Pharmacology Flashcards
What is the MOA of Mycophenolate Mofetil?
Humoral -mediated immunity,S-phase(DNA)
* Prodrug of mycophenolicacid(MPA)— needs to be hydrolyzed to be active
* Inhibits inosine monophosphate dehydrogenase (IMPDH)
* IMPDH = enzyme necessary for de novo purine synthesis
* Type2IMPDH(lymphocytes)»Type1(mostcells)
* Inhibits B- and T-cell proliferation and clonal expansion
* Downregulates expression of adhesion molecules
What are the adverse effects of Mycophenolate Mofetil?
- GI (anorexia, vomiting, diarrhea) * (Papillomatosis)
- (Allergic reactions)
What is the MOA of leflunomide? SE?
PYRIMIDINE SYNTHESIS INHIBITOR that inhibits autoimmune T-cell proliferation + AB production of B-cells
- Reversible inhibition of dihydro-orotate dhydrogenase
Prodrug that is metabolized by intestinal mucosa and liver to active metabolite (teriflunomide)
SE: GI, eles, hemorhage, leukopenia, thrombocytoenia, anemia, hypercholestelonemia
How is mycophenolate excreted and metabolized?
Enterohepatic recirculation – secondary plasma
peak 4-12 hours after oral administration
90% excreted in urine, mostly as MPAG
What are the adverse effects of leflunomide?
- GI (anorexia, vomiting, diarrhea)
- Spontaneous bleeding
- Myelosuppression
- Hepatotoxicosis
What is the MOA of chlorambucil?
- Alkylating agent: cross links DNA
- Humeral and cell-mediated immunity
- B cells > T cells
- Cell-cycle-NON-specific
- Prodrug
- Liver→active metabolite (Phenylacetic acid)
What are adverse effects of chlorambucil?
- GI (anorexia, vomiting, diarrhea)
- Myelosuppression (delayed- 1 month)
- Alopecia (esp. Poodles)
- Neurological side-effects in cats
What is the MOA of cyclophosphamide (cytoxan)?
- Alkylating agent:crosslinksDNA
- Humeral and cell-mediated immunity
- B cells > T cells * Prodrug
- Liver→4-hydroxycyclophosphamide + acrolein
Safe for MDR
What are the adverse effects of cyclophosphamide?
- Acrolein→sterile hemorrhagic cystitis - Furosemide might reduce risk
- GI
- Alopecia (esp. Poodles)
- Myelosuppression
What is the MOA of glucocorticoids?
- Humoral and cell-mediated immunity
Cytoplasmic receptor with DNA sequence binding
(1) ↓ mononuclear phagocytic activity: ↓ Fc receptor expression;
↓ macrophage antigen presentation to TH (immediate)
(2) Elution of antibodies from surface of target cells (immediate)
(3) ↓ inflammatory cell migration into tissues (immediate)
(4) Suppress production of immunoglobulins (delayed)
What are adverse effects of glucocorticoids?
- Iatrogenic hyperadrenocorticism
- (GI ulceration)
- Recurrent UTI
- Pancreatitis
- Diabetogenic
What is the MOA of cyclosporine?
Calcineurin inhibitor
Immunosuppressive that focuses on cell-mediated immunity (T-lymphocytes)
Binds intracellular receptors immunophilins (cytophilin) –> Inhibits calcineurin (phosphatase) blocking dephosphorylation of NFAT (transcription factor)
Inhibits IL-2,Il-3,IL-4,TNF-alpha
Cytochrome P450A - enterocytes and liver
It’s a substrate of P-glycoprotein - enterocytes
What are the side effects of cyclosporine?
- GI (anorexia, vomiting, diarrhea)
- Gingival hyperplasia
- Hypertrichosis, hirsutism
- Papillomatosis
- (heptatotoxicosis,nephrotoxicity),(lymphoma)
Is cyclosporine to be given with or without food?
Food decreases oral absorption (dogs, not cats)
What is the MOA of azathioprine?
Thiopurine (purine [adenine, guanine] analog)
Cell-mediated immunity, especially lymphocytes
S-phase (DNA)
What breeds have reduced activity of TPMT? What does this mean?
- REDUCED ACTIVITY: Giant Schnauzers, CATS
➔↑ risk of myelosuppression
What breed has increased activity of TPMT?
Alaskan Malamutes
Any contraindications between allopurinol and azathioprine?
- Dose reduce if receiving allopurinol (XO inhibitor)
What are the adverse effects of azathioprine?
- GI (anorexia, vomiting, diarrhea)
- Myelosuppression (leukopenia > anemia,
thromobytopenia) - Hepatotoxicosis (idiosyncratic)
- Secondary infections
- Acute pancreatitis
What is the MOA of zolendronate? SE?
Inhibit osteoclast mobilization of
bone.
SEs- nephrotoxicity, esophagitis/e-stricture, nausea, diarrhea, hypocalcemia,
hypophosphatemia, hypomagnesemia
What is the MOA of Toceranib (Palladia)? What it is used for? What are the SE?
Receptor Tyrosine Kinase Inhibitors
MCT, AGASACA, GIST, Metastatic OSA
SEs- GI ulceration, proteinuria, myelosuppression, GI, muscle and joint pain, hypopigmentation
What is the MOA of Diazoxide (benzoderivative)? What is it used for?
MOA. - inhibits insulin secretion from pancreatic B-cells by inhibition of the ATP-dependent K+ channel
Used for insulinomas
What is the MOA of Streptozoon? Uses? SE?
MOA: cytotoxic to pancreatic B-cells
SEs- nephrotoxic, diabetes, vomiting
Uses: insulinoma
What is the MOA of ketoconoazole and SE?
Ketoconazole- cytochrome P450 inhibitor inhibits multiple enzymes in the steroid synth. path.
Hepatotoxicity
What are H2 receptor blockers?
famotidine, ranitidine, cimetidine (also inhibits P450)
What are H1 receptor blockers?
diphenhydramine, phenothiazines, meclizine, dimenhydrinate
What is the MOA of amphotericin B? SE?
macrolide antibiotic that binds to the ergosterol in the cell membrane and
alters its permeability –> leakiness and cell death
SEs- nephrotoxicity by binding to renal tubular epithelium, acute anaphylaxis
What are first tier abx?
-cephalosporins (cefpodoxine, cefocevin)
-amoxicillin clauv
-clindamycin
-potentiated sulfas
What are second tier abx?
-doxy, minocycline
-chloramphenicol
-fluoroquinolones
-rifampin
- ahminoglycosides
What are third tier abx?
-linazolid
-vancomycin
-teicoplanin
MOA of cerenia (maropitant)
Neurokinin-1 receptor antagonist
Inhibit binding of substrate P to NK1R in vomiting center, CTZ< GIT
Visceral analgesia, anti-inflammatory
MOA ondansetron
5HT3 receptor ANTAGONIST
Inhibits serotonin-induced stimulation of afferent
MOA cisapride
5HT-4 receptor AGONIST - enhances release of Act at myenteric plexus w/o stimulating nicotinic or muscarinic receptor or without inhibiting acetylcholinesterase activity
5HT2alpha receptor AGONIST on colonic smooth muscle
5HT1 + 5HT3 ANTAGONIST of cholinergic neurons
MOA erythromycin
Prokinetic, macrolide abx
Bacteriostatic, unless high concentrations or Strep
Time dependent
Macrolines bind 50S ribosomal unit
MOA doxycycline
Tetracyclin abx
Time dependent, bacteriostatic abx - inhibits protein synthesis by reversibly binding to 30S ribosomal subunit
Tetracyclines used for: most Mycoplasma, spirochetes (including Borrelia burgdorferi, Lepto, Chlamydia, Anaplasma, Ehrlichia, Rickettsia), some Mycobacterium spa
Some gram positive activity
What defect is found in herding breeds that cautions to use certain medications?
4-bp deletion in the ABCB1 gene (previously MDR1 gene)
What chemotherapeutics are not safe for dogs. with ABCB1 gene depletion?
Doxorubicin
Mitoxantrone
Vincristine
Vinblastine
Paclitaxel and docetaxel
What is the MOA of slentrol?
Not on the market anymore
Dirlotapide - triglyceride transfer protein inhibitor –> blocks trig uptake into enterocytes an causes satiety
MOA and SE ifosfamide
Antineoplastic
Alkylating agent
chemical reactivity is nonspecific - alkylation of cancer cell DNA strains
SE: neutropenia, damage to urinary bladder epithelium, nephrotoxic (primarily on prox and distal tubules), GI signs, neurotoxic, alopecia, ELEs
MOA of clopidogrel
ADP receptor (PY2) binds irreversibly
Chemo drug that cases arrest in M-phase
Vincristine, vinblastine, Paclitaxel and docetaxel
Chemo drug that effects S-phase
Cytosar, Gemcitabine, 5-FU
Alkylating chemo drugs
Chlorambucil
Melphalan
Cycloposphamide
Lomustine
Dacarbazine
Streptozotocin
platinum chemo drugs
Cisplatin, carboplatin
MOA and SE diazoxide
Direct vasodilator/hyperglycemic
Activates K channels
Used to tx insulinomas - most common SE hyper salivation, V, D, tachycardia
SE: hematologic abnormalities (agranulocytosis, aplastic anemia, thrombocytopenia), pancreatic, DM, cataracts, Na/H2o retention
MOA and SE oclacitinib
Apoquel
JAK kinase ibhibitor
Antipruritic, anti-inflammatory
SE (most common): diarrhea, vomiting, anorexia
MOA and SE amphotericin B
Antifungal
Binds to sterols (primarily ergosterol) in fungal cell membrane
SE: nephrotoxic (renal vasoconstriction reduces GFR
Lipid complex and liposomal - more hydrophobic so reduces nephrotoxic qualities– mediates uptake in reticuloendothelial cells in liver and decreases dose to kidneys
MOA pimobendan
Ca2+ sensitizer (via PDEi3i)
Vasodilator
MOA TMS
Potentiated sulfonamide antimicrobial – inhibit enzymes in folic acid pathway –> inhibit bacterial thymine synthesis
Bacteriostatic - sulfonamides
Bactericial - trimethoprim
Spectrum
-Gram positive (Nocardia, most streptococci, staphylococci)
-Gran neg (Enterobacteriaceae)
-Good penetration to PROSTATE
Inefective against: Pseudomonas, protozoa (Pneumocystis, Coccidia, Neospora, Toxo)
SE: KCS, acute neutrophilic hepatitis w icterus, V, D, fever, hemolytic anemia, urticaria, facial swelling, PUPD, cholestasis
-Clinical hypothyroidism
-Acute hypersensitivity – type I (anaphylaxis), type III (formation of antigen:ab complex) - more common in large dogs (Doberman, Samoyeds, mini schnauzer)
MOA and SE enrofloxacin
Fluoroquinolone
Inhibit bacterial topoisomerase II (DNA gyrase) + topoisomerase IV –> prevent DNA supercoil and synthesis
Bactericidal and concentration dependent
SE: GI, rarely ELEs, ataxia, seizures
Cats: ocular toxicity (mydriasis, retinal degeneration, blindness)
- cats have AA changes in ABCG2 transporter in BBB
Articular cartilage abnormalities in young, growing animals
MOA and SE propantheline
Quaternary antimuscarinis -antispasmodic/antisecretorry effects of diarrhea
Use: AV block, detrusor hyperreflexia or urge incontinence
MOA: antimuscarinic (similar to atropine)
-does not cross BBB
SE (similar to atropine): dry mouth an eyes, urinary hesitancy, tachycardia, constipation
-V, hypersalivation cats
Drug to use for inflammatory brain disease
Cytosar -affects S-phase
SE: myelosupppression, decreased PLT
MOA and SE calcitriol
Vitamin D analog
Bind yo vite receptors to decrease PTH
How do we tx Babesia Gibson?
Atovaquone and azithromycin
MOA and SE Atovaquone
Oral antiprotozoal agent
With azithro - also good for tx cats w/Cytauxzoon
MOA: targets protozoan mitochondrial electron transport
SE: vomiting
What is the tx for Pneumocystosis in dogs
First line: Potentiated sulfonamides
Second line: Atovaquone
MOA and SE of azithromycin
Macrolide abx
Bacteriostatic
MOA: Inhibit protein synthesis of 50S ribosomal subunits in bacteria
Use: tx of bacteria, rickettsial, protozoal info, reduce gingival hyperplasia caused by cyclosporine, canine papillomatosis
SE: GI
How to tx Cytaux
Atovaquone and azithromycin
What drug do we give a pheochromocytoma? MOA? SE?
Phenoxybenzamine
MOA: non-selective alpha adrenergic antagonist, vasodilador – chemical sympathomimetic
No effects on beta or PNS
SE: associated with alpha blockade (hypotension, weak, dizzy, GI, meiosis, increased IOP, Na retention, tachycardia
What drug is the primary to use ion USMI? MOA? SE?
Phenylpropanolamine (Proin)
MOA: non-selective alpha AGONIST -sympathomimetic - indirectly stimulates alpha and to less extent beta (release of NE)
Side effects: hypertension, restlessness/anxiety, tachycardia, increased IOP, hepatic glycogenolysis
MOA L-asparagonase?
-enzyme derived from E. colia dn wrinia carotovora
MOA: catalyzes asoaraginase into ammonia + aspartic acid
SE: *Hypersensitivity after repeated uses -hypersensitivity reactions (including anaphylaxis)
-elevated liver enzymes (reversible)
-hypercoagulability with thrombous formation
-pancreatitis (dogs only)
-myelosuppression (less common), moreso when combined with vincristine
How to tx tritrichomonas? SE/MOA?
Ronidazole
MOA: 5-niitroimidazole - converted by hydrogenosome into polar autootix anion radicals
SE (similar to metro): tremors, ataxia, seizure, neurotoxicity
What medication to give during acetaminophen toxicity? SE?
Silymarin (milk thistle) - liver protectant
SE: V, anorexia, itching
Tx for copper toxicity?
D-penicillamine
MOA: chelating agent (Cu, Fe, mercury)
SE: -anorexia, vomiting, diarrhea – frequent! (giving with food can decrease this)
-teratogen
-long term effects: anemia (normocytic or microcytic) and glycogen storage of liver, glomerulonephritis, proteinuria
MOA and SE trilostane?
MOA: competitive inhibitor of 3-B-hydroxysteroid dehydrogenase
SE: electrolyte derangements (hypoNa, hyperK, , V, D, A
MOA/SE PENICILLINS?
MOA:
-Inhibit penicillin binding proteins (PBP) – enzymes involved in building bacterial cell wall
-Only active against rapidly multiplying organisms
-Gram negative lipopolysaccharide decreases antibiotic penetration
-Time dependent
-Bactericidal
-low VD
MOA of panoquell
Leukocyte function-associated antigen 1 (LFA-1) antagonist
