MicroB Antimicrobials Anti-Viral Agents Flashcards
2 examples of entry inhibitors and their mechanisms
- […] - chemokine receptor antagonist. binds to host cell […] coreceptor, blocking binding of viral gp120.
- […] - inhibits fusion of viral and cell membranes mediated by gp41 and CD4 interactions
2 examples of entry inhibitors and their mechanisms
- Maraviroc - chemokine receptor antagonist. binds to host cell CCR5 coreceptor, blocking binding of viral gp120.
- Enfuvirtide - inhibits fusion of viral and cell membranes mediated by gp41 and CD4 interactions
Therefore for Maraviroc, it’s only useful for HIV strains that express preference for CCR5. HIV strains can alternatively express preference for CXCR4, or both (dual tropic)
THEREFORE NEED TO TEST PATIENT FOR TROPISM
And since we are here, resistance to entry inhibitors can develop via a shift in tropism or due to gp120 mutations (allow virus binding even in presense of Maraviroc entry inhibitor)
3 examples of HIV Protease Inhibitors
1. Darunavir
2. Lopinavir
3. Atazanavir
It is used with combination with PK boosters, which increases the T1/2 of the above drugs (by being substrates and inhibiting […])
1. […]
2. Cobicistat
3 examples of HIV Protease Inhibitors
1. Darunavir
2. Lopinavir
3. Atazanavir
It is used with combination with PK boosters, which increases the T1/2 of the above drugs (by being substrates and inhibiting CYP450)
1. Ritonavir
2. Cobicistat
“Mn- CaRd”
5 examples of NRTIs are mnemonic “TEALZ”
1. T[…]
2. E[…]
3. A[…]
4. L[…]
5. Z[…]
The 3 that are effective for Hep B are […]
The 2 that are both cytosine analogues are […]
- Therefore DO NOT co-administer!! common sense lol
Recall that 2 NRTIs are required to form the backbone of a fully suppressive antiretroviral regimen!
5 examples of NRTIs are mnemonic “TEALZ”
1. Tenofovir (A) (TDF & TAF)
2. Emtricitabine **(C)
3. Abacavir** (G)
4. Lamivudine (C)
5. Zidovudine (T)
The 3 that are effective for Hep B are ETsL
The 2 that are both cytosine analogues are* E&L*
- Therefore DO NOT co-administer!! common sense lol
Recall that 2 NRTIs are required to form the backbone of a fully suppressive antiretroviral regimen!
TEALZ, analogous to ACGCT nucleotides
Z not bolded cuz not important~
FYI, L least toxic.
Acyclovir, ganciclovir and valganciclovir are eliminated via […].
Acyclovir, ganciclovir and valganciclovir are eliminated via renal route.
90%!!!!
THEREFORE be careful NOT TO GIVE PATIENTS WITH RENAL FAILURE
adverse effects of ganciclovir and valganciclovir
1. […]
2. GIT-related: diarrhea, nausea, vomiting
3. irreversible aspermatogenesis at high dose
4. potential mutagenicity and carcinogenesis
adverse effects of ganciclovir and valganciclovir
1. myelosuppression (particularly neutropenia)
2. GIT-related: diarrhea, nausea, vomiting
3. irreversible aspermatogenesis at high dose
4. potential mutagenicity and carcinogenesis
“Myelosuppression is condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets”
Adverse effects of HIV protease inhibitor (TRIPLE H!!!)
1. GI disturbance (nausea, vomitting and diarrhea)
2. […]
3. […]
4. […]
5. Fat maldistribution (eg. fat loss from extremities) (when drug is used chronically)
6. Skin rashes
7. Pregnancy: Category C Darunavir, Lopinavir
8. Category B Ritonavir
Adverse effects of HIV protease inhibitor (TRIPLE H!!!)
1. GI disturbance (nausea, vomitting and diarrhea)
2. Hyperglycaemia
3. Hyperlipidemia
4. Hyperbilirubinemia (Hepatic injury)
5. Fat maldistribution (eg. fat loss from extremities) (when drug is used chronically)
6. Skin rashes
7. Pregnancy: Category C Darunavir, Lopinavir
8. Category B Ritonavir
Lots of adverse effects because of their effects on the liver (being substrates and inhibitors for CYP450)
not clozed means familiarize but dont memorize. study smart!!!
Anti HHV agents and their mechanisms
-
Acyclovir/ Valacyclovir(prodrug version)
- it is a acyclic […] nucleoside analogue that is phosphorylated by viral thymidane kinase to acyclovir monophosphate and then by host enzymes to acyclovir triphosphate
- stops replication in herpes by […] or […]ly inhibiting viral DNA polymerase, or […] the DNA chain
- for […], […], […], some EBV(HHV4)-mediated infections
- Accumulates in patients with […] failure (precaution: give drug slowly over 1h or more, ensure adequate hydration)
- Valacyclovir has greater oral […] than acyclovir -
Ganciclovir/ Valganciclovir(prodrug version)
- Also a acyclic […] nucleoside analogue, ganciclovir diphopshate and triphosphate are formed by cellular enzymes.
- competitively inhibits […] for incorporation into DNA, preferentially inhibits viral rather than host cellular DNA polymerase :”))
- causes […] of DNA elongation
- for all herpes virus, but esp […] (IMPT!!!)
- Over 90% is eliminated unchanged by renal excretion through glomerular filtration and tubular secretion. Consequently , it accumulates in patients with severe […] insufficiency
Anti HHV agents and their mechanisms
-
Acyclovir/ Valacyclovir(prodrug version)
- it is a acyclic guanine nucleoside analogue that is phosphorylated by viral thymidane kinase to acyclovir monophosphate and then by host enzymes to acyclovir triphosphate
- stops replication in herpes by inactivating or* competitively inhibiting viral DNA polymerase, or *terminates the DNA chain
- for HSV1, HSV2, HHV3 (VZV), some EBV(HHV4)-mediated infections
- Accumulates in patients with renal failure (precaution: give drug slowly over 1h or more, ensure adequate hydration)
- Valacyclovir has greater oral bioavailability than acyclovir -
Ganciclovir/ Valganciclovir(prodrug version)
- Also a acyclic guanine nucleoside analogue, ganciclovir diphopshate and triphosphate are formed by cellular enzymes.
- competitively inhibits deoxyguanosine triphosphate for incorporation into DNA, preferentially inhibits viral rather than host cellular DNA polymerase :”))
- causes eventual cessation of DNA elongation
- for all herpes virus, but esp CMV (IMPT!!!)
- Over 90% is eliminated unchanged by renal excretion through glomerular filtration and tubular secretion. Consequently , it accumulates in patients with severe renal insufficiency
HSV 1 and 2 more effective in converting acyclovir than HHV3. therefore more effective on HSV1 and 2.
TLDR,
both guanine analogues
both inhibits DNA polymerase
both accumulates in kidney.
Acyclovir for HSV1-4, Ganciclovir for all but esp CMV
AntiRetroViral regimen (ARV) for a treatment-naive patient generally consists of 3 drugs:
1. […] in combination with
2. a 3rd active ARV drug
- […], or
- […], or
- […]
AntiRetroViral regimen (ARV) for a treatment-naive patient generally consists of 3 drugs:
1. two NRTIs in combination with
2. a 3rd active ARV drug
- Integrase inhibitor (INSTI), or
- Protease inhibitor (PI) with a PK enhancer, or
- NNRTI
NRTIs = nucleoside reverse transcriptase inhibitors
NNRTI = non nucleoside reverse transcriptase inhibitor i.e Efavirenz)
INSTI = integrase strand transfer inhibitor
Before Abacavir is administered, patients should be tested for […]!!!
- If patient is positive, giving Abaclavir will cause[…]
Before Abacavir is administered, patients should be tested for HLA B5701!!!
- If patient is positive, giving Abaclavir will cause Fatal hypersensitivity syndrome
Fatal hypersensitivity syndrome includes 2 or more of the following symptoms (fever, rash, GI or respiratory complications)
Classes of Anti HIV drugs
- […]
- […]
- […]
- […]
- […]
- […]
Classes of Anti HIV drugs
- Nucleoside reverse transcriptase inhibitors (NRTI)
- Non-nucleoside reverse transcriptase inhibitors (NNRTI)
- Protease inhibitors
- Integrase inhibitors
- inhibitors of HIV fusion with host cell
- Chemokine receptor antaganist (CCR5)
Most impt is NRTI. treatment always include 2 drugs from NRTI, addon drugs from other classes
Attach tons of diagrams cuz I OCD!!
Example of NNRTI drug:
1. […]
Example of NNRTI drug:
1. Efavirenz
Cannot dont know la cuz there is only 1 impt one lol
Failure of an antiretroviral regimen = persistent increase in plasma […] concentrations, despite continued treatment with that regimen.
Failure of an antiretroviral regimen = persistent increase in plasma HIV RNA concentrations, despite continued treatment with that regimen.
Integrase inhibitors work by binding and inhibiting the catalytic site of the […], terminating […] into the host genome.
3 examples of HIV Integrase inhibitors are
1. Dolutegravir
2. Elvitegravir
3. Raltegravir
Just familiarize can with the names can alr~
Integrase inhibitors work by binding and inhibiting the catalytic site of the HIV integrase, terminating **integration of HIV DNA **into the host genome.
3 examples of HIV Integrase inhibitors are
1. Dolutegravir
2. Elvitegravir
3. Raltegravir
Just familiarize can with the names can alr~
“Red the Gravir”
Like tetracyclines and fluoroquinolones, […] absorption in the gut is decreased by divalent, cations, antacids (chelation) and should be taken 2 hours before
Like tetracyclines and fluoroquinolones, Integrase Inhibitors absorption in the gut is decreased by divalent, cations, antacids (chelation) and should be taken 2 hours before
FOOD DRUG INTERACTIONS YO!
So now it has become….Wheels and flowers and integrase inhibitors dont go well with milk nor antacid nor iron supplements lol….
Long term toxicity of antiretroviral therapy.
1. […]
2. […]
Long term toxicity of antiretroviral therapy.
1. metabolic syndrome
2. HIV lipodystrophy syndrome
Main downside to NNRTI: […]
Main downside to NNRTI: low genetic barrier to resistance –> prone to drug resistance
should never be added as a sole agent to a failing regimen
Mechanism of
NRTI: […]
NNRTI: […]
Mechanism of
NRTI: competitive inhibitor of HIV-1 reverse transcriptase
NNRTI: NON-competitive inhibitor of HIV-1 reverse transcriptase
would be nice if sys pharm also this simple
MOA of HIV Protease Inhibitor:
Protease inhibitors bind to the […], hence preventing the production of […] from the […]
- HIV protease can no longer release individual core proteins
- New HIV particles unable to mature or become infectious :)
MOA of HIV Protease Inhibitor:
Protease inhibitors bind to the site where protein cutting occurs, hence preventing the production of viral proteins from the long multiprotein chain
- HIV protease can no longer release individual core proteins
- New HIV particles unable to mature or become infectious :)
For understanding: Viral proteins are produced as part of long multiprotein chain, which must be cut into smaller fragments by the enzyme protease in order to form mature, functional proteins. So if cannot cut, means….hehe.
NRTI drugs that have anti-Hep B effects:
[…]
NRTI drugs that have anti-Hep B effects:
Emtricitabine, Tenofovir, Lamivudine (ETL)
Mentioned in another card but high yield la so hehe
note that if you suddenly withdraw these drugs, patient’s Hep B can flare
- solution: reduce dosage slowly :)
Resistance in HIV Protease Inhibitors is less common because of high genetic barrier to resistance (contrast w Integrase inhibitors)
But that doesnt mean u give it alone lol. Still give in combination with other HIV drugs to achieve optimal suppression of HIV!!!
Start HAART therapy only when CD4+ count is below 350 cells/μl
HAART = highly active antiretroviral therapy
AIDS is when CD4+ is below 200 cells/μl
I dont think they test this directly, but if you write this in MEQs, its a bonus! :))
Tenofovir Disoproxil Fumarate (TDF) vs Tenofovir AlaFenamide (TAF)
- […] have more favourable effects on […] and […] markers (newer)
- Hence for patients with chronic kidney disease, the better choice is […]
If a patient with both HIV and HBV is being treated with TDF, sudden discontinuation of TDF leads to […]
Tenofovir Disoproxil Fumarate (TDF) vs Tenofovir AlaFenamide (TAF)
- TAF have more favourable effects on renal and bone markers (newer)
- Hence for patients with chronic kidney disease, the better choice is TAF
If a patient with both HIV and HBV is being treated with TDF, sudden discontinuation of TDF leads to severe acute exacerbation hepatitis
