Drugs Flashcards
What are the mechanisms of action of Sam-e
Increases intracellular cysteine leading to increased hepatic glutathione synthesis
Increases methylation of phospholipids and DNA which promotes membrane stability and controls production of inflammatory cytokines.
Increases hepatoprotective polyamines
What is the mechanism of action of telmisartan?
- Angiotensin II receptor (type AT1) antagonist which acts to inhibit the effects of angiotensin —> less vasoconstriction, decreased aldosterone synthesis, decreased sodium and water retention and less renal, vascular and cardiac remodelling.
- In the kidney, angiotensin II may result in glomerular capillary hypertension and increased protein in the glomerular filtrate, which could trigger or potentiate interstitial fibrosis —> reduce proteinuria
- Antifibrotic - liver disease
What if the mechanism of action of allopurinol?
Xanthine oxidase inhibition —> decreases formation of uric acid by blocking the conversion of hypoxanthine to xanthine, and of xanthine to uric acid.
Used in leishmania and ammonium urate uroliths
What if the mechanism of action of allopurinol?
Xanthine oxidase inhibition —> decreases formation of uric acid by blocking the conversion of hypoxanthine to xanthine, and of xanthine to uric acid.
Used in leishmania and ammonium urate uroliths
May get xanthine uroliths!
What fluoroquinolone has the widest spectrum of activity?
Pradofloxacin (just not anaerobes)
What percentage of cats have a food responsive enteropathy?
A) 60%
B) 45%
C) 70%
D)65%
A) 60%
Maropitant
Neurokinin 1 receptor antagonist
Crtz and emetic center
Should not be used with calcium channels antigonists as has an affinity for calcium channels
Ondansetron
Serotonin 5ht3 antagonist
Crtz and vagal afferents
Metoclopramide
Dopamine receptor antagonist, at higher doses 5HT3 antagonist
Crtz and smooth muscle ( D2 antagonism,stimulation of muscarinic Ach and 5HT4) - gastric emptying and duodenal contractions.
Nb. dopamine is less important in the feline crtz
Chlorpromazine and prochlorperazine
Dopamine2 M1 and H1 receptor antagonist
Crtz and emetic center
Omeprazole, pantoprazole, esomeprazole, lansoprazole
Protein pump inhibitors
* lansoprazole - may not be effective orally in cats
Sucralfate
Disaccharide complexed with aluminum, dissociates to sucrose pentosulphate and aluminum hydroxide when exposed to gastric acid. Binds to gastric acid and prevents hydrogen diffusion, inactivates pepsin, absorbs BA and increases mucosal pg synthesis
Domperidone
Anti emetic - d2 antagonist , Leishmania treatment - reduces risk of developing clinical disease
Crtz and gi smooth muscle - cannot pass the bbb
Sulfasalazine
Prodrug - active ingredient is 5- aminosalicylic acid (mesalamine)
Anti inflammatory effect in the LI due to the resident a bacteria metabolizing the prodrug.
Decreases prostaglandin and leukotriene synthesis by the colonic mucosa
S/e KCS, acute pancreatitis, vomiting
*reduced dosage in cats due to toxicity
Chlorambucil
Cystostatic alkylating agent which inhibits the proliferation of rapidly growing cells.
Reduces the infiltrating inflammatory cells of the intestines
S/e bone marrow suppression
Cyclosporine
Decreased IL-2 to inhibit cell mediated immunity
Budesonide
Potential glucocorticoid (15x more than pred)
High local but low systemic activity
Designed for targeted release in the ileum and colon in humans
Lactulose
A nonabsorbable disaccharide that is metabolized by colonic bacteria into short chain fatty acids. These are an energy source of bacteria that shifts the micro biome to have fewer urease producing positive bacteria and favors bacteria that utilize ammonia.
Short chain fatty acids can acidify colonic content, trap ammonia, and provide an ammonia sink.
Short Chain fatty acids act as osmotic laxatives to speed the removal of tract ammonia, urea, producing bacteria, and nitrogen within the colon.
Spironolactone
Potassium, sparing, diuretic, aldosterone antagonist (inhibits the mineral cortisone antagonist) to counter the effects of raas activation, in cases of ascites.
Mitigate hepatic fibrosis and sinusoidal capillarisation
D penicillamine
Copper chelating agent
S/e can cause, vomiting, diarrhea, and anorexia better, when given with a small amount of food, glomerulonepathy or dermatological, lesions, are uncommon
Cisapride
Serotinergic 5HT4 agonist in the myenteric plexus —> releases Ach to increase mobility from the LOS downwards
Spironolactone
Inhibits mineralocorticoid receptors (ie action of aldosterone), which produces diuresis because of reduced sodium resorption - more water excreted. Lowers bp. Potassium maintained
Ddavp
Synthetic vasopressin
Causes release of vWF into the circulation.
Cryoprecipitate
Contains high concentrations of VWF and factor 8 and some fibrinogen
Smaller volumes needed than ffp
Vitamin K1
Active form of vitamin k
Administered orally with a fatty meal to go straight to the portal circulation.
Rivaroxaban, apixaban
Reversibly binds free and clot bound factor xa, preventing the conversion of prothrombin to thrombin.
Targeting clot bound Xa means that it can target continued clot formation.
Bioavailability of rivaroaban: 60% in dogs
Apixaban is 85% in cats
Aspirin
NSAID that inhibits platelet cox 1 and the production of thromboxane A2 thus reducing platelet aggregation.
Not reversible
Less effective in cats compared to clopidogrel.
Clopidogrel
Binds irreversibly to platelet surface ADP receptor - ABP2y12 and inhibits platelet aggregation.
Glucocorticoids
Lipid soluble, rapid oral absorption.
Wide distribution throughout the body.
She t0.5 0.5-4h
Dexamethasone is the most potent and has the longer half life.
Mechanism:
Cytosolic glucocorticoid receptor, translocates to the nucleus after ligand binding.
- decrease cytokines and chemotaxines via activator protein I and NFkB on activated B cells.
- inhibit other transcription factors which regulate genes for inflammatory cytokines.
- promote lymphocyte apoptosis through upregulation of Bcl 2 proteins.
- inhibit phospholipase A2 and eosinosanoid generation by induction of annexin 1 - decrease inflammation.
Cats: reduced hepatic biotransformation of prednisone, give prednisolone. Less sensitive to the affects of glucocorticoids.
Nb. Can unmask diabetes and cardiac disease.
Azathioprine
Mechanism:
- metabolized into thioguanine nucleotides.
- these are incorporated into DNA (less so RNA) which is cytotoxic
- promotes apoptosis of activated T cells, reduced proliferation of B and T lymphocytes.
Lag time for action: 2-6 weeks.
S/e:
Myelosuppression: progressive neutropenia, thrombocytopaenia and pancytopenia. Worse myelosuppression in cats so contraindicated..
Hepatoxicosis - worse if glutathione depletion, GSD overrepresented.
Pancreatitis reported in dogs, but not confirmed to be causal link.
*most cases s/e are reversible within 1-8 weeks of tapering/ discontinuing.
Mycophenolate mofetil
Prodrug for mycophenolic acid.
Rapidly absorbed, highly protein bound.
Significant variation in half life and absorption between individuals.
Mechanism: PURINE SYNTHESIS INHIBITOR
- non competitively irreversibly inhibits inosine 5 monophosohate dehydrogenase - rate limiting step for purine synthesis.
- therefore impairs proliferation of b and t lymphocytes.
- metabolized by the liver, and derivatives are excreted in the urine.
S/ e
Gastrointestinal upset. - visiting, diarrhea, anorexia, haem diarrhoea, necroenterocolitis reported in dogs with high doses.
Leflunomide
Prodrug of teriflunomide
Very good oral bioavailability
Rapid t0.5 in dogs, reaches steady state in 4-5 days.
Mechanism: PYRIMIDINE SYNTHESIS INHIBITOR
- inhibits lymphocyte proliferation by inhibiting dihydro- orotate dehydrogenase.
- reduces cd25 expression - lymphocytes less responsive to IL-2
- inhibits JAK1,2, NFkB and cox-2.
- increases generation of Treg.
S/e
GI - diarrhea (worse in dogs than cats)
Mild thrombocytopaenia
Mild liver enzyme increase
Blood dyscrasias
Cyclosporine
Cyclic polypeptide of fungal origin.
Widely distributed, highly conc in erythrocytes.
Metabolized by cytochrome 450, excreted in bile
Mechanism: INHIBITS CALCINEURIN
- prevents dephosphorylation of the nuclear factor of activated T cells and cytokines transcription.
- less IL-2 = less T and B cells
S/e
GI upset - 30% of dogs.
Secondary infections including cutaneous papillomatosis.
Reversible gingival hyperplasia
Increased incidence of neoplasia documented in cats - majority lymphoma
Neoplasia in dogs : histiocytoma, lymphoma, mct, scc, papilloma virus associated harmatoma.
Increased risk of systemic toxoplasmosis
Drugs with inhibit cytochrome 450 will prolong activity - azoles, need to reduce the dose
Risk of nephrotoxicity with aminoglycosides, trimeth sulph, and NSAIDs
- Which of the following best describes the mechanism of action of glucocorticoids (GCs)?
A) They bind to nuclear receptors, resulting in gene upregulation.
B) They inhibit transcription factors like AP-1 and NFκB, leading to reduced pro-inflammatory cytokines.
C) They enhance the activation of pro-inflammatory pathways, promoting immune responses.
D) They directly activate G protein-coupled receptors on immune cells. - What is the primary consequence of glucocorticoid-induced lymphocyte apoptosis?
A) Enhanced T-cell proliferation
B) Reduced effector function in T- and B-lymphocytes
C) Increased dendritic cell activation
D) Augmented chemotaxis of neutrophils - Which of the following transcription factors is inhibited by glucocorticoids to suppress inflammation?
A) AP-1
B) STAT3
C) NFκB
D) Both A and C - What is the most common adverse effect of glucocorticoids in pets?
A) Hypoglycemia
B) Polyuria and polydipsia
C) Increased liver function
D) Hypotension - Which of the following is a known adverse effect of glucocorticoid use in cats?
A) Hepatic necrosis
B) Fluid retention leading to diabetes
C) Muscular hypertrophy
D) Enhanced immune responses - Which enzyme is primarily responsible for converting prednisone to its active form, prednisolone, in dogs?
A) 11β-hydroxysteroid dehydrogenase
B) Xanthine oxidase
C) Thiopurine methyltransferase
D) Aldosterone synthase - What is the main reason why glucocorticoid-induced diabetes is rare in dogs?
A) Dogs are not sensitive to glucocorticoid-induced insulin resistance.
B) The glucocorticoid dose required to cause diabetes in dogs is extremely high.
C) Fluid retention due to glucocorticoids does not affect dogs’ blood glucose.
D) Dogs have lower-affinity glucocorticoid receptors. - What is the mechanism of action of azathioprine (AZA) in suppressing the immune system?
A) Inhibition of calcineurin-dependent T-cell activation
B) Incorporation of thioguanine nucleotides into DNA, leading to apoptosis of activated T-cells
C) Inhibition of JAK-STAT signaling
D) Suppression of cyclooxygenase (COX)-2 activity - Which of the following is the primary active metabolite of azathioprine (AZA)?
A) 6-Mercaptopurine (6-MP)
B) Thioguanine nucleotides (TGNs)
C) 6-Methylmercaptopurine
D) 6-Thioguanosine - What is a significant adverse effect of azathioprine (AZA) in dogs?
A) Hepatotoxicosis
B) Acute kidney failure
C) Hypertension
D) Hyperglycemia - Mycophenolate mofetil (MMF) exerts its immunosuppressive effect by inhibiting which enzyme?
A) Inosine monophosphate dehydrogenase (IMPDH)
B) 11β-hydroxysteroid dehydrogenase
C) Phospholipase A2
D) Xanthine oxidase - Which cell type is most affected by mycophenolate’s inhibition of inosine 5′ monophosphate dehydrogenase (IMPDH)?
A) Erythrocytes
B) Activated T-lymphocytes
C) Dendritic cells
D) Neutrophils - What is a common adverse effect of mycophenolate mofetil (MMF) in both humans and dogs?
A) Severe muscle atrophy
B) Gastrointestinal upset (vomiting, diarrhea)
C) Myelosuppression leading to thrombocytosis
D) Hyperglycemia - What metabolic pathway is primarily responsible for the inactivation of azathioprine (AZA)?
A) Thiopurine methyltransferase (TPMT)
B) 11β-hydroxysteroid dehydrogenase
C) Xanthine oxidase
D) Cytochrome P450 enzymes - What is the primary mechanism by which leflunomide reduces lymphocyte proliferation?
A) Inhibition of dihydro-orotate dehydrogenase
B) Blockade of JAK-STAT signaling
C) Inhibition of inosine monophosphate dehydrogenase
D) Suppression of NFκB activation - In which of the following conditions does leflunomide show therapeutic efficacy?
A) Chronic lymphocytic leukemia
B) Inflammatory bowel disease (IBD)
C) Rheumatoid arthritis
D) Cushing’s disease - Which of the following is a primary adverse effect of leflunomide in dogs?
A) Diarrhea
B) Cardiac arrhythmias
C) Hyperglycemia
D) Renal failure - The half-life of teriflunomide (the active metabolite of leflunomide) in dogs is approximately: A) 15-17 days
B) 21-25 hours
C) 12 hours
D) 2-3 days - Which immunosuppressive drug is considered most likely to cause necrotizing enterocolitis when given at high doses in dogs?
A) Azathioprine
B) Mycophenolate mofetil
C) Leflunomide
D) Dexamethasone - What is the primary reason for the variation in plasma concentrations of mycophenolate mofetil (MMF) in cats?
A) Differences in drug metabolism in the liver
B) Decreased oral bioavailability
C) Rapid urinary excretion
D) Differences in absorption rates across tissues
Answers:
B
B
D
B
B
A
A
B
B
A
A
B
B
A
A
C
A
B
B
A
Famcyclovir
Inhibits viral DNA polymerase, inhibiting replication of FHV
Lysine
Antagonists arginine which is required for viral replication
Interferon
Cytokines to limit cell to cell viral spread
Side effect of enrofloxacin
Retinal degeneration in cats
Lidocaine
First choice treatment for ventricular arrhythmias. may be useful for atrial fibrillation if no structural change is present.
Side effects include gastrointestinal signs and neurotoxicity (especially in cats ).
Mexilitine
Treatment for ventricular arrhythmias, chronic long-term management.
Longer half life compared to lidocaine and less hepatic metabolism .
Side effects include anorexia, vomiting, nausea . Less neurotoxic in dogs than lidocaine, but very neurotoxic in cats and contraindicated.
