3. IntroductionIntroduction
• Human influenza viruses are members of theHuman influenza viruses are members of the
orthomyxovirusorthomyxovirus family, which consists of the genera:family, which consists of the genera:
influenzainfluenza AA,, BB, and, and CC virus, andvirus, and ThogovirusThogovirus (in ticks).(in ticks).
• In humans, only influenzaIn humans, only influenza AA andand BB viruses are ofviruses are of
epidemiological interest.epidemiological interest.
•The main antigenic determinants of influenzaThe main antigenic determinants of influenza AA andand BB
viruses are theviruses are the haemagglutininhaemagglutinin (H or HA)(H or HA) andand
neuraminidaseneuraminidase (N or NA)(N or NA) transmembrane glycoproteins.transmembrane glycoproteins.
(IMAGE-1) & (IMAGE-2)(IMAGE-1) & (IMAGE-2)
•The new pandemicThe new pandemic H1N1(2009)H1N1(2009) causes FDA and othercauses FDA and other
health agencies to prepare many educational noteshealth agencies to prepare many educational notes
(VIDEO-1(VIDEO-1))
4. How H1N1 virus infect the cell ?How H1N1 virus infect the cell ?
• Influenza viruses are usually transmitted via airInfluenza viruses are usually transmitted via air
droplets, and subsequently contaminate the mucosa ofdroplets, and subsequently contaminate the mucosa of
the respiratory tract.the respiratory tract.
•After onlyAfter only 6 hours6 hours the first influenza viruses are shedthe first influenza viruses are shed
from infected cells.from infected cells.
•Part of the viral proteins, such as thePart of the viral proteins, such as the fusion peptidefusion peptide andand
NS2NS2, act as toxins to promote the production of, act as toxins to promote the production of
influenza virus. (VIDEO-2).influenza virus. (VIDEO-2).
• Rapid bacterial growth, most commonlyRapid bacterial growth, most commonly StreptococcusStreptococcus
pneumoniaepneumoniae,, Staphylococcus aureusStaphylococcus aureus, and, and HaemophilusHaemophilus
influenzaeinfluenzae,, may begin in the very early phase of viralmay begin in the very early phase of viral
replication.replication.
5. How we can control the panademicHow we can control the panademic
H1N1 FluH1N1 Flu
• TheThe GeneralGeneral lineslines ofof controllingcontrolling H1N1H1N1 includeinclude::
A) Treatment of Already Diagnosed Cases.Treatment of Already Diagnosed Cases.
B) Prophylaxis and Prevention of Infection.B) Prophylaxis and Prevention of Infection.
By:By:
i) General Hygienici) General Hygienic
Measures .Measures .
(hands washing, ….etc)(hands washing, ….etc)
ii) Pharmacological Treatment.ii) Pharmacological Treatment.
iii) Vaccination.iii) Vaccination.
7. Antiviral Drugs For H1N1Antiviral Drugs For H1N1
• Currently Available Antiviral Agents for the TreatmentCurrently Available Antiviral Agents for the Treatment
or Prophylaxis of H1N1 Flu include:or Prophylaxis of H1N1 Flu include:
A.A. The Adamantanes :The Adamantanes :
(Amantadine(Amantadine andand Rimantadine)Rimantadine)
B. TB. The New class of Neuraminidase Inhibitorshe New class of Neuraminidase Inhibitors
1. Oseltamivir1. Oseltamivir [TamifluTamiflu]
. 2. Zanamivir2. Zanamivir [RelenzaRelenza]
• (VIDEO-3)
9. Mechanism of ActionMechanism of Action
• The influenza virus enters its host cell by Receptor-mediatedReceptor-mediated
Endocytosis.Endocytosis.
• AcidificationAcidification of the endocytotic vesicles is required for the
dissociation of the M1 protein from the ribonucleoprotein
complexes. The hydrogen ions needed for acidification pass
through the M2 channel.
• Amantadine & Rimantadine inhibit the replication of
influenza-A viruses by interfering with the uncoating of the
virus inside the cell.
• They are M2 inhibitorsM2 inhibitors, block the ion channel formed by the
M2 protein that spans the viral membrane(Sugrue 1991,(Sugrue 1991, Bui
1996 ).).
10. PharmacokineticsPharmacokinetics
• Amantadine is well absorbedAmantadine is well absorbed orallyorally..
• Maximum drug concentrations (Maximum drug concentrations (CmaxCmax) are) are directly dose-relateddirectly dose-related
for doses of up to 200 mg/day.for doses of up to 200 mg/day.
• In healthy volunteers,In healthy volunteers, peak concentrationpeak concentration were reachedwere reached after 3after 3
hourshours and theand the half-life was 17 hourshalf-life was 17 hours..
• Amantadine is primarily excretedAmantadine is primarily excreted unchangedunchanged in the urine byin the urine by
glomerular filtrationglomerular filtration andand tubular secretiontubular secretion..
• The clearance is also reduced in patients withThe clearance is also reduced in patients with renalrenal
insufficiencyinsufficiency: the elimination half-life increases: the elimination half-life increases twotwo toto threethree foldfold
or greater when creatinine clearance is less thanor greater when creatinine clearance is less than 40 ml/min40 ml/min..
• Amantadine isAmantadine is not removednot removed byby haemodialysishaemodialysis..
• As the excretion rate of amantadineAs the excretion rate of amantadine increasesincreases rapidly when therapidly when the
urine isurine is acidicacidic, the administration of urine acidifying drugs may, the administration of urine acidifying drugs may
increase the elimination of the drug from the body.increase the elimination of the drug from the body.
11. IndicationsIndications
Amantadine is effective against all influenza A butAmantadine is effective against all influenza A but not againstnot against
influenza Binfluenza B virus, because thevirus, because the protein M2protein M2 is unique tois unique to
influenza Ainfluenza A viruses.viruses.
• For bothFor both preventionprevention andand treatmenttreatment of Influenza-A,of Influenza-A,
Amantadine isAmantadine is similarsimilar to Rimantadineto Rimantadine (Stephenson 2001,(Stephenson 2001,
Jefferson 2004).Jefferson 2004).
• Comparative studies indicate thatComparative studies indicate that adverseadverse effectseffects werewere
significantlysignificantly more commonmore common withwith AmantadineAmantadine thanthan
RimantadineRimantadine (Jefferson 2004).(Jefferson 2004).
• Amantadine is also indicated in the treatment ofAmantadine is also indicated in the treatment of Parkinson’sParkinson’s
diseasedisease and drug-induced extrapyramidal reactions.and drug-induced extrapyramidal reactions.
• TheThe low efficacylow efficacy of amantadine together with the relativelyof amantadine together with the relatively
high rate of adverse eventshigh rate of adverse events cause use of amantadine to because use of amantadine to be
discouraged in seasonal and pandemic influenzadiscouraged in seasonal and pandemic influenza (Jefferson(Jefferson
2006)2006)
12. DosageDosage && AdministrationAdministration::
Adult doseAdult dose::
• The daily dosage of amantadine for adults isThe daily dosage of amantadine for adults is 200 mg200 mg..
-- TwoTwo 100 mg100 mg tabletstablets
(or(or fourfour teaspoonfuls of syrup) as ateaspoonfuls of syrup) as a onceonce daily dosedaily dose..
oror
- One Tablet of- One Tablet of 100 mg100 mg twicetwice a day.a day.
PediatricPediatric dosedose::
• Lower total daily doses should be calculated on the basis of :Lower total daily doses should be calculated on the basis of :
{{ 4.4 to 8.8 mg/kg/day}.
• Low efficacyLow efficacy, of amantadine and the high risk of occurrence
of gastrointestinal and CNS adverse effects do not
recommend the administration of amantadine in children.
13. ToxicityToxicity
Major side effects::
• Gastrointestinal symptomsGastrointestinal symptoms . mainly nauseamainly nausea
but also vomiting, diarrhoea, constipation, andbut also vomiting, diarrhoea, constipation, and
loss of appetite are theloss of appetite are the
• CNS toxicityCNS toxicity may manifest as dizziness, nervousness,may manifest as dizziness, nervousness,
agitation, difficulty concentrating and insomnia.agitation, difficulty concentrating and insomnia.
Less frequently (1-5 %) adverse reactions are:
• Depression, anxiety and irritability, hallucinations,Depression, anxiety and irritability, hallucinations,
confusion, anorexia,confusion, anorexia,
• Dry mouth,Dry mouth, constipationconstipation, ataxia,, ataxia,
• Livedo reticularisLivedo reticularis,
• PeripheralPeripheral oedemaoedema,,
• Orthostatic hypotensionOrthostatic hypotension, headache,, headache,
• Somnolence, dream abnormality, agitation, andSomnolence, dream abnormality, agitation, and
fatigue.fatigue.
14. Drug InteractionsDrug Interactions:
Amantadine should not be given together withAmantadine should not be given together with::
Benzodiazepines,, Tricyclic Antidepressants,,
Dicyclomine, some, some Antihistamines,, Opiate agonists andand
certaincertain Antihypertensive medications.medications.
Such combinations can causeSuch combinations can cause::
dizzinessdizziness,, confusionconfusion, light, light headednessheadedness, or, or faintingfainting..
• Co-administration ofCo-administration of ThioridazineThioridazine can worsen the tremor incan worsen the tremor in
elderly patients withelderly patients with Parkinson.s diseaseParkinson.s disease..
• Co-administration ofCo-administration of QuinineQuinine oror QuinidineQuinidine with amantadinewith amantadine
has been shown to reduce thehas been shown to reduce the renal clearancerenal clearance ofof
amantadine by aboutamantadine by about 30 %.30 %.
16. Mechanism of Action:Mechanism of Action:
• TheThe neuraminidase enzymeneuraminidase enzyme is responsible foris responsible for
cleavingcleaving sialic acid residuessialic acid residues on newly formed virionson newly formed virions
and plays an essential role in the release and spreadand plays an essential role in the release and spread
of progeny virions.of progeny virions.
• Oseltamivir and zanamivir are potent and selectiveOseltamivir and zanamivir are potent and selective
inhibitors of theinhibitors of the neuraminidase enzymeneuraminidase enzyme of theof the
influenzainfluenza viruses Aviruses A andand BB..
• When exposed to Oseltamivir, the influenza virionsWhen exposed to Oseltamivir, the influenza virions
aggregateaggregate onon thethe surfacesurface ofof the hostthe host cellcell, thereby, thereby
limiting the extent of infection within the mucosallimiting the extent of infection within the mucosal
secretionssecretions (McNicholl 2001).(McNicholl 2001).
17.
18. IndicationsIndications
• Oseltamivir is indicated in the prophylaxisprophylaxis of H1N1 flu and for the
treatmenttreatment of uncomplicated acute illness due to H1N1 flu in
patients 1 year and older1 year and older who have been symptomatic for no
more than 2 days2 days.
PharmacokineticsPharmacokinetics
• Oseltamivir is readily absorbedreadily absorbed from the gastrointestinal tract.
• After conversion to the active metabolite oseltamivir carboxylateoseltamivir carboxylate
in the liver, it distributes throughout the body, including the
upper and lower respiratory tract (Doucette 2001).
• The active metabolite is detectable in plasma within 30 minutes30 minutes
and reaches maximum concentrations after 3 to 4 hours.
• Plasma protein binding is 3 %3 %.
• The drug and the active metabolite are excreted by glomerular
filtration and active tubular secretion without further metabolism
(Hill 2001) .
19. Dosage & Administration:Dosage & Administration:
A.A. TreatmentTreatment
• Oseltamivir, 75 mg75 mg bidbid for 5 days, to adults with naturally
acquired febrile influenza when started within 36 hours of
the onset of symptoms.
.
• Pediatric patients or adults who cannot swallow capsules,
receive oseltamivir 30, 45 and 60 mg oral suspension twicetwice
dailydaily.
• RecommendedRecommended dosedose::
Body Weight Recommended Dose for 5
Days
≤ 15 kg 30 mg twice daily
> 15 kg to 23 kg 45 mg twice daily
> 23 kg to 40 kg 60 mg twice daily
> 40 kg 75 mg twice daily
20. B. Prophylaxis,B. Prophylaxis,
• The recommended dose is 75 mg75 mg once dailyonce daily for at least 7
days.
• The oral dose of oseltamivir suspensionsuspension for paediatric
patients aged 1 year1 year and older following contactcontact with an
infected individual is:
Body Weight Recommended Dose for 7 Days
≤ 15 kg 30 mg once daily
> 15 kg to 23 kg 45 mg once daily
> 23 kg to 40 kg 60 mg once daily
> 40 kg 75 mg once daily
21. ToxicityToxicity
• The most frequent side effects are nauseanausea and
vomitingvomiting which are generally of a mild to moderate
degree and usually occur within the first 2 days of
treatment.
• RashRash, swelling of the face or tongue, toxic epidermal
necrolysis
• HepatitisHepatitis, abnormal liver function tests.
• Arrhythmias.Arrhythmias.
• SeizuresSeizures, confusion.
• Aggravation of diabetes.diabetes.
22. ResistanceResistance
• A major problem facing us is the development of new H1N1
virus strains resistantresistant to the currently available neuraminidase
inhibitors. This were noticed in USA.
Contraindications:Contraindications:
• Oseltamivir is notnot indicated for the treatment of influenza in
paediatric patients younger than 1 year1 year.
• Oseltamivir should be used during pregnancy onlyonly if the
potential benefit justifies the potential risk to the foetus
(Pregnancy Category C).
Drug InteractionsDrug Interactions
• Pharmacology and pharmacokinetic studies suggest that
clinically significant drug interactions are unlikelyunlikely (Tamiflu
2005).
• Neither oseltamivir nor oseltamivir carboxylate is a substrate
for, or inhibitor of, cytochrome P450 isoforms.
23. VaccinationVaccination
• Inactivated vaccineInactivated vaccine (vaccine that has killed
virus in it) is injectedinjected into the muscle, like
the annual flu shot.
• AA live, intranasal vaccinelive, intranasal vaccine (the nasal spray vaccine) is also available.
• Groups recommended to receive 2009 H1N1 vaccine first are:Groups recommended to receive 2009 H1N1 vaccine first are:
1.1. Pregnant womenPregnant women •
2.2. People whoPeople who livelive with orwith or care for infants younger thancare for infants younger than 66 monthsmonths of age.of age.
3.3. Health careHealth care andand emergencyemergency medical personnelmedical personnel..
4. Anyone from 6 months through 24 years of ageAnyone from 6 months through 24 years of age
5. Anyone from 25 through 64 years of age withAnyone from 25 through 64 years of age with certain chronic medicalcertain chronic medical
conditionsconditions or a weakened immune system.or a weakened immune system.
• (VIDEO-4)(VIDEO-4)
24. Problems of VaccinationProblems of Vaccination
Mild problemsMild problems:
• • Soreness, redness, tenderness, or swelling where the shot
was given
• FaintingFainting (mainly adolescents) • HeadacheHeadache, muscle aches •
fever • nausea.
If these problems occur, they usually begin soon after the
shot and last 1-2 days.
Severe problemsSevere problems:
• • Life-threatening allergic reactionsallergic reactions to vaccines are very rare.
If they do occur, it is usually within a few minutes to a few
hours after the shot.
• Some inactivated 2009 H1N1 vaccine contains a preservative
called thimerosalthimerosal to keep it free from germs. Some people
have suggested that thimerosal might be related to autism.
• (VIDEO-5) & (VIDEO-6)(VIDEO-5) & (VIDEO-6)..
25. • How you can protect yourself andHow you can protect yourself and
your family From H1N1 Flu byyour family From H1N1 Flu by
Natural ProductsNatural Products ??
26. 1. Colloidal Silver Solution1. Colloidal Silver Solution..
• Colloidal Silver appears to be a powerful, natural antibiotic and
preventative against infections.
• The presence of colloidal silver near a virus,
fungus, bacterium or any other single celled
pathogen disablesdisables its oxygen metabolismoxygen metabolism
enzymeenzyme, its chemical lung, so to say.
• Within a few minutes, the pathogen suffocatessuffocates
and dies, and is cleared out of the body by the
immune, system.
• Long term use may lead to renal failure and irreversible
Blue pigmentation of skin.
28. OurOur RecommendationRecommendation::
(Anti flu syrupAnti flu syrup)
• One tea sp.f. fresh Nigella sativaNigella sativa.
• One tea sp.f. fresh GingerGinger.
• Add hot water to make infusate.
• Sweeten it with one table sp.f. Natural HoneyNatural Honey
• Add lemonelemone juice.
** To be taken once or twice dailyTo be taken once or twice daily..