Herpes virus infections

HSV 1: diseases of the mouth, esophagus, face, skin or brain

HSV 2: infections of genitalia, rectum, skin, hand or meninges

Anti-herpes virus agents

1. Acyclovir 6. Ganciclovir & Valganciclovir
2. Cidofovir 7. Docosanol
3. Famiciclovir & Penciclovir 8. Idoxuridine
4. Fomivirsen 9. Trifluridine
5. Foscarnet
Chemistry Spectrum MOA pK/excretion/route Side effects Clinical uses
1. Acyclovir Acyclic guanine Limited to herpes : c. inhibitor of : widely distributed Nausea, diarrhea, rash, More
nucleoside analog virus esp. viral DNA in body fluids: headache, renal toxicity beneficial in
Valacyclovir w/o a hydroxyl on the HSV 1 polymerase – vesicular fluid, or neurotoxicity*, initial
(prodrug) -> side chain EBV inhibition of aqueous humor, neutropenia in infections than
converted to CMV protein synthesis CSF neonates recurrent ones
acyclovir after
oral : incorporated : concentrated in :higher doses
administration into viral DNA -> breast milk, Pregnancy: increased req’d for VZV
in healthy chain terminator amniotic fluid, frequency of congenital infections
adults (suicide placenta anomalies
-> 1st pass into inactivation)
intestinal & : low percutaneous
hepatic Resistance: absorption after
metabolism impaired administration
production of
thymidine kinase T1/2: 2.5 hours
:altered viral DNA Excretion: kidneys
polymerase

2. Cidofovir metabolized to T1/2: 2.6 hours Nephrotoxicity, CMV retinitis

active Very low oral neutropenia, uveitis in HIV-infected
diphosphate cy bioavailability patients
cellular enzyme - Pregnancy: mutagenic,
> c. inhibition & Distribution gonadotoxic,
substrate for DNA approximates total embrytoxic, teratogenic
polymerase body water -> category C

Cleared by kidneys
3. Famciclovir Guanosine nucleoside Same as acyclovir C. inhibitor of Vs acyclovir: 1/100 Headache, diarrhea,
& Penciclovir analog (vs HSV and VSV) DNA polymerase - as potent but nausea, rash,
> inhibits DNA present in higher confusional states,
Prodrug: synthesis concentrations for hallucinations
famiciclovir – prolonged period
no intrinsic Pregnancy: mutagenic
antiviral T1/2: 7-20 hours @ high conc.
activity : low bioavaiability Safety use in pregnancy
<5% (famci has not yet established
good absorption -
rapildly converted
to penci)

: food slows
absorption but
does not reduce
availability
: excreted by
kidneys

4. Fomivirsen 21 base Antisense therapy Route: IV CMV

phosphothioate for viral infections infections
oligonucleotide resistant to
Cidofovir
Ganciclovir
Foscarnet

5. Foscarnet Pyrophosphate Inhibitory for all -Blocks -low oral Nephrotoxicity* CMV-retinitis
analog pyrophosphate bioavailability Symptomatic Acyclovir-
HIV binding site for -good availability if hypocalcemia resistant HSV
HSV viral polymerase given IV Hypomagnesemia and
-inhibits cleavage -excreted by Hypokalemia VZV infections
of pyrophosphate kidneys Tremors, irritability
from seizure
deoxynucleotide Hallucinosis
triphosphate
6. Ganciclovir Acyclic guanine Inhibitory to all Phosphorylated - Valganciclovir: Myelosuppression*
& nucleoside analog CMV > triphosphate rapidly absorbed & Neutropenia
Valganciclovir similar to acyclovir incorporated into hydrolysed Thrombocytopenia
HSV DNA -> Headache
Prodrug: preferentially Ganciclovir: ave. Behavioural changes
valganciclovir inhibits viral DNA 61% bioavailability
polymerase Pregnancy: teratogenic,
T1/2: 2-4 hours embryotoxic,
Excretion: through reproductive toxicity,
kidneys myelotoxic - category C

7. Docosanol Long chain saturated - Blocks fusion of Route: topical Treatment of

alcohol viral envelope & recurrent
cellular orolabial
membranes herpes

- inhibits viral
entry into cell

8. Idoxuridine Iodinated thymidine HSV and Inhibits DNA Pain HSV keratitis
analog poxviruses synthesis Pruritus
Inflammation
Lacks selectivity edema
& inhibits growth
of uninfected
cells

9. Trifluridine Fluorinated Adenovirus -inhibits Hypersensivity reaction Treatment of

pyrimidine nucleoside CMV vaccinia thymidylate irritation keratoconjunc
HSV 1 and 2 synthase tivitis
& recurrent
-inhibts epithelial
incorporation of keratitis
thymidine
triphosphate
incorporation
into DNA
Anti-influenza agents

1. Amantadine & Rimantadine

2. Oseltamivir
3. Zanamivir

Chemistry Spectrum MOA pK/excretion/route Side effects Clinical uses

1. Amantadine & Tricyclic amines Influenza A viruses - inhibit viral -well absorbed after Nervousness -seasonal
Rimantadine uncoating (early) oral administration Light-headedness prophylaxis for
Rimantadine is 4-10 -large volumes of Insomnia influenza A
times more active -alter hemagglutinin distribution: nasal Loss of appetite
than amantadine processing (late) secretions, saliva, Nausea -treatment for
serum influenza A
-rimantadine more in -neurotoxic effect H1N1
nasal mucus increased by
ingestion of
T1/2: amantadine: 12- antihistamines and
18 hrs psychotropic or
Rimantadine: 24-36 hrs anticholinergic drugs

Excretion: through Pregnancy: category

kidneys C

2. Oseltamivir Transition state of Influenza A & B -inhibitor of influenza -rapidly absorbed, Nausea, abdominal Effective
Prodrug: oseltamivir analog of sialic acid A&B cleaved by esterase in discomfort, emesis – treatment for
phosphate neuraminidases GI tract & liver to prevented by food influenza A & B
oseltamivir carboxylate intake infections
Neuraminidases- -80% bioavailability
cleaves terminal -food does not reduce Pregnancy: does not Healthy adults:
sialic acid residues, availability but reduces impair fertility, not 75 mg 2x daily
destroys receptors intolerance teratogenic but for 5 days
on cell surface, safety in preg. Has Children 1-2 y/o:
essential for release T1/2: 6-19 hrs not been established weight adjusted
of virus from infected Excretion: kidneys -catergory C dosage
cells -> aggregation -
> reduced spread -prophylaxis
during influenza
season
3. Zanamivir Sialic acid analog Influenza A & B Neuraminidase -low oral bioavailability Wheezing & Prevention &
inhibitor -available in oral bronchospasm in pts treatment of
inhalation of dry w/p underlying influenza A & B
powder airway disease illnesses
-after inhalation:
15%LRT Acute deterioration Treatment: 10
80% in oropharynx in pts with asthma or mg 2x daily (2
-bioavailability of 4- COPD inhalations) for 5
17% days
-t1/2: 2.5-5 hrs after Pregnancy: category
oral inhalation C
: 1.7 hrs after IV

Excretion: kidneys

Anti-hepatitis C agents

Hepatitis C – one of most chronic virus infections in the developed world

- Associated with significant mortality & morbidity

- If left untreated can cause progressive hepatocellular injury -> fibrosis -> cirrhosis
- Major risk factor hepatocellular CA
- Does not integrate into chromosomal DNA
- Does not establish latency
- Theoretically curable
- Current standard of care: combination of PEG alfa & ribavirin

Chemistry Spectrum MOA pK/route/Excretion Side effects Clinical uses

1. interferons Cytokines with ff -active JAK-STAT signal Oral administration:
activities: transduction pathway no detectable IFN
Antiviral -> nuclear levels in serum or
Immunomodulatory translocation of increase in
Antiproliferative cellular protein synthetase activity
complex -> binds to in mononuclear cells
genes -> protein
synthesis: IM administration:
oligodenylate >80% absorbed,
synthetase peaks @ 4-6 hrs
: protein kinase
 T1/2; 3-8 hrs.
Oligoadenylate Catabolism: liver &
synthetase -> activate kidney
cellular
endoribonuclease ->
cleave both cellular &
viral single stranded
RNAs

Protein kinase ->

phosphorylates &
inactivates a protein
involved in protein
synthesis
->may be an effector
of apoptosis

MOA: induces a
phosphodiesterase ->
prevents peptide
elongation

PEG + INFEREON = PEGINTERFERON

PEG – polyethylene glycol

PEGylation – slows absorption, decreases clearance, increase & prolongs serum concentration

Available products
Pegasys (peginterferon alfa 2A)
Pegintron (peginteron alfa 2B)

Side effects: acute influenza-like syndrome (fever, chills, headache, myalgia, arthralgia, vomiting and diarrhea)
: depression, myelosuppression*
: neurotoxicity: somnolence, confusion, behavioural disturbance
: thyroiditis & hypothyroidism
: cardiovascular events: hypotension & tachycardia
: children: alopecia & personality changes
Pregancy: not established

Comments: increase hematologic toxicity of ribavirin & zidovudine

: increase neurotoxicity & cardiotoxicity of other drugs
: monitor thyroid & liver tests during therapy

Clinical uses: treatment of condyloma acuminatum

Chronic HBV & HCV infection
Kaposi’s sarcoma in HIV patients other malignancies multiple sclerosis

Peginterferon in HBV infections

-use is associated with: loss of HBV DNA, HBeAG (indicator of viral replication)
Development of anti-Hbe antibody
Biochemical & histological improvement
-dose: 5MU/day or 10 MU in adults
6 MU/m2 in children 3x a week for 4-6 weeks
-prompt decline of plasma HBV DNA & polymerase activity
-remissions sustained in 80% of patients

Peginterferon in HCV infections

-3 MU 3X weekly -> 50-70% aminotransferase normalization, loss of plasma viral RNA
-high relapse rates
-sustained virologic remission only in 10-25% of patients
-sustained remission -> long term histological improvement, reduce hepatocellular CA

Ribavirin – enhances efficacy of interferons PEGIFN alfa 2 a (180 µg once weekly for 48 weeks) + ribavirin (1000-12000 mg/day) in divided doses = sustained viral
response rates

Pegifn in papillomavirus
-intralesional injection – complete clearance of warts
-relapse occurs in 20-30% of patients

Peg ifn in other viral infections

-HSV infections
-CMV infections in renal transplant patients
-antiretroviral effects in HIV patients
-broad spectrum antiviral activity vs respiratory viruses except for adenoviruse
2. Ribavirin Purine nucleoside Influenza virus Ribavirin Actively taken up by Conjunctival irritation : Chronic HCV
analog with a Parainfluenza monophosphate: c. nucleoside Rash (+PEGIFB)
modified base & D virus inhibits cellular inosine transporters in prox. Transient wheezing : RSV bronchitis &
ribose sugar Respiratory 5 phosphate Small bowel Reversible pneumonia in
syncytial viruses dehydrogenase -> : oral b.a. 50% deterioration in hospitalized
Phosphorylated by interference with GTP : ext. accumulated in pulmonary function children – gen. not
host cell enzymes synthesis -> nucleic plasma -> steady recommended
acid synthesis prod state in 4 wks. Systemic: anemia : severe influenza
interference : may be given oral (erythrophagocytosis) infection
IV, or by aerosol Fatigue, cough, rash, : txt of
Ribavirin triphosphate: administration pruritus, nausea, immunosuppressed
c. inhibits GTP : large volume of insomnia, dyspnea, pts w/ adenovirus,
dependent capping of distribution, depression vaccinia, measles
viral Mrna negligible protein
: C. inhibits influenza binding Pregnancy: category X
virus transcriptase act :hepatic
: multiple sites of metabolism, renal
action excretion
: enhance viral lethal
mutagenesis

Anti hepatitis B agents

1. Adefovir
2. Entecavir
3. Lamivudine
4. Telbivudine

Anti hepatitis B agents

Hepatitis B: transcribed into DNA -> integrated into host chromosomal DNA -> lifelong infection
: chronic HBV develop active hepatitis -> fibrosis & cirrhosis
: increases incidence of hepatocellular CA
 Chemistry Spectrum MOA pK/route/excretion Side effects Clinical uses
1. Adefovir Adefovir dipivoxil – Inhibitory in vitro vs Adefovir dipivoxil -> Higher affinity for Nephrotoxicity & Limited to HBV
prodrug of adefovir DNA and RNA deesterified to HBV DNA tubular dysfunction infections
Acyclic phosphonate viruses adefovir (active polymerase – azotemia,
Nucleotide analog of drug) T1/2: 5-18 hrs -> hypophosphatemia, Reduce serum HBV
AMP : converted by feasible once daily acidosis, glycosuria DNA levels by 99% in
cellular enzymes to dosing Proteinuria – pts with HBVe-
diphospate -> c. reversible after antigen positive
inhibitor of viral pK: dipivoxil – months of d/c chronic HBV
DNA polymerases & rapidly absorbed & : lower dose (10
reverse hydrolysed by mg/day) –
transcriptases -> esterases in the headache, abd.
chain terminator of intestine & blood Discomfort, diarrhea
viral DNA synthesis : b.a. 30-60% & asthenia
: food does not
affect b.a. Pregnancy: category
: eliminated C
unchanged in the
urine
: t1/2: 5-7.5. hrs.
2. Entecavir Guanosine : Selective act. Vs -Time to peak in 0.5- Treatment of
nucleoside analog HBV polymerase 1.5 hrs chronic HBV
-s.state is reached in infection in adults
: Entecavir 6-10 days of once with active viral
triphosphate daily dosing replication
competes w/ -food decreases
endogenous Cmax by 44-46% and -RD is 0.5 mg once
deoxygunaosine AUC by 18-20% - daily
triphosphate – taken on an empty
inhibits all activities stomach
of DNA polymerase: -extensively
base priming distributed in tissues
Reverse t. of neg 13% bound to
strand from mRNA proteins
Synthesis of pos -excreted
strand of HBV DNA unchanged in the
kidneys
Comments:
- Superior to lamivudine in degree of suppression – more frequent fall of HBV DNA to undetectable levels
- Has negligible resistance (<1%) for up to 4 years; ***Active against adefovir –resistant HBV
3. Lamivudine Nucleoside analog HBV infection -Inhibits HIV r. Generally well- Chronic HBV
transciptase & HBV tolerated infcetion
DNA polymerase
Increase in
-enhanced viral aminotransferase
activity in combi
with adefovir or
penciclovir vs
hepadnaviruses
Comments: prolonged therapy -> halving risk or clinical progression & dev’t of hepatocellular CA

4. Telbivudine Synthetic thymidine HBV infection Competes w/ Once daily dosing – Increase in Chronic HBV
nucleoside analog natural substrate s. state in 5-7 days creatinine kinase, infection with
thymidine-5- T1/2: 14 hrs. nausea, diarrhea, evidence of viral
triphosphate -> -given w/o regard to fatigue, myalgia, replication &
inhibition of HBV food myopathy evidence of
polymerase -> chain -widely distributed elevation of
termination in the tissues aminotransferase
-excreted
unchanged in the
urine
Comments: prolonged therapy -> halving risk or clinical progression & dev’t of hepatocellular CA

Human Immunodeficiency Virus (HIV)

- Can establish chronic persistent infection
- Gradual onset of symptoms
- Replication is constant after infections
- Hosts: humans & primates
- 2 families: HIV 1 and HIV 2
- Retrovirus with small RNA genome (9300 base pairs)

Principles of HIV chemotherapy

Goal: suppress viral replication as much and as long as possible
- Start therapy for those with CD4 count of <350 cells/mm3
- Recommended for: HIV infected pregnant women
HIV nephropathy
Concurrent HBV infection regardless of CD4 count
- Key problem: resistance – use drug
Combinations + patient education
- current standard of care: use of at least 3 drugs simultaneously for entire duration of treatment -> undetectable load (plasma HIV RNA < 50 copies/ml) within
24 weeks of txt
- failure of regimen: defined as persistent increase in HIV RNA in patient with previously undetectable virus

Anti-HIV drugs

 Entry Inhibitors
1. Maraviroc

 Nucleoside & nucleotide reverse transcriptase inhibitors (NRTIs)

1. Ziduvudine
2. Stavudine
3. Lamivudine
4. Abacavir
5. Tenovir
6. Emtricitabine
7. Didanosine

 Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

1. Neviparine
2. Efavirenz

 Integrase inhibitor
1. Raltegavir

 Protease inhibitors
1. Saquinavir
2. Ritonavir
3. Enfuvirtide
 Chemistry spectrum MOA pK Side effects Clinical uses
Entry Inhibitors Blocks binding of -dose dependent Generally well- HIV infected adults
1. Maraviroc HIV outer envelope -food decrease b.a. tolerated with baseline
protein to CCR5 as much as 50% Little significant evidence of CCR5-
chemokine receptor -76% bound to toxicity tropic HIV
proteins
Active only against T1/2: 10.6 hrs.
CCR5-TROPIC hiv
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Reverse transcriptase- RNA dependent DNA polymerase: converts viral RNA to proviral DNA – incorporated into host cell chromosome
-analogs that competitively inhibit reverse transcriptase
-prevent infection of susceptible cells; do not eradicate virus from the cells harbouring the proviral DNA
-enter cells – phosphorylated by host enzyme – generates synthetic substrates for enzyme (reverse transcriptase)
-inhibit viral polymerase but not host DNA polymerase – selectively toxic
-most are cleared by renal excretion, except zidovudine & abacavir (hepatic glucuronidation)

1. Ziduvudine Synthetic thymidine HIV1, HIV2 and Zidovudine :absorbed rapidly Fatigue, malaise,
analog Human T cell triphosphate :reaches peak conc. myalgia, nausea,
Lymphotropic terminates w/n 1 hr anorexia, headache,
viruses (HTLV I and elongation of :t1/2: 4 hrs (RD: 300 insomnia
II) proviral DNA mg BID) : bone marrow
:undergoes rapid 1st suppression
Active in -z. monophosphate pass hepatic :nail
lymphoblastic & inhibits thymidylate metabolism hyperpigmentation
monocytic cells, less kinase -> reduces : food slows absorp. :skeletal muscle
active in chronically amount of But does not affect myopathy
infected cells intracellular AUC – may be given :hepatic toxicity –
thymidine regardless of food rare but fatal
triphosphate intake
:parent drug crosses
the BBB
:detectable in
breastmilk, semen &
fetal tissue; conc.
Higher in male
genital tract than in
peripheral
Precautions: increased concentration with probenecid, fluconazole, atovaquone, atovaquone & valproic acid
: should not be used with stavudin
2. Stavudine Synthetic thymidine HIV 1 and HIV 2 Similar to Well absorbed Peripheral HIV-infected adults
analog zidovudine : peak is achieved neuropathy & children including
w/n 1 h Lactic acidosis neonates
:b.a. is not affected Hepatic steatosis
by food Acute pancreatitis
:conc. Is higher in (when combined w/
pts w/ low body didanosine)
weight – decrease Assoc. with fat
dose wasting
:drug penetrates (lipoatrophy)
well into CSF Headache, nausea,
:plasma protein rash
binding is <5%
:excreted by the
kidneys
Precautions: increased neuropathy when administered with other neuropathic medications: isoniazid, ethambutol, phenytoin, vincristine

3. Lamivudine Cytidine analog HIV 1, HIV 2, HBV Enters cells by :oral b.a. of 80% One of the least HIV in adults and
passive diffusion :not affected by toxic children > 3 months
food Neutropenia, of age
:once daily dosing of headache, nausea
300 mg
:excreted in the
urine
:does not bind to
plasma proteins
:higher conc. In male
genital tract (like
zidovudine)
4. Abacavir Carbocyclic Terminates :oral b.a. of 80% :fatal : for HIV 1 infection
guanosine analog elongation of :nor regard to food hypersensitivity + other retroviral
proviral DNA intake syndrome (fever, agents
:metabolized by the abd. Pain, GI :effective in
liver complaints, rash, combination w/
:50% bound to malaise, fatigue) other nucleoside
plasma proteins analogs & protease
:t1/2 up to 21 hours :respiratory inhibitors
– OD regimen complaints
(cough,dyspnea) – : combined w/
less common zidovudine +
-median time of lamivudine (trizivir)
onset: 11 days w/n 6 : combined w/
weeks of initiating tx lamivudine
(epzicom)
: immediate d/c :used in adult &
drug once sx are pediatric px > 3 mos.
noted, cannot be Of age
reintroduced
5. Tenovir Nucleotide analog HIV infection : c. inhibitor of viral
reverse
transcriptase
:incorporated into
HIV DNA to cause
chain termination
:low affinity for DNA
polymerase –
selectively toxicity
6. Emtricitabine Cytidine analog HIV 1, HIV 2 and Similar to :absorbed rapidly one of the least
HBV lamivudine :oral b.a. 93% toxic antiretroviral
:food reduces Cmax drug
but does not affect :prolonged exposure
Precaution: not AUC -hyperpigmentation
susceptible to any :t1/2 8-10 hrs of the skin
known drug Intracellular :elevated
interaction triphosphate up to transaminases
-d/c may cause 39 hrs -> once daily :hepatitis
rebound dosing :pancreatits
:excreted in the
urine
7. Didanosine Purine nucleoside HIV 1, HIV 2 and Dideoxyadenoside HIV infection in
analog HTLV 1 5-triphosphate – adults & children in
terminates combi with other
elongation of antiretroviral drugs
proviral DNA
Comments: has been supplanted by less toxic drugs
-avoid in pxs with pancreatitis or neuropathy
-avoid co-administration of drugs that can cause pancreatitis or neuropathy
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
-induce conformational change in the 3D structure of the enzyme
-reduce enzyme activity
-act as non-competitive inhibitors
-do not require intracellular phosphorylation
-virus-stain specific
-active vs HIV 1, not HIV 2
-all undergo hepatic metabolism
-half lives ranges 24-72 hrs – allow daily dosing
-inducers of CYP3A4
-all except etravirine are susceptible to drug resistance
-rashes occur frequently – mild and self-limited
-rare cases of Steven-Johnson syndrome
1. Neviparine Dipyridodiazepinone HIV 1 :well absorbed Rash, pruritus – HIV infection in
NNRTI :b.a. not affected by usually w/n 6 weeks adults & children in
food/antacids for tx – usually combi w/ other
:readily crosses resolves w/ use retroviral agents
placenta :single dose for
: found in breastmilk pregnant HIV-
– used for infected pts to
prevention of prevent vertival
mother-child transmission
transmission :for infants &
:t1/2 25-30 hrs children >15 days
old
2. Efavirenz Dihy HIV1 :well absorned fr. PK: CNS or
drobenzoxazine GIT tract psychiatric side
:peak plasma conc. effects: dizziness
In 5 hrs. impaired
:diminished abs. of concentration,
drug w/ increased disturbing dreams,
dosing insomnia, frank,
:high fat meal pscyhosis –
increases b.a. by generally resolve
22% w/n 4 wks of
:99% bound to therapy
plasma proteins
:taken @ bedtime to Pregnancy:
reduce side effects unequivocally
:t1/2 40-55 hrs- teratogenic in
once daily dosingh primates
:women of
childbearing
potential shld use 2
methods of birth
control; avoid
pregnancy while on
this med
Integrase inhibitor
Chromosomal integration: defining characteristic of retroviral life cycle
: allows viral DNA to remain in host cell nucleus for a prolonged period of latency
Human DNA: does not undergo excision & reintegration -> excellent target for antiviral intervention

1. Raltegavir Potent vs HIV 1 and Blocks the catalytic :peak conc. After 1-3
HIV 2 activity of HIV hrs of PO dosing
encoded integrase- :biphasic elimination
prevents integration :highly variable PK
of virus DNA into :eliminated via
host chromosome glucuronidation

HIV protease inhibitor

Structure: peptide like chemical
MOA: competitively inhibit action of viral aspartyl protease
Proteases: cleave precursor polypeptides components of the virus (structural & enzymatic)
: prevents the formation of infectious mature form of the virus -> 100-1000 mean decrease in plasma HIV RNA conc w/n 12 wks
: clearance through hepatic metabolism
:t1/2: 1.8-10 hrs -> once or BID dosing
:highly protein bound
:toxicity – potential metabolic drug interactions
:side effects – nausea, vomiting, diarrhea – generally resolve w/n 4 wks of strating treatment
: Comment – potential activity, favourable resistance profiles, common component of regimens for treatment-experienced pxs

1. Saquinavir Peptidomimetic Inhibits both HIV1 :oral b.a. is low due

hydroxyethylamine and HIV2 replication to hepatic 1st pass –
give w. ritonavir to
increase b.a.
-eliminated through
biliary sys. And feces
Precautions: do not coadminister other CYP3A4 inducers: rifampicin, phenytoin, or carbamazepine
Comments: no longer used in developed countries bec. Of high pill burden; remains popular in combi w/ ritonavir in resource-limited settings
2. Ritonavir Active vs both HIV 1 :rapid absorption Gi disturbances:
and HIV 2 :food doesn’t affect vomiting, diarrhea,
b.a. nausea, anorexa,
abd. Pain, taste
perversion
Comment: used as pharmacokinetic enhacer
: most potent CYP3A4 inhibitor –increaases plasma conc. Prolongs elimination time
: do not give w/ meds with narrow therapeutic index: midazolam, triazolam, fentanyl & ergot derivatives
3. Enfuvirtide 36 Amino acid Blocks interaction :only approved Injection site
synthetic peptide bet. N36 and C34 antiretroviral to be reactions – pain,
seq. by binding to administered erythema,
hydrophoblic groove parenterally induration of site of
in N36 – prevents : route of injection
formation of helix elimination has not
critical for memb. been established
fusion & viral entry :t1/2 – 3.8 hrs twice
into the cell daily administration
Comments: expensive to manufacture
: must be administered SQ BID
: received for pxs who failed all other feasible antiviral drugs