Lit Pharmacology, Toxicology Flashcards
What were in the differences in pharmacokinetics of IV ampicillin between azotemic and healthy dogs?
Monaghan JVIM 2021
Azotemic dogs had higher peak ampicillin concentration (~4.5x), greater half-life (~6x), greater AUC (731.04 vs 33.57), significantly lower clearance & lower volume of distribution vs healthy dogs.
*Consider dose/frequency adjustment in azotemic dogs.
What are the potential effects of dexmedetomidine sedation on abdominal US changes in dogs, and the risk factors?
Seitz JVIM 2021
Transient GB wall thickening (>2mm) in 24% dogs, and peritoneal effusion.
Risk factors - longer duration of sedation sig associated with GB wall thickening, but NOT recumbency.
Which plasma extracellular vesicle (EV)-associated microRNAs (miRNAs) were affected during/post administration of doxorubicin in dogs with sarcoma?
How did changes in these biomarkers correlate to other traditional cardiac biomarkers & echo findings?
Beaumier JVIM 2020
Downregulation of miR-107 & miR-146a vs upregulation of miR-502.
miR-502 upregulation was detected before 3rd chemo dose + before significant changes in cTnI or echo parameters.
*Significant cTnI changes occurred only 1 month post-tx completion, correlated with LV ejection fraction & LVIDd.
1) What were the common clinical signs & CBC abnormalities in dogs following anthracycline overdose?
2) What was the short-term outcome for these dogs?
Lawson JVIM 2021
1) CSx: D+ (63%), anorexia (56%), V+ (38%), lethargy (31%), nausea (25%)
CBC: neutropenia (94%) - usually high-grade, not responsive to filgrastim; thrombocytopenia (88%), anemia (63%).
2) Death uncommon (12.5% or 2/16 dogs), most recovered with supportive care (mostly hospitalised).
What adverse effects were associated with robenacoxib administration in cats for management of chronic MSK disease?
King JVIM 2021
Overall well tolerated when given over 4-12 wks. Incidence of AE similar in RCXB vs placebo cats (47% vs 41%).
Increased creatinine (but subclinical)
Mostly GIT (V+, D+, anorexia)
What was one major adverse effect noted in cats that received frunevetmab?
Gruen JVIM 2021
Skin lesions (alopecia, lumps) in most cats resolved with topical or systemic tx (abx, anti-histamines, topical steroids), small % did not improve.
DDAVP - MOA, indications, SE?
DDAVP administration to dogs on prednisolone treatment to alleviate PUPD may result in what complication?
Galati JVIM 2021
Synthetic ADH analogue. Central DI. Hyponatremia (excessive free water retention).
Hyponatremia (worry about excessive free water if no PUPD observed with prednisolone + receive DDAVP. USG also remains concentrated).
Mycophenolate mofetil (MMF) - MOA?
Adverse effects - incidence & which? in dogs receiving MMF to treat IMD?
Fukushima JVIM 2021
MOA: mycophenolic acid is a metabolite of MMF - selectively and reversibly inhibits inosine 50-monophosphate dehydrogenase (IMPDH), which is a rate limiting enzyme of de novo synthesis of the nucleotide guanine. As rapidly growing cells like lymphocytes have a high demand for guanine nucleotide, inhibition of IMPDH results in arrest of proliferation of both T & B lymphocytes –> immunosuppression
Incidence ~25.9% (34/131) dogs.
GI AE most common (24.4%).
Also hematologic (neutropenia 4%, anaemia 4%, thrombocytopenia 4%) & dermatologic 1.5%.
No sig diff among dogs with/without potential AEs wrt sex, age, BW, MMF dosage.
- What is the MOA of zolendric acid (ZA), indications, and potential AE?
- What adverse effects were noted with IV ZA in dogs for the abovementioned indications?
Brewer JVIM 2021
1. Nitrogen-containing bisphosphonate or aminobisphosphonate. Inhibits bone resorption.
Indications - management of bone pain (ostealgia) & hypercalcemia (of malignancy) in dogs.
AE - AKI, hypophosphatemia, hypokalemia, hypocalcemia (reported in humans).
- Progressive azotemia in 8 dogs (8.4%) - not associated with cumulative dose. V+ (2 dogs, 2%), pancreatitis (1 dog, 1%), cutaneous ulceration (1 dog), D+ (1 dog).
Which 2 body systems are affected with grape/raisin toxicity in dogs?
What clinical manifestations?
Survival rate?
Schweighauser JVIM 2020
Renal + neuro.
Renal - severe (grade 4-5) AKI.
Neuro - Severe forebrain, cerebellar, or vestibular signs –> reversible functional brain injury. 73% dogs.
53% survival (similar to non-GRT causes of AKI).
In cats receiving doxorubicin for tx of various neoplasms, what was the
a) incidence of creatinine elevation >/=30% from baseline?
b) average time to onset of a), and
c) risk factors associated with a)?
Kopecny JVIM 2020
a) 34%
b) 4 months
c)
- Single-agent doxo (vs multi agent CHOP)
- Pre-existing CKD
- Neutropenia or anemia during chemo
- No. of RT treatments under GA.
a) Which 2 of 3 acid suppressants evaluated were superior (achieved goals established for treatment of gastroduodenal ulceration in people – based on increasing the gastric pH ≥3 for 75% of the day) during the first 72 hours of treatment in dogs?
b) What were the differences in time effect for mean pH, mean percentage time (MPT) intragastric pH >4, MPT >3 between use of 3 gastroprotectants in a population of healthy dogs?
Kuhl JVIM 2020
a) Famotidine CRI (1mg/kg followed by 8mg/kg IV CRI) & esomeprazole. VS pantoprazole (standard doses).
b) No sig differences
What was the effect of metronidazole on a) time to resolution of diarrhoea, and b) detection rate of C. perfringens in faecal cultures of dogs?
Langlois JVIM 2020
MTZ tx can shorten duration of D+ & decrease faecal culture detection of C. perfringens in some dogs with acute non-specific D+.
MOA & effects of the following drugs on gastric emptying (GE) & motility index (MI) of antral contractions in healthy cats?
- Metoclopramide
- Erythromycin
- Exenatide
Husnik JVIM 2020
- Metoclopramide: shorten GE, increase MI. MOA: sensitises upper GI s.m. to ACh effects. NB: does not stimulate gastric, pancreatic, biliary secretions, nor colonic motility.
- Erythromycin: shorten GE, increase MI. MOA - motilin agonist, initiates interdigestive type III migrating motor complexes (MMCs).
- Exenatide: delays GE initially. MOA GLP-1 analogue (incretin, reduces post-prandial hyperglycemia).
What is calprotectin?
What was the effect of omeprazole administration on faecal calprotectin & GI dysbiosis index (DI) n dogs receiving carprofen without risk factors for GI bleeding?
Jones JVIM 2020
Calprotectin aka S100A8/A9 = protein complex expressed & released into the extracellular space by activated macrophages & neutrophils at sites of inflammation.
Coadministration of omeprazole & carprofen significantly increased faecal calprotectin concentration & DI vs baseline/carprofen alone.
What clinical manifestation is common in dogs following envenomation by the European adder (Vipera berus)?
Which quantitative clinical parameter had an association with this clinical manifestation?
Harjen JVIM 2020
Ventricular arrhythmias (57% dogs)
CTnI concentration. Dogs with arrhythmias had sig higher CTnI at 12, 24 & 36hrs.
Which immunosuppressive drugs had significant effects on IL-2 & IFN-γ expression in dogs?
What are the clinical implications during treatment?
Archer JVIM 2020
Prednisone & cyclosporine. Mean IL-2 & IFN-γ values were significantly lower before vs after treatment - with cyclosporine being more suppressive than prednisone.
(NOT azathioprine, mycophenolate or leflunomide)
Use of these 2 drugs have the ability to influence results when utilizing pharmacodynamic monitoring of cyclosporine tx.
What was the impact of prophylactic gastroprotectants (omeprazole and/or famotidine) on GI signs in dogs with neoplasia treated with single-agent piroxicam?
Shaevitz JAVMA 2021
Both omeprazole (~85%) & famotidine (80%) were associated with more frequent & severe GI AEs in these dogs vs placebo (36%) by 8 weeks.
DO NOT recommend prophylactic PPIs & H2-blockers in dogs with cancer receiving NSAIDs.
What gene mutation was identified in cats that dveloped neurotoxicity following topical eprinomectin administration?
Mealey JAVMA 2021
Eprinomectin = macrocyclic lactone.
Homozygous for ABCB11930_1931del TC mutation.
Lamotrigine toxicosis in dogs
- Clinical manifestations
- Tx?
Lamotrigine = anti-epileptic drug (humans), lipophilic.
CSx - seizures, obtundation, tachyarrhythmias (VPCs/VTach > VFib if severe), death possible
Tx - IV lipid emulsion, supportive care
