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ACVIM Specialty Exam (2023) > Tricky drugs > Flashcards

Tricky drugs Flashcards

1
Q

Emodepside
- MOA
- Indications
- Cats/dogs?
- Adverse effects

A
  • Anti-parasitic. Binds to latrophilin receptor presynaptically –> signal transmission cascade –> release of inhibitory neuropeptides into the synaptic gap –> induces inhibition & flaccid paralysis of the pharyngeal and somatic musculature of nematodes.
  • Effective against GI nematodes. Used for resistant hookworm infestation. Combo with praziquantel expands spectrum of activity to include cestodes +/- trematodes.
  • PO (dogs), topical (cats)
  • SE: dogs - minimal. Cats - licking/excessive grooming, scratching treatment site, salivation, lethargy, alopecia, agitation. V+. D+, ocular irritation, respiratory irritation, shaking/tremors.
  • HW testing before using drug, as can cause rapid death of microfiliaria –> fatal anaphylactic reaction.
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2
Q

Exenatide
- MOA
- Indications
- Cats/dogs?
- Adverse effects

A
  • Glucagon-like peptide-1 (GLP-1) receptor agonist. GLP = incretin hormone, secreted by GIT in response to food intake.
  • MOA: slow gastric emptying –> decrease post-prandial hyperglycemia; induce satiety. Roles in glucose homeostasis.
  • Adjunctive tx of Type 2 DM with insulin & diet (cats). Intermediate (BID) & extended release (q7d) formulations.
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3
Q

Rabacfosadine
- MOA
- Indications
- Adverse effects

A

MOA:
* Nucleotide analog antineoplastic prodrug.
* Preferentially taken up by lymphoid cells & metabolized to 9-(2-phosphonylmethoxyethyl guanine) –> inhibits DNA synthesis/repair after being doubly phosphorylated.

Indications: canine LSA (conditionally licenced drug)
* Naive cases (multi-agent) & relapsed cases (single agent - 74% response rate).
* More effective in B-cell vs T-cell LSA.
* 1mg/kg IV q21d

AE: dose-dependent
* Dermatopathy - otitis externa or focal erythematous skin lesions on dorsum & inguinal regions
* GI
* Neutropenia (less common)
* Idiosyncratic pulmonary fibrosis (PF) - rare but life-threatening, usually develops late post-tx (median 4-5mths).

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4
Q

Metamizole
- MOA
- Indications
- Adverse effects

A

Analgesic without negative impact on mucosal perfusion.
Anti-pyretic & spasmolytic agent.
MOA: inhibits central COX-3 & activation of the opioidergic + cannabinoid systems.

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5
Q

Dipyridamole
- MOA
- Indications
- Adverse effects

A

CURATIVE consensus (2022 update)
- Similar to clopidogrel. Anti-platelet drug - inhibit ADP-induced platelet aggregation
- HWD (reduce embolic risk from dead worms)

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6
Q

Ticlopidine
- MOA
- Indications
- Adverse effects

A

CURATIVE consensus (2022 update)
- Anti-platelet drug. Thienopyridine. Irreversibly blocks the P2Y12 component of ADP receptor on surface of platelets –> without ADP, fibrinogen cannot bind to platelet surface & promote aggregation.
- HWD (reduce embolic risk from dead worms)

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7
Q

Prasugrel, cangrelor, ticagrelor
- MOA
- Indications
- Adverse effects

A

Anti-platelet drugs
P2Y12 receptor inhibitor

P2Y12 receptor: crucial role in ADP-mediated generation of thromboxane A2 (another important platelet activator). Signaling events downstream of the P2Y12 receptor also potentiate agonist-induced dense granule release and procoagulant activity.

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8
Q

Dipyrone/Metamizole
- MOA
- AE

A

Centrally acting atypical NSAID
Inhibits peripheral COX-1 & COX-2 mediated production of PGs.
Also thought to inhibit PGE2 production via blocking COX 3 in the CNS (similar to acetaminophen)
+/- agonist activity on cannabinoid & opioid systems
+/- anti-spasmodic activity (bradykinin-induced spasms) on the GIT w/o significantly changing intestinal motility.

AE:
- V+, salivation
- Inhibits platelet aggregation (dogs) - bleeding. Increased risk of bleeding with SSRI, TCAs, other NSAIDs (contraindicated).
- Nephrotoxicity (increased risk with other amp B, aminoglycosides, cyclosporin, TMPS etc.)
- Myelosuppression (increased risk with chloramphenicol)
- Agranulocytosis (humans) - avoid drug direct contacting skin/injection
- Hepatocellular injury (increased risk if combined with panadol)

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9
Q

Milrinone
- MOA
- Indications
- AE

A
  • PDE 3 inhibitor in cardiac m. & vascular s.m. (same class as Pimobendan). Positive inotrope (contractions) & vasodilator (little chronotropic effects - ie HR). Reduces afterload & SVR.
  • Given IV
  • (In ACVIM PH consensus) - may improve RV function & act as a positive inotrope.
  • People: PHT, acute/chronic HF
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10
Q

Imatinib, Beraprost, Bosentan
- Collective main indication
- MOA

A

Novel drugs for treatment of pulmonary hypertension.
Imatinib: PDGF antagonist
Beraprost: Prostacyclin agonist
Bosentan: Endothelin-1 antagonist

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11
Q

Dirlotapide
- MOA
- Indications
- AE

A

Drug no longer marketed? (According to plumbs)

  • GI-selective microsomal triglyceride transfer protein inhibitor (inhibits intestinal triglyceride transport proteins) - blocks formation & release of lipoproteins into circulation. Reduced fat absorption + causes satiety signal (peptide YY) from lipid-filled enterocytes.
  • Management of obesity in dogs (suppresses appetite, increase faecal fat, promote weight loss)
  • SE (dose dependent) : V+ most common in 1st mth & 3-4hrs post dosing, D+, lethargy, anorexia, salivation, constipation, dehydration. Mild-moderate ALT elevation early in to (decreased over time) reported in clinical trials.
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12
Q

Sacubitril/valsartan (Entresto)
- MOA
- Indications

A

ARB/NEP inhibitor.

NEP (Neprilysin) = enzyme that cleaves natriuretic peptides protective against RAAS activation.
In people, drug was found to decrease RAAS activation, inhibit RAAS hormones, decrease breakdown of endogenous NPs & decrease the occurrence of aldosterone breakthrough (documented in 32% of MMVD dogs with CHF).

JVIM paper evaluated drug use in B2 MMVD dogs - no significant changes in clin path parameters, decreased urinary aldosterone/creatinine ratios. No SE noted but small study.

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13
Q

Fondaparinux
- Cats/dogs?
- MOA
- Indications
- SE

A
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14
Q

Altepase
- Cats/dogs?
- MOA
- Indications
- SE

A
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15
Q

Abciximab, tirofiban, eptifibatide
- Collective MOA
- Indications

A

Anti-platelet drugs
𝛼IIb𝛽3 integrin inhibitors

Platelet integrin αIIbβ3 receptor: binds soluble fibrinogen, vWF, fibronectin, and vitronectin –> essential for platelet aggregation.

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16
Q

Abciximab, tirofiban, eptifibatide
- Collective MOA
- Indications

A

Anti-platelet drugs
𝛼IIb𝛽3 integrin inhibitors

Platelet integrin αIIbβ3 receptor: binds soluble fibrinogen, vWF, fibronectin, and vitronectin –> essential for platelet aggregation.

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17
Q

Pirfenidone
- MOA
- Indications
- AE

A

MOA: antifibrotic, antioxidant, and anti-inflammatory effects.
Indications: idiopathic pulmonary fibrosis (people). Dogs unknown benefit. Topical eye drops trialled to prevent fibrosis post glaucoma shunt sx.

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18
Q

Nintedanib
- MOA
- Indications
- AE

A
  • Intracellular inhibitor of multiple tyrosine kinases with potent antifibrotic and anti-inflammatory effects
  • Indications: idiopathic pulmonary fibrosis (people). Dogs unknown benefit.
  • GI signs (even low doses)
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19
Q

Zidovudine (Azidothymidine) & tenofovir
- MOA
- Indications
- AE

A

Anti-virals. Nucleoside inhibitors of RNA reverse transcriptase.
Potential therapy for FIV & FeLV (good data for FIV, less effective for FeLV)
AE - BM suppression (as AZT also inhibits cellular polymerases)

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20
Q

Menatetrone
- MOA
- Indication

A
  • Vitamin K2 analogue
  • Used for MDS in cats, may promote differentiation of myeloid leukemic cell lines.
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21
Q

Ranolazine
- MOA
- Indication
- Contraindications

A
  • Inhibits late Na channels in atrial myocytes (suppresses depolarisation & myocyte excitement)
  • Potential treatment for AFib
  • Contra: uncorrected hypoK, hepatic impairment, congenital Q-T syndrome (people)
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22
Q

Ivabradine
- MOA
- Indications

A
  • Selectively inhibits the pacemaking I-f (funny) current in the SA node (Na inward current).
  • Negative chronotrope, without negative inotrope effects (so minimal effects on myocardial function).
  • Studies in MMVD (dogs), preclinical HCM & HCM-LVOTO (cats) but no strong recommendations for use yet.
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23
Q

Sacubitril/Valsartan
- MOA
- Indications

A

Sacubitril - inhibits neprilysin (enzyme which degrades natriuretic peptides)
Valsartan: ARB.
Anti-hypertensive as combo
Studies on use as RAAS inhibitor in stage B2 MMVD

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24
Q

Phentolamine
- MOA
- Indication

A

Short acting competitive alpha adrenergic blocker
Intraoperative hypertension during phaeochromocytoma removal sx

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25
Q

Metyrapone
- MOA
- Indication

A

Inhibitor of 11B-hydroxylase (converts 11-deoxycortisol to cortisol) & aldosterone synthase
- Potential HAC tx (no reports in vet med due to $$, limited availability)

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26
Q

Aminoglutethimide
- MOA
- Indication
- AE

A
  • Inhibits cholesterol to pregnenolone conversion as well as multiple other steroid hormone pathways
  • Tx HAC
  • SE: GI signs, liver enzyme elevations
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27
Q

Benzimidazole
- MOA
- Indication

A
  • Nitroimidazole anti-parasitic (drug family same as metronidazole)
  • Trypanosoma cruzi (Chagas disease)
28
Q

Methotrexate
- MOA
- Indication
- SE

A
  • Inhibits folic acid reductase & thus production of purine & pyrimidines. Cell cycle S-phase specific
  • Anti-neoplastic (CNS neoplasia). Potential use as a immunosuppressant - IMGN
  • SE: GI upset, BM suppression, nephrotox, CNS toxicity
29
Q

Vancomycin
- Drug class
- MOA
- Indication
- SE

A
  • Glycoprotein, inhibits cell wall (peptidoglycan) synthesis by binding to AAs. Inhibits baterial cell membrane permeability & affects bacterial RNA synthesis.
  • SE: nephrotoxicity, ototoxicity.
  • Indication: G+ infections only. Reserved for systemic life-threatening MDR Staph or Enterococcus. NB: bactericidal time-dependent abx, but is bacterioSTATIC agaginst Enterococcus.
30
Q

Fosfomycin
- Drug class
- MOA
- SE
- Indication

A
  • Synthetic phosphonic acid derivative
  • Irreversibly inhibits bacterial phosphoenolpyruvate required for bacterial cell wall peptidoglycan synthesis
  • SE: NEPHROTOXIC IN CATS (do not use). D+ in dogs.
  • Indication: MDR UTI, urinary excretion, prostatits, pyelonephritis
31
Q

Linezolid
- Class
- MOA
- Indications
- SE

A
  • Oxazolidinone antibiotic (restricted use; important in people)
  • Binds to the bacterial 23S ribosomal RNA of the 50S subunit&raquo_space; inhibits bacterial protein synthesis. Prevents the formation of the 70S initiation complex needed for the bacterial translation process.
  • Weak non-selective monoamine oxidase inhibitory effects.
  • Time-dependent.
  • MDR G+ infections. NB little safety data in vet patients. Bacteriostatic vs enterococcus & staphs, bactericidal vs streps.
  • ## SE: anaemia, thrombocytopenia. potentially GI
32
Q

Isoniazid
- MOA
- Indication
- SE

A
  • MOA: inhibits mycobacterial cell wall synthesis by inhibiting lipid & DNA synthesis.
  • May be used for chemoprophylaxis for animals housed with people with TB. Also part of tx for M bovis and M tuberculosis in dogs.
  • SE: hepatotoxicity, CNS signs, GI, thrombocytopenia, CVS
33
Q

Clofazimine
- Indication
- MOA
- SE

A
  • Antimycobacterial; may be used for non-tuberculous mycobacterial infections (leprosy-like, M avium).
  • NB: highly impt in people (multi drug protocol for leprosy tx)
  • Binds to mycobacterial DNA & inhibits growth
  • Some anti-inflammatory & IS effects
  • +/- activity against Leishmania spp.
  • Slowly bactericidal against myobacteria. INEFFECTIVE against most other bacteria, fungi, protozoa.
34
Q

Etomidate
- MOA
- Potential indications
- SE

A

Short acting IV anaesthetic agent (used for critical patients due to minimal CVS effects).
Suppresses adrenocortical function - study showed efficacious in cats. Potential use for HAC.

35
Q

Capromorelin
- MOA
- Indications
- Contraindications
- SE

A

Ghrelin-receptor agonist. Stimulates GH & IGF-1 release.
Also regulates pancreatic, cardiac, gastric function.
Anti-inflam & immunomodulatory effects.

Appetite stimulant (dogs not >4d, cats up to 21d for CKD)
Insulinoma (counteract hypoglycemia)

Avoid in HST cats. Caution - DM, hepatic dz, renal/cardiac dz, dehydration.
SE: anxiety, GI signs, PD, hypersalivation, abdo discomfort, lethargy. Increased BUN & phos reported.
Cats - UTI, URTI, CKD progression, hypotension & bradycardia (can be severe)

36
Q

Sulfonylureas
- Example of drug
- MOA
- Indication
- AE

A

Glipizide
Oral hypoglycemic. Insulin secretagogue - triggers release of stored insulin by exocytosis from beta cells.
Type 2 DM (cats) - 30-40% success
AE:
- Hypoglycemia
- V+ (usually subsides after 2-5d)
- Hepatotoxicity, increased LE, cholestasis – monitor q1-2wks, stop if CSX or if ALT >500
- HyperBIL, icterus – stop, restart when icterus resolved at lower dose ~2wks, stop permanently if recurs.
- May accelerate beta-cell loss - concurrent stimulation of amylin & insulin secretion). Amylin may form toxic intracellular fibrils or amyloid deposits within the pancreatic islet&raquo_space; further B-cell dysfunction & loss&raquo_space; permanent insulin dependency & pancreatic amyloidosis.
- Weight gain.

37
Q

Tadalafil, Vardenafil
- MOA
- Indications

A

PDE-5 inhibitors. Longer acting cf sildanefil.
Potential tx for PH in dogs (more studies needed)
Systemic hypotension, pulmonary oedema

38
Q

Milrinone
- MOA
- Indications

A

PDE3i (similar to pimobendan), given IV
Inodilator
Potential adjunct tx for canine PH (effective in experimental study), but need more data

39
Q

Levosimendan
- MOA
- Indications
- AE

A

Similar to pimobendan. Positive inotrope (calcium sensitization) + vasodilator (PDE3 inhibition).

40
Q

Bosentan, sitaxsentan, ambrisentan
- Drug class/MOA
- Indications

A

Endothelin-1 antagonists
Mediates vasodilation
Theoretical benefit in reducing PAP & pulmonary vascular resistance&raquo_space; tx PH (no data in dogs)

41
Q

Epoprostenol (IV), treprostinil (IV/SQ), iloprost (inhalant)
- Drug class/MOA
- Indications

A

Prostacyclin analogues
Vasodilator + platelet inhibitor
Tx of PH (people, $$ & impractical in dogs)

42
Q

Dihydrotachysterol (DHT)
- MOA
- Indications
- AE

A
  • Synthetic Vit D analogue, doesn’t require renal activation (hydroxylation) like Vit D2 or D3. Rapid onset of action, shorter half-life, greater effect on mineralization of bone salts vs Vit D.
    Indications:
  • PLE dogs with hypovit D (consideration rather than strong recommendation). Rickets (people).
  • Primary hypoPTH (dogs)
43
Q

Tetrahydrolipstatin
- MOA
- Indications
- What must be supplemented when administering this drug?

A

Reversible inhibitor of gastric lipase, inhibits TG hydrolysis & FFA absorption. Used for weight loss (in conjunction with diet).
Must supplement fat-soluble vitamins (THL interferes with absorption).

44
Q

Dirotapide & miratapide
- Drug class?
- MOA?
- SE

A

Microsomal Triglyceride Transfer Protein (MTP) Inhibitors

Interfere with intestinal fat absorption + reduce appetite.
- Achieves these by reducing formation of chylomicrons from FAs & proteins in cytoplasm of enterocytes –> intracellular fat accumulation stimulates peptide YY release from enterocytes into the circulation. Peptide YY = peripheral hormone that helps to regulate food intake by suppressing appetite & producing a satiating effect in the hypothalamus (and other centers of the brain).
Promotes SLOW but constant weight loss. DIrlotapide given continuously, mitratapide given in 2-3 wk pulse tx (with 2-3wk break).
SE: V+, D+, altered liver function tests.

45
Q

Aliskiren
- MOA
- Indications

A

Direct renin inhibitor
Systemic hypertension (people). No studies in dogs/cats yet.

46
Q

Eplerenone
- MOA

A

Synthetic mineralocorticoid antagonist
(more selective for mineralocorticoid atagonist than spironolactone; less risk of AE from androgen receptor binding (inhibit testosterone binding & increase estradiol levels).

47
Q

Candesartan, irebsartan, valsartan
- Drug class, MOA

A

Angiotensin receptor blocker (block ATII binding to Type 1 receptors (AT1-R))

48
Q

Methysergide
- MOA
- Indication

A

Serotonin receptor antagonist
Tx Scottie cramp - should see improvement in 2hrs

49
Q

Tiludronic acid
- Drug class
- MOA

A

Bisphosphonate
Bind to hydroxyapatite in bone –> reduce bone resorption & destruction by inhibiting osteoclast activity.

50
Q

Methenamine mandelate
- MOA
- Indication

A

Antibiotic.
Limited use to urinary tract dz.
Releases formaldehyde & ammonia on hydrolysis.
Bactericidal in acidic environment, needs acidic urine to work. Less effective with urease-producing bacteria

51
Q

Oseltamivir (Tamiflu)
- MOA
- Indications

A

Anti-viral. Neuraminidase inhibitor. (Neuraminidase = surface glycoprotein of influenza A and B. It cleaves sialic acid residues on the surface of infected cells, allowing new virus particles to be released from host cells. It also prevents aggregation of virus particles after they are released and facilitates spread of the virus through the mucus of respiratory tract by cleaving sialic acid residues in mucin.)

influenza virus , adjunctive tx in canine parvovirus (CPV) enteritis - may limit viral ability to pass through intestinal mucosa & infect intestinal crypt cells.

52
Q

Decoquinate
- MOA
- Indications

A

Coccidiostat. Quinolone derivative.
Inhibits protozoal mitochondrial electron transport & interferes w/ sporozoite development.

Adjunctive tx for hepatozoonosis (dogs), Sarcocystis myositis (dogs)

53
Q

Imidocarb diproprionate
- MOA
- Indications
- AE

A
  • Combines with protozoal DNA nucleic acids, causes DNA to unwind & denature, inhibits cell repair & replication. Also alters parasite’s ability to regulate glucose.

Note extra-label in cats & dogs.
Babesia spp. (more effective in canis > gibsoni), Hepatozoon canis (doesn’t eliminate gamonts) & Americanum. Ehrlichiosis – doesnn’t clear organism. +/- cytauxzoonosis, feline hemoplasmosis (Bartonella, mycoplasma). IM/SQ (not IV).

AE: cholinergic signs activity (premed with atropine). Acute hepatic or renal tubular necrosis possible. Hepatic injury, pain/swelling at injection site. Incr CK, oncogenic. Narrow therapeutic index (9.9mg/kg is toxic).

54
Q

Colchicine
- MOA
- Indications
- AE

A

**Anti-fibrotic **(collagenase activity stimulation).
Alkaloid that binds to b-tubulin; inhibits cell division during metaphase by interfering with sol-gel formation & mitotic spindle assembly
Anti-inflammatory - modulates chemokine & prostanoid production, inhibits neutrophil & endothelial cell adhesion molecules, eventually decreases neutrophil degranulation, chemotaxis, and phagocytosis.
Blocks synthesis & secretion of SAA (APP) by hepatocytes.

  • Sharpei fever, amyloidosis (before renal insufficiency). Plumb’s says adjunct tx for hepatic fibrosis/cirrhosis but NOT proven to be beneficial.
  • AE: COMMON. BM suppression, neuro signs, anorexia, D+
55
Q

Hydralazine
- MOA
- Indications

A

Semicarbazide-sensitive amine oxidase (SSAO) inhibitor.
Systemic arterial vasodilator (arterioles > veins). Acts on vascular s.m., reduces SVR & BP. essure (BP).
Alters cellular Ca metabolism in s.m., interferes with Ca mvts & prevents initiation and maintenance of the contractile state.
Adjunct tx for CHF, systemic hypertension

56
Q

Amrinone, milrinone, cilostazol
- Drug class, MOA
- Indications

A
  • PDE-III inhibitors (similar to pimobendan)
  • Inhibit cAMP + Ca-sensitizing effect on myocardial contractile proteins (increase affinity of cTnC for Ca2+)
  • Balanced (A + V) vasodilation –> reduces preload & afterload
  • Provide inotropic support e.g. acute management of DCM, MMVD
57
Q

Triamterene
- MOA

A

K+ sparing diuretic

58
Q

Dabigatran etexilate
- MOA

A

Direct oral thrombin (FII) inhibitor

59
Q

Methenamine
- MOA
- Potential indications
- AE

A

Antiseptic, metabolised to formaldehyde. Non-specific antibacterial effects.
- Activity vs G+ (Staphs, Enterococcus), G- (E. coli, Enterobacter spp, Klebsiella spp, Proteus spp, Pseudomonas). Some effects against fungal UTIs.
- Less effective vs urease-producing bacteria (drug also increases urine pH). aeruginosa), but may be less effective against those bacteria that produce urease (and increase urine pH).
- Extra-label for recurrent UTI (no evidence to support use)
- AE: avoid in liver dz - drug produces NH3, metabolic acidosis. Avoid co-admin with sulfonamides, renal dz

60
Q

Labetalol
- MOA
- Indications

A

Alpha & beta adrenergic blocker
Emergency tx for hypertensive crisis

61
Q

Aglepristone
- MOA
- Indication

A

Synthetic steroid. Competitive progesterone receptor antagonist. 3x affinity (dogs) & 9x affinity (cats) for uterine P4 receptors cf endogenous P4.

Tx of progestogen-induced HST in dogs (if OVH is not an option) - improves glycemic control with insulin therapy.
(Also termination of pregnancy, induction of parturition, adjunctive tx for pyometra).

62
Q

Oxybutinin
- MOA
- Indications

A

Urinary antispasmodic. Direct antimuscarinic (atropine-like) & spasmolytic (papaverine-like) effects on smooth muscle. Spasmolytic effects predominant on the detrusor muscle (bladder) & GIT, no effects on vascular s.m.

Overactive bladder in dogs

63
Q

Streptozocin
- MOA
- Indications
- AE

A
  • Alkylating agent
  • Refractory insulinoma - mets or non-resectable (acts on GLUT-2 receptors on panc beta cells, liver, GIT)
  • Highly nephrotoxic (PT necrosis & vacuolization, Fanconi-type syndrome, nephrogenic DI), myelotox, hepatotox
64
Q

Amiloride, triamterene
- MOA
- Indications

A
  • Na channel blockers (K+ sparing)
  • DISTAL nephron diuretics
  • Similar MOA as MRAs (spironolactone), but differs by acting directly on luminal membrane Na channels to inhibit Na influx > decreases Na+/K+ ATPase pump activity on the basolateral membrane > decrease Na reabsorption & K excretion.

Used to increase efficacy & counteract K+-wasting effects of proximal site diuretics. E.g. refractory CHF.

65
Q

Nifedipine
- MOA
- Indications

A

Calcium channel blocker - s.m. relaxation
Ureteral obstruction (medical expulsive therapy)

66
Q

Labetalol
- MOA
- Indications

A

Alpha & beta adrenergic blocker
Emergency tx for hypertensive crisis

ACVIM Specialty Exam (2023) (20 decks)

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