Drugs COPY Flashcards
sad sad sad time
Amphotericin B
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
Nystatin
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
AE: -Nephrotoxicity is the major side effect.
● Adequate hydration status may decrease toxicity.
-Idiosyncratic hypotension and arrhythmias
● Test doses
-Electrolyte disturbances
● K+ , Mg++
-Fever, chills, and rigors
Clinical use: -Systemic fungal infections
Fluconazole & voriconazole
Antifungal
Azole
MOA: inhibit ergosterol synthesis;
Fluconzaole:
Drug interactions occur
Active against candida albicans
Voriconazole:
Major drug interactions through inhibition of mammalian cytochrome p450
● This is also the case with Itraconazole
Aspergillus- active against
- Very potent inhibitor of cytochrome p450
Capsofungin
Antifungal
Class: Echinocandins
MOA: beta-(1,3)-glucan inhibitor. Beta-(1,3)-glucan is an integral part of the fungal cell wall
Terbinafine
Antifungal
-blocks squalene epoxidase
AE: Liver function abnormalities, hepatitis
Isoniazid (INH)
Antituberculosis
MOA: Inhibition of synthesis of mycolic acid in cell wall
INH is a prodrug
- Catalase/peroxidase enzyme (katG) metabolizes isoniazid to active form in cell
- Strains which fail to metabolize isoniazid due to defective catalase/peroxidase are resistant to isoniazid
Metabolism:
◦ Metabolized in the liver by N-acetyl transferase. Rate of acetylation is genetically determined as an autosomal recessive trait. Does not alter therapy clinically except for weekly administration schedules.
Clinical use:
1) Treatment of latent tuberculosis (positive PPD without active disease)
2) Combination therapy for active TB at any stage
AE:
Hepatitis
◦ Can occur at any time but peak incidence is within the first 4-8 weeks. Hepatic failure can ensue and lead to death if drug is continued.
Neurotoxicity
◦ is mediated by increased excretion of pyridoxine and concomitant administration of B6 is always given when INH is used
Rifampin
Antituberculosis
MOA: Inhibits DNA dependent RNA polymerase of mycobacterial cells. Human enzyme is insensitive to effects of the drug.
(RNA-DNA polymerase= RNA reverse transcriptase)
MOR: Alteration of DNA-dependent, RNA polymerase, (rpoB).
Absorption:
◦ Excellent oral absorption; wide distribution, including CNS.
Metabolism
◦ Hepatic via cytochrome P-450 (deacylation). Induces its own increased metabolism.
AE:
Hepatotoxicity generally manifests as cholestatic changes ( increased Alk. Phos., increased bili) but can also be necroinflammatory with elevated transaminases. INH and rifampin may potentiate hepatotoxicity of the other agent.
Major major drug interactions!!!
Increased metabolism of coumarin, oral contraceptives, and phenytoin may occur. Interaction with verapamil causes marked reduction in verapamil levels.
Pyrazinamide
Antituberculosis
MOA: Inhibition of fatty acid synthesis
-converts drug to pyrazinoic acid at acid pH
-prodrug
MOR: unknown
AE:
Hepatotoxicity / Hepatitis
Gout - drug can cause elevated uric acid levels causing gout
Ethambutol
Antituberculosis
MOA:
Possibly interferes with arabinosyl transferase, an enzyme that polymerizes arabinose into arabinan
MOR:
Mutations in the gene cluster but not a specific target identified
AE: Retrobulbar neuritis(optic neuritis) ◦ Usually develops as decreased acuity and change in color vision (yellow and green).
Associated with high doses.
Peripheral neuropathy can also occur.
Acyclovir
Antivirals: Herpes
MOA:
Chain termination: removal of acyclovir triphosphate addition
-Acyclovir triphosphate is present in 40-100 fold higher concentrations in HSV infected cells. The triphosphate form inhibits DNA polymerase and is incorporated into viral DNA as function as a chain terminator.
Most commonly used:
Valacyclovir
Maraviroc
Anti HIV
MOA:
CCR5 Chemokine Receptor Antagonist
Enfuvirtide
Antiviral: HIV
-MOA:
binding a region of the HIV envelope glycoprotein gp41 and preventing viral fusion with the target cell membrane
- Formulation: Polypeptide
- SQ twice daily
Zivodudin
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance; since low fidetly, environment is highly favorable to resistance
Zidovudine: Myeolosuppression
Abacavir: rash (fatal)
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Abacavir
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance
Abacavir: Rash (fatal) Hypersensitivity reactions Check for HLA-B*5701 Increased risk of cardiac sx
Emtricitabine: Rash (mild) [MOST COMMONLY USED]
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Emtricibatine
- Anti HIV
- Nucleoside Reverse Transcriptase Inhibitors
MOA:
Inhibition of viral RNA-dependent DNA polymerase: Nucleoside triphosphates competitively inhibit reverse transcriptase also inhibits cellular alpha-DNA polymerase 100-fold less avidly.
Incorporation of the triphosphate into the chain leads to chain termination.
MOR: Single nucleotide change can confer resistance
Emtricitabine: Rash (mild) [MOST COMMONLY USED]
Class toxicities:
- Lactic acidosis/hepatic steatosis
- Probably responsible for lipodystrophy
Prone to fidelity
Tenofovir
Anti HIV
Nucleotide RTI
Already monophosphorylated
problems with renal toxicity (disoproxil»_space; alafenamide)
New tenofovir alafenamide formulation has less renal toxicity
Major toxicities include abnormalities of calcium and phosphate, increased bone fragility, and renal dysfunction.
Efavirenz
Anti HIV
Non-nucleoside Reverse Transcriptase Inhibitors:
MOA: Work on RT at a site distinct from the active site (These drugs do NOT look like nucleoside analogs)
[Inhibits reverse transcriptase]
AE: CNS effects , Variable p450 activity
Raltegravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
AE:
Raltegravir:
First integrase inhibitor
Very few side effects - myositis
Not metabolized by CYP3A (cytochrome p450)
Better tolerated, higher CD4 counts, few adverse effects, lower lipids than efavirenz containing regimens.
Can now be recommended as first line therapy
Elvitgravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
Elvitegravir: Part of quad pill
Dolutergravir
Anti HIV
-Integrase inhibitors
MOA: Cornerstone of therapy for HIV
Dolutegravir: can be used in less than three drug regimens; requires more than 1 mutation to receive full resistance
Dolutergravir: once daily
Ritonavir
Anti HIV:
Protease inhibitor
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
Ritonavir:
-GI intolerance, almost exclusively used to “boost’ other drugs
-Boosting: Ritonavir is very potent CYP3A inhibitor
Given with other protease inhibitors not for its HIV protease activity, given to increase both drug level and half-life of co-administered PI
Boosting: boost serum level and half life; given in combination with other protease inhibitors
Cobicistat
Anti HIV:
Protease inhibitor
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
Cobicistat:
- protease enhancer
- A pharmacoenhancer
- An analogue of ritonavir but devoid of HIV protease activity
- Drug is metabolized by CYP3A and the metabolite irreversibly inhibits CYP3A
- NEITHER inhibit ALL
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
Darunavir
MOA: The major viral genes gag and gag-pol are transcribed as polyproteins requiring several proteolytic cleavages for viral proteins to be produced. l
The HIV protease is an aspartyl peptidase (Renin is an aspartyl peptidase) which has very specific cleavage site in the HIV polypeptide.
PI: Adverse effects- The agents differ individually but all share a variable and potent inhibition of the cytochrome p450 system. The drugs are also metabolized via p450.
