Antibiotics, Antifungals, Antivirals Flashcards

Question

Reasons for ABx stewardship and scope of its use

Answer 1

ACVIm 2015 guidelines, AAFP, AAHA Guidelines Also think ISCAID Resp/Urinary guides - strong evidence in human med that ABx use contributes to AMD development. Limited/circumstantial evidence this could cause resistant infection in small animals - Low to moderate evidence of ABx causing resistance in animal med, but given human evidence is likely to be the case. Also recent publications on outbreak of carbapenem resistant ESBL E. coli in veterinary hospitals where there was over-prescription of this antimicrobial. vet hospitalisation was also a key risk factor of presence of AMR in prospective longitudinal study oin Switzerland - Aim is through modification of use of medications we can reduce this risk

Answer 2

1. Prevent disease occurrence/reecurrence (vaccination, husbandry, address predisposing health issues) 2. Reduce ABx use (confirm bacterial cause - not all fever is bacterial; consider if culture results are clinically relevant) 3. Improved ABx use - consider site of action, pathogen susceptibility and patient facotrs in prescription - duration should be until clinical/microbiological cure is documented, extended courses are not needed even in MDR infections (if using appropriate ABx) - Strive for definitive diagnosis of infection - De-escalate based on C+S - Recommended laboratory withholding of sensitivity data for more critical antimicrobials. - restrict ABX to prescription only (OTC may increase risk of inappropriate use though no data to back this up)

Answer 3

- longer treatments are NOT need for MDR infections - Use of human generic ABx shoul dbe avoided due to unknown PK/PD data - in-house cultures due to risk of misdiagnosis, culture of contaminants and biosafety - Screening cultures not recommended (think subclinical UTI) - Avoid use of ABx for their immunomodulatory or other effects.

Answer 4

All inhibit fungal ergosterol synthesis (key component of cell wall). More efficacy against yeast, intrinsic resistance in fungi that lack this cell wall component. GIVE THEM WITH FOOD TO IMPROVE ABSORPTION ANTACIDS IMPAIR ABSORPTION Ketoconazole - first gen drug. Can inhibit normal steroid hormone production, induce liver toxicity. Tx of malassezia but not Aspergillus Good tissue penetration but not CSF Clotrimazole - ver poor bioavailability, use topically can be effective Itraconazole - effective for Crypto, some Asper coverage and most other molds. Poor CNS penetration. GI and hepatic adverse effects - dose dependent. Vasculitis in cats No urine excretion Fluconazole - no Asper coverage, narrower spectrum of other fungi. Good tissue distribution, can enter CNS for Crypto GI and hepatic side effects Posaconazole - broad spectrum and good tissue penetration (perhaps not as good into CNS). GI upsets are main reported AE but uncommon. Mild liver enzyme increase not affecting treatment. Voriconazole - broadest spectrum, best penetration. V $$ Cytp450 inducer, may cause GI upset and liver tox.

Answer 5

Irreversibly binds fungal wall sterols forming a pore which leaches intracellular electrolytes and neutrients Also has immunomodulatory effects on macrophage activity increase Used for progressive, severe systemic fungal infections. Broad spectrum. Given IV or SC. Use lipid complexed formulation to reduce AE AEs: nephrotoxicity through reduced renal blood flow and possible inherent toxicity to tubular cells. May cause RTA. Also GI upsets and cardiac arrhythmias reported.

Answer 6

Reversible inhibition of squalene cyclase in fungal ergosterol synthesis for cell wall. Has synergistic effects with azole antifungals. Concentrates in the skin and hair. Used primarily as a single agent for dermatophytes but can enhance efficacy of azoles in treatment of systemic infections AEs: GI upset, liver toxicity, periocular swellings

Answer 7

2 JAAHA studies - compounded formulation had significantly lower, and subtherapeutic in 12%) levels compared to generic or brand name formulations. Some on brand name/generic had potentially toxic serum levels - randomised crossover design trial comparing compounded to namebrand formula. Found compounded formulations poorly absorbed. But also that liquid formulations were much better absorbed than formulated capsules.resulting in a need for lower dose of liquid formulations

Answer 8

GS and Remdes - nucleoside analogues. Small molecules that enter cells and interfere with viral synthersis incorporating into transcript and causing termination of synthesis Good oral bioavailability (unpublished); AEs: injection site pain/inflammation, urolithiasis Molnupiravir - prodrug that is converted to active nucleoside analogue that causes translation mutations in viral RNA transcription --> lethal mutagenesis PK and PD not published in cats (very small study) anecdotally may cause more side effects. Used as back up for GS/Rem if treatment failure

Answer 9

Zidovudine and Fozivudine both are nucleoside analogues that inhibit viral replication Fozivudine is preferentially activated by lymphocytes so has less haematological AEs compared to Zidovudine which can cause non regenerative anaemia. Limited evidence of efficacy, may reduce viral load in affected cats, and/or help improve QoL by impairing secondary infections. As these are viruses many cats live with and not develop secondary complications it is difficult to know true impact of these treatments without longitudinal prospective trials in a large cohort

Answer 10

Thymidine kinase activated drug, TK is produced by viral infected cells and then other cellular machinery further activates the product resulting in accumulation of ac tive metabolite in virally infected cells. The active metabolite interferes with viral DNA synthesis Acyclovir caused severe AEs when used parenterally, and poor efficacy topically Famciclovir is better tolerated and can help to reduce disease severity (though limited evidence ofr this).

Answer 11

Not a direct antiviral but inhibits host cell mRNA translation proteins that virus hijacks for replication thus inhibiting viral replication. May also non-specifically enhance immune defence. Improved clinical signs and decreased viral shedding in 16 FIV/FeLV cats May also reduce clinical signs and mortality associated with canine/feline parvo May be that effects are more on inhibition of 2ry infections than on interference with the parvovirus itself.

Answer 12

Binds to mycobacterial DNA and inhibits replication, ineffective against other bacteria and fungi. May also work on Leishmaniasis Used in various mycobacterial infections ideally based on sensitivity testing AEs: changes colour of secretions to orange, GI upset, possible hepatotoxicity (limited information)

Answer 13

Tx of ascarids and hookworms in dogs and cats (Toxocara, Uncinaria, Ancylostoma) Cholinergic agonist that inhibits nicotinic receptors of parasites to act as a neuromuscular blocking agent Poorly absorbed from GIT, acts locally on intestinal worms. Rare AEs: vomiting, diarrhoea, anorexia short lived

Answer 14

An avermectin that affects chloride channel activity in the nervous system of nematodes/arthropods causing parasite paralysis and death Used off label in treatment of Spirocerca lupi infections and some mites May see mydriasis, lethargy, blindness. Avoide in MDR1 dogs.

Answer 15

human antimalarial drug that reduces viral load by preventing cell lysis and thus completion of viral replication Continuous administration necessary as does not stop viral replication. AEs: vomiting, increase SDMA possible renal damage.

Antibiotics, Antifungals, Antivirals Flashcards

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