this ppt gives an overview about viruses and anti virus in head and neck

1. VIRUSES AND ANTI VIRUS
PRESENTER : DR.S.AKSHAYA
MODERATOR : DR.SAGAYARAJ

2. LEARNING OBJECTIVES
 WHAT ARE THE DIFFERENT ANTI VIRAL AGENTS
 MECHANISM OF ACTION
 PHARMACOKINETICS
 ADVERSE EFFECTS
 DOSAGES

3. INTRODUCTION
 Viruses are obligate intracellular parasites , their replication depends primarily on
the synthetic process of host cells .
 An effective antiviral agent must be able to block viral entry or exit or the activity
inside the host cells .

4. MECHANISM OF ACTION
 VIRAL REPLICATION REQUIRES SEVERAL STEPS
1. Attachment to host cell via receptor
2. Viral entry into the cell by endocytosis or fusion
3. Release of viral genome a.k.a uncoating
4. Replication of viral genome
5. Protein synthesis and assembly
6. Release of virus from the host cells by neuroaminidase .

5. MECHANISM OF ACTION
 Anti viral agnets potentially targets any of these stages to control the infection .

6. CLASSIFICATION
 AGENTS AGAINST CORONA VIRUS
 AGENTS AGAINST HSV (Herpes simplex virus ) , VZV (Varicella zoster virus)
 AGENTS AGAINST CMV(Cytomegalo virus)
 ANTI INFLUENA AGENTS
 AGENTS AGAINST RSV (Respiratory syncytial virus)
 ANTIHEPATITIS AGENTS

7. AGENTS AGAINST CORONA VIRUS
 REMEDESIVIR
 MONOCLONAL ANTIBODY
 IL6 INHIBITORS – TOCILIZUMAB
 FAVIPIRAVIR

8. CORONA VIRUS – INFECTIVE CYCLE

9. REMEDESIVIR
 It is a prodrug of GS-441524 (c-adenosine)
 It acts as a nucleotide analog to inhibit RNA synthesis .
 Only parentral use
 Dose : 200mg IV stat followed by 100mg OD X 4days
 Adverse effects :
1. Respiratory failure
2. Low albumin, low potassium, low count of red blood cells, low count of thrombocytes,
and elevated bilirubin
3. Gastrointestinal distress, elevated transaminase levels in the blood
4. Infusion site reactions

10. REMEDESIVIR

11. MONOCLONAL ANTIBODY
 What are MAB :
A monoclonal antibody is an artificially made antibody made by cloning a
unique white blood cell.
Eg:
Bamlanivimab and Etesevimab
Casirivimab plus imdevimab

12. MONOCLONAL ANTIBODY
 Bamlanivimab MOA – It binds to the spike protein S of the virus and blocks its
entry into the host cell

13. MONOCLONAL ANTIBODY

14. MONOCLONAL ANTIBODY
 DOSE OF BAMLANIVIMAB :
700mg IV single dose over 60 minutes .
One vial of bamlanivimab contains 700mg/20ml

15. MONOCLONAL ANTIBODY
 Adverse drug reaction :
1. Infusion related reaction
2. Nausea , vomiting
3. Dizziness
4. Pruritis
5. Headache
6. Liver enzymes alteration as it is excreated via liver enzymes .

16. TOCILIZUMAB
 It is also a MAB used against IL6 receptor
 MOA – It acts against IL6 receptor and prevents the binding of cytokines , and thus
preventing the excess inflammatory response in covid patients
 Dose 8mg/kg upto 800mg – second dose after 12-24 hours
 Adverse effects : runny nose , common cold , dizziness ,
headache

17. FAVIPIRAVIR
 It is an antiviral drug widely used to treat covid 19 virus
 MOA :
Favipiravir enters the cell and is
converted into favipiravir-RTP
F-RTP inhibits RNA dependant
RNA polymerase of CoV2
This will inhibit viral replication

18. FAVIPIRAVIR
 Half life : 2-5.5 hours
 Route of excretion – renal
 Dosage adult:
1800mg stat after 12 hours 1800 mg stat followed by 800mg BD for 5 days .
ADVERSE EFFECTS :
Nausea , diarrhea
Leukopenia
Elevated liver enzymes
Dellirium , confusion (rare)

19. AGENTS AGAINST HSV / VZV
 ACYCLOVIR
 VALCYCLOVIR
 FAMCICLOVIR
 TRIFLURIDINE

20. ACYCLOVIR
 It is an acyclic guanosine derivative.
 It has clinical activity against HSV-1/2 and VZV, EBV,HHV6 , CMV

21. ACYCLOVIR
 MECHANISM OF ACTION :
 Acyclovir requires activation before its start of action
ACYCLOVIR
MONOPHOSPHATE
DIPHOSPHATE
TRIPHOSPHATE
VIRAL THYMIDINE
KINASE

22. ACYCLOVIR
 Acyclovir triphosphate inhibits viral DNA polymerase which inturn leads to
termination of viral replication .
 Pharmacokinetics :
1. Bioavailablity – oral is low 15-20% and is unaffected by food
2. Clearance – renal (glomerular filtration and tubular secretion )
3. Half life 2.5-3hours

23. ACYCLOVIR
 RESISTANCE OF ACYCLOVIR – ALTERATION IN VIRAL THYMIDINE KINASE
 ADVERSE EFFECTS :
Generally well tolerated
Minor side effects : nausea , diarrhoea , headache
IV infusion – renal toxicity
CNS – delirium comfusion

24. ACYCLOVIR
ORAL
 Varicella treatment – 800mg qid x 5 days
 Zoster treatment – 800mg 5 times x 7-10 days
INTRAVENOUS
Varicella/zoster – 10mg/kg q8h x 7 days

25. VALACYCLOVIR
 It is a L-Valyl ester of acyclovir . It is rapidly converted into to acyclovir after oral
administration via first pass metabolism in liver .
 Mechanism of action is same as acyclovir
 Pharmacokinetics :
1. Bioavailablity – oral 54-70%
2. Half life – 2.5-3 hours
3. Excreartion – renal route

26. VALCYCLOVIR
 Adverse effects :
1. It is generally well tolerated although minor side effects include nausea , headache
, vomiting , rash
2. At higher doses confusion , hallucinations and seizures are reported
3. HIV patients on chronic valcyclovir – severe GI intolerance , thrombotic
thrombocytopenic purpura / haemolytic uremic syndrome .

27. VALCYCLOVIR
ORAL
 Varicella – 20mg/kg TID x 5 days max 1gm
 Zoster 1gm TID x 7 days

28. FAMCICLOVIR / PENCICLOVIR
 It is a diacetyl ester prodrug of 6 deoxypenciclovir an acyclic guanosine analog .
 After administration famciclovir is rapidly deactylated and oxidized by first pass
metabolism to penciclovir
 It is active in vitro against HSV 1/2 , VZV , EBV , HBV .

29. FAMCICLOVIR / PENCICLOVIR
 Mechanism of action :
After activation into triphosphate it attaches to viral DNA polymerase and inhibits
viral replication .
 PHARMACOKINETICS :
1. Bioavailablity – oral 70%
2. Half life – 7-20 hours
3. Route of elimination – renal route
4. Metabolism – liver

30. FAMCICLOVIR / PENCICLOVIR
 Adverse effects :
1. Oral famciclovir is generally well tolerated although headache , nausea diarrhoea
may occur

31. FAMCICLOVIR / PENCICLOVIR
ORAL
 Herpes – 500mg BD x 7 days
 Zoster – 500mg TID X 7 days
INTRAVENOUS
Acyclovir resistant HSV /VZV – 40-60mg/kg q8h until healed
PENCICLOVIR – TOPICAL APPLICATION

32. TRIFLURIDINE
 It is a fluorinated pyrimidine nucleoside that inhibits viral DNA synthesis in HSV
1/2 , CMV .
 MOA – it inhibits viral DNA synthesis by incorporating into viral DNA polymerase
 Incorporation into both viral and host DNA prevents its systemic use
 However cutaneous application of trifluridine solution alone or in combination
with interferon alpha have been successfully used in acyclovir resistant HSV
infection.
 Comes as a topical applicant

33. AGENTS AGAINST CMV
 GANCICLOVIR
 VALGANCICLOVIR
 FOSCARNET
 CIDOFOVIR

34. GANCICLOVIR
 It is an acyclic guanosine analog .
 MOA :
CMV INFECTED CELL
GANCICLOVIR
viral
phosphotransferase
GANCICLOVIR TRIPHOSPHATE

35. GANCICLOVIR
 Ganciclovir triphosphate inhibits viral DNA polymerase and causes termination of viral
chain elongation .
 It has invitro activity against :
CMV , HSV , VZV , EBV , HHV 6/8
Pharmacokinetics :
Bioavailablity – oral is low hence administered IV
Half life : 4 hours
Route of elimination : renal

36. GANCICLOVIR
 Adverse effects :
Most common adverse effects is myelosuppression
Minor side effects include nausea diarrhea fever rash headache
CNS toxicity includes confusions , seizures , psychiatric disturbance .

37. GANCICLOVIR
INTRAVENOUS
 CMV – 5mg/kg q12h x 14-21 days
followed by 5mg/kg/day 5 times a week

38. VALGANCICLOVIR
 It is an L-Valyl ester prodrug of ganciclovir
 After administration it is hydrolysed to ganciclovir by esterase in intestinal wall
and liver .
 PHARMACOKINETICS :
1. Oral bioavailablity is high 60%
2. Half life :
3. Route of excreation : renal

39. VALGANCICLOVIR
ORAL
 CMV – 900mg BD x 21 days
Followed by 900mg daily

40. FOSCARNET
 It is an inorganic pyrophosphate analog that inhibits Herpes DNA polymerase ,
RNA polymerase and HIV reverse transcriptase directly without requiring
activation.
 Foscarnet is effective in treatment of end organ CMV disease , (retinitis , colitis ,
esophagitis ) , including ganciclovir resistant disease . Its also effective against
acyclovir resistant HSV and VZV infections .

41. FOSCARNET
 PHARMACOKINETICS :
1. Bioavailablity - Available in IV formulation , poor oral availability and GI intolerance
2. Half life – 3-7hrs
3. Route of excreation – renal route
 Adverse effects :
1. Minor adverse effects – nausea , vomiting , anemia
2. CNS toxicity – hallucinations , seizures , headache
3. Potential adverse effects include renal impairment , hypo or hyper calcemia , hypo or
hyperphosphatemia , hypokalemia and hypomagnesemia

42. FOSCARNET
INTRAVENOUS
 60mg/kg q8h x 14-21 days
Followed by 90-120mg/kg/day

43. CIDOFOVIR
 It is a cytosine nucleotide analog with in vitro activity CMV , HSV1/2 , VZV , EBV , HHV6/8,
Adenovirus , Poxvirus , polyomavirus
 In contrast to ganciclovir phosphorylation of cidofovir to active diphosphate is independent of
viral enzymes
 Hence this antiviral can used against other resistant drugs .
 MOA – It is a potent inhibitor of and as an alternative substrate for viral DNA polymerase ,
competitively inhibiting DNA synthesis and becoming incorporated into the viral DNA chain

44. CIDOFOVIR
 PHARMACOKINETICS :
1. Bioavailablity – oral is low hence used as intravenous
2. Half life : 17-65 hrs
3. Route of excretion – renal tubular excretion
 Adverse effects :
1. Primary adverse effects is dose dependant proximal tubular nephrotoxicity
2. Proteinuria , metabolic acidosis , Fanconi’s anemia are less common.
3. Uveitis , ocular hypotony

45. CIDOFOVIR
INTRAVENOUS
 5mg/kg/week x 2 weeks
 Followed by 5mg/kg/every week

46. ANTI-INFLUENZA AGENTS
 OSELTAMIVIR & ZANAMIVIR
 AMANTADINE & RIMANTADINE

47. OSELTAMIVIR & ZANAMIVIR
 These are neuroaminidase inhibitors
 Analogs of sialic acid
 MOA – they interfere with the release of influenza virus from host cells thus halting
the spread of infection within the respiratory tract
 These agents comptetively and reversibly inhibit viral neuroaminidase

48. OSELTAMIVIR & ZANAMIVIR
 ADMINISTRATION :
1. Early administration is crucial because replication of influenza virus peaks at 24-72
hours after the onset of illness
2. Initiation of a 5 day course of therapy within 48 hrs after the onset of illness decreases
the duration of symptoms , viral shedding and transmission.
 PHARMACOKINETICS :
 OSELTAMIVIR :
1. Bioavailablity – oral is high 80%
2. Half life – 6-10hrs
3. Excreation – renal

49. OSELTAMIVIR & ZANAMIVIR
 ZANAMIVIR
1. Half life – 2.8hrs
2. Route of excreation – renal
 ADVERSE EFFECTS :
 Oseltamvir :
1. Potential adverse effects include nausea, vomiting, headache
2. CNS- delirium

50. OSELTAMIVIR & ZANAMIVIR
 ZANAMIVIR :
1. Cough , bronchospasm , reversible decrease in pulmonary functions and transient
nasal and throat discomfort .

51. OSELTAMIVIR & ZANAMIVIR
 DOSE OSELTAMIVIR :
1. 75mg BD for five days for treatment
2. 75mg OD for prevention
 DOSE ZANAMIVIR :
1. 10mg BD for 5 days
2. 10mg OD for prevention

52. AMANTADINE & RIMANTADINE
 Amantadine and its alpha methyl derivative , rimantadine are tricyclic amines of
adamantane family
 MOA- they block the M2 proton ion channel of the virus particle and inhibit the
uncoating of the viral RNA within the infected cells .
 Rimantadine is 4-10 times more active than amantadine
 ADMINISTRATION :
1. When begun within 1-2 days after onset of illness , the duration of fever and
systemic systems is reduced by 1-2 days

53. AMANTADINE & RIMANTADINE
 PHARMACOKINETICS :
 Amantadine:
1. Bioavailablity – it is well absorbed 67%
2. Half life – 12-18hrs
3. Route of excreation – renal
 Rimantadine :
1. Bioavailablity – well absorbed 40%
2. Half life – 24-36hrs
3. Route of excretion – renal

54. AMANTADINE & RIMANTADINE
 Adverse effects :
 Most common adverse effect is gastrointestinal – nausea , anorexia
 CNS- Nervousness , difficulty in concentrating , insomnia , light headedness
 Most serious – delirium , hallucination , seizures
 Drug interaction – with antihistamines , anticholinergics trimethoprim-
sulphmethoxazoles .

55. AMANTADINE & RIMANTADINE
 DOSE :
 Both are given at
 100mg BD or 200mg OD for treatment
 100mg OD for prevention

56. AGENTS AGAINST RSV
 RIBAVIRIN
 PALIVIZUMAB

57. RIBAVIRIN
 It is a guanosine analog that is phosphorylated intracellular by host cell enzyme .
 MOA- It inhibits the replication of DNA and RNA virus by inhibiting RNA
dependent polymerase
 PHARMACOKINETICS :
1. Bioavailablity – 45-64% , oral availability increases with high fat meal , decreases
with administration of antacids
2. Half life – 9.5hrs
3. Route of excretion – renal

58. RIBAVIRIN
 Adverse effects :
1. Depression , fatigue , irritability , rash , cough , insomnia , nausea , pruritis
2. Contraindications to ribavirin is end stage anemia , renal failure , ischemic vascular
disease , teratogenic
 DOSE : Ribavarin is administered by nebulizer – 20mg/ml for 12-18hours per day

59. OTHER ANTI VIRAL
 INTERFERON ALPHA
 ANTI HIV :
1. PROTEASE INHIBITORS
2. NRTI
3. NNRTI

60. ANTI HIV AGENTS – PROTEASE
INHIBITORS
 MOA :
1. During the last stage of HIV growth cycle , the gag and gag pal gene products are
translated into polyprotein and these become immature budding particles .
2. The HIV proteases is responsible for cleaving these precursor molecule to produce
the final proteins
3. By preventing the post translational cleavage of gag pol polyproteins protease
inhibits the viral protein processing – leads to immature viral protein production

61. ANTI HIV AGENTS – PROTEASE
INHIBITORS
DRUG DOSE ADVERSE EFFECTS
Indinavir 100-200mg BD Nephrolithiasis , nausea
,headache, asthenia ,
blurred vision
Lopinavir 800mg/day– 200mg QID Diarrhea , abdominal pain ,
nausea ,
hypertriglyceridemia ,
hepatotoxic (severe cases)
Nelfinavir 750mg TID/ 1250mg BD Diarrhea , nausea ,
flatulence

62. ANTI HIV AGENTS – NRTI
 Nucleoside and nucleotide reverse transcriptase inhibitor
1. It is considered the backbone of anti-retroviral therapy
2. MOA – It acts by competitive inhibition of HIV reverse transcriptase by
incorporating into growing viral DNA chain and causing premature chain
termination .

63. ANTI HIV AGENTS – NRTI
DRUG DOSE ADVERSE EFFECTS
Lamivudine 150mg BD nausea ,headache,
dizziness , fatigue
Stavudine 30-40mg BD Peripheral neuropathy ,
lipodystrophy ,
hyperlipidemia
Zidovudine 200mg TID , 300mg BD Nausea , headache ,
insomnia , macrocytic
anemia

64. ANTI HIV AGENTS – NNRTI
 MOA – The NNRTI bind directly to HIV-1 reverse trancriptase resulting in allosteric
inhibition of RNA and DNA polymerase activity
DRUG DOSE ADVERSE EFFECTS
Nevirapine 200mg BD nausea ,headache, rash ,
occasional fulminant
hepatitis
Rilpivirine 25mg QID Insomnia , rash ,
depression , liver enzymes
.

65. INTERFERONS
 Interferons are natural proteins produced by cells of immune system in response
to foreign particles like viruses bacteria parasites etc
 Three classes of interferon – alpha , beta , gamma
 I alpha and beta – produces by all cells in response to viral infections
 I gamma – produced by T and NK cells in response to cytokines

66. INTERFERONS
 MOA :
 They induce the following enzymes :
1. Protein kinase which inhibits protein synthesis
2. Oligo adenylate synthase – degrades viral m RNA
3. Phosphodiestrase – inhibits t RNA

67. INTERFERON
 Acts against HBV , HCV , HPV , Tumors like hairy cell leukemia , Kaposi sarcoma
 PHARMACOKINETICS:
1. Bioavailablity - <1% - oral
2. Administered IV SC INTRALESIONALLY
3. Half life – 1-4 hrs

68. REFERENCES
 BASIC AND CLINICAL PHARMACOLOGY – LANGE
 SCOTT BROWN OTORHINOLARYNGOLOGY

69. THANK YOU