Pharmacology

Front 1

Neuraminidase Inhibitors
Mech?

Back 1

Zanamivir, Oseltamivir (active carboxylate metabolite in liver). Inhibit NA enzyme which catalyzes release of progeny particles from their sialic acid cell anchors. Limit infection to one round of replication. Zanamivir (ITN) better than oselta (per os). Effective against Influenza A,B & H1N1.

Front 2

Amantadine
Mech?

Back 2

Inserts into M2 ion channels preventing viral genetics' release therefore preventing viral uncoating. Active against Influenza A.

Front 3

Amantadine.
PKs?

Back 3

1. Oral absorption is good
2. Renal elimination mainly
3. half-life 16hrs

Front 4

Amantadine.
SEs?
Resistance?

Back 4

1.CNS (cause release of dopamine), nervousness, sedation, sleepiness.
2. Nausea, vomiting, loss of appetite

changes to AAs in matrix of virus lead to resistance.

Front 5

Acyclovir
Mech?

Back 5

1. acycloguanosine nucleotide derivative
2. phosphorylated preferentially by viral thymidine kinase (3Ps)
3. tri-phosphate form inhibits DNA polymerase

spectrum: HSV-1,-2, Epstein-Barr, Vericella-Zoster (chicken pox)

Front 6

Acyclovir
PKs?

Back 6

1. Oral absorption is 13-21%
2. Elimination renal
3. half-life 4hr

Valacyclovir more absorption (54%), prodrug: converted by liver esterases to acyclovir

Front 7

Acyclovir
SEs?
Resistance?

Back 7

1. Reversible renal dysfunction (crystal nephropathy; drink lots of water)
2. i.v. can cause thrombophilibitis
3. neurotoxicity: lethargy, seizures, confusion

Resistance by low production of thymidine kinase, and change to DNA polymerase.

Front 8

Gancyclovir
Mech.

Back 8

1. monophosphate by cellular deoxyguanisine kinase, and further to tri-p by kinases in cytomegalovirus infected cell

spectrum: HSV-1,-2, Vericella Zoster, Epstein Barr, Cytomegalovirus

Front 9

Gancyclovir
SEs?

Back 9

1. crystal nephropathy reversible
2.i.v. can cause throbophlibitis
3. Neurotoxicity: lethargy, confusion, seizures
4. neutropenia, thrombocytopenia

Front 10

NRTIs - Zidovudine
Mech?

Back 10

tri-phosphorylated by cellular kinases, and this blocks Reverse Transcriptase (RT)

Front 11

NRTIs - Zidovudine
PKs?

Back 11

1. Oral absorption 60%
2. Good penetration to tissues
3. Liver metabolism
4. half life 1.1hrs

Front 12

NRTIs - Zidovudine
SEs?
Resistance?

Back 12

1. Nausea/vomiting
2. Neutropenia/Anemia
3. headache/insomnia

RT mutations lead to resistance.

Front 13

NNRTIs - Efavirenz
Mech?

Back 13

non competitive binding to RT leads to conformational change

Front 14

NNRTIs - Efavirenz
PKs?

Back 14

1. Oral absorption increased with fatty meals
2. liver metabolism
3. half life 50 hrs

Front 15

NNRTIs - Efavirenz
SEs?
Resistance?

Back 15

1. Rash and hepatotoxicity
2. CNS; vivid dreams, insomnia, difficulty concentrating

Resistance occurs

Front 16

Protease inhibitors - Saquinavir
Mech?

Back 16

targets processing machinery of proteins. Viral enzymes and proteins are made as a poly-protein

Front 17

Protease inhibitors - Saquinavir
PKs?

Back 17

1. Oral absorption 4%, increased with food (1800%)
2. hepatic metabolism (CYP3A4)
3. often given with ritanovir to increase levels and decrease resistance

Front 18

Protease inhibitors - Saquinavir
SEs?
Resistance?

Back 18

1. Diarrhea and abdominal pain
2.hyperlipidemia (on the back)
3. well tolerated generally

Some resistance by protease mutations