGS WILL AFFECT NEVIRAPINE:

38. Thank You so much