ID Lecture 14: Pharmacology & Med Chem of Misc Antimicrobials | Quizlet

What are the Nitroaromatic Antibacterials?

Nitrofuranition (Macrobid)

Metronidazole (Flagyl)

Tinidazole (Tindamax)

What are the Antimycobacterial agents?

Rifamycins

Isoniazid

Pyrazinamide

Ethambutol

What are the Leprostatic drugs?

Clofazimine

Dapsone

MOA of Nitrofuranitoin

inhibits DNA and RNA functions through an unclear mechanism

When is Nitrofurantoin used?

prophylaxis or treatment of acute UTIs when kidney function is NOT impaired

Nitrofurantoin SOA

Staph, Strep

E. coli

Cirtobacter

Klebsiella

Does Nitrofurantoin have activity against pseudomonas?

NO

What are the resistance mechanisms of bacteria against Nitrofurantoin?

Trick question - there is little to no resistance!

ADRs of Nitrofurantoin

N/V

Pulmonary toxicity

What is the cause of pulmonary toxicity with Nitrofurantoin?

chronic use causes pulmonary toxicity through generation of oxygen radicals

How is Nitrofurantoin eliminated?

renally

Metronidazole MOA

metabolically reduced to create oxygen radicals (highly reactive) that interfere with DNA and RNA function

When is Metronidazole used?

anaerobic and protozoal infections

Metronidazole SOA

Protozoa

Anaerobes

What is considered to be first line treatment for C. difficile infections?

Metronidazole

What are the bacterial resistance mechanisms against Metronidazole?

acquired oxygen scavenging capabilities that deactivate the drug

ADRs of Metronidazole

HA

N/V

Diarrhea

Dry mouth

Metallic taste

Disulfram-like rxns

Nitroaromatic antibacterials are associated with what side effect?

Disulfram-like reactions

How is Metronidazole eliminated?

renally

Tinidazole MOA

same as Metronidazole - metabolically reduced to create oxygen radicals (highly reactive) that interfere with DNA and RNA function

Tinidazole SOA

Protozoal infections

First line for amoebiasis

How is TInidazole metabolized?

in the liver by CYP3A4 enzymes

ADRs of Tinidazole

Disulfram-like rxn

Nausea

Bitter taste

Itchiness

HA

Fatigue

Dizziness

Methenamine MOA

general antiseptic activity - becomes ammonia and formaldehyde in acidic environments

Which antimicrobial agent becomes ammonia and formaldehyde?

Methenamine

Which antimicrobial agent is contraindicated in liver disease?

Methenamine

ADRs of Methenamine

GI

Painful urination

Rashes

Heamturia

Crystalluria

Fosfomycin (Monurol) MOA

inhibits enolpyruvial transferase - by catalyzing an early step in cell wall synthesis

SOA of Fosfomycin

E. coli

E. facealis

When is Fosfomycin used?

treatment of uncomplicated UTIs

Resistance develops quickly with which antimicrobial agent?

Fosfomycin

Mupirocin (Bactroban) MOA

inhibits bacteiral isoleucyl tRNA synthase to prevent incorporation of isoleucine into bacterial proteins

Why is Mupirocin limited to topical use?

hydrolysis in vivo inactivates the drug

SOA of Mupirocin

staph and strep skin infections

What causes Leprosy?

Mycobacterium leprae

What causes tuberculosis?

Mycobacterium tuberculosis

What causes MAC?

mycobacterium avium-intracellulare

What are the first line agents for mycobacteria?

Rifamycins

Isoniazid

Pyrazinamide

Ethambutol

What are the second line agents for mycobacteria?

Ethionamide

PAS

Cycloserine

Capreomycin

Kanamycin

Fluoroquinolones

Isoniazid MOA

prodrug that is activated by oxidation by the katG enzyme which causes the drug to become reactive and acylates another enzyme that is involved in the biosynthesis of mycolic acid

- end result: decreases production of mycolic acid to degrade spores

Static or cidal: Isoniazid

Cidal

What are the bacterial resistance mechanisms against Isoniazid?

loss of the kat G gene

Isoniazid is considered to be a __________.

prodrug

ADRs of Isoniazid

Hepatotoxicity

Rash

HA

N/V

Peripheral neuropathy

Rifamycins

Rifampin

RIfabutin

Rifapentine

MOA of Rifamycins

inhibit DNA-dependent RNA polymerase

Rifabutin structure

isobutyl group

Rifampin structure

macrocyclic antibiotic

Rifapentine structure

How is Rifabutin metabolized?

CYP3A enzymes

How are Rifamycins eliminated?

bile and feces

Rifamycin antimycobacterial activity is best optimized by a high ____________.

Cmax/MIC

Pyrazinamide MOA

MOA is unclear but likely a prodrug that is converted to pyrazinoic acid that cause pH changes that inhibit growth

ADRs of Pyrazinamide

Hepatotoxicity

Hyperuricemia

Arthralgia

N/V

Ethambutol MOA

exact MOA unknown BUT seems to inhibit cell wall synthesis

Which isomer of Ethambutol is more active?

+ isomer (by 200-500x)

Static or cidal: Ethambutol

Static

What is the bactieral resistance mechanisms against Ethanbutol?

Overexpression of the arabinosyl transferase gene

How does Ethambutol express synergy with other drugs?

damages cell wall to improve the penetration of other drugs

How is Ethambutol eliminated?

renally

When is Ethambutol used?

M. tuberculosis

MAC

M. kanzasii

ADRs of Ethambutol

ADRs are rare

decreased visual acuity

Rash

Drug fever

Bedaquiline (Sirturo) MOA

ATP synthase inhibitor

What is the FDA warning for Bedaquiline?

Increased mortality and QT prolongation

Dapsone MOA

inhibits folate synthesis (similar to sulfonamides)

ADRs of Dapsone

Hemolysis

Methemoglobinemia

What is a contraindication of Dapsone?

G6PD deficiency

What is the main use of Dapsone?

Brown recluse spider bites

Clofazimine (Lamprene)

Leprostatic drug with direct antimycobacterial and immunosuppressive activity

ADRs of Clofazimine

Reddish-black discoloration of skin and body secretions