Exam 5: Antimicrobials Flashcards
mechanisms of drug resistance
not enough drug, structure change in drug target, drug antagonist, drug inactivation (enzyme produced from microbe)
superinfection
new infection that appears during the course of tx of primary infection
difficult to treat - typically resistant
yeast infection example
selection of abx
identify organism
drug sensitivity
host factors - functioning immune sys? allergies? site of infection? foreign body (cath)?
empiric therapy
abx selection based on initial presentation and common microbes found with the problem
ex. guy comes in immediately after getting a cut
acute therapy
lab -> cult/sent, abx started immediately with broad-spectrum abx
ex. guy comes in days later and with swollen, red leg (worry for sepsis)
tx principles
monitor first dose
patient ed - no sharing and complete course
major ADRs
hypersensitivity, superinfections, organ toxicities (ear, liver, kidney)
situations for prophylactic abx tx
UTI, COPD, pre-op, dental procedures, bacterial endocarditis, bites/wounds/STD exposures, neutropenic, labor and delivery
not abx but vaccines also
gram positive examples
cocci - staph, strep
bacilli - mycobacterium, antracis
gram negative examples
pseudomonas - gonorrhea, h. pylori, salmonella
drug therapy for UTIs
*Trimethoprim/sulfamethoxazole (first line)Bactrim
*Nitrofurantoin(first line)
* Fosfomycin (first line)
*Phenazopyridine (Pyridium) –> AZO, not abx
enzymes needed for HIV replication
reverse transcriptase, protease, integrase
HAART
highly active antiretroviral therapy for HIV/AIDs CD4 count <500
penicillin
“beta-lactam” abx - weaken cell wall membranes and bacteria lysis
narrow (PCN G) to broad spectrum (amoxicillin) to extended spectrum (piperacillin)
ADRs: common hypersensitivity (anaphylaxis), GI, interfere w/ contraceptives
no PO - stomach acid, can’t penetrate gram neg walls, inactivated by penicillinase
ampicillin/amoxicillin
broad spectrum (worry about super infections)
use: gram + or - (e. coli)
ADRs: rash, GI upset
commonly used with other abx to inhibit beta-lactamase (augmentin ex)
beta-lactamases
bacteria that resist penicillin through enzymes that inactivate the beta-lactam ring of the drug
cephalosporins
“beta-lactam” abx - weaken cell wall membranes and bacteria lysis
broad spectrum and more effective with higher gen (against gram -)
minimal ADRs - cross allergy to PCN, superinfections, poor GI absorption (IV/IM)
implications: no alcohol (Disulfiram-like), promotes bleeding (warfarin), C.diff concerns
different generations of cephalosporins
1st Generation; Cefazolin (Ancef) ; Cephalexin (Keflex)
2nd Gen: Cefuroxime (Ceftin); Cefaclor (Ceclor)
3rd Gen: Ceftriaxone (Rocephin); Ceftazidine (Fortaz)
4th Gen: Cefipime (Maxipime)-
5th Gen: Ceftaroline (Teflaro)- Effective: MRSA and VRSA
imipenem
“beta-lactam” abx - weaken cell wall membranes and bacteria lysis
broad spectrum - gram + and -; only IV
resists beta-lactamases
vancomycin
MOA: inhibitor of cell wall synthesis (binds to precursors of cell wall)
use: severe C. diff or MRSA
ADRs: nephrotoxic (peak/trough/creatinine), ototoxic, rapid infusion -> “red man syndrome”
widely used in hospital, only IV infusion (thrombophlebitis), SLOW IV push
tetracylclines
broad spectrum, bacteriostatic, gram +/-, mostly 2nd line r/t resistance
-cycline (doxy)
MOA: inhibits protein synthesis -> blocks mRNA translation
use: anthrax, chlamydia, cholera, acne, h. pylori, periodontal disease
ADRs: GI irritation, binds to calcium -> teeth trouble, superinfections, hepatotoxic, nephrotoxic, photosensitive, **teratogenic
interactions: chelates w/ metal ions (avoid calcium, iron, magn, alumin, zinc) -> 2 hours apart
erythromycin
macrolide - broad spectrum, bacteriostatic (inhibits protein synthesis)
use: bordetella pertussis, w/other abx for pna and chlamydia, resp & skin infx
ADRs: very safe, GI effects, **QT prolongation
Interactions: antidysrythmics, hepatic enzyme inhibitor (incr. levels of other drugs)
azithromycin/clarithromycin
easier dosing than erythro (Qday or BID) and help with resistance to erythro
clindamycin
broad spectrum, bacteriostatic (inhibits protein synthesis)
limited to anerobic infx (does not cross BBB) -> severe strep A and gangrene (c. perfrigens)
abdominal and pelvic infx
**big risk for C. diff
C. diff tx
IV replacement, electrolyte management, vancomycin
drugs to slow GI motility should not be used
linezolid
**MDROs - reserved for VRE and MRSA
ADRs: diarrhea, N/V, HA, **myelosuppression (monitor CBC)
aminoglycosides
narrow spectrum, bactericidal
Gentamicin, amikacin, tobramycin, neomycin
use: aerobic gram- bacilli - used in GI for rapid affect
only IM/IV - highly polar (not absorbed in GI and doesn’t cross BBB)
ADRs: ototoxicity and nephrotoxicity **need trough levels, skeletal muscle relaxation and neuromyo blockade (paralysis + resp depress)
sulfonamides & trimethoprim
Tri-metho-prim / Sulfa-methoxazole (Bactrim; Septra) -> **UTIs
MOA: Disrupt synthesis tetrahydrofolate -> derivative of folic acid
ADRs: hypersensitivity (mild to severe Stevens-Johnson syndrome-flu-like & blisters), hemolytic anemia, kernicterus, renal injury w/ crystalluria
fluoroquinolones
-floxacin (cipro, levo)
broad spectrum, uses: resp, UTI, GI, skin/bone, prevent anthrax exposure
MOA: disrupt DNA replication & cell division
ADRs: GI, CNS, superinfection, photosens, tendons, QT prolong, hypoglycemia
decreased levels by dairy, antacids
increases levels of warfarin and theophylline *monitor for tox
metronidazole
(Flagyl) abx and antiprotozoal - only anaerobic orgs, broad spectrum
GI, GU, CNS, bone, joint infx - prophylactic for surgeries
IV = slow, PO = metallic taste/GI upset
ADR: CNS (HA/dizzy/seiz), rash, Stevens johnson, GI upset
no alcohol (Disulfiram-like)
bacitracin
MOA: Inhibits cell wall synthesis > cell lysis and > cell death
only topical, gram +, skin infx - lots of combo meds
nitrofurantoin
(Macrobid) broad spectrum
uncomplicated, lower UTIs -> prophylactic
ADRs: GI upset, pulm (hypersensitivity), heme (CBC), hepatotoxic, peripheral neuropathy, birth defects, CNS
Implications: Monitor renal function, UOP, BMs, respiratory status, CBCs, liver function
take w/ food, no driving, dizzy/drowsy, increase fluids
phenazopyridine
urinary analgesic (Azo)
MOA: acts locally in urinary tract mucosa to produce analgesic and relief from S/S
bright orange urine -> invalidates UA results, need culture
Amphotericin B
broad spectrum antifungal, highly toxic (IV, no PO), used for systemic fungal infx
increases permeability of cell membrane (fungistatic and cidal)
**safety alert
ADRs: infusion reactions, nephrotoxic, hypokalemia, bone marrow suppress., liver failure, arrythmias, phlebitis
monitor creatinine and electrolytes
fluconazole
broad spectrum antifungal w/ lower tox, PO or IV
inhibits liver enzymes (inc other meds)
systemic mycoses and candidiasis
ADRs: N/V/D, abd pain, HA, stevens johnson synd
other -azoles
itraconazole = liver inj and card suppress
ketaconazole = hepatotoxic
Caspofungin
echinocandins
MOA: disrupts biosynthesis of cell wall
IV only
Use: systemic infx that are intolerant/unresponsive to other meds
Nystatin
polyene abx
MOA: alters cell membrane permeability
topical or PO - mild GI upset and rare rash
acyclovir
antiviral - PO, topical, IV
MOA: Inhibits viral replication by suppressing synthesis of viral DNA
herpes simplex & varicella
ADRs: n/v, HA, dizzy, skin irritant, phlebitis, reversible nephrotoxicity
implications: lower dose for renal impairment
ganciclovir
synthetic antiviral - IV, PO, topical
only approved for cytomegalovirus in immunocompromised
ADRs: **black box warning - granulo and thrombocytopenia, teratogenic, carcinogenic
implications: lower dose for renal, monitor CBC
interferon alfa
MOA: block viral entry into cells by binding to receptor cells
use: hepatitis - SQ or IM
ADRs: flu-like sumptoms, depression, SI, GI, alopecia
ribavirin
unclear MOA - use HEP C
broad spectrum antiviral, PO
ADRs: hemolytic anemia, teratogenic, flu-like, autoimmune disorders w/interferon
simeprevir/grazoprevir
protease inhibitors
MOA: protease=enzyme required for replication
HEP C
ADRs: hepatic inj, photosen, rash
take w/ food
daclatasvir & sofosbuvir
NS5A & NS5B inhibitors
used w/ other hep C drugs
ADR: HA, fatigue, lots of drug inter.
lamivudine
MOA: inhibits viral DNA synthesis for Hep B and HIV
ADR: lactic acidosis, hepatomegaly, pancreatitis
oseltamivir
Tamiflu
grab more from book *
remdesivir
EUA for covid
shorter recovery time, not sufficient to help mortality
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs/NNRTI)
MOA: suppress synthesis of viral DNA by reverse transcriptase
**black box: fatal lactic acidosis w/ hepatic steatosis
zidovudine
NRTI
no longer used other than perinatal transmission
(Retrovir or AZT)
ADR: **black box - severe anemia, neutropenia, lactic acidosis w/ hepatomegaly, myopathy
abacavir
NRTI
(Aizgen or ABC)
ADRs: **same black box as other NRTIs, hypersensitivity, MI
no alcohol
lopinavir/ritonavir
Protease inhibitor
most effective antiretroviral - reduces HIV viral count to undetectable
ADRs: ^BGL, lipodystrophy, hyperlipid, dec. card contract, hepatotoxicity
lots of drug interactions
raltegravir
Integrase stand transfer inhibitors (INSTIs)
MOA: stops action of integrase so HIV DNA is NOT integrated into the T cell’s DNA. HIV daughter cells are not made
ADRs: relatively well tolerated, watch liver enzymes, insomnia
enfuvirtide
Fusion inhibitors - block entry into CD4 T cells
used for infx resistant to other drugs
maraviroc
CCR5 antagonists - 50-60% of HIV strains must bind with CCR5 to enter cell
also used when resistant
common OIs w/ HIV/AIDs
** greatest risk <200 CD4
Pneumocystis carinii (jiroveci) pneumonia – Bactrim (TMP/SMZ)
Cytomegalovirus retinitis (CMV) – Ganciclovir
M. tuberculosis – 4-Drug for TB;
Cryptococcal meningitis – Amphotericin B
HSV or VZV - Acyclovir
Candidiasis – “azole”
abx for common infx
Staph -
C. diff - clindamycin
