Drugs

Question 1

What are the mechanisms of action of Sam-e

Answer 1

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

Question 2

What is the mechanism of action of telmisartan?

Answer 2

1. 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.
2. 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
3. Antifibrotic - liver disease

Question 3

What if the mechanism of action of allopurinol?

Answer 3

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

Question 4

What if the mechanism of action of allopurinol?

Answer 4

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!

Question 5

What fluoroquinolone has the widest spectrum of activity?

Answer 5

Pradofloxacin (just not anaerobes)

Question 6

What percentage of cats have a food responsive enteropathy?

A) 60%
B) 45%
C) 70%
D)65%

Answer 6

A) 60%

Question 7

Maropitant

Answer 7

Neurokinin 1 receptor antagonist

Crtz and emetic center
Should not be used with calcium channels antigonists as has an affinity for calcium channels

Question 8

Ondansetron

Answer 8

Serotonin 5ht3 antagonist

Crtz and vagal afferents

Question 9

Metoclopramide

Answer 9

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

Question 10

Chlorpromazine and prochlorperazine

Answer 10

Dopamine2 M1 and H1 receptor antagonist

Crtz and emetic center

Question 11

Omeprazole, pantoprazole, esomeprazole, lansoprazole

Answer 11

Protein pump inhibitors
* lansoprazole - may not be effective orally in cats

Question 12

Sucralfate

Answer 12

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

Question 13

Domperidone

Answer 13

Anti emetic - d2 antagonist , Leishmania treatment - reduces risk of developing clinical disease

Crtz and gi smooth muscle - cannot pass the bbb

Question 14

Sulfasalazine

Answer 14

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

Question 15

Chlorambucil

Answer 15

Cystostatic alkylating agent which inhibits the proliferation of rapidly growing cells.
Reduces the infiltrating inflammatory cells of the intestines
S/e bone marrow suppression

Question 16

Cyclosporine

Answer 16

Decreased IL-2 to inhibit cell mediated immunity

Question 17

Budesonide

Answer 17

Potential glucocorticoid (15x more than pred)

High local but low systemic activity
Designed for targeted release in the ileum and colon in humans

Question 18

Lactulose

Answer 18

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.

Question 19

Spironolactone

Answer 19

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

Question 20

D penicillamine

Answer 20

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

Question 21

Cisapride

Answer 21

Serotinergic 5HT4 agonist in the myenteric plexus —> releases Ach to increase mobility from the LOS downwards

Question 22

Spironolactone

Answer 22

Inhibits mineralocorticoid receptors (ie action of aldosterone), which produces diuresis because of reduced sodium resorption - more water excreted. Lowers bp. Potassium maintained

Question 23

Ddavp

Answer 23

Synthetic vasopressin
Causes release of vWF into the circulation.

Question 24

Cryoprecipitate

Answer 24

Contains high concentrations of VWF and factor 8 and some fibrinogen
Smaller volumes needed than ffp

Question 25

Vitamin K1

Answer 25

Active form of vitamin k Administered orally with a fatty meal to go straight to the portal circulation.

Question 26

Rivaroxaban, apixaban

Answer 26

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

Question 27

Aspirin

Answer 27

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.

Question 28

Clopidogrel

Answer 28

Binds irreversibly to platelet surface ADP receptor - ABP2y12 and inhibits platelet aggregation.

Question 29

Glucocorticoids

Answer 29

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. Membrane bound GC receptors: - intercalate into the cell membranes and disrupt sodium and calcium transport - reduced archidonic acid generation. Cats: reduced hepatic biotransformation of prednisone, give prednisolone. Less sensitive to the affects of glucocorticoids. Nb. Can unmask diabetes and cardiac disease. Cats are less susceptible to the effects, possibly due to lower affinity of receptors Dose on lean bw

Question 30

Azathioprine

Answer 30

Mechanism: - prodrug for 6 mercaptopurine (metabolized by HGPRT) - metabolized into thioguanine nucleotides. (Nb. Cats have sig lower erythrocyte TPMT activity) - these are incorporated into DNA (less so RNA) which is cytotoxic via cell cycle cheakpoints - promotes apoptosis of activated T cells by binding to RAc-1 and G protein which results in reduced proliferation of B and T lymphocytes. - metabolites are eliminated in the urine 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.

Question 31

Mycophenolate mofetil

Answer 31

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 (most potently inhibits type 2 in activated lymphocytes)- rate limiting step for purine (guanine) synthesis. - therefore impairs proliferation of b and t lymphocytes. - rapidly absorbed and highly protein bound. Onset in 2-6day. - metabolized by the liver to glucuronide and derivatives, and derivatives are excreted in the urine. S/ e Gastrointestinal upset. - visiting, diarrhea, anorexia, haem diarrhoea, necroenterocolitis reported in dogs with high doses. Myelosuppression, hepatopathy and pancreatitis reported in humans.

Question 32

Leflunomide

Answer 32

Prodrug of teriflunomide (metabolized in liver, intestines and plasma) 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

Question 33

Cyclosporine

Answer 33

Cyclic polypeptide of fungal origin. Lipophilic so Widely distributed, highly conc in erythrocytes. Effect in 24-48hr Metabolized by cytochrome 450, excreted in bile Mechanism: INHIBITS CALCINEURIN - binds to calcineurin and prevents dephosphorylation of the nuclear factor of activated T cells (NFAT) 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

Question 34

1. 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. 2. 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 3. 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 4. What is the most common adverse effect of glucocorticoids in pets? A) Hypoglycemia B) Polyuria and polydipsia C) Increased liver function D) Hypotension 5. 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 6. 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 7. 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. 8. 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 9. 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 10. What is a significant adverse effect of azathioprine (AZA) in dogs? A) Hepatotoxicosis B) Acute kidney failure C) Hypertension D) Hyperglycemia 11. 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 12. 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 13. 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 14. 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 15. 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 16. 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 17. Which of the following is a primary adverse effect of leflunomide in dogs? A) Diarrhea B) Cardiac arrhythmias C) Hyperglycemia D) Renal failure 18. 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 19. 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 20. 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

Question 35

Famcyclovir

Answer 35

Inhibits viral DNA polymerase, inhibiting replication of FHV

Question 36

Lysine

Answer 36

Antagonists arginine which is required for viral replication

Question 37

Interferon

Answer 37

Cytokines to limit cell to cell viral spread

Question 38

Side effect of enrofloxacin

Answer 38

Retinal degeneration in cats

Question 40

Lidocaine

Answer 40

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 ).

Question 41

Mexilitine

Answer 41

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.

Question 42

Thiazide diuretics

Answer 42

Distal consulted tubule Na Cl cotransporter inhibition S/e hyperglycemia, impair# potassium dependent insulin release

Question 43

Azidothymidine or zidovudine

Answer 43

Inhibit fiv reverse transcriptase Can reduce viral load S/e severe anaemia, neutropenia and GI signs