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Pharmacology Semester II > Exam III Antivirals > Flashcards

Exam III Antivirals Flashcards

1
Q

What are Viruses?

A

Microscopic parasite that replicates inside another organism’s cells.

3 structural parts

Nucleic acid (RNA or DNA)

Protein Coat - Protects genetic material

Envelope - Fatty protective shield, liposomal surface of the cell

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2
Q

Steps of Viral replication

A
  1. Attachment and entrance
  2. Synthesis of proteins
  3. Assembly of new Virus
  4. Release of new virus particles

Repeat

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3
Q

Antiviral Agent MOA

A

Antivirals are virustatic, toxic to host cell, most effective against rapidly replicating virus, not effective against a latent virus.

Locations of action

Block at Vitral attachment/entrance

Blocked while attempting penetration

Blocked from uncoating

Block Nucleic Acid synthesis

Blocked Late protein synthesis

Blocked Packaging/assembly

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4
Q

Influenza Virus

A

Causes acute respiratory illness

3 types

Influenza A

  • Most common*
  • Most pathogenic (epidemics)*
  • Different subtypes (based on surface antigen H/N etc)*

Influenza B

Influenza C

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5
Q

Special considerations regarding Influenza Drugs

A

Pregnancy

Oseltamivir

Children

Oseltamivir - Any age for treatment/ >3month old for prevention

Zanamivir: treatment > 7y.o. / prevention > 5y.o.

Peramivir: treatment > 2y.o.

Baloxavir: treatment > 12 y.o.

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6
Q

Herpesvirus Family

A

Large Family of DNA viruses

HHV-1: Herpes Simplex Virus 1 (HSV 1) -> Oral Lesions

HHV-2: Herpes Simplex Virus 2 (HSV 2) -> Genital Lesion

HHV-3: Varicella Zoster Virus (VZV) -> Chicken Pox / Shingles

HHV-4:Epstein-Barr Virus (EBV) -> mononucleosis/ lymphoma

HHV-5: Cytomegalovirs (CMV)

HHV6a/6b/7: Roseolavirus

HHV-8: Kaposi’s Sarcoma

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7
Q

HHV: Antiviral agents

A

Nucleoside Analogs

Synthetic analogs of pyrimidines and purines -> inhibit viral replication

Competitive inhibition of DNA polymerase

Incorporation and termination of viral DNA chain

Inactivation of DNA Polymerase

Miscellaneous agents

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8
Q

Amantadine

A

Used for Prevention/treatment of Flu A - If started within 48 hours shortens duration of symptoms by half.

MOA - Blocks viral particle uncoating and nucleic acid release into host cell -> inhibits viral replication

50-90% excreted unchanged in urine

Half-life 16-17 Hrs

Dose: 200mg/day or 100mg bid x3-5 days, initiate within 48 hrs of symptom onset - 100mg PO daily in elderly PTs - D/C within 24-48 Hrs of symptom resolution

Pregnancy - Cat C avoid in breastfeeding

Monitor SCr at baseline

Used in Parkinsons - Crosses BBB -> increases CNS dopaminergic response

CDC recommends against use in Flu A in the US due to high level of amantadine resistance among currently circulating strands.

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9
Q

Rimantadine

A

Treatment and prophylaxis of Flu A

MOA: Inhibits Viral uncoating and replication

Excreted in Urine

Half-Life: 25 Hrs, longer in PTs > 70 y.o., 50 Hrs in PTs w/ severe hepatic impairment

Dose: 100mg bid x3-5 days, initiate within 48 Hrs of Symptom onset - 100mg PO in elderly PTs - D/C within 24/48 Hrs of symptom resolution

Pregnancy: Cat C avoid use in Breastfeeding

Monitor: SCr at baseline/ LFTS

Available in Tabs or Syrup

CDC recommends against use in Flu A in the US due to high level of rimantadine resistance among currently circulating strands.

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10
Q

Currently used Influenza Drugs

A

Oseltamivir (tamiflu)

Zanamivir (Relenza)

Peramivir (Rapivab)

Indicated for treatment and prevention of Flu A & B (Peramivir only for treatment)

MOA: Inhibits neuraminidase of Flu A&B -> Prevents release of virions from the host cell and prevents entry into the cell.

Bolaxavir marboxil (Xofluza)

Newest Flu A&B drug.

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11
Q

Osetamivir

A

Prodrug: Converts to oseltamivir carboxylate

99% eliminated in Urine

Half-Life: 6-10 Hrs

Dose:

  • Treatment - 75mg PO BID x5 days (may extend in immunocompromised)*
  • Prophylaxis - 75mg PO QD w/ in 48 hours of exposure, give throughout exposure period and x7 days after last known exposure.*
  • Renal Adjustments required*

Pregnancy: Drug of choice for Flu treatment - Safe for Breastfeeding

Available in Cap, Susp and Generic

>98% of currently circulating Flu virus in US is Oseltamivir-susceptible

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12
Q

Zanamivir

A

Administered via oral inhaler

    • Co-administer w/ bronchodilator*
    • Do not reconstitute in liquid or nebulize*

Eliminated unchanged in Urine

Half-Life: 2.5-5 Hrs, 19 Hrs in severe Renal impairment

Dose:

  • Treatment: 10mg (2puffs) inhaled Q12 x 5days - Start within 48 Hrs of onset*
  • Prophylaxis: 2 puffs inhaled QD (duration dependent on setting)*

Avoid in milk allergy -> contains milk proteins as vehicles

Caution if asthma/COPD

>99% of currently circulating Flu virus in US

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13
Q

Peramivir

A

Available as IV -> requires admin by health care provider

Eliminated primarily unchanged in Urine

Half-Life: 20 Hrs

Dose:

  • 600mg IV x 1 w/in 48 Hrs of onset*
  • CrCl < 50ml/min -> requires adjustment*
  • Administer over 15-30 min*

Monitor: renal function at baseline

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14
Q

Baloxavir Marboxil

A

FDA approved OCT 2018

MOA: Inhibits viral polymerase acidic protein endonuclease activity -> inhibits viral replication

Excreted mostly in feces

Half-Life: 80 Hrs

Dose:

  • 40-79kg: 40mg PO x1*
  • >80kg: 80mg PO x1*
  • Start w/in 48 Hrs of onset*

Separate from dairy products and calcium-fortified beverages

Cost - $150

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15
Q

Trifluridine

A

Indicated in ocular HSV (HSV Keratoconjunctivitis and epithelial keratitis)

Dose 1 GTT in eye Q2H while awake (max 9GTT/Eye/Day) x 21 days

Ophthalmic solution

Negligible systemic absorption

Refrigeration required

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16
Q

Cidofivir

A

Only indicated for treatment of CMV retinitis in AIDs PTs (Not 1st line agent)

Has active metabolite

Eliminated 80-100% unchanged in urine

Half-Life:

  • Parent drug - 3Hrs*
  • Active Metabolite - 17 Hrs*

Dose:

  • Induction 5mg/kg IV weekly x 2 Weeks*
  • Maintenance 5mg/kg IV Q2 Weeks*

PT needs to be hydrated and co-administer probenecid

Monitor: SCr, Urine protein w/in 48 Hrs before each dose, WBC w/diff before each dose.

Black box warning: renal impairment (resulting in HD), neutropenia, carcinogen/teratogen

17
Q

Acyclovir

A

Indicated for HSV, VZV, CMV (limited), EBV (Limited)

Only effective against actively replicating virus -> not effective against latent virus

Eliminated in Urine

Half-Life: 2-3 Hrs

Multiple formulations - IV (hydrate), Oral, Topical

Dosing: Varies based on stage of disease

Poor bioavailability

Monitor renal function

18
Q

Valacyclovir

A

Prodrug of acyclovir -> better availability

Indicated in HSV/VZV

Oral formulation only

Dosing depends on stage of disease (less frequent than acyclovir 1-2 QD)

Monitor SCr at baseline

DO NOT CONFUSE with Valcyte/Keflex

19
Q

Famciclovir

A

Indicated in prevention and treatment of HSV/VZV infections

Prodrug of penciclovir

Eliminated primarily in Urine

Half-Life: HSV-1: 10 Hrs, HSV-2: 20 Hrs, VZV: 7 Hrs

Dose

  • TID-BID (bioavailability is > acyclovir)*
  • Dose is dependent on stage of disease*

Monitor SCr

20
Q

Penciclovir

A

Indicated in recurrent herpes labialis

Active metabolite of famciclovir

Available as topical formulation only

Dose:

Apply Q2H while awake x4 days

21
Q

Valganciclovir

A

Indicated in prevention and treatment of CMV infections

Prodrug of ganciclovir

Eliminated Renally

Half-Life: 4 Hrs (intracellular 18 Hrs)

Dose:

  • Available as Oral formulation only*
  • Caries based on disease*
  • Administer w/food*

Monitor: SCr / pregnancy test / CBC w/diff

22
Q

Ganciclovir

A

Indicated in treatment and prevention of CMV infections

Acyclovir Analog

Eliminated in Urine

Half-Life: Oral - 5 Hrs, IV - 3.5 Hrs

Dose:

  • IV admin*
  • Administer slowly in large peripheral or central vein*
  • HYDRATE -> renal toxic*

Monitor: SCr/Pregnancy test/CBC/ platelets

23
Q

Foscarnet

A

MOA: inhibits viral specific DNA polymerases -> prevents DNA synthesis

Does not require activation by kinases -> effective for HSV deficient in kinases

Indicated in prevention and treatment of CMV, treatment of HSV/VZV

Effective in acyclovir-resistant HSV/VZV

Eliminated in Urine

Half Life: 3-4 Hrs (plasma), 45-130 Hrs (terminal)

Dose:

  • IV formulation only*
  • Requires Hydration*

Monitor: SCr/Electrolytes/CBC w/diff/ ECG

Pharmacology Semester II (21 decks)

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