Drugs, toxins Flashcards
A cat presents for acute ataxia and vocalizing. On physical exam, it is hypothermic and has elevated TELs. What toxicity do you suspect?
Marijuana
JVIM 2021, Kulpa
What effect does robenacoxib have on creatinine in healthy and CKD (IRIS 2-3) cats treated for 4-12 weeks?
Mild but probably clinically irrelevant increase
JVIM 2021, King
An aggressive German shepherd is sedated for an abdominal ultrasound to investigate acute vomiting (concern for FB). AUS shows GB thickening and “double rim sign”.
–What is the likely cause?
–When could you recheck to bolster your suspicion?
–Sedation with dexdomitor
–GB thickening should resolve in 12-24hrs
JVIM 2021, Seitz
Which is a better protocol for plane and duration of sedation while minimizing cardiovascular depression?
hydromorphone/alfaxalone vs hydro/alfax/midaz
Hydro/alfax/midaz – since benzos have minimal CV effects, adding midaz is better than increasing dose of alfax
JVIM 2021, Wheeler
What is the MoA of mycophenolate?
Myco –> mycophenolic acid –> selective and reversible inhbition of inosine-5’monophosphate dehydrogenase (IMPDH) –> can’t make guanine –> lymphocytes can’t proliferate
JVIM 2021, Fukushima
Regarding GI adverse effects in dogs treated with mycophenolate:
–Frequency?
–Median time to onset?
–At least 2 possible MoAs?
–Not dose dependent – possible explanation?
–24%
–10d after starting myco
–MoAs:
1) Metabolite acyl-glucoronide (acyl-MPAC) is cytotoxic
2) Hydrolysis metabolite N-(2-hydroxyethyl) morpholine is irritating (rabbit model)
3) Dysbiosis (rat model)
–Widely variable pharmacokinetics from dog to dog
JVIM 2021, Fukushima
For mycophenolate, what are two possible adverse effects (other than GI) and their frequency? Do they resolve with discontinuation?
–Neutropenia 4% – may be persistent despite d/c’ing myco
–Dermal eruptions 1.5% – resolve with d/c
JVIM 2021, Fukushima
PU/PD is a common side effect of pred. How does desmopressin affect the behavior, USG, and Na? What does this imply about the mechanism of PU/PD?
Desmopressin –> decr PU/PD, incr USG, decr Na
Means PU/PD from pred is (at least partially) due to ADH antagonism (release vs receptor)
JVIM 2021, Galati
Describe at least 3 mechanisms by which vincristine helps in the treatment of ITP. What is the median time to Plt >40K?
–Incr megakaryocyte fragmentation
–Inhibits plt phagocytosis
–Inhibit formation and function of anti-Plt Ab
–Median 3-5d to plt >40K
JVIM 2021, LaQuaglia
JVIM 2021, Allen
Regarding neutropenia associated with vinc 0.02mg/kg (tx for ITP):
–Frequency?
–Degree?
–One risk factor and possible mechanism? How to avoid this?
–Effect on outcome?
–15% (large ITP study) to 50% (healthy research dogs)
–Most were NOT severe
–Cyclosporine –> neutropenia was more likely and more severe. Inhibition of CYP450 –> decr vinc clearance. Takes 5d to clear vinc – start cyclosporine after that.
–No effect on survival but did have longer hospital stay
JVIM 2021, LaQuaglia
JVIM 2021, Allen
How do serum gastrin levels correlate with likelihood and severity of GI ulceration with meloxicam use?
Incr gastrin –> more likely to have an ulcer. Higher = more severe.
JVIM 2021, Elfadadny
What is the purpose of enteric coating on omeprazole?
Degrades at a certain pH –> lets the drug survive the stomach and released in duodenum
JVIM 2021, Gaier
The goal for PPI tx is for gastric pH to be ____ for ____% of the day. BID omeprazole achieves this for ___% of the day, by day ____ of tx.
Gastric pH >/=3 for 75% of the day
Omeprazole BID –> pH >/=3 for 90% of the day by day 2 of tx
JVIM 2021, Gaier
For dogs with creat >4.0, how frequently should you dose ampicillin 22mg/kg IV to maintain an appropriately high MIC?
SID is sufficient (but small study and relationship between GFR and creat is not linear – so interpret with caution)
JVIM 2021, Monoghan
What is diuretic braking and why does this happen?
Furosemide CRI –> decr urine production after a few hours due to RAAS activation
JVIM 2021, Adin
What is the effect of ACEi and spironolactone on diuretic braking?
No effect – probably escape mechanisms to make AT II
JVIM 2021, Adin
What are at least 3 possible mechanisms of systemic hypertension secondary to renal disease?
–Impaired Na handling
–Excessive RAAS activation
–Hyperactive sympathetic NS
–Endothelial factors
JVIM 2021, Fowler
Which was most effective for lowering BP and UPC in PLN dogs and two possible explanations:
–ACEi alone
–Telmisartan alone
–ACEi+Telmisartan
ACEi+telmisartan
Possibly because 1) case selection bias (more severely affected dogs in Tel only group) vs 2) ACEi+Tel truly more effective
Lots of limitations in this retrospective study – interpret with caution
JVIM 2021, Fowler
How often do ACEi or ARBs need to be discontinued due to hyperkalemia?
Infrequent – most hyperkalemia is modest
JVIM 2021, Fowler
What are the basic mechanisms that maximize duration of action for the following:
–Traditional long acting insulin (such as glargine)
–AKS-267c (once weekly insulin)
–Traditional long acting insulins manipulate the SQ depot (to cause slow absorption) and receptor affinity (since once it’s absorbed by the cell, it’s degraded)
–AKS-267c: insulin + Fc –> binds host Fc neonatal receptor (FcRn – ubiquitous, found on most/all cell types) –> endocytosis –> intracellularly recycled
JVIM 2021, Gilor
How do glargine vs AKS-267c (weekly insulin) compare in terms of clinical DM control, glycemic variability, and hypoglycemic events?
AKS-267c had decr glycemic variability, similar clinical control, no hypoglycemic events
JVIM 2021, Gilor
What are the gastric pH goals (pH and proportion of the day) for the following situations (adopted from human med):
–Duodenal ulceration
–Esophagitis
–Optimal clot formation (ex: if severe GI bleed)
In healthy dogs, how do IV esomeprazole, IV pantoprazole, and famotidine CRI compare with respect to the goals above? Which maintained the highest pH the longest?
–Duodenal ulceration >/= 3 for 75% of the day
–Esophagitis >/= 4 for 2/3 of the day
–Optimal clot formation (ex: if severe GI bleed): >6
Esomeprazole and famotidine performed similarly and reached these goals. Pantoprazole 1mg/kg BID did not reach these goals. Esomeprazole had the highest duration of pH >5 and >6.
JVIM 2020, Kuhl
In healthy cats, how do PO esomeprazole, dexlansoprazole, and lansoprazole compare with respect to pH goals for duodenal ulceration?
For the lansoprazole, how does this compare with IV use?
Esomeprazole was the only tx to achieve pH >/= 3 for 3/4 of the day.
PO lansoprazole (pill or liquid) did absolutely nothing – previously shown to be effective IV in cats.
JVIM 2020, Ryan
What is the difference between esomeprazole and omeprazole, and how is this advantageous? Why might this advantage not apply to cats?
Omeprazole is a racemic mixture, R- and S-omep. Esomeprazole is just S-omep, which is more slowly metabolized by CYP450 –> longer T1/2. Cats have little to none of that particular CYP450 (CYP2C), so there may be no difference in omep vs esomep metabolism.
JVIM 2020, Ryan
How did intestinal permeability (measured with plasma iohexol and LPS), fecal calprotectin (marker of intestinal inflamm), and dysbiosis differ between PPI/NSAID dogs, NSAID only, and controls?
What can we infer about prophylactic PPI usage with NSAIDs for protection against GI ulceration?
PPI/NSAID: higher dysbiosis index and calprotectin, no difference in intestinal permeability.
Thus, prophylactic PPI is probably not beneficial (dysbiosis and inflamm can incr risk of GI ulceration)
JVIM 2020, Jones
Clopidogrel is frequently prescribed for platelet inhibition.
–How does its effect alone compare with clopidogrel+pred in healthy dogs?
–How does clopidogrel responsiveness change over time when used alone vs with pred?
Greater effect when given with pred – appears synergistic. Most healthy dogs overresponded but hypercoagulopathic IMHA dogs may benefit from the synergy.
Clopidogrel responsiveness wanes over time (by ~1mo) when used alone, but not with pred.
JVIM 2020, Thomason
How does Purina HA affect the microbiome and metabolome in healthy dogs?
No change – so can infer it will not damage them in chronic GI dogs
JVIM 2020, Pilla
Metronidazole x2 weeks in healthy dogs had many adverse effects on the microbiome and metabolome.
–Were adverse effects on metabolites (vitamins, antioxidants, etc) worse in serum vs feces or the same?
–C. hiranonis was reduced. What are two of its major roles?
–Was there complete, partial or no recovery of the microbiome by 2 weeks post metro? 4 weeks?
–Worse in feces
–BA producer, protects from C. diff infection
–Partial recovery by 2 weeks, still not fully recovered at 4 weeks
JVIM 2020, Pilla
Clavamox is often prescribed to treat acute diarrhea. How did the following differ between clavamox and placebo for the following:
–Clinical course
–Prevalence of resistant E. coli (and did this change the last day of tx vs 3 weeks post tx?)
–Prevalence of C. diff
–No difference in clinical course
–Minimal resistant E. coli pre-tx, clavamox group median 100% of strains at 6 days, 10% at 21 days post tx
–No C. diff pre-tx, 38% clavamox dogs on day 6 (penicillins are also a risk factor in people for C. diff)
JVIM 2020, Werner
What is the basic mechanism of erythromycin and metoclopramide, respectively?
Which portion(s) of the GIT are affected by the promotility effects of erythromycin and why?
How do onset of action and overall efficacy of erythromycin vs metoclopramide compare for gastric motility and emptying?
Erythromycin: motilin agonist, most receptors are in the duodenum and fewest in the colon
Metoclopramide: serotonin receptor agonist (5HT4 > 5HT3), dopamine receptor agonist (stomach)
Erythromycin had ~1hr faster onset of action but overall it and metoclopramide performed similarly
JVIM 2020, Husnik
What are the basic MoAs for:
–Cyclosporine
–Mycophenolate, azathioprine
–Leflunamide
–Cyclosporine: inhibit calcineurin in T cells –> decr IL-2, IFN-gamma –> decr lymphocyte function
–Mycophenolate, azathioprine: purine synthesis inhibitors –> decr B and T cell function
–Leflunomide: pyrimidine synthesis inhibitor –> decr B and T cell function
JVIM 2020, Archer
Regarding pred, azathioprine, mycophenolate, cyclosporine, and leflunamide:
–Which suppressed IL-2 and IFN-gamma? Which was the most and second most effective?
–How can this help in therapeutic drug monitoring?
–There is (very little, some, wide) variation in drug levels for all (except pred – no assay) between dogs despite being given the same mg/kg dose.
–IL-2 and IFN-gamma suppression: cyclosporine 99.7% for both, pred 77 and 84% respectively, the other drugs had no effect
–Can monitor IL-2 and IFN-gamma suppression for drug efficacy
–Wide variation –> highly variable interdog metabolism
JVIM 2020, Archer
Which were different in dogs with and without ACE gene polymorphisms? Elaborate on your answer(s) – how could it affect treatment with RAAS inhibitors?
–Baseline ACE activity
–Suppression of AT II and metabolites with ACEi
–Aldosterone with ACEi
–Aldosterone : AT II ratio ACEi
Polymorphism dogs had higher aldosterone and ald : AT II ratio but everything else was the same. Means they’re making aldosterone via other routes (aldosterone breakthrough) and indicates a need for multimodal tx.
JVIM 2020, Adin
Regarding PEG aspiration:
–At least 3 basic mechanisms of toxicity?
–Treatment to combat this?
–At least two strategies to reduce risk of regurge/vomiting PEG?
Mechanisms: 1) osmosis –> airway edema, 2) compromised surfactant and mucociliary clearance, 3) direct membrane damage, 4) sometimes anaphylaxis
Tx: airway suctioning and lavage
Decr risk of vomit/regurge: antiemetic (cerenia > metoclopramide), administer at slower rate, have only experienced people give it (if using gavage in unsedated dogs)
JVIM 2020, Santaella
Regarding grape/raisin toxicity in dogs:
–Proportion with neuro signs?
–Mostly affecting what portion of the brain?
–Do neuro signs resolve in survivors? (full, partial, no resolution)
–Overall survival rate?
– >75% had neuro signs
–Forebrain
–Fully resolve
–Survival 53%
JVIM 2020, Schweighauser
What are two clinical indications for zoledronic acid?
Regarding adverse effects of zoledronic acid:
–Overall prevalance?
–Most common AE? Any predisposing factor(s)?
–Rare AE but associated with cumulative dose?
Indications = bone pain, hypercalcemia
AEs 11%, most commonly azotemia. Incr risk w/ NSAIDs (but not cumulative dose).
Very long duration of tx and high cumulative dose can cause jaw osteonecrosis.
JVIM 2020, Brewer
What were the effects on activity level and ability to do activities in a study of geriatric cats treated with gabapentin?
What proportion had adverse effects?
Reduced activity but improved ability to do stuff
AEs in 50% (sedation, ataxia, weakness, muscle tremors)
JAVMA 2018 Guedes
Regarding gabapentin pharmacokinetics:
–High or low oral bioavailability?
–Is accumulation with repeat dosing an issue?
High (95%)
No – so do not need to adjust dose w/ long term tx
JVIM 2019 Adrian
What characteristics (protein binding, volume of distribution) make a toxin a good candidate for treatment with therapeutic plasma exchange?
High prot binding, low Vd
JVIM 2019 Rosenthal
In a study of 11 dogs with NSAID overdose treated by therapeutic plasma exchange (and other interventions), what % had adverse effects?
Name two AEs
What effect did AEs have on outcome?
55%
Clots in filter, bleeding, hypotension
None – all survived to discharge
JVIM 2019 Rosenthal
Does transdermal fentanyl decrease, increase, or have no effect on minimum necessary isoflurane dose?
What effect does naloxone have on heart rate?
Decrease
Increase
JAVMA 2018 Grasso
What effect does trazodone have on helathy cats?
–Echo
–BP
–None
–Lower w/o any change to HR
JFMS 2019 Fries
True or False: Imepitoin had no effect on noise phobia in dogs compared to placebo.
False – worked well compared to placebo
JVIM 2019 Engel
In a small study of healthy research cats, what was the frequency of inducing emesis with the following drugs?
Hydromorphone 0.1mg/kg SQ
Dexmed 7mcg/kg IM
Hydro 75% – so, good choice for emesis
Dexmed 57% – also more likely to cause sedation, bradycardia
JVECC 2019 Nystrom
Which of the following meds/med combos are associated with GI ulceration?
Which is the worst?
How long til peak ulcerative effect?
How does this affect your treatment of dogs with concurrent immune mediated disease and hypercoagulability?
Pred alone
Aspirin alone
Clopidogrel alone
Pred + aspirin
Pred + clopidogrel
Pred/aspirin»_space; pred alone, aspirin alone, pred/clop
Clop alone –> no incr risk
Peak ulceration at 2 weeks, but still see new lesions at 3 weeks
So, rx pred/clop over pred/aspirin
JVIM 2019 Whittemore
Steroids can increase plasma volume in cats. Based on a small study N=10 cats:
–How could you use proBNP for monitoring?
–Was hyperglycemia a significant driver?
Study found that proBNP incr from baseline in 1/3 of cats but did not reach statistical significance. Would be reasonable to use baseline and >60% incr during tx rather than upper ref interval.
No change in BG during tx – not a big driver for incr plasma volume
JVIM 2019 Block
What did a small study (N=10 healthy cats) find regarding mycophenolate?
–Effect on total mononuclear cells and CD4/CD8 ratio?
–Predictable or variable pharmacokinetics?
–Proportion with adverse effects at higher doses (15mg/kg TID)?
–Taken together, what conclusion do you draw regarding whether to use mycophenolate in cats?
No effect even at high doses BUT all high dose cats developed diarrhea, suggests doses high enough to reach efficacy would not be tolerated
Variable pharmacokinetics (same as in dogs and people)
**Caveats – may have needed longer to see benefit; may not have been measuring benefit the best way
JVIM 2020 Slovak
In a 3 day experimental study, which reached PPI tx goals? Did any had diminishing effect over time?
Famotidine boluses (low dose)
Famotidine boluses (high dose)
Famotidine CRI
Famotidine CRI only. Still reaching goals by day 3 but diminishing effect (likely developing tolerance).
JVIM 2019 Hedges
True or False: An experimental study showed some benefit in appetite and stool quality in dogs given abx with a synbiotic vs without.
True – but some flaws with study design
JVIM 2019 Whittemore
What are four things that increase the risk for gastroesophageal reflux post op? (Signalment, weight, sx site, recovery)
How do the following given pre-op affect risk?
Cerenia
Reglan
Higher risk for GER if male, overweight, GI sx (biggest risk with OR 30), post op dexmed CRI
No effect
JAVMA 2019 Fransson
Does mannitol cause significant osmotic diuresis?
Does it matter if it is bolus or bolus + CRI?
Does either method maintain the effect? Why or why not?
No. Effect is immediate but mild and transient.
Doesn’t matter if bolus or bolus+CRI. Plasma mannitol decreases rapidly regardless, probably due to elimination and redistribution to other extracellular fluids.
Overall, not a good option to help oliguric dogs.
JVIM 2019 Segev
Regarding osteonecrosis secondary to bisphosphonates:
–Basic mechanism?
–What bone/site is usually affected and why?
–Acute, chronic, or idiosynchratic reaction?
–Does d/c’ing bisphosphonate help?
Accumulation of bisphosphonates in bone matrix –> kills osteoclasts –> bone necrosis
Usually affects jaw b/c higher rate of bone turnover
Chronic, cumulative dose
Unknown. Long T1/2 in people and dogs (3yrs), unknown in cats.
Can give med mgmt a try (ex: abx) but probably need surgical debridement.
JVIM 2019 Larson
True or False: In cats with anticoagulant rodenticide ingestion, decontamination is usually effective in preventing coagulopathy.
False. Decontamination did not affect likelihood of prolonged coags later on. So, ALWAYS check PT 48hrs post exposure.
JVECCS 2018 Walton
Dermatology refers a dog to you for hyporexia, weight loss, lethargy, and polydipsia. His skin disease is stable and has been managed with chronic high dose ketoconazole. What is your top differential based on this information alone?
Iatrogenic Addison’s
JVIM 2019 Hernandez-Bures
What is Duloxetine used to treat in people? Dogs who overdose develop what syndrome?
Depression
Serotonin syndrome
JAVMA 2019 James
True or False: Theophylline TDERM SID is effective at maintaining therapeutic plasma concentrations.
False
JFMS 2019 Barnoski
