Tricky drugs Flashcards
Emodepside
- MOA
- Indications
- Cats/dogs?
- Adverse effects
- 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.
Exenatide
- MOA
- Indications
- Cats/dogs?
- Adverse effects
- 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.
Rabacfosadine
- MOA
- Indications
- Adverse effects
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).
Metamizole
- MOA
- Indications
- Adverse effects
Analgesic without negative impact on mucosal perfusion.
Anti-pyretic & spasmolytic agent.
MOA: inhibits central COX-3 & activation of the opioidergic + cannabinoid systems.
Dipyridamole
- MOA
- Indications
- Adverse effects
CURATIVE consensus (2022 update)
- Similar to clopidogrel. Anti-platelet drug - inhibit ADP-induced platelet aggregation
- HWD (reduce embolic risk from dead worms)
Ticlopidine
- MOA
- Indications
- Adverse effects
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)
Prasugrel, cangrelor, ticagrelor
- MOA
- Indications
- Adverse effects
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.
Dipyrone/Metamizole
- MOA
- AE
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)
Milrinone
- MOA
- Indications
- AE
- 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
Imatinib, Beraprost, Bosentan
- Collective main indication
- MOA
Novel drugs for treatment of pulmonary hypertension.
Imatinib: PDGF antagonist
Beraprost: Prostacyclin agonist
Bosentan: Endothelin-1 antagonist
Dirlotapide, Mitratapide
- MOA
- Indications
- AE
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.
Sacubitril/valsartan (Entresto)
- MOA
- Indications
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.
Fondaparinux
- Cats/dogs?
- MOA
- Indications
- SE
Abciximab, tirofiban, eptifibatide
- Collective MOA
- Indications
Anti-platelet drugs
𝛼IIb𝛽3 integrin inhibitors
Platelet integrin αIIbβ3 receptor: binds soluble fibrinogen, vWF, fibronectin, and vitronectin –> essential for platelet aggregation.
Pirfenidone
- MOA
- Indications
- AE
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.
Nintedanib
- MOA
- Indications
- AE
- 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)
Zidovudine (Azidothymidine) & tenofovir
- MOA
- Indications
- AE
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)
Menatetrone
- MOA
- Indication
- Vitamin K2 analogue
- Used for MDS in cats, may promote differentiation of myeloid leukemic cell lines.
Ranolazine
- MOA
- Indication
- Contraindications
- 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)
Ivabradine
- MOA
- Indications
- 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.
Sacubitril/Valsartan
- MOA
- Indications
Sacubitril - inhibits neprilysin (enzyme which degrades natriuretic peptides)
Valsartan: ARB.
Anti-hypertensive as combo
Studies on use as RAAS inhibitor in stage B2 MMVD
Phentolamine
- MOA
- Indication
Short acting competitive alpha adrenergic blocker
Intraoperative hypertension during phaeochromocytoma removal sx
Metyrapone
- MOA
- Indication
Inhibitor of 11B-hydroxylase (converts 11-deoxycortisol to cortisol) & aldosterone synthase
- Potential HAC tx (no reports in vet med due to $$, limited availability)
Aminoglutethimide
- MOA
- Indication
- AE
- Inhibits cholesterol to pregnenolone conversion as well as multiple other steroid hormone pathways
- Tx HAC
- SE: GI signs, liver enzyme elevations
Methotrexate
- MOA
- Indication
- SE
- 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
Vancomycin
- Drug class
- MOA
- Indication
- SE
- 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.
Fosfomycin
- Drug class
- MOA
- SE
- Indication
- 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
Linezolid
- Class
- MOA
- Indications
- SE
- Oxazolidinone antibiotic (restricted use; important in people)
- Binds to the bacterial 23S ribosomal RNA of the 50S subunit»_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
Isoniazid
- MOA
- Indication
- SE
- 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