TB, Anti-fungals, Anti-viral Charts Flashcards by Stephanie Davison

What is the MOA of Isoniazid

inhibits cell wall synthesis (mycolic acid)
-bactericidal
[intracellular]

How well did you know this?

Not at all

Perfectly

What is the absorption and metabolism of isoniazid

well absorbed orally

- metabolized by acetylation (fast and slow acetylators)

How well did you know this?

Not at all

Perfectly

What is the spectrum of Isoniazid

Tuberculosis

How well did you know this?

Not at all

Perfectly

What are the adverse reactions of Isoniazid

Allergic rxns
Hepatotoxicity (fast acetylators)
Neuritis (slow acetylators)-> tx w/ vit. B6 (pyridoxine)
Insomina

How well did you know this?

Not at all

Perfectly

The primary reason for the use of drug combinations in the treatment of tuberculosis is to:
A.  Reduce the incidence of adverse effects
B.  Enhance activity against metabolically inactive mycobacteria
C.  Ensure patient compliance with the drug regimen
D.  Delay of prevent the emergence of resistance
E.  Provide prophylaxis against other bacterial infections

D.  Delay of prevent the emergence of resistance

How well did you know this?

Not at all

Perfectly

Initial therapy for active TB is typically

Initial therapy 2 months: “RIPE”

Rifampin + INH (isoniazid) + PZA (pyrazinamide) + Ethambutol

How well did you know this?

Not at all

Perfectly

Multidrug therapy is recommended for most mycobacterial infections. However, which of the following may be treated with a single drug?
A.  Disseminated M. avium complex infections
B.  Latent TB infections
C.  Leprosy
D.  Systemic tuberculosis
E.  None of the above

What is the drug that can be used?

B.  Latent TB infections

Isoniazid

How well did you know this?

Not at all

Perfectly

How do you treat latent TB infection

Isoniazid daily or 2x week DOT [6-9months]

OR if INH sensitive:
Isoniazid + pyridoxine (vit. B6 for 9 months

How well did you know this?

Not at all

Perfectly

A 24-year-old patient receiving combination therapy for the treatment of tuberculosis becomes pregnant, although she had been using oral contraceptives (estrogen + progestin). Which of the following drugs is responsible for the interfering with the contraceptive action, resulting in medication failure?
A.  Ethambutol
B.  Isoniazid
C.  Pyrazinamide
D.  Rifampin
E.  Streptomycin

D.  Rifampin

How well did you know this?

Not at all

Perfectly

How do you treat active TB in someone who is pregnant

INH + Rifampin + ethambutol (+ pyrazinamide if co-infected w/ HIV or suspected drug resistance)

How well did you know this?

Not at all

Perfectly

Which statement about the use of isoniazid (INH) in the treatment of TB is FALSE?
A.  INH is bactericidal against actively growing tubercle bacilli
B.  Native Americans are fast acetylators and may require higher doses
C.  Symptoms of peripheral neuritis may occur during treatment
D.  INH may induce the metabolism of certain drugs
E.  Patients should take pyridoxine (vitamin B6) daily

D.  INH may induce the metabolism of certain drugs

How well did you know this?

Not at all

Perfectly

Mycolic acids are major components of mycobacterial cell walls. Which of the following drugs inhibits the synthesis of this component? 
A.  Ethambutol 
B.  Isoniazid 
C.  Pyrazinamide 
D.  Rifampin 
E.  Streptomycin

B.  Isoniazid

How well did you know this?

Not at all

Perfectly

What is the MOA of rifampin

-inhibition of RNA polymerase
-bactericidal
[intracellular]

How well did you know this?

Not at all

Perfectly

What is the absorption and elimination of rifampin

well absorbed orally

- hepatobillary excretion (DQCRIMES)

How well did you know this?

Not at all

Perfectly

What is the spectrum of rifampin

Tuberculosis
Gram positive cocci
Gram negative rods: pseudomonas, H. influenza, Legionella
Anerobes
Atypicals: mycoplasma, chlamydia

How well did you know this?

Not at all

Perfectly

What are adverse reactions of rifampin

Hepatotoxic
Colors secretions orange/red (urine, sweat, tears, permanent staining of contact lenses)
INDUCER of CYP1A2, 2C9-19, 3A4

How well did you know this?

Not at all

Perfectly

Select the FALSE statement concerning rifamycin antibiotics:
A.  Rifampin can be used as chemoprophylaxis in close contacts of patients with meningococcal disease
B.  Rifapentine can be given once weekly for treatment of active TB infections
C.  Rifabutin is a weaker inducer of CYP450 and is preferred over rifampin for TB treatment in HIV patients on HAART
D.  Rifamycins are inhibitors of DNA-dependent RNA polymerase
E.  Rifamycins are bacteriostatic against M. tuberculosis

B.  Rifapentine can be given once weekly for treatment of active TB infections

E.  Rifamycins are bacteriostatic against M. tuberculosis

How well did you know this?

Not at all

Perfectly

What is the MOA of pyrazinamide

uncertain
[intracellular]
-basteriostatic

How well did you know this?

Not at all

Perfectly

Describe the absorption, distribution and elimination of pyrazinamide

well absorbed orally
widely distrubted (100% to CNS)
hepatic metabolism

*dosage reduction required in both renal and hepatic impairment

How well did you know this?

Not at all

Perfectly

What is the spectrum of pyrazinamide

Tuberculosis

How well did you know this?

Not at all

Perfectly

What are adverse reactions of pyrazinamide

Hepatotoxicity
Hyperuricemia–> gout
Drug rash
Avoid in children unless crucial to therapy

How well did you know this?

Not at all

Perfectly

What is the MOA of ethambutol

inhibits cell wall synthesis (arabinosyltransferase)

- bacteriostatic

How well did you know this?

Not at all

Perfectly

Describe the absorption, distribution and elimination of ethambutol

well absorbed orally
concentrates in lungs
renal and fecal excretion

How well did you know this?

Not at all

Perfectly

What are adverse reactions of ethambutol

Optic neuritis (visual acuity reduction, retinal damage)

2. Avoid in children bc of difficulty monitoring visual acuity

How well did you know this?

Not at all

Perfectly

``` A 34-year-old male has returned to the for his 1-month check-up after starting treatment for tuberculosis. He is receiving isoniazid, rifampin, ethambutol, and pyrazinamide. He states that he feels fine, but now is having difficulty reading his morning newspaper and feels he may need to get glasses. Which of the TB drugs may be causing his decline in vison? A.  Ethambutol B.  Isoniazid C.  Pyrazinamide D.  Rifampin ```

A.  Ethambutol

``` A 27-year-old male, former heroin user, has been on methadone maintenance for the past 13 months. Two weeks ago he had a positive TB skin test (PPD) and chest radiograph evidence of upper lobe infection. He was started on standard 4 drug antimycobacterial therapy. He has come to the ED complaining of “withdrawal symptoms” and seeking more methadone. Which of the following antimycobacterial drugs is likely to have caused the patient’s acute withdrawal reaction? A.  Ethambutol B.  Isoniazid C.  Pyrazinamide D.  Rifampin E.  Streptomycin ```

D.  Rifampin *to prevent w/drawal == Rifabutin?

What are polyene detergents antifungal agents?

1. amphotericin B | 2. Nyastatin

What are Imidazole antifungal agents

1. Ketoconazole 2. Clotrimazole 3. Miconazole

What are Triazole antifungal agents

1. fluconazole | 2. itraconazole

What are allylamine antifungal agents

Terbinafine

How do you treat dermatophyte fungal infections (cutaneous mucocutaneous)

1. Generally conservative with use of topical antifungal agents (clotrimazole, miconazole, terbinafine)

How do you typically treat fungal nail infections

- generally requires systemic therapy | - Itraconazole or terbinafine

How do you treat Candida (esp. albicans)

1. Topical clotrimazole or nystatin for mucocandidiasis 2.  Try fluconazole via systemic (oral) route if no response

How do you treat systemic fungal infections? | [Blastomycosis, Coccidioidomycosis, Cryptococcosis, Histoplasmosis]

1. Long term therapy with systemic amphotericin B infusions generally required

How do you treat opportunistic systemic fungal infections? | [Candida albicans, Aspergillus fumigatus, Pneumocystis carinii]

1. Candidiasis: Fluconazole 2. Aspergillosis: Amphotericin B 3. Pneumocystis pneumonia: TMP-SMX

___ are the most broad ABX and can cause fungal infections

Tetracyclines

``` Interactions between this drug and cell membrane components can result in the formation of pores lined by hydrophilic groups present in the drug molecule: A.  Fluconazole B.  Amphotericin B C.  Itraconazole D.  Nystatin E.  Ketoconazole F.   Terbinafine ```

B.  Amphotericin B D.  Nystatin

What is the MOA of amphotericin B and nyastatin

- binds to ergosterol, forming pores in membranes with loss of vital intracellular constituents - fungicidal

What is the absorption and elimination of amphotericin B and nyastatin

- poor oral: IV or topical only - slowly excreted by kidneys plus hepatobiliary (half life= 15 days) * *CANNOT CROSS BBB Nystatin: topical only

amphotericin B has LESS selective toxicity because it also binds to __ in mammalian cells

cholesterol components

What is the spectrum of amphotericin B

``` *broad-- choice for life threatening systemic infections (esp. immunocompromised) A-Aspergillosis B-Blastomyces C-Cryptococcosis D-Deep candida E- Extracutaneous sporotrichosis ```

What are adverse reactions of amphotericin B

1. Nephrotoxicity (80%--nearly in all) 2. infusion rxn w/ fever/chills---> tx w/ acetaminophine- diphenhydramine prior) 3. anemia (secondary to nephrotoxicity and decreased erythropoeitin synthesis)

``` The dose-limiting toxicity of amphotericin B is: A.  Hepatitis B.  Hypotension C.  Infusion-related adverse effects D.  Myelosuppression E.  Renal tubular acidosis ```

E.  Renal tubular acidosis *nephrotoxic

What is the use of Nystatin

superficial candidal infections

what are adverse reactions of Nystatin

well tolerated topically | -mild GI upset if swallowed

``` Which of the following antifungal agents is most commonly associated with renal insufficiency? A.  Fluconazole B.  Amphotericin B C.  Itraconazole D.  Nystatin E.  Ketoconazole ```

B.  Amphotericin B

What is the MOA of triazoles

like imidazole, but more selective inhibition of fungal P450

Describe the absorption and elimination of triazoles Fluconazole: Itraconazole:

Fluconazole: - IV/PO - renal excretion - enters CNS for meningitis*** Itraconazole: - IV/PO/topical - hepatic metabolism

Describe the spectrum/clinical use of Fluconazole

1. Vaginal candidiasis (single dose) 2. Oropharyngeal and esophageal candidiasis 3. Cryptococcal meningitis

Describe the spectrum/clinical use of Itraconazole

**BROADER THAN fluconazole (includes aspergilliosis) 1. systemic therapy for superficial dermatophytosis and onychomycosis (nails)

``` Which drug is most appropriate for oral (systemic) use in the treatment of vaginal candidiasis? A.  Clotrimazole B.  Fluconazole C.  Flucytosine D.  Nystatin E.  Amphotericin ```

B.  Fluconazole

What are adverse effects of fluconazole

*well tolerated 1. Lesser effect on CYP450 metabolism 2. alopecia 3. GI upset 4. Hepatitis

What are adverse effects of itraconazole

1. CHF 2. HA 3. Inhibits CYP450 drug metabolism (similar to ketoconazole) 4. N/V/D

Select the true statement regarding the pharmacology of fluconazole: A.  It is an inducer of hepatic drug-metabolizing enzymes B.  It does not penetrate the blood-brain barrier C.  It is highly effective in the treatment of aspergillosis D.  It has the least effect of all azoles of hepatic drug metabolism E.  Oral bioavailability is less than that of ketoconazole

D.  It has the least effect of all azoles of hepatic drug metabolism

What is the MOA of Imidazole

inhibit P450 ergosterol synthesis, altering membrane permeability

Describe the absorption, distribution, and elimination of imidazole: 1. Ketoconazole: 2. Clotrimazole/Miconazole:

1. Ketoconazole: - IV/PO/Topical - crosses placental but poorly into CNS * *MUST TAKE W/ FOOD (best absorption w/ low pH) - hepatic metabolism - excreted in breast milk 2. Clotrimazole/Miconazole: - topical only

Describe the spectrum/clinical use of Ketoconazole

1. systemic infections (ie. candidiasis) | * declining use due to toxicity

Describe the spectrum/clinical use of Clotrimazole/Miconazole

oral and vaginal candidiasis

what are adverse reactions of ketoconazole

1. Blocks adrenal steroid synthesis (decrease testosterone) 2. Rash 3. Urticaria 4. N/V/anorexia 5. Cyp450 inhibition 6. Hepatotoxicity (increase LFTs) 7. Gynecomastia

``` If amphotericin B is administered to patient CK, she should be premedicated with: A.  Diphenhydramine B.  Ibuprofen C.  Prednisone D.  Fentanyl E.  Scopolamine ```

A.  Diphenhydramine B.  Ibuprofen C.  Prednisone

What is the MOA of Terbinafine

inhibits squalene oxidase reducing ergosterol synthesis

Describe the absorption, distribution, and elimination of Terbinafine

- well absorbed PO/topical - distributed well - metabolized by hepatic P450

What are the clinical uses of Terbinafine

1. oral for toe/finger nail infection-onychomycosis | 2. topical for athletes foot - tinea cruris, tinea corporis

What are adverse reactions of Terbinafine

1. Taste alteration 2. HA 3. Inhibition of CYP450 4. Rash 5. Diarrhea

``` A 56-year-old female with diabetes presents for routine foot evaluation with her podiatrist. The patient complains of thickening of the nail on the right big toe and a change in the color (yellow). The podiatrist diagnoses the patient with onychomycosis of the toenails. Which of the following is the most appropriate choice for treating this infection? A.  Itraconazole B.  Ketoconazole C.  Nystatin topical D.  Terbinafine E.  Clotrimazole topical ```

D.  Terbinafine

``` Cryptococcal meningitis is a serious life-threatening opportunistic fungal infection that is a concern in immunosuppressed patients. The drug that is commonly used as a prophylactic measure in HIV and bone marrow transplant patients is: A.  Clotrimazole B.  Amphotericin B C.  Fluconazole D.  Itraconazole E.  Trimethoprim-sulfamethoxazole ```

C.  Fluconazole

What are anti-influenza drugs

1. Oseltamivir/Zanamivir | 2. Amantadine/Rimantadine

What are drugs for HSV-VZV

1. Acyclovir 2. Valacyclovir 3. Ganciclovir

What is the MOA of Oseltamivir/Zanamivir

*Neuramindidase inhibitors | Inhibit viral neuramindase to decrease viral budding decrease infectivity

``` Neuraminidase inhibitors are most effective when started how long after symptom onset? A.  Within 24 hours B.  Within 48 hours C.  Within 72 hours D.  Within 96 hours E.  Within 5 days ```

B.  Within 48 hours

Describe the absorption and elimination of Oseltamivir

- administered PO as prodrug | - renal elimination

Describe the absorption and elimination of Zanamivir

- inhaled to respiratory tract | - renal elimination

What are the clinical uses of Oseltamivir

1. prophylaxis and tx of Influenza A and B-- start w/in 48 hrs of sx 2. decreases severity and duration 3. can use in children 1+ and adults

What are the clinical uses of Zanamivir

1. prophylaxis and tx of influenza A and B-- start w/in 2 days of sx 2. decreases LRT complications and duration 3. Can use in 7y/o+

``` Antiviral treatment is recommended for which of the following with suspected influenza? A.  Adults ≥ 65 years old B.  Residents of nursing homes C.  Immunosuppressed patients D.  All of the above ``` Influenza vaccination is recommended for?

D.  All of the above anyone over 6 months

What are adverse reactions of Oseltamivir

1. N/V/Abdominal pain * Decreased if taken w/ food 2. HA 3. Fatigue 4. Preg . C

What are adverse reactions of Zanamivir

1. transient nasal and throat discomfort 2. Bronchospasm/cough 3. Preg. C

``` A 75-year-old man with chronic obstructive pulmonary disease is diagnosed with suspected influenza based on his complaints of flu-like symptoms that began 24 hours ago. Which of the following agents is most appropriate to initiate for the treatment of influenza? A.  Ribavirin B.  Oseltamivir C.  Rimantadine D.  Acyclovir E.  Zanamivir ```

B.  Oseltamivir

A 28-year-old woman in her 4th month of pregnancy was exposed to family members with documented influenza and she has had influenza-like symptoms for one day. When you suggest treatment with an antiviral drug, she asks whether the drug could hurt her baby. You could her that: A.  Pregnant women are at high risk for complications of influenza B.  Oseltamivir appears to be safe for use during pregnancy C.  No adequate studies of oseltamivir have been done in pregnancy D.  Oseltamivir is pregnancy category C E.  All of the above

E.  All of the above

What is the MOA of Amantadine/Rimanadine

inhibit viral uncoating by block of viral M2 proton channel

Describe the absorption, distribution and elimination of Amantadine/Rimanadine

- good oral (PO) - accumulates in lungs - [R] has poor CNS penetration - [A]: renal elimination - [R]: hepatic elimination

What is the clinical uses of Amantadine/Rimanadine

-Prophylaxis and treatment of influenza A--- limited current use due to resistance **

What are adverse reactions of Amantadine/Rimanadine

[A]: 1. Concentration difficulty 2. HA 3. Insomina 4. LH 5. GI upset [R]: better tolerated-- poor CNS penetration

``` A patient receives a drug that is converted to acyclovir in the body. Which antiviral action is exerted by this agent? A.  Inhibition of viral uncoating B.  Inhibition of DNA polymerase C.  Inhibition of viral entry D.  DNA chain termination E.  Prevention of viral maturation ```

B.  Inhibition of DNA polymerase D.  DNA chain termination

What is the MOA of acyclovir and analogs (Valacyclovir)

- phosphorylated by viral thymidine kinase--> inhibits viral DNA - Selectively toxic - 1st phosphorylation step by Herpes- encoded thymidine kinase (only occurs in infected cells)

How does Acyclovirs have selective toxicity

- 1st phosphorylation step by Herpes- encoded thymidine kinase (only occurs in infected cells) - Acyclovir triphosphate inhibits viral DNA polymerase (more sensitive than human DNA polymerase)

``` Acyclovir would be ineffective against HSV strains with loss of expression of: A.  M2 proton channel B.  Dihydrofolate reductase C.  Reverse transcriptase D.  Thymidine kinase E.  Neuraminidase ```

D.  Thymidine kinase

The most common resistance in acyclovir/valacyclovir is ___

reduction or loss of expression of viral TK (thymidine kinase)

Describe the absorption, distribution, and elimination of acyclovir

- Poor oral (15-30%) Need 3-5 doses/day - Administered topical/PO, IV - cross cell membrane--> trapped intracellularly - Renal elimination

Describe the absorption, and elimination of Valacyclovir

- Prodrug of acyclovir (80-90% F)-- BID | - renal elimination

``` Which of the following patient groups may require acyclovir dosage adjustments from the usual recommended mg/kg adult doses? A.  Neonates B.  Patients taking St. John’s wort C.  Patients taking cimetidine D.  Chronic kidney disease patients E.  Pregnant patients ```

A.  Neonates D.  Chronic kidney disease patients *poor renal fxn

``` A 24-year-old female is diagnosed with genital herpes simplex infection. Which of the following agents is indicated for use in this diagnosis? A.  Acyclovir B.  Cidofovir C.  Foscarnet D.  Ganciclovir E.  Valacyclovir F.   Zanamivir ```

A.  Acyclovir E.  Valacyclovir

What are the clinical uses of acyclovir and valacyclovir

1. primary HSV1 and 2 infections (best w/in 48-72 hrs) 2. Recurrent HSV 1 and 2 (episodic or chronic suppressive tx) 3. Disseminated varicella zoster infection (IV) 4. primary VZV-- requires 2-3x higher dose than HSV 5. recurrent VZV (shingles)- best if begun early <72hrs *mucosal, genital, encephalitis

What is the oral tx of primary HSV1 or 2

acyclovir (3-5 doses/day) or valacyclovir (bid) for 7-10d

``` The drug of choice for the treatment of serious or disseminated varicella-zoster infections is: A.  Famciclovir B.  Valacyclovir C.  IV acyclovir D.  Cidofovir E.  Foscarnet ```

C.  IV acyclovir

What is the treatment for primary VZV infection (chicken pox)

1. Symptomatic tx of fever in children 2. Acyclovir QID for 5 d in adults if uncomplicated 3. acyclovir IV TID for 7 d if severe or immuncompromised

``` Treatment of fever in an 8-year-old with chicken pox can be most safely managed with which of the following OTC antipyretic agents? A.  Acetaminophen B.  Aspirin C.  Celecoxib D.  Ibuprofen E.  Any of the above ```

A.  Acetaminophen D.  Ibuprofen

What is the treatment for shingles

1. Oral acyclovir (3-5 doses/day) or valacyclovir (bid) for 7d 2.   IV acyclovir (tid x 7d) if immunosuppressed or severe complications **need higher doses of acyclovir for varicella zoster

What are adverse reactions of Acyclovir/valacyclovir

* generally tolerated orally 1. HA 2. N/V 3. CNS effects w/ high dose ie. IV or VAL (confusion, hallucinations, seizures) 4. Renal toxicity w/ IV route--- minimize w/ hydration 5. Preg. B

What medication is OTC that treats HSV1 labialis (decrease healing time by 15 hrs 4.8-->4.1 days)

Docosanol (topical)