Module 4 - Anti-Infectives Flashcards
What is the MOA of tetracyclines?
- The tetracyclines are bacteriostatic to multiplying bacteria by inhibiting protein synthesis. Both passive diffusion & energy-dependent active transport systems are necessary for tetracyclines to cross bacterial cell membranes & reach ribosomes.
- Tetracyclines bind at the 30S ribosomal subunit.
- Resistance develops by changes in the active transport system as well as changes in the binding sites. Cross-resistance among all tetracyclines is common.
What are the indications for using tetracyclines?
Tetracyclines are a group of bacteriostatic antibiotics with a wide range of activity against gram-positive and gram-negative bacteria plus some other organisms
- 1st line drugs for mycoplasma, chlamydia, the spirochete of Lyme disease, rickettsia causing Rocky Mountain spotted fever, and lymphogranuloma venereum
- Acne
- Comunity acquired pneumonia
What are the s/x associated with tetracyclines?
- GI distress (nausea, vomiting, and epigastric burning)
- tetracycline-resistant bacterial enteritis can occur.
- Diarrhea - may result from the irritative effect of tetracycline but must be distinguished from pseudomembranous coliti
- IV administration causes phlebitis and IM causes pain due to the irritating effect.
- Tetracyclines are deposited in the dentin of teeth of the fetus when given to pregnant women or children under age 8, resulting in hypoplasia and brown discoloration of the tooth
What drugs interact w/ tetracyclines?
- Antacids, iron or calcium supplements, and magnesium laxatives (di- and tri-valent cations) interfere with the absorption of all tetracyclines. Food decreases absorption of all except minocycline and doxycycline
- Cholestyramine or colestipol decrease absorption (and blood level) of all tetracyclines.
- Oral estrogen-containing contraceptives may have reduced contraceptive reliability during tetracycline use. (Interaction is questioned).
- Enzyme inducers (phenobarbital, carbamazepine, phenytoin, and rifampin): shorten the half- life of doxycycline from a normal time of 16-17 hours to 10 hours.
What type of drug is Vancomycin and what is its MOA?
Type: Glycopeptide
MOA: Vancomycin acts by inhibiting synthesis of cell walls of sensitive bacteria (gram-positive cocci), at a location different than the action of the beta-lactams.
What are the s/x of Vancomycin?
- skin rash
- chills and fever called “red man (or red neck) syndrome”
- Red man syndrome occurs if the drug is infused too rapidly
- hypotension
- phlebitis
- ototoxicity and nephrotoxicity
What are the Alternatives to vancomycin in the treatment of MRSA?
linezolid (DOC), quinupristin/dalfopristin, daptomycin, rifampin, gentamicin, trimethoprim and doxycycline
What type of drug is Gentamicin and what is its moa?
Type: Aminoglycoside
MOA: They water-soluble drugs and are rapidly bactericidal for aerobic gram-negative bacteria by virtue of their ability to inhibit protein synthesis by binding to 30S subunits of bacterial ribosomes & they also dissolve the cell envelope.
Because gentamicin is less costly and as efficacious as tobramycin and amikacin, gentamicin is the preferred aminoglycoside for most indications
What are the indications for using Aminoglycosides?
- Treatment of sepsis due to aerobic gram-negative enteric bacteria
- Treating infections by Ps aeruginosa, E coli, Kl pneumonia, Serratia marcescens, and Proteus organisms
- They are effective against gram-positive cocci but must be used in combination with a cell wall-active agent
With what frequency have aminoglycosides been administered?
- Aminoglycosides traditionally have been administered q8h
- Several studies advocate once daily dosing with the same daily dose as when given in divided doses.
- Once daily dosing in patients with good renal function is claimed to be less nephrotoxic and possibly more efficacious
What are the adverse effects associated with Aminoglycosides?
- Ototoxicity - manifests as vestibular (N/V, vertigo, disruption of balance) or auditory (impairment of hearing dysfunction) or both and is a result of the accumulation of aminoglycoside (plasma concentration) in the perilymph of the inner ear
- Nephrotoxicity - Aminoglycosides are the major nephrotoxic cause of acute tubular necrosis. They accumulate in the renal cortex & the incidence of nephrotoxicity depends on the specific drug, duration of treatment, total dose, & predisposing factors (advanced age; preexisting renal disease, concomitant administration of other nephrotoxic substances, and hypotension.).
- Skeletal muscle weakness
What are some drugs that interact with aminoglycosides?
- Amphotericin B, loop diuretics, cisplatin, cyclosporine or vancomycin may result in increased ototoxicity and/or nephrotoxicity.
- Halogenated hydrocarbon anesthetics, citrated blood, & neuromuscular blocking agents may enhance or prolong skeletal muscle weakness.
What type of drug is Amphotericin B and what is its MOA?
Type: Antifungal
MOA: Antifungal activity depends on the ability of the drug to bind to a sterol moiety (ergosterol), causing pores to form in the cell membrane, increasing permeability, and allowing leakage of small molecules. Once a clinical response has been elicited, therapy can be continued with maintenance therapy with an oral azole.
What are the indications for using Amphotericin B?
- It is administered IV as a colloid for systemic effect (do NOT use an in-line filter)
- It is used in the treatment of serious systemic fungal infections such as cryptococcal, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, and disseminated candidiasis.
What are the s/x of Amphotericin B?
- Adverse effects are common and some serious (“Amphoterrible”). 80% of patients suffer impaired renal function
- Infusion-related reactions are nearly universal and consist of fever, chills (fever & chills 50% “shake & bake”), muscle spasms, vomiting, headache, and hypotension
- To decrease severe side effects, give aspirin, acetaminophen, antihistamines, and antiemetics before infusion. Small doses of IV corticosteroids before infusion may decrease febrile reactions
What are the benefits of using Liposomal amphotericin [AmBisome] vs amphotericin B?
- It is approved for the treatment of aspergillosis or any progressive fungus infection that does not respond to conventional therapy.
- The liposomal formulation delivers a much higher dose of amphotericin with reduced liver toxicity
What type of drug is metronidazole and what is its MOA?
- Type: Antiprotozoal
- MOA: Metronidazole’s mechanism of action is unclear. It has a selective toxicity to anaerobic or microaerophilic microorganisms, probably forming chemically reactive intermediates that involve reactions with DNA, proteins, and membranes.
What are the indications for using metronidazole?
- It is effective against Trichomonas vaginalis, Entameba histolytic and Giardia lamblia
- It also displays antibacterial activity against all anaerobic cocci and most anaerobic gram-negative bacilli including Bacteroides and anaerobic spore-forming gram-positive bacilli.
- It is the drug of choice for treating mild to moderate Clostridium difficile infection (pseudomembranous colitis)
What are the s/x of using metronidazole?
- Side effects are rarely serious.
- Most common are headache (18%), nausea (10%), dry mouth, metallic taste (9%) & vaginitis (15%), GI irritation may be lessened by taking the drug with meals.
- Neurotoxic effects (dizziness, vertigo, convulsions) are rare as is hepatitis
- Metronidazole is a weak enzyme inhibitor and may increase serum levels of phenytoin, warfarin and lithium.
What type of drug is Rifampin and what is its MOA?
- Type: Broad spectrum antibiotic
- MOA: It inhibits DNA-dependent RNA polymerase of mycobacterium, leading to suppression of chain formation and ribonucleic acid synthesis in bacteria. Resistance develops quickly if rifampin is used alone, and there is cross-resistance with other rifamycins. Rifampin is bactericidal to M. tuberculosis, atypical mycobacteria & M. leprae
What are the indications for using Rifampin?
- Used in the treatment of TB & Prophylaxis against meningococcal disease in household contacts of patients with meningococcal meningitis
- Unlabeled uses include infections that have failed to respond to other antibiotics and treatment of leprosy.
What are the s/x of Rifampin?
Most common (less than 4%) side effects are rash (0.8%), fever (0.5%), and nausea & vomiting (1.5%). Rare are thrombocytopenia, anemia, hepatic dysfunction, and hepatorenal syndrome, the latter when the drug is used sporadically or less than twice weekly
Rifampin imparts a harmless orange color to urine, sweat, tears, and soft contact lenses.
What are some drug interactions with rifampin?
The rifamycins are potent enzyme inducers (1A2, 2C9, 3A4) and importantly decrease the serum level and effectiveness of a number of drugs including warfarin, methadone, glucocorticoids, estrogens, cyclosporine, beta blockers, sulfonylureas, disopyramide, quinidine, ketoconazole, methadone, theophylline and others.
What type of drug is Isoniazid and what is its MOA?
- Type: tuberculostatic (for resting organisms) and tuberculocidal
- MOA: It inhibits the synthesis of mycolic acids, important constituents of the mycobacterial cell wall.
What are the s/x of Isoniazid?
- Peripheral neuropathy can be minimized by prophylactic therapy with pyridoxine (vitamin B6) 25-50 mg/day. (Peripheral neuropathy results from isoniazid-induced deficiency of pyridoxine.)
- Liver damage has occurred (2nd leading cause of liver transplants)
- Most prominent reactions are rash (2%), fever (1.2%), jaundice (0.6%) and peripheral neuritis
What type of drug is interferon and what is its moa?
Type: Glycoproteins / Antivirals
MOA: interferons are glycoproteins produced by cells infected with viruses. Interferons bind to specific receptors and inhibit cell proliferation
What are the indications for using interferons?
- Interferons have been administered in Europe as a nasal spray for rhinovirus infections.
- In the US two alpha interferons are marketed for treatment of hairy cell leukemias but they are also useful in treatment of hepatitis, particularly non-A, non-B hepatitis (basically hepatitis C)
What type of drug is Zidovudine (Retrovir) and what is its MOA?
- Type: Nucleoside reverse-transcriptase inhibitor
- MOA: Nucleoside reverse transcriptase inhibitors (NRTI) are incorporated into viral DNA as a false nucleoside. This results in proviral DNA chain termination and blocking further viral replication.
