Antiviral Lecture

ANTIVIRAL/ANTIFUNGAL ANTIVIRAL/ANTIFUNGAL AGENTSAGENTS

MA. LENY ALDA G. JUSAYAN, MD

Department of Pharmacology

ANTIVIRAL AGENTSANTIVIRAL AGENTS

VIRUSES:Single or double stranded DNA or RNA

enclosed in a protein – CAPSIDObligate intracellular parasiteReplication depends on synthetic processes of

the host cellAntiviral drugs must either block entry or exit

from cell or be active inside the host cell

VIRAL REPLICATION:VIRAL REPLICATION:

Adsorption and penetration into susceptible host cells

Uncoating of viral nucleic acid Synthesis of early regulatory proteins Synthesis of RNA or DNA Synthesis of late regulatory proteins Assembly (maturation) of viral particles Release from cells

ANTI-HERPES/ ANTI VZVANTI-HERPES/ ANTI VZV

ANTIHERPES/VZV AGENTSANTIHERPES/VZV AGENTS

ACYCLOVIR FAMCICLOVIR VALACYCLOVIR

PENCICLOVIR TRIFLURIDINE VIDARABINE DOCOSANOL

ACYCLOVIRACYCLOVIR

Acyclovir (9-[2-hydroxy) methyl]-9-H- guanine

Acyclic guanosine derivative against HSV1, HSV2, & VZV

Weaker activity against EBV, CMV, Human Herpes Virus 6

MECHANISM OF ACTION:MECHANISM OF ACTION:

REQUIRES 3 PHOSPHORYLATION STEPS:Converted to monophosphate derivative by

virus-specified thymidine kinase Selective activation of acyclovir Active metabolites accumulates only in infected

cellsConverted to di and triphosphate

compounds by the host’s cellular enzymes

EFFECTS:EFFECTS:

Acyclovir triphosphate inhibits viral DNA synthesis

Acts as a chain terminator because it lacks 3’ hydroxyl group

Competitive inhibition of deoxyGTP for viral DNA polymerase = binds to DNA template as irreversible complex

Cont.Cont.

RESISTANCE:• HSV: absence of partial production of

viral thymidine kinase, altered thymidine kinase substrate specificity, altered viral DNA polymerase

• VZV: mutation in VZV thymidine kinase, mutations in viral DNA polymerase

PHARMACOKINETICS:PHARMACOKINETICS: Oral bioavailability ranges from 15-20 % and

decreases with increasing dose, unaffected by food

Relative oral bioavailability increases to 3-5 fold approx. 70% following valacyclovir administration

Distributes widely in body fluids including vesicular fluid, aqueous humor & CSF

Concentrated in breast milk, amniotic fluid, & placenta

Percutaneous absorption is low

Half-life: 3 hours (normal renal function) 20 hours (anuria)

Readily cleared by dialysis but not by peritoneal dialysis

IV- treatment of choice for herpes simplexOral – herpes labialisTopical – high concentration in herpetic

lesions

THERAPEUTIC USES:THERAPEUTIC USES:

First and recurrent genital herpes:– 200 mg 5x daily for 10 days – oral– 5 mg/kg per 8 hrs – IVRecurrent: 400 mg 2x daily or 200 mg 3x

daily


ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTION

– higher dosesCMV PROPHYLAXIS

SIDE EFFECTS:SIDE EFFECTS:

TOPICAL PREPARATIONS- mucosal irritation & transient burning to genital lesions

ORAL – nausea, diarrhea, rash, headache,renal insufficiency, neurotoxicity

IV- renal insufficiency (crystalline nephropathy), CNS side effects

PENCICLOVIRPENCICLOVIR

Penciclovir (9-[4-hydroxy-3-hydroxymethylbut-1-yl]guanine)

An acyclic guanine nucleosideActive metabolite of famciclovirRecurrent herpes labialisTopical – 1% cream


Inhibitor of viral DNA synthesis Initially phosphorylated by viral thymidine

kinase Penciclovir triphosphate is a competitive

inhibitor of viral DNA polymerase 100 fold less potent in inhibiting DNA

polymerase than acyclovir but present in higher concentration and prolonged periods in infected cells


Intravenous form- 5 mg/kg per 8-12 hrs for 7 days is comparable to acyclovir in tx of mucocutaneous HSV infection

Topical 1% penciclovir cream applied every 2 hrs while awake for 4 days shortens healing time and symptoms by about 1 day in recurrent labial HSV


Mutagenic at high concentrationsNo clinically important drug interactions

have identified

FAMCICLOVIRFAMCICLOVIRDiacetyl ester prodrug of 6 deoxy

penciclovir and lacks intrinsic viral activity

Rapidly converted to by first pass metabolism to PENCICLOVIR

HSV-1, HSV-2, VZV, EBV, HBV

FAMCICLOVIR:FAMCICLOVIR:

Comparable to valacyclovir in treating zoster and reducing associated pain in older adults

500 mg TID x 10 days is comparable to high dose of acyclovir in treating zoster in immunocompromised patients & in opthalmic zoster

Associated with dose-related reductions in Hepatitis B Virus DNA and transaminase levels in patients with chronic HBV hepatitis

Rapidly converted by first-pass metabolism to penciclovir

Does not cause chain termination– Lower affinity for viral DNA polymerase than

acyclovir triphosphate

Achieves a higher intracellular concentrations & more prolonged intracellular effect

PHARMACOKINETICS:PHARMACOKINETICS:

70% bioavailability after oral administrationIntracellular half life: 10 hrs – HSV 1

20 hrs – HSV 2

7 hrs- VZV

TRIFLURIDINETRIFLURIDINE(Trifluorothymidine)(Trifluorothymidine)

Flourinated pyrimidine nucleoside that has an in vitro inhibitory activity against HSV 1 & 2 , CMV, vaccinia certain adenoviruses

Inhibits viral DNA synthesis Does not require activation by viral thymidine

kinase Phosphorylated intracellularly into its active

form by host cellular enzymes Competes with thymidine triphosphate for

incorporation by viral DNA polymerase Incorporation into both viral and cellular DNA

prevents its systemic use


Trifluridine monophosphate irreversibly inhibits thymidylate synthetase

Trifluridine triphosphate is a competitive inhibitor of thymidine triphosphate incorporation into DNA by DNA polymerases

CLINICAL USES:CLINICAL USES:

Topical : 1% solutionPrimary keratoconjunctivitis & recurrent

epithelial keratitis due to HSV 1 & 2 Topical trifluridine is more active than

idoxuridine & comparable to vidarabine in HSV ocular infections

Combination with Interferon alfa – acyclovir resistant HSV infections

ADVERSE EFFECTS:ADVERSE EFFECTS:

Discomfort upon instillation Palpebral edemaHypersensensitivity reaction, irritations

& superficial punctate or epithelial keratopathy

VALACYCLOVIRVALACYCLOVIR

L- valyl ester of acyclovir Rapidly converted to acyclovir after oral

administration Serum levels are 3-5x greater than acylcovir

IV or oral Treatment of primary and recurrent genital

herpes & herpes zoster infections Prevents CMV disease in postransplant

patients Oral preparation

Elimination half-life: 2.5-3.0 hours High dose:

– gastrointestinal intolerance- Thrombotic microangiopathies (TTP,

hemolytic-uremic syndrome)

VIDARABINEVIDARABINE Adenosine analog with an in vitro activity

against HSV, VZV, & CMV Phosphorylated intracellularly by host

enzymes to form ara-ATP and then inhibits viral DNA polymerase

Vidarabine triphosphate is incorporated into both viral & cellular DNA

Decreases viral activity

Cont.Cont.

3% ointment – acute keratoconjunctivitis, superficial keratitis, recurrent epithelial keratitis (HSV1 &2)

IV vidarabine – HSV encephalitis,neonatal herpes, VZV infection

DOCOSANOLDOCOSANOL

Saturated 22-carbon aliphatic alcohol Inhibits fusion between the plasma

membrane & HSV envelopePrevents viral entry into cells & subsequent

viral repliction10% topical cream- 5x daily

ANTI-CMV AGENTSANTI-CMV AGENTS

ANTI-CMV AGENTSANTI-CMV AGENTS

GANCICLOVIR CIDOFOVIR FOMIVERSEN

VALGANCICLOVIR FOSCARNET

GANCICLOVIRGANCICLOVIR

(9-[1,3-dihydroxy-2-prpoxymethyl]guanine)Acyclic guanosine analog that requires

triphosphorylation for activation prior to inhibiting viral DNA polymerase

Similar structure to acyclovir except in having additional hydroxymethyl group on the acyclic side chain

MECHANISM OF ACTION:MECHANISM OF ACTION: Monophosphorylated intracellularly by a virus-

induced enzyme Phosphorylation is catalyzed by a viral thymidine

kinase during HSV, phosphotransferase encoded gene during CMV infection

Ganciclovir di & triphosphate formed by cellular enzymes

Triphosphate is a competitive inhibitor of deoxyguanosine triphosphate incorporation into DNA, inhibits viral rather than cellular DNA polymerase

Viral DNA incorporation causes cessation of DNA chain elongation


Oral bioavailability is 6-9% following ingestion with food & less in the fasting state

CSF concentration are approximately 50 % of those in serum

IV, oral, intraocular implant

Elimination half life: 4 hoursIntracellular half-life: 18 hoursCleared by hemodialysis


Delay progression of CMV retinitis in AIDS – IV ( foscarnet )

CMV colitis & esophagitis - IV CMV infection in transplant patient - IV/oral CMV pneumonitis CMV retinitis – intraocular implant/intravitreal

administration CMV, HSV1, HSV2, EBV & HHV-8

ADVERSE REACTIONS:ADVERSE REACTIONS:

MyelosuppressionCNS toxicityVitreous hemorrhage, retinal detachmentNeutropenia (2nd wk)CNS (headache, behavioral changes,

convulsions, coma)Infusion related phlebitis, azotemia, anemia,

rash, fever, liver function test abnormalities

DRUG INTERACTION:DRUG INTERACTION:

Additive myelosuppression– Zidovudine, azathioprine or mycophenolate

mofetil

Increase levels– Probenicid, trimethoprim

Increase levels of didanosine

VALGANCICLOVIRVALGANCICLOVIR

L- valyl ester prodrug of ganciclovir Hydrolyzed to active compound ganciclovir by

intestinal & hepatic enzymes Well absorbed & rapidly metabolized in

intestinal walls & liver to gancilovir CMV retinitis CMV disease in high risk kidney, heart, &

kidney-pancreas transplant patients


Bioavailability after oral administration: 60%

Should be taken with foodElimination - renal

CIDOFOVIRCIDOFOVIR

(1-[(S)-3-hydroxy-2-(phosphonomethoxy)-propyl]cytosine dihydrate)

Cytosine nucleoside analog with inhibitory activity against human herpes, papiloma, polyoma, pox, & adenoviruses

Phosphorylation to active diphosphate is independent of viral enzymes

After phosphorylation it acts as potent inhibitor of and as an alternative substrate to viral DNA polymerase

Competitively inhibits DNA synthesis & becoming incorporated into viral DNA chain


Penetration into the CNS or eye have not been well characterized

Terminal half-life is 2.6 hrs , cidofovir diphosphate half-life is 17-65 hrs

Poor CSF penetration IV administration must be administered with

probenicid (2-3 hours before infusion) to block active tubular secretion & decrease nephrotoxicity


CMV, HSV 1, HSV 2, VZV, EBV, HHV-6, HHV-8, adenoviruses, poxvirus, poliomyxoviruses, HPV

CMV retinitisPolyoma virus associated progressive

multifocal leukoencephalopathy syndrome associated with AIDS

FOSCARNETFOSCARNET

Phosphonoformic acid inorganic pyrophosphate analog that inhibits viral DNA polymerase, RNA polymerase & HIV reverse transcriptase directly without requiring activation by phosphorylation

Taken up slowly by cells & does not undergo significant intracellular metabolism

Reversibly blocks the pyrophosphate binding site of the viral polymerase but not in human & transcriptase enzyme

Inhibits cleavage of pyrophosphate from deoxynucleotide triphosphates


Nephrotoxicity Symptomatic hypocalcemia or hypercalcemia Hyper or hypophosphatemia hypomagnesemia Saline preloading may reduce the risk of

nephrotoxicity Concurrent administration with pentamidine

exacerbates both nephrotoxicity & hypocalcemia

DRUG INTERACTION:DRUG INTERACTION: Nephrotoxic potential

– amphotericin B, pentamidine, aminoglycosides Hypocalcemia

– pentamidine Penile ulcerations

– foscarnet Anemia

– zidovudine CNS toxicity

– imipenem Chromosomal damage

– foscarnet


CMV retinitis, colitis, esophagitisAcyclovir- resistant HSV infection &

VZV infectionHSV, VZV, CMV, EBV, HHV-6, HHV-8,

HIV

FOMIVERSENFOMIVERSEN

21mer-phosphorothioate oligonucleotideFirst FDA approved antisense therapy

Binding to target mRNA results in inhibiton of immediate early region 2 protein synthesis – inhibiting viral replication

Injected intravitreally in CMV retinitis

DRUG MECHANISM/VIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 & 2, varicella zoster

Produce abnormal thymidine kinase

Skin irritation, burning, crystalline nephropathy

IV/PO. Administer slowly. CNS level=50% serum level. Decrease dose w/ kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea, headache PO. Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis. No effect on RNA viruses

Resistance develops

Photophobia, irritation of conjunctiva & eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster & genital herpes

Minimal toxicity. Headache

PO. Decrease dose with renal dysfunction.

Ganciclovir Metabolized by thymidine kinase to triphosphate . Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis & severe systemic CMV infections

Some resistant strains lack thymidine kinase. Cannot activate drug.

Granulocytopenia, thrombocytopenia

IV/PO. Excreted unchanged in urine. Decrease dose with renal dysfunction.

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS – DNA & RNA VIRUSES

Cidofovir Metabolized to diphosphate form. Otherwise like ganciclovir.

CMV retinitis Nephrotoxicity may be reduced by hydration & coadministration of Probenicid. Neutropenia.

Foscarnet Analog of pyrophosphate. Competes for pyrophosphate site in viral but not human, DNA polymerase & reverse transcriptase

CMV retinitis Does not need phosphorylation, it is active against thymidine kinase –deficient strains

Renal toxicity, seizures, hypocalcemia, fever, anemia, diarrhea, nausea

IV. >80% excreted unchanged in the urine. CSF penetration variable. Reduce dose with renal dysfunction.

Deposited in bone & teeth. Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment & prophylaxis of influenza A

Depression, CNS toxicity, CHF, orthostatic hypotension, urinary retention

PO. Excreted unmetabolized.

Rimantadine Analog of amantadine , inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects, risk of seizure

PO. Prolonged elimination w/ renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function.

Aerosol administration. Absorbed systemically.

May precipitate in ventilator tubing.

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

STAGES OF HIV REPRODUCTIONHIV entry into the CD4 cells

HIV’s genetic information stored on a single stranded RNA instead of the double-stranded DNA

HIV uses an enzyme known as reverse transcriptase to convert its RNA into DNA

HIV DNA enters the nucleus of the CD4+ cell and inserts itself into the cell’s DNA

HIV DNA instructs the cell to make many copies of the original virus

New virus particles assembled and leave the cell ready to infect other CD4+ cells

Fusion Inhibitors Non-Nucleoside Reverse

Transcriptase Inhibitors

Nucleoside/NucleotideAnalogues

Protease Inhibitors

•A novel class of antiretroviral agents that inhibit the fusion of HIV with target cell membranes. •Fusion inhibitors are administered by subcutaneous injection.

•The newest class of antiretroviral agents, non-nucleoside transcriptase inhibitors (NNRTIs) •Stop HIV production by binding directly onto reverse transcriptase and preventing the conversion of RNA to DNA. •These drugs are called "non-nucleoside" inhibitors because even though they work at the same stage as nucleoside analogues, they act in a completely different way.

•The first effective class of antiretroviral drugs. •They act by incorporating themselves into the DNA of the virus, thereby stopping the building process. •The resulting DNA is incomplete and cannot create new virus

•Protease inhibitors work at the last stage of the virus reproduction cycle.• They prevent HIV from being successfully assembled and released from the infected CD4+ cell.

NUCLEOSIDE REVERSE NUCLEOSIDE REVERSE TRANSCRIPTASE TRANSCRIPTASE

INHIBITORS:INHIBITORS: Competitive inhibition of HIV 1 reverse transcriptase

& can be incorporated into the growing viral DNA chain to cause termination

Bind directly to HIV reverse transcriptase, block both DNA & RNA dependent DNA polymerase activities

Prevent transfer of information that would allow virus to replicate & survive

Activity against HIV 1, HIV 2 Mitochondrial toxicity – inhibition of mitochondrial

DNA polymerase gamma Lactic acidosis & severe hepatomegaly with steatosis

NUCLEOSIDE REVERSE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS:TRANSCRIPTASE INHIBITORS:

ZIDOVUDINE DIDANOSINE STAVUDINE

LAMIVUDINE ZALCITABINE ABACAVIR EMTRICITABINE

ZIDOVUDINE ZIDOVUDINE (Azithymidine, AZT)(Azithymidine, AZT)

Deoxythymidine analog Decrease rate of clinical disease progression &

prolong survival of HIV infected individuals Well absorbed from the gut & distributed to most

body tissues & fluids Eliminated by renal excretion following

glucorinadation in the liver Combination therapy with other retroviral agents

enhance potency and delay resistance

CLINICAL USES:CLINICAL USES:HIV – associated dementia &

thrombocytopeniaReduce rate of vertical transmission

(mother-newborn) by 23% - 14 and 34 weeks of gestation and during labor

Newborn – syrup from birth – 6 weeks

ANTIRETROVIRAL AGENTS IN ANTIRETROVIRAL AGENTS IN PREGNANCY:PREGNANCY:NRTIs: Zidovudine, lamivudine,

didanosine, stavudine, abacavir, emtricitabine

NNRTIs: NevirapinePROTEASE INHIBITORS: Nelfinavir,

saquinavir S, indinavir, lopinavir, ritonavir


Myelosuppression – most commonThrombocytopenia, hyperpigmentation

of nails, myopathy, anxiety, confusion & tremulousness

Fatal lactic acidosis & severe hepatomegaly w/ steatosis

DIDANOSINE (ddl)DIDANOSINE (ddl) Synthetic analog of deoxyadenosine Chewable, dispersable tablet, enteric coated Contains phenylalanine ( 36.5 mg) & Na (1380

mg) Should be taken on an empty stomach Food, fluroquinolones & tetracycline should be

given 2 hrs before didanosine Buffered powder (oral solution), chewable

tablests, enteric coated tablets

DRUG INTERACTIONDRUG INTERACTION

Interferes with the absorption of the ff. drugs: (powder and tablets)– indinavir, delavirdene, dapsone, itraconazole

PRECAUTIONS:PRECAUTIONS:

PhenylketonuriaNa restricted diets


Dose –dependent pancreatitisPainful peripheral distal neuropathyDiarrhea, hepatitis, esophageal

ulceration, cardiomyopathyCNS toxicityPrecipitate gouty attacksOptic neuritis

LAMIVUDINE (3TC)LAMIVUDINE (3TC)

Cytosine analog ,synergistic with other antiretroviral nucleoside – Stavudine, Zidovudine

Oral bioavailability exceeds 80% & is not food dependent

Used in combination therapy Approved for the treatment of chronic

Hepatitis B infection

RESISTANCE:RESISTANCE:

M184V mutation in regimens that are not fully suppressive

K65R mutation is associated with reduced susceptibility to lamuvudine, abacavir, tenofovir and emcitricitabine


Headache, insomnia, fatigue, gastrointestinal discomfort

DRUG INTERACTION:DRUG INTERACTION:

Increase lamivudine bioavailability– trimethoprim-sulfamethoxazole

Inhibit intracellular phosphorylation of one another in vitro (decrease potency)– zalcitabine

ZALCITABINE (ddC)ZALCITABINE (ddC)

Cytosine analog with synergistic anti-HIV1 activity with a variety of antiretrovirals against both zidovudine sensitive & resistant strains

Associated with dose-dependent peripheral neuropathy

Oral & esophageal ulcerations Increase bioavailability in combination w/

probenicid or cimetidine Decrease bioavailability in combination w/

antacids & metoclopramide

STAVUDINE (D4T)STAVUDINE (D4T)

Thymidine analogHigh oral bioavailability, not food dependentDose-related peripheral sensory neuropathyPancreatitis, arthralgias, elevation of serum

aminotransferases

ABACAVIR ABACAVIR Guanosine analog Well absorbed during oral administration (83%) Unaffected by food Metabolized by alcohol dehydrogenase &

glucuronosyltransferase to inactive metabolites Fatal hypersensitivity reactions Nausea, vomiting, diarrhea, headache, fatigue Hyperglycemia, hypertriglyceridemia & lactic

acidosis

RESISTANCE:RESISTANCE:

Requires at least 2 or 3 concomitant mutations:– M184V, L74V, D67N – develop slowly

K65R– reduced susceptibility to lamivudine, abacavir,

tenofovir and emtricitabine

EMTRICITABINE (FTC)EMTRICITABINE (FTC)

Flourinated analog of lamivudine Long intracellular half-life (>39 hours)Contains propylene glycolOral solutions contraindicated in children,

pregnant women, patients with renal & hepatic failure, using metronidazole & disulfiram


Headache, diarrhea, nausea & astheniaHyperpigmentation of the palms/soles

USE OF ANTITRETROVIRAL USE OF ANTITRETROVIRAL DRUGS IN PREGNANCY:DRUGS IN PREGNANCY:NRTIs

– zidovudine, lamivudine– Didanosine, emtricitabine, stavudine, abacavir

NNRTIs– nevirapine

Protease inhibitors– nelfinavir, saquinavir-S– Indinavir, lopinavir, ritonavir

NUCLEOTIDE INHIBITORNUCLEOTIDE INHIBITOR

TENOFOVIRTENOFOVIR

Competitively inhibits HIV reverse transcriptase & cause chain termination after incorporation to DNA

Indicated for use in combination with other antiretroviral agents

NON-NUCLEOSIDE REVERSE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR:TRANSCRIPTASE INHIBITOR: Bind directly to a site on the HIV –1 reverse

transcriptase Blockade of RNA & DNA dependent DNA

polymerase activities Binding site is near but distinct from that of

the NRTI’s Neither compete w/ nucleoside triphosphate

nor require phosphorylation to be active

NON-NUCLEOSIDE REVERSE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS:TRANSCRIPTASE INHIBITORS:

NEVIRAPINE EFAVIRENZ

DELAVIRDENE

NEVIRAPINENEVIRAPINE

Oral bioavailability is > 90%Not food dependentUsed as a component of a combination

antiretroviral regimenEffective in the prevention of

transmission of HIV from mother to newborn

Causes severe life threatening rashes

DELAVIRDENEDELAVIRDENE

Oral bioavailability of about 85 % Metabolized to inactive metabolites by the

CYP3A & CYP2D6 P450 enzymes Plasma concentrations are reduced by

antacids, didanosine, phenytoin, phenobarbital, carbamazepine, rifabutin, rifampin, nelfinavir & saquinavir

Concentrations increased by clarithromycin, fluoxetine, & ketoconazole

EFAVIRENZEFAVIRENZ

Principally metabolized by CYP3A4 &CYP2B6 to inactive hydroxylated metabolites

Principal adverse effects: CNS (dizziness, drowsiness, insomnia, headache, confusion, amnesia, agitation, delusions, depression, nightmares, euphoria)

Pyschiatric symptoms rashes

PROTEASE INHIBITORSPROTEASE INHIBITORS

Responsible for cleaving precursor molecules (immature budding particles)

Results in the production of immature, non-infectious viral particles

Block protease activity within the HIV virus – essential for the maturation

Associated w/ spontaneous bleeding in hemophilia A & B

PROTEASE INHIBITORS:PROTEASE INHIBITORS:

SAQUINAVIR INDINAVIR AMPRENAVIR LOPRENAVIR/

RITONAVIR TIPRANAVIR

RITONAVIR NELFINAVIR ATAZANAVIR FOSAMPRENAVIR

SAQUINAVIRSAQUINAVIR

Saquinavir H- hard gel capsule – poor bioavailability, should be taken w/n 2 hrs after a fatty meal

Saquinavir S – soft gel capsule – improved absorption 3x than hard gel capsule

Subject to first pass-metabolism by CYP3A4 Levels are increased by ritonavir, nelfinavir,

delavirdene, indinavir, ketoconazole, clarithromycin, & grapefruit juice

RITONAVIRRITONAVIR

An inhibitor of HIV 1 & HIV 2 proteasesHigh bioavailability that is increased

with foodCommon adverse effects: GIT

disturbances, paresthesias, inc aminotransferase level, altered taste, hypertriglyceridemia

INDINAVIRINDINAVIR

Specific inhibitor of the HIV- 1 & HIV-2 proteases

Higher CSF penetrationMust be consumed in empty stomach

for maximal absorptionMost common adverse effects are

indirect hyperbilirubinemia & nephrolithiasis due to crystalization

NELFINAVIRNELFINAVIR

Higher absorption in the fed stateCommon adverse effects: diarrhea &

flatulence

AMPRENAVIRAMPRENAVIR

Rapidly absorbed from the GIT & can be taken w/ or w/o food

High fat meals decrease absorptionCommon adverse effects: nausea,

vomiting, diarrhea, perioral paresthesias, rash

Steven johnson’s syndromeInhibits CYP3A4 activity

LOPRINAVIR/RITONAVIRLOPRINAVIR/RITONAVIR

Combination that subtherapeutic doses of ritonavir inhibit the CYP3A mediated metabolism of lopinavir

Maintains potent viral suppression & prevents resistance

Ritonavir – pharmacokinetic enhancer

TIPRANAVIRTIPRANAVIR

Bioavailability is increased when taken with a fatty meal

Should be taken with ritonavirContraindicated in liver insufficiency, sulfa

allergy

FUSION INHIBITORSFUSION INHIBITORS

ENFUVIRTIDE (T-20)ENFUVIRTIDE (T-20)

Newly approved antiretroviral agentBlocks entry into the cellAdministered subcutaneously in

combination with other retroviral agents

ANTI-HEPATITIS AGENTSANTI-HEPATITIS AGENTS

ANTIHEPATITIS AGENTS:ANTIHEPATITIS AGENTS:

LAMIVUDINE INTERFERON ALFA INTERFERON ALFA

2b ENTECAVIR

ADEFOVIR DIPIVOXIL

INTERFERON ALFA 2a

PEGYLATED INTERFERON

LAMIVUDINELAMIVUDINE

Can be safely administered to patients with decompensated liver disease

ADEFOVIRADEFOVIR

Phosphorylated by cellular kinases to the active diphosphate metabolite

Competitively inhibits HBV DNA polymerase

Chain termination after incorporation into viral replication

INTERFERON ALFAINTERFERON ALFA

Endogenous proteins that exert complex antiviral immunomodulatory & antiproliferative activities through cellular metabolic process

Enzyme induction, suppression of cell proliferation, immunomodulatory activities & inhibition of viral replication

Inhibition of viral penetration & uncoating Treatment of both HBV & HCV

INTERFERON ALPHA 2aINTERFERON ALPHA 2a

Approved for the treatment of chronic hepatitis C, AIDS associated Kaposi’s sarcoma hairy cell leukemia, chronic myelogenous leukemia

INTERFERON ALPHA 2bINTERFERON ALPHA 2b

Only preparation licensed for treatment of HBV & acute HCV

Leads to loss of HbeAg, normalization of aminotransferases

Administered subcutaneously or intramuscularly

Hairy cell leukemia, malignant melanoma, follicular non-Hodgkin’s lymphoma, AIDS related kaposi’s sarcoma, & chronic hepatitis C

PEGYLATED INTERFERON PEGYLATED INTERFERON ALFAALFA

Recently introduced for treatment of chronic hepatitis C

Longer terminal t ½ with slower clearance

Interferon- Interferon-β Interferon-

Chronic hepatitis B & C

Relapsing-remitting multiple sclerosis

Chronic granulomatous disease

Genital warts caused by papilloma virus

Hairy- cell leukemia

Kaposi’s sarcoma

RIBAVIRINRIBAVIRIN

Guanosine analog that is phosphorylated intracellularly by host cell enzymes

Interferes w/ the synthesis of guanosine triphosphate

Inhibit capping of viral messenger RNA Inhibit viral RNA dependent RNA polymerase of

certain viruses Influenza A, parainfluenza, RSV,

paramyxoviruses, HCV & HIV 1

ANTI-INFLUENZA AGENTSANTI-INFLUENZA AGENTS

AMANTADINE/RIMANTADINEAMANTADINE/RIMANTADINE

(1-aminoadamantane hydrochloride) -methyl derivative - rimantadine Inhibits uncoating of viral RNA influenza A

within infected cell thus preventing replication Effectively reduce the duration of symptoms

of influenza when administered w/n 48 hrs of onset

Primary target is M2 proteins

ZANAMIVIR/OSELTAMIVIRZANAMIVIR/OSELTAMIVIR

Neuroaminidase inhibitorsInhibits replication of both influenza A & B5 day course regimen for both influenza A &

BDelivered by inhalation – ZANAMIVIROral - OSELTAMIVIR

UNCLASSIFIEDUNCLASSIFIED

PALIVIZUMABPALIVIZUMAB

Prevention of RSV in high risk infants

IMQUIMOD

•Immune response modifier effective in topical treatment of external genitalia & perianal warts

DRUG MECHANISM & VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of hyman immunodeficiency viirus causing termination of the viral DNA chain

HIV. Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches, nausea, myalgias, anemia, neutropenia, macrocytosis

PO. Well absorbed, rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase & incorporates into viral DNA.-Nucleotides fail to bind to ddATP bec it lacks free 3’ OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy, pancreatitis, diarrhea, headache, insomnia, vomiting, nausea, rash, abdominal pain

IV/PO. Partially metabolized in liver, excreted in the urine. Toxicity may be enhanced by renal or hepatic dysfunction.

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate w/c inhibits HIV reverse transcriptase & DNA polymerase. Prevents DNA elongation.

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease .Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress, headache, neurologic symptoms. Indinavir associated w/ increase risk for kidney stones

PO. Metabolized by P450 in liver. Reduce dose in patients with liver disease. Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV. Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash, fever, nausea, headache

PO. Well absorbed. Nevirapine crosses placenta & has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

POST-TESTPOST-TEST

1. Inhibits step # 1 in HIV replication:A. NRTI B. fusion inhibitors

2. Inhibits step #2 in HIV replication:A. fusion B. NNRTIs

3. Inhibits step # 3 in HIV replication:A. protease inhibitors B. NRTIs

4. Inhibits step #4 in HIV replication:A. protease inhibitors B. NRTIs

5. Virus that undergoes endocytosis:A. HIV B. influenza

6. Enzyme inhibited by antiretroviral agents:A. reverse transcriptase B. DNA polymerase

7. Drug for influenza A infection:A. Amantadine B. zidovudine

8. Drug used for HIV that is used in the tx of HBV:A. lamivudine B. amantadine

9. Drug used in the treatment of RSV:A. amantadine B. rimantadine

10. Drug used in the treatment of perianal warts:A. imquimod B. amantadine

ANTIFUNGAL AGENTSANTIFUNGAL AGENTS

SYSTEMIC ANTIFUNGAL SYSTEMIC ANTIFUNGAL DRUGS FOR SYSTEMIC DRUGS FOR SYSTEMIC

INFECTIONINFECTION

AMPHOTERICN BAMPHOTERICN B

Polyene antifungal Discovered by Gold & coworkers in 1956 Produced by Streptomyces nodosus Heptane macrolide w/ 7 conjugated double

bonds in the trans position & 3-amino-3,6- dideoxymannose connected to the main ring by a glycoside bond

Amphotericin polyene macrolide Nearly insoluble in water

PREPARATIONS:PREPARATIONS:

1) Colloidal suspension of amphotericin B & Na deoxycholate (DOC) –IV

• 50 mg amphotericin B, 41 mg deoxycholate

• Addition of electrolyte to infusion solution causes colloid to aggregate

2) Amphotericin B Colloidal Dispersion• contains roughly equimolar amounts of

Amphotericin B & cholesteryl sulfate• Forms a colloidal solution when

dispersed in aqueous solution

CONT. CONT.

3) Unilamellar Vessicle FormulationAmphotercin B 50 mg + 350 mg of lipid

in 10% molar ratio

4) Amphotericin B Lipid Complex• Amphotericin B 35% +

dimyristolphosphatidylcholine & glycerol

ANTIFUNGAL ACTIVITY:ANTIFUNGAL ACTIVITY:

Candida sp., C. neoformans, B. dermatidis, H. capsulatum, Sporothrix schenkii, C. immitis, Paracoccidioides brazilienzes, Aspergillus sp., Penicilium marneffei, Mucormycosis

Limited activity to Leishmania, braziliensis, Naegleria fowleri

No antibacterial activity


Poorly absorbed from the GIT Oral preparation is only effective in fungi

within the lumen of the GIT Serum t ½ is 15 days Widely distributed in tissues 2-3% CSF concentration


Antifungal activity depends on the binding with ERGOSTEROL

Alters the permeability of the cell by forming amphotericin B associated pores in the cell membrane

Combines with lipids along the double rich bond & associates with H2O molecules along the OH-rich side

Pores allow leakage of intracellular ions & macromolecules CELL DEATH


Candida esophagitis Meningitis caused by coccidioides Mucormycoses Invasive aspergillosis Extracutaneous sporothrichosis Cryptococcosis Candida cystitis Mycotic corneal ulcers & keratitis


A) INFUSION-RELATED TOXICITY: fever & chills, muscle spasms, vomiting,

headache, & hypotension

B) SLOWER TOXICITY: renal damage

o Reversible renal injuryo Irreversible renal injury- renal tubular injury

FLUCYTOSINE (5-FC)FLUCYTOSINE (5-FC)

antimetabolite Discovered in 1957 Fluorinated pyrimidine related to florouracil &

floxuridine Spectrum of activity is narrower than that of

amphotericin


Available in oral preparation Well absorbed (>90%) with serum Concentration peaking 1-2 hrs Poorly protein bound Penetrates well body fluids & CSF T ½ is 3-4 hrs


Taken up by fungal cells via CYTOSINE PERMEASE

Converted intracellularly to 5 FU 5-fluorodeoxyuridine monophosphate & 5-fluorouridine triphosphate inhibit RNA & DNA synthesis

5-FU 5-FlucytosineCytosine permease

UMP pyrophosphate

5-FUMP 5-FUDP 5-FUTP

Ribonucleide reductase

5-F-dUMP

RNA

Thymidine synthase

DUMP dTMP

CLINICAL USE:CLINICAL USE:

Cryptococcal meningitisCandida speciesDermatiaceous molds that cause

chromoblastomycosis


Leukopenia & thrombocytopeniaRashNausea/vomiting, diarrhea, severe

enterocolitis

AZOLES:AZOLES:

IMIDAZOLES :KetoconazoleMiconazoleClotrimazole

TRIAZOLES:ItraconazoleFluconazoleVoriconzaole

MECHANISM OF ACTION:MECHANISM OF ACTION: Inhibition of sterol 14 α-demethylase Impair the biosynthsesis of ergosterol for the

cytoplasmic membrane accumulation of 14-α-methylsterols

Impairing functions of membrane bound enzymes such as ATPase & enzymes of electron transport system inhibits growth of fungi

Reduction of ergosterol synthesis by inhibition of cytochrome P450 enzymes

Specificity for fungal than human cytochrome P450 enzymes


Candida speciesCryptococcus neoformansEndemic mycoses

DRUG INTERACTIONS:

All azole drugs affect mammalian cytochrome P450 systems of enzymes

KETOCONAZOLEKETOCONAZOLE

First oral azole introduced into clinical use Increase propensity to inhibit mammalian

cytochrome P450 enzymes Less selective for fungal P450 Inhibition of mammalian P450 interferes with

biosynthesis of adrenal & gonadal steroid hormones

Interaction with P450 enzymes can alter the metabolism of other drugs leading to enhanced toxicity

Cont.Cont.

Reaches the keratinocytes efficiently Concentration in vaginal fluids is

approaches that in plasma


Blastomycosis, histoplasmosis, coccidiodomycosis, pseudallescheriasis

Paracoccidiodomycosis, ringworm, tinea versicolor, chronic mucocutaneous candidiasis

Candida vulvovaginitis, oral & esophageal candidiasis


Dose-dependent anorexia, nausea, vomiting

Inhibits steroid biosynthesis in patients endocrine abnormalities

DRUG INTERACTIONS:DRUG INTERACTIONS:

Increases cyclosporine levelsEnhances arrythmogenic effects of

cissaprideH2 antagonists increases gastric pH,

interfere with the absorption of ketoconazole

Rifamycins increased hepatic metabolism

ITRACONAZOLEITRACONAZOLE

Available in capsule & solutions (oral & IV) Capsule form is best absorbed in the fed

state Oral solution is best absorbed in the fasting

state Metabolized in the liver by the CYP3A4

isoenzyme system Does not affect mammalian steroid synthesis Reduced bioavailability when taken with

rifamycins

Cont.Cont.

Azole of choice for dimorphic fungi histoplasma, blastomyces, sporothrix

Oral solution is effective for use in oropharyngeal & esophageal candidiasis

Onychomycosis can be treated with either 200 mg OD X 12 wks or as 200 mg BID X 1 wk out of each month

FLUCONAZOLEFLUCONAZOLE Fluorinated bistriazole Good water solubility & CSF penetration Azole of choice in the treatment & secondary

prophylaxis of cryptococcal meningitis Available in oral & IV form plasma concentrations of astemizole,

cissapride, cyclosporine, rifampin, rifabutin, sulfonylureas, theophylline & warfarin

VORICONAZOLEVORICONAZOLE Newest triazole to enter clinical trials Availabale in oral & IV Well absorbed orally with bioavailability >90% Low propensity to inhibit mammalian

cytochrome P450 Same as itraconazole in its spectrum of

action Good activity against candida species fluconazole-resistant species such as C.

krusei, dimorphic fungi, pathogenic molds including aspergillus

ECHINOCANDINSECHINOCANDINS

Large cyclic peptides linked to a long chain fatty acid

Caspofungin, micafungin, anidulafunginCandida and aspergillus but not

cryptococcus neoformansIV forms only

MECHANISM OF ACTIONMECHANISM OF ACTION

Inhibits the synthesis of β (1-3) glucan Disruption of the fungal cell wall and cell death The glucan synthesis inhibitors are, collectively,

agents that are presumed to block fungal wall synthesis

Inhibition of this enzyme results in depletion of glucan polymers in the fungal cell, resulting in an abnormally weak cell wall unable to withstand osmotic stress

CLINICAL USE:CLINICAL USE:

CASPOFUNGIN Disseminated mucocutaneous candida infections Empiric antifungal therapy during febrile

neutropenia

MICAFUNGIN Mucocutaneous candidiasis Prophylaxis of candida infections in bone marrow

transplant patients

ANIDULAFUNGIN– esophageal candidiasis– Invasive candidiasis– septicemia

SYSTEMIC ANTIFUNGAL SYSTEMIC ANTIFUNGAL DRUGS FOR DRUGS FOR

MUCOCUTANEOUS MUCOCUTANEOUS INFECTIONSINFECTIONS

GRISEOFULVINGRISEOFULVIN

Practically insoluble in waterFungistatic in vitro for dermatophytes

microsporum, epidermophytom & trichophyton

No effect on bacteria & other fungi


Production of multinucleate cells as the drug inhibits fungal mitosis

Causes disruption of the mitotic spindle by interacting with polymerized microtubules – critical step in cellular division

Deposited in the newly forming skin where it binds to keratin

Administered 2-6 wks for skin & hair infections


Mycotic disease of the skin, hair & nails due to Microsporum, Trichophyton, or Epidermophyton

Tinea capitis (M. canis)Ringworm of the glabrous skinTinea corporis, cruris (T. rubrum, T.

mentagrophytes)Hyperlkeratosis (T. rubrum)


Allergic syndromehepatitis

TERBINAFINETERBINAFINE Synthetic allylamine Available in oral formulation Used in the treatment of dermatophytoses especially

onychomycosis Keratophillic, fungicidal Inhibits the enzyme SQUALENE EPOXIDASE Leads to the accumulation of the sterol squalene Allylamines work in a conceptually similar fashion to azole

antifungals by inhibiting the synthesis of ergosterol Allylamines act at an earlier step in the ergosterol synthesis

pathway OD X12 wks achieves 90% cure rate for onychomycosis

TOPICAL ANTIFUNGAL TOPICAL ANTIFUNGAL AGENTSAGENTS

Superficial fungal infections confined to the striatum corneum, squamous mucosa or cornea

Ringworm, candidiasis, tinea versicolor, tinea nigra, fungal keratitis

Not successful for mycoses of the nails & hair No place for the treatment of subcutaneous

mycosis

POLYENE ANTIFUNGAL POLYENE ANTIFUNGAL AGENTSAGENTS

NYSTATINNYSTATIN

Polyene macrolideStructurally similar to Amphotericin BToxic for parenteral administrationAvailable in creams, ointments,

suppositoriesOropharyngeal thrush, vaginal

candidiasis, intertriginous candidal infections

AMPHOTERICIN BAMPHOTERICIN B

Topical form (Fungizone)Cutaneous & mucocutaneous

candidiasisLotion, ointment & cream

IMIDAZOLE & TRIAZOLE FOR IMIDAZOLE & TRIAZOLE FOR TOPICAL USE:TOPICAL USE:

CLOTRIMAZOLECLOTRIMAZOLE

Available as 1% cream, lotion, & solution

1% or 2% vaginal cream or vaginal tablets

Skin applications – BIDVaginal applications – 100 mg tab OD

at bedtime X 7 days or 200 mg OD X 3 days

MICONAZOLEMICONAZOLE Readily penetrates the striatum corneum of

the skin Persists for >4 days after application Safe for use during pregnancy for vaginal

use Ointment, cream, solution, spray, powder

or lotion Vaginal cream, suppositories Tinea pedis, tinea cruris, & tinea versicolor

CICLOPIROXAMINECICLOPIROXAMINE

Broad spectrumFungicidal to C. albicans, E. flocosum,

M. canis, T. mentagrophytes, T. rubrumInhibits the growth of Malassezia furfurPenetrates the dermis

HALOPROGINHALOPROGIN

Halogenated phenolic ether Fungicidal to various species of

Epidermophyton, Pityrosporum, Microsporum, Trichophyton & Candida

Poorly absorbed through the skin Converted to thrichlorophenol in the body Cream or solution BID X 2-4 wks Principal use for tinea pedis Tinea cruris, tinea versicolor, tinea corporis

NAFTIFENENAFTIFENE

Inhibit squalene-2,3- epoxidaseInhibits biosynthesis of ergosterolFungicidal activity1% cream or gelTopical treatment of tinea cruris & tinea

corporisCutaneous candidiasis & tinea

versicolor

DRUG ACTION CLINICAL USE UNDESIRABLE EFFECTS

PHARMACOKINETICS NOTES

Amphotericin B Disrupts plasma membrane of fungal cells, greater affinity for ergosterol

DOC: systemic fungal infections, fungal meningitis & fungal urinary tract infections

Poor therapeutic index (toxic at therapeutic dose). Fever & chills, nephrotoxicity, nausea, headache, thrombophlebitis, anemia, hepatotoxicity, cardiotoxicity

Slow IV for systemic infections; intrathecal for meningitis, bladder irrigation for cystitis. No need to reduce dose with renal dysfunction.

CBC, urinalysis, liver enzymes, BUN, Crea, & electrolytes should be checked before and during tx

Nystatin DOC: Intestinal candidiasis or oral thrush

Few adverse effects

PO. Negligible absorption, fecal excretion

.

Ketoconazole Impairs synthesis pf ergosterol

DOC: P. brasiliensis, thrush, chronic mucocutaneous candidiasis, dermatophytes

Nausea, diarrhea, headaches, rsh, dizziness, fatal hepatic necrosis, gynecomastia.Risk of cardiac arrhythmia with Terfenadine

PO. Acid pH required for dissolution. Absorption decreased by food, antacids, cimetidine

Follow LFTs. Stop during signs of liver abnormalities

Fluconazole Inhibits fungal cytochrome P450. Damages plasma membrane by inhibiting sterol demethylation

Systemic histoplasmosis, blastomycosis, coccidiomycosis or sporotrichosis. Opportunistic cryptococcosis, candidiasis, candidal thrush, vaginitis, esophagitis

Nausea, headache, rash, vomiting, diarrhea

PO/IV. Long half life. Excellent penetration of CSF, eye, urine. Hepatic metabolism

No effect on testosterone synthesis.

ANTIFUNGAL DRUGS

Itraconazole Aspergillosis, histoplasmosis, coccidiomycosis, sporotrichosis, paracoccidiomycosis, tinea or candidal infections

Nausea, edema, hepatitis. No gynecomastia or breast pain. Risk of fatal cardiac arrhythmias w/ terfenadine

PO. Requires acidic environment for absorption

No effect on testosterone synthesis

Clotrimazole unknown DOC: candida dermatophyte infections of the skin

topical

Miconazole Vaginal candidiasis, severe systemic fungal infections

Phlebitis, pruritus, nausea, fever, rash, vomiting

Vaginal suppositories/ topical/IV

Flucytosine Deaminated to 5-FU by the fungus. Incorporated into RNA. Metabolized to 5-FdURD w/c inhibits thymidilate synthetase

Leucopenia, nausea, diarrhea, Inc LFTs, bone marrow depression

Easily penetrates CNS. Renal excretion

Fungal resistance develops

Griseofulvin Interferes w/ synthesis & polymerization of nucleic acids

Dermatophytes of hair, skin, & nails. Up to 6 months tx may be required

Headaches, GI upset, dec memory & judgement, leucopenia, teratogenic

PO. Water insoluble, powder absorbed fairly well, administration w/ fatty meal aids absorption

Contraindicated w/ pregnant women. Drug binds to keratin of growing tissues

Terbinafine Inhibits squalene epoxidase that converts squalene to ergosterol in fungi

Toenail infection due to trichophyton species

Neutropenia, skin infections, ophthalmic toxicity

PO. Long half life. Good tissue penetration

Monitor blood counts

MISCELLANEOUS MISCELLANEOUS ANTIFUNGAL AGENTSANTIFUNGAL AGENTS

UNDECYCLENIC ACIDUNDECYCLENIC ACID

Yellow liquid with a characteristic rancid odor

Fungistatic, fungicidal w/ prolonged useFoam, ointment, cream, powder, spray

powder, soap & liquidRingworm, tinea pedis

BENZOIC ACID & SALICYLIC BENZOIC ACID & SALICYLIC ACIDACID

Whitfield’s ointmentCombines fungistatic activity of benzoic

acid w/ keratolytic action of salicylic acidMainly for the treatment of tinea pedisEradication occurs after the infectd

stratum corneum is shedSalicylate accelerates the

desquamation

PROPIONIC ACID & CAPRYLIC PROPIONIC ACID & CAPRYLIC ACIDACID

Treatment of dermatomycosesLow efficacy

POTASSIUM IODIDEPOTASSIUM IODIDE

Treatment of mucocutaneous sporotrichosis

Antiviral Lecture

Health & Medicine

Transcript of Antiviral Lecture