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. CLASSIFICATIONOF ANTI-
RETROVIRAL DRUGS (ANTI-HIV
DRUGS):Nucleoside reverse
transcriptase
inhibitors (NRTIs):
Zidovudine, Stavudine, Lamivudine, Abacavir, Zalcitabine, Emtricitabine,
Didanosine.
Non-Nucleoside
reverse transcriptase
inhibitors (NNRTIs):
Efavirenz, Nevirapine, Delaviridine.
Protease inhibitors
(PIs):
Saquinavir, Indinavir, Nelfinavir, Amprenavir, Fosamprenavir, Ritonavir,
Lopinavir, Atazanavir.
Nucleotide reverse
transcriptase
inhibitors (NTRTIs):
Tenofovir
Entry/Fusion
inhibitors:
Enfuvirtide

4. ITRODUCTION OF NEVIRAPINE:
the trade
name Viramune
used to treat and
prevent HIV/AIDS
specifically HIV-1
It is antiretroviral
medication
Used to prevent mother
to child spread during
birth
Taken by mouth

5. HISTORY:
NEVIRAPINE WAS DISCOVERED BY
HARGRAVE AT BOEHRINGER
INGELHEIM PHARMACEUTICALS
NEVIRAPINE WAS APPROVED FOR
MEDICAL USE IN THE UNITED
STATES IN 1996.
ACCORDING TO WORLD HEALTH
ORGANIZATION'S LIST OF
ESSENTIAL MEDICINES IT IS
SAFE MEDICINES NEEDED IN
A HEALTH SYSTEM
AVAILABLE AS A GENERIC
MEDICATION
NEVIRAPINE WAS THE FIRST
NNRTI APPROVED BY THE U.S.
FOOD AND DRUG
ADMINISTRATION(FDA).
WAS APPROVED ON JUNE 21,
1996 FOR ADULTS AND
SEPTEMBER 11, 1998 FOR
CHILDREN.
WAS ALSO APPROVED IN EUROPE
IN 1997

6. IMPORTANT
INFORMATION
:
Drug Class: Non-nucleoside ReverseTranscriptase
Inhibitors
Nevirapine is always used in combination with other
HIV medicines.
Nevirapine comes in three different forms: immediate-
release tablets ,oral suspension (a liquid) ,extended-
release tablets.
The immediate-release tablet and liquid forms of
nevirapine are approved for use in adults and children
15 days and older.
The extended-release tablets are for use in adults and
in children 6 years of age and older

7. MECHANISMOF 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
REPRESENTATIO
N:
■ 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 C15H14N4O
■ 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:
Poloxamer 407 were obtained from Hetero Labs
(Hyderabad, India)
Hydroxypropyl methylcellulose (HPMC) was
obtained from Merck India Ltd. (Mumbai)
Sodium lauryl sulphate (SLS), Poloxamer were
obtained from Hi Media Laboratories (Mumbai,
India)
Tween 80 and dichloromethane were obtained from
S. D. Fine-Chem. Ltd. (Mumbai, India)
PVPK30 and carboxymethylcellulose were obtained
from Merck India.
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 wereTo dissolve nevirapine (a cyclo mixture and a sonicator) were
used
■ Dichloromethane chosen as the solvent (showed good solubility of 10 mg/ml)
ethanoland methanol
dichlorometh
ane,
isopropanol acetone ethyl acetate

16. TWO STEP
MECHANISM:
FIRST STEP:
Precipitation using the solvent
evaporation technique
SECOND STEP:
high-pressure
homogenisation

17. MECHANISM:
PROCEDURE OF FIRST STEP:
the drug dissolved in the solvent at room temperature.
This solution was added drop wise using a syringe needle into different volumes of
water containing different amounts of surfactant on a magnetic stirrer.
Stirring was performed at room temperature and volatile solvents were allowed
to evaporate.
Stirring was kept for 3 h leading to precipitation of nanosuspension of the drug.
Variety of nanosuspension formulations were prepared using different
surfactants .

18. MECHANISM:
PROCEDURE
OF 2ND STEP:
The nanosuspension from step I was homoginised using Diax 900
homogeniser (Heidolph, Germany) for 5 min
The above prepared suspension was then subjected to sonication
for 20 min using an ultrasonicator (Probe 12T, Bandelin)
This suspension was then passed through high-pressure
homogenisation in for 10 cycles at 10 000 psi Using Emulsiflex-c5
HPH

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
areY181C 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 ofAIDS. It may also help prevent
transmission of HIV to others, including from mother to child during
birth.

25. Antiretroviral
therapy
Has the following positive effects on HIV:
stops it from multiplying in the blood
reduces viral load, which is the number of HIV copies in the blood
increases the number of CD4 cells, which are immune cells that HIV targets, to improve
immune system function
slows down and prevents the development of stage 3 HIV, or AIDS
prevents transmission
reduces the severity of complications and increases survival rates
keeps virus counts low in the blood

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 inThailand showed that
prophylaxis with single-dose nevirapine in
addition to zidovudine is more effective than
zidovudine alone

29. SIDE
EFFECTS:
AFTERTAKING NAVIRAPINE IFYOU HAVETHESE
SIGHNS
Allergy
Liver problem
Skin problem
Autoimmune disorders
Change in body shape

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—
I. fever
II. night sweats
III. swollen glands
IV. mouth sores
V. diarrhea
VI. stomach pain
VII. weight loss

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

36. WHAT
OTHER
DRUGS
WILL
AFFECT
NEVIRAPIN
E:
Not all possible interactions are listed here.Tell your
doctor about all your current medicines and any you
start or stop using, especially
antiviral medication to treat hepatitis C
an antibiotic or antifungal medicine
birth control pills or hormone replacement therapy
a blood thinner (warfarin and others)

37. WHAT
OTHER
DRUGS
WILL
AFFECT
NEVIRAPIN
E:
ergot medicine
(dihydroergotaminE, ergonovine and others)
heart or blood pressure medication
medicine to prevent organ transplant rejection
seizure medication.
This list is not complete and many other drugs
can interact with nevirapine
This includes prescription and over-the-counter
medicines, vitamins, and herbal products

38. THANK
You so much