Pharmacology (not done) Flashcards
What is the MOA of lidocaine/pramoxine?
Sodium channel antagonist –> interferes with impulse production and action potential in nerves
What is the MOA of capsaicin?
TRPV1 agonist on C nerve fibers –> depolarization and neural desensitization
What is the MOA of topical menthol?
TRPM8 antagonist –> cooling sensation (no major benefits in dogs to date)
What is the MOA of antihistamines?
H1 receptor antagonists –> competitively block formation of histamine-receptor complex
What is the MOA of maropitant for itch?
Neurokinin-1 receptor inhibitor
What is the MOA of lokivetmab?
Anti-canine IL-31 mAB –> binds to circulating IL-31 and prevents it binding to its receptor
What is the MOA of ranevetmab?
Anti-canine nerve growth factor mAB (fails to prevent atopic itch)
What is the MOA of gabapentin and pregabalin?
GABA analog (inhibitory neurotransmitter) –> inhibits voltage-gated Ca channels in spinal cord –> reduces central neural hypersensitization
What is the MOA of topiramate?
NMDA receptor antagonist –> increases GABA activity and inhibits glutamate activity –> less neuronal excitability
What is the antipruritic MOA of butorphanol?
Mixed kappa-opioid agonist and mu-opioid antagonist
Would naloxone be potentially antipruritic?
Yes because it is a mu-opioid antagonist
What is the antipruritic MOA of amantadine?
NMDA receptor antagonist –> less neuronal excitability
What is the MOA of amitriptyline?
Tricyclic SSRI –> inhibits reuptake of serotonin –> increased neural impulses
What is the MOA of clomipramine?
Tricyclic SSRI –> inhibits reuptake of serotonin
(potent SSRI but not very specific)
What is the MOA of fluoxetine?
Bicyclic SSRI–> inhibits reuptake of serotonin
(very selective)
What is the MOA of doxepin?
SNRI –> inhibits reuptake of serotonin and norepi –> increased neurotransmission
Also has potent anti-H1 receptor properties
What is the MOA of mirtazapine?
SNRI –> antagonizes serotonergic and noradrenergic receptors
(useful for nocturnal pruritus)
How does vitamin E help in treatment of SNP?
Reduces damage from lipid peroxidation
What drug has been associated with a drug-induced panniculitis?
KBr
What is the MOA of itraconazole?
inhibits 14alpha demethylase –> prevents conversion of lanosterol to ergosterol
At which pH is oral itraconazole best absorbed?
Acidic (so giving with food helps)
What cutaneous adverse effect has been associated with itraconazole in dogs?
Vasculitis/ulcers (>10 mg/kg dose)
What is the MOA of ketoconazole?
Inhibits lanosterol 14alpha demethylase –> ergosterol depletion, accumulation of toxic sterols in the cell membrane
Which antifungal interferes with endogenous steroid synthesis?
Ketoconazole
What azole does not require food for optimal absorption?
Fluconazole
Which oral antifungal medication has the highest MIC (and thus the least efficacy) against dermatophytes?
Fluconazole
What is the MOA of terbinafine?
reversibly inhibits squalene epoxidase –> prevents conversion of lanosterol to cholesterol/ergosterol
Does terbinafine affect cytochrome P450?
No
What oral antifungal has the lowest MIC against Microsporum sp. and Trichophyton spp?
Terbinafine
What is the MOA of griseofulvin?
Arrests metaphase –> inhibition of nucleic acid synthesis and cell mitosis
Interferes with spindle microtubules
What is a potential side effect of griseofulvin in cats?
Bone marrow suppression (idiosyncratic)
What is the MOA of lufenuron for dermatophytosis?
disrupts chitin synthesis (this drug is NOT recommended for tx)
What are the primary side effects of meglumine antimoniate?
Cellulitis/abscesses at injection site
Nephrotoxicity
What is the MOA of allopurinol for tx of Leishmania?
Hypothanine compound –> metabolized by Leishmania and produces an inosine analogue –> analogue incorporated into Leishmania RNA –> faulty protein translation and inhibition of multiplication
How should allopurinol be administered?
Orally with a low purine diet
How does marbofloxacin help with treatment of Leishmania?
Increases production of NO by macs –> increased kill
Stimulates TNF-a production
When should TT4 be assessed for a patient on once-daily dosing of thyroid supplement?
Pre-pill/at time med is due (>1.5 mcg/dL is adequate)
What medication is FDA-approved for treatment of Cushing’s disease?
Trilostane
You have a dog on unequal doses of trilostane BID. After which dose should an ACTH stim be done for dose monitoring?
3-5 hr after the higher dose is given
How long should glucocorticoids be withdrawn prior to an ACTH stim or LDDST?
Oral/otic/opthalmic short-acting: 2 weeks
long acting: 4 weeks
At what time of day should a blood sample be collected when monitoring a hyperthyroid cat on methimazole?
Any time of day (does not matter when the med was given)
What is the effect of food on absorption of levothyroxine?
Reduces absorption (best given on empty stomach)
What is the MOA of methimazole?
Inhibits thyroid peroxidase
What are the main SE of lomustine?
Myelotoxicity
What is the MOA of doxorubicin?
Antitumor antibiotic that inhibits topoisomerase II
What is the MOA of imiquimod?
Activation of TLR7 –> secretion of IFN-a, TNF-a, IL-6
Activation of Langerhans cells
Activation of macs, NK cells, B-cells
What type of cells are targeted by palmitoylethanolamide (PEA)?
Mast cells
What is the MOA of PEA?
Mast cell stabilizer
What causes PEA to be released by the body?
Stress and tissue damage
True or false: skin levels of PEA are higher in healthy dogs compared to atopic dogs
False - they are 30-fold higher in atopic dogs
What is the active ingredient in Redonyl Ultra?
Ultra-micronized palmitoylethanolamide (PEA)
Are glucocorticoids lipophilic or non-lipophilic?
Lipophilic
Where are glucocorticoid receptors located?
In the cell cytoplasm
What occurs after a glucocorticoid binds to its receptor in the cytoplasm?
It translocates into the nucleus via importins
What does a ligand-bound glucocorticoid receptor bind to within the cell nucleus to reduce inflammation?
Glucocorticoid response elements (+GREs)
What genes are produced once a +GRE is bound by a ligand-bound glucocorticoid receptor?
Annexin-A1 (ANAX1)/lipocortin 1
GC-induced leucine zipper (GLIZ)
Mitogen-activated protein kinase phosphatase 1 (MPK1)
Besides directly interacting with DNA, how else can glucocorticoid receptors affect gene transcription?
Tethering: interaction with transcription factors themselves
What family of proteins is synthesized when a ligand-bound glucocorticoid receptor binds to DNA?
IkBs
How to IkBs affect inflammation?
They inhibit NF-kB, a major transcription activator for inflammation
How do glucocorticoids affect NF-kB?
They increase the amount of IkBs, which inhibit NF-kB activity
What 2 DNA sequences can ligand-bound glucocorticoid receptors bind to?
+GREs
nGREs
How do glucocorticoids affect leukotriene synthesis?
They enhance lipocortin production –> inhibits PLA2 –> interrupts arachidonic acid metabolism –> less leukotriene synthesis
What type of T-cells are primarily inhibited by glucocorticoids?
Th1
What cytokines are reduced by glucocorticoids?
IL-1
IL-6
IL-8
IL-12
TNF-a
IFN-gamma
(Th1 cytokines)
What cytokines are upregulated by glucocorticoids?
IL-4
IL-10
IL-13
What transcription factor is upregulated by glucocorticoids and what cell type is subsequently upregulated?
FoxP3
Treg cells
In which species do glucocorticoids not have any effect on neutrophil phagocytosis?
Horses
Goats
How do glucocorticoids reduce acute inflammation?
Prevent vasodilation and prevent increased vascular permeability
Which glucocorticoids have less sodium retention activity?
Prednisone/prednisolone
methylprednisolone
Which glucocorticoid has a high degree of sodium retention activity?
Hydrocortisone
What enzyme converts prednisone to prednisolone and where does this occur?
11-beta-hydroxysteroid dehydrogenase type 1
Liver
A dog with hepatic disease requires glucocorticoids. You have a choice between prednisone and prednisolone - which should be chosen?
Prednisolone (liver is responsible for conversion of prednisone to prednisolone)
Why are cats less responsive to typical steroid doses?
They have fewer glucocorticoid receptors in the liver and skin and receptors have lower affinity
What medication is derived from the fungus Beauveria nivea/Tolypocladium inflatum?
Cyclosporine
What class of drugs is cyclosporine?
Calcineurin inhibitor
What transcription factor is dephosphorylated by calcineurin?
Nuclear factor of activated T-cells (NFAT)
What is the MOA of cyclosporine?
Binds to cyclophilin intracellularly (within T-cells) –> this complex binds to calcineurin and inhibits its dephosphorylating activity –> prevents translocation of NFAT into the cell nucleus –> suppressed cytokine production and impaired T-cell activation
What cytokines are upregulated by NFAT activity in the nucleus?
IL-2
IL-4
TNF-a
TNF-gamma
True or false: It is acceptable to use compounded cyclosporine formulations in dogs.
False
What enzyme metabolizes cyclosporine and where does this occur?
CYP3A family (CYP3A4, CYB3B5)
occurs in liver
What mutation in dogs would warrant you to be cautious of CsA dosing as typical dosing could cause excessive immunosuppression?
MDR1
Why is cyclosporine a potential concern in patients with an MDR1 mutation?
It is a substrate of the p-glycoprotein efflux pump–> can accumulate if pump is defective due to MDR1 mutation (reduced biliary excretion)
What would the expected response to typical CsA doses be in a dog with diabetes?
Less response to typical dose due to increased clearance/reduced half-life
How long is it “safe” to store Atopica capsules in the freezer at -20 degC?
1 month
What type of drug is azathioprine?
pro-drug of 6-mercaptopurine (6-MP)
Which metabolites of azathioprine have no immunosuppressive effect?
6-thiouric acid
6-merthymecaptopurine (6-MMP)
What metabolite of azathioprine has cytotoxic/immunosuppressive effects?
6-thioguanine nucleotide (6-TGN)
What are the 3 metabolites of azathioprine?
6-thioguanine nucleotide (immunosuppressant)
6-thiouric acid (not immunosuppressant)
6-merthymecaptopurine (not immunosuppressive)
In what parts of the body does azathioprine conversion to 6-mercaptopurine occur?
RBCs
Intestinal wall
Liver
Which enzymes result in conversion of 6-MP to inactive metabolites?
Xanthine oxidase
Thiopurine-S-methyltransferase (TMPT)
Which enzyme results in the conversion of 6-MP into a cytotoxic metabolite?
Hypoxanthine-guanine phosphoribosyl-transferase (HPRT)
Which enzyme converts 6-mercaptopurine into 6-merthymecaptopurine?
Thiopurine-S-methyltransferase (TPMT)
Which enzyme converts 6-mercaptopurine into 6-thiouric acid?
xanthine oxidase
What enzyme converts 6-mercaptopurine into 6-thioguanine nucleotide?
hypoxanthine-guanine phosphoribosyl-transferase (HPRT)
How does azathioprine affect DNA synthesis?
It’s active metabolite (6-TGN) acts as a false purine –> incorporated into DNA –> mutated DNA, cell cycle stops
What cells are most affected by azathioprine?
Actively dividing cells (T-cells, B-cells, thrombocytes)
How does azathioprine affect leukocyte adhesion to endothelium?
6-MP inhibits RAC1 which is important for formation of ICAM-1 and VCAM-1
How does azathioprine affect T-cell migration, adhesion, and proliferation?
Inhibits RAC1 and BCL-XL
Responses from which T-cell subset are primarily blocked by CsA?
CD4+ (T-helper)
How long after dosing does oral CsA reach peak blood levels?
2 hours
Why should allopurinol be avoided when using azathioprine?
It inhibits xanthine oxidase –> causes more production of the cytotoxic metabolite of AZA (6-TGN)
What drugs should be avoided when using allopurinol for treatment of Leishmaniasis?
Anticoagulants
Azathioprine
Cyclophosphamide
Diuretics
TMS
Urinary acidifiers
Why should azathioprine be avoided in cats?
They are deficient in thiopurine-S-methyltransferase and therefore make less of the inactive metabolite and more of the cytotoxic metabolite –> increased risk of myelosuppression
What breed of dog is more susceptible to azathioprine toxicity and why?
Giant Schnauzers
They have less active thiopurine-S-methyltransferase activity, leading to more production of cytotoxic metabolites
What breed of dog may require higher doses of azathioprine and why?
Alaskan Malamutes
They have higher thiopurine-S-methyltransferase activity and therefore make more inactive metabolites
Combining azathioprine with which other immunosuppressant can cause an increased risk of pancreatitis?
Glucocorticoids
What are 3 primary side effects of azathioprine?
GI upset
Myelosuppression
Hepatotoxicity
What is the median time to onset of AZA-induced hepatotoxicity?
14 days (so check within 2 weeks of starting)
What type of drug is chlorambucil?
Alkylating agent (nitrogen mustard group)
What is the active metabolite of chlorambucil and where does this conversion occur?
Phenylacetic acid
Occurs in liver
How long could it take to see the therapeutic effects of chlorambucil?
2 weeks
What is the MOA of chlorambucil?
Converted into phenylacetic acid–> causes cross-linking of DNA at the guanine-N7 position –> DNA mutation and cell death
What type of cells is chlorambucil most effective on?
Lymphoid cells (esp B-cells)
What are the potential adverse effects of chlorambucil?
GI
Myelosuppression
Myoclonus
Fanconi syndrome
What is the brand name of chlorambucil?
Leukeran
What is the active metabolite of mycophenolate mofetil?
Mycophenolic acid (MPA)
What is the MOA of mycophenolate?
Converted to active metabolite MPA –> inhibits inosine monophosphate dehydrogenase enzyme (IMPDH) in the de novo pathway –> inhibition of guanine nucleotide synthesis –> less DNA production –> fewer lymphocytes
How is mycophenolate eliminated from the body in humans and dogs?
Glucuronidation
What is the suspected elimination route of mycophenolate in cats?
Glucosidation (and therefore the lack of glucuronyl transferase enzyme is unlikely to be of major concern because glucuronidation does not occur in this species)
What are the primary side effects of mycophenolate?
GI upset
Which JAK is preferentially inhibited by oclacitinib?
JAK1
What are the 4 JAK family members?
JAK1
JAK2
JAK3
TYK2
What occurs once a cytokine binds to a cytokine receptor attached to JAKs?
The JAKs are phosphorylated –> STATs bind and are phosphorylated –> STATs released into cytoplasm and bind other STATs –> STATs translocate into nucleus and bind to DNA for gene transcription
What JAKs are associated with the binding of cytokines involved in hematopoiesis and innate immunity?
JAK2/JAK2
JAK2/TYK2
What cytokines have been shown to be reduced when using high extra-label doses of Apoquel?
IL-2
IL-15
IL-18
IFN-gamma
(inhibition of T-cell proliferation)
What are potential adverse effects of high doses of Apoquel in dogs?
Impaired T-cell proliferation –> increased infection risk
What JAKs are typically used by IFN-gamma receptors?
JAK1
JAK2
What JAKs are used by IL-4 receptors?
JAK1
JAK3
How does oclacitinib suppress Th2 responses?
Inhibits production of IL-2, IL-4, IL-6, IL-13
How does oclacitinib block itch signaling?
Inhibits production of IL-31 and TSLP
What is the primary cell type affected by Bruton’s tyrosine kinase inhibitors?
B-cells
Which topical steroid has been demonstrated to have minimal effect on adrenocortical function?
Mometasone furoate
What does tacrolimus bind to in order to suppress the NFAT pathway?
FK506 binding protein (aka FKBP12)
What is the definition of AZA-induced hepatotoxicity?
ALT >2-fold the upper limit of the ref range
What metabolite is responsible for the cytopenias seen with AZA?
6-TGN
What would be expected in a dog with a thiopurine methyltransferase enzyme deficiency if given AZA?
Elevated thioguanine nucleotides –> cytopenia
What would happen to blood CsA concentrations in a dog on cyclosporine who is given barbiturates?
Reduced CsA blood levels
Is isotretinoin a first- or second-generation retinoid?
first (non-aromatic and do not act selectively on receptors)
True or false: oral bioavailability of Vitamin A is improved with food intake.
True (it’s lipophilic)
How is retinol transported in the serum?
Via retinol binding protein (RBP) + transthyretin
What antibiotics may increase serum levels of retinoids?
Tetracyclines
Macrolides
Is etretinate a first- or second-generation retinoid?
Second
Is acitretin a first- or second-generation retinoid?
Second
What labwork changes should be monitored with isotretinoin use?
Hypertriglyceridemia
Hypercholesterolemia
LE elevation
What clinical side effects may be seen with isotretinoin use?
KCS/conjunctivitis
Pruritus
GI upset
Hyperactivity
Which retinoids are ineffective in WHWT epidermal dysplasia?
Isotretinoin
Etretinate
Acitretin
If choosing between Sandimmune and Neoral for a patient prescribed CsA, which would you prefer to use?
Neoral (microemulsion)
What are the main cytokines affected by CsA?
IL-2* (less T-cell proliferation)
IL-3
IL-4* (less B-cell activation)
G-CSF (less neut release)
TNF-a*
IFN-gamma*
TGF-B (enhanced by CsA)
What drugs can INCREASE CsA in the blood?
Azoles
Diltiazem
Doxycycline
Erythromycin
Methylpred
What drugs can DECREASE CsA concentration in the blood?
Phenytoin
TMS
Phenobarb
Rifampin
How does retinoid acid enter the cell nucleus?
Binds to either retinoic acid receptors or retinoid X receptors (RXRs)
You have a choice between prescribing isotretinoin or acitretin to a patient. You want to avoid side effects as much as possible, which would you choose?
Etretinate (2nd gen=more selectivity and less potential for SE)
What type of drug is pentoxifylline?
Methylxanthine derivative
What cytokines are suppressed by pentoxifylline?
IL-1
IL-6
TNF-a
What is the metabolite of hydroxyzine?
Cetirizine
What drug is a natural metabolite of retinol?
Retinoic acid
You want to prescribe a Basset hound a retinoid to help with seborrhea. Which retinoids would you AVOID?
Isotretinoin
Acitretin
(these are ineffective)
What is the MOA of cyclophosphamide?
Alkylating agent that causes cross-linking of DNA
What is the active metabolite of cyclophosphamide?
4-hydroxycyclophosphamide
What metabolite of cyclophosphamide is responsible for causing sterile hemorrhagic cystitis?
acrolein (excrete in urine)
Besides the liver, where else is CsA primarily metabolized?
Intestinal cells
What is the suspected MOA of CsA-induced gingival hyperplasia?
Increased fibroblast activity and ECM deposition
What is the effect of CsA on platelets?
Increased platelet synthesis of thromboxane A2 -> vasoconstriction and hypercoagulability
What is the most reliable method of therapeutic drug monitoring of CsA?
High pressure liquid chromatography (HPLC)
What is the primary antibody present in human IVIG?
IgG
What TLR does imiquimod bind to?
TLR7
What cytokines are secreted when imiquimod binds to TLR7?
IFN-a
IL-12
TNF-a
What type of T-helper cell response dominates in a patient being treated with imiquimod?
Th1
What is the MOA of leflunomide?
Converted into A77-1726 –> inhibits protein tyrosine kinase and dihydro-orotate dehydrogenase –> reduced pyrimidine synthesis –> reduced lymphocyte proliferation
What are the main side effects of leflunomide?
LE elevations
Thrombocytopenia
GI upset
Lethargy
Hemorrhage
What is the typical onset of action of Cytopoint?
1-3 days
What amino acid is melatonin derived from?
Tryptophan
What cytokines are decreased in response to oclacitinib?
IL-2
IL-4
IL-6
IL-13
IL-31
What drugs should you be cautious about using with melatonin?
Benzodiazepines
What neurotransmitter can be transformed into melatonin?
Serotonin
What is the expected effect of norepinephrine on melatonin synthesis?
It increases melatonin synthesis
Does darkness inhibit or enhance melatonin synthesis?
Enhances
What cytokines are produced in response to melatonin?
IL-2
IL-6
IL-12
What T-cell subset is enhanced by melatonin?
CD4+ (T-helper)
What T-helper response is promoted by melatonin?
Th2
What is the effect of melatonin on GnRH secretion?
Inhibitor
Where is mycophenolate metabolized?
Liver
What enzyme turns mycophenolate into an inactive metabolite?
Glucuronyl transferase
A dog is on an antacid and you want to prescribe it mycophenolate. What is an important consideration for the formula of mycophenolate used in this case?
Use an enteric-coated tablet (antacid will raise gastric pH and affect absorption of MMF)
What JAK is primarily involved in hematopoiesis and myelopoiesis?
JAK2
What immunomodulatory medication has been associated with fatal disseminated toxoplasmosis in an FIV+ cat?
Apoquel
What is the active form of vitamin B3 called?
Niacinamide
A client bought nicotinamide for their dog when you requested they purchase niacinamide. Is this okay to use?
Yes they are the same drug
Describe the anti-inflammatory properties of tetracyclines.
Inhibit MMPs
Decrease IL-1, IL-6, IL-8, TNF-a
Suppress leukocyte chemotaxis via inhibition of MCP-1 and IL-8
Decrease IgE and histamine release
Inhibit phospholipase A2
Describe the anti-inflammatory effects of niacinamide.
Stabilizes mast cells
Suppresses ICAM-1 expression
Suppresses MHC II expression
Inhibits phosphodiesterases
Inhibits nitric oxide synthase
Which cytokines are reduced by niacinamide?
IL-1B
IL-6
IL-8
TNF-a
Why would you recommend avoiding tetracyclines in young animals?
Slows fetal skeletal development
Discolors deciduous teeth
Doxycycline is often given with food to reduce GI upset. Which foods should be avoided and why?
Calcium-containing products should be avoided as they will decrease the absorption of doxy (give 1-2 hours separate)
Will antacids affect doxycycline use?
Yes - they will decrease its absorption so separate by 1-2 hours
What is the MOA of 5-FU?
Pyrimidine analog –> binds to thymidylate synthase–> interferes with synthesis of thymidine and is mis-incorporated into DNA –> reduced DNA/RNA synthesis
What are the active metabolites of 5-FU?
FUMP
FdUMP
FdUTP
What are the indications for 5-FU?
Carcinomas
Osteosarcoma
HSA
TVT
MCT
What species should not be treated with 5-FU?
Cats
A dog is presented after ingesting a portion of his owner’s 5-FU tube. What are the likely side effects?
Hyperammonemia
Seizures
Diarrhea
(death likely)
What is the MOA of colchicine?
alkaloid which binds to microtubule proteins –> alters cell function
What processes are inhibited by colchicine?
Neutrophil chemotaxis
IL-1 production
Histamine release
Ig secretion
Degranulation of lysosomes
Collagen synthesis (stims collagenases)
What are the side effects of colchicine?
GI upset
Neutropenia
Renal toxicity
Peripheral neuropathy
What are the indications for colchicine in dogs?
EBA
Shar Pei fever
What type of drug is dapsone?
Anti-mycobacterial antibiotic
What is the antibacterial MOA of dapsone?
Competes with para-amino-benzoate for the active site of dihydropteroate synthetase –> inhibits folic acid synthesis
Describe the anti-inflammatory properties of dapsone.
Decreases neutrophil chemotaxis
Decreases complement activation
Decreases lysosomal enzyme synthesis
Why is dapsone use contraindicated in cats?
Fatal hemolytic anemia and neurotoxicity
What are the primary SE of dapsone in dogs?
Hepatotoxicity
Anemia
Leukopenia
What type of drug is hydroxychloroquine?
Aminoquinolone anti-malarial
What TLR is inhibited by hydroxychloroquine?
TLR9
In which canine conditions has hydroxychloroquine been utilized?
ECLE
GDLE
Where are interferons metabolized?
Kidneys
What is lomustine also known as?
CCNU
What type of drug is CCNU?
nitrosurea alkylating agent
What is the MOA of CCNU?
binds at the O-6 of guanine –> DNA cross-linking –> cytotoxicity
What are the primary SE of lomustine?
Bone marrow toxicity> Hepatotoxicity
What are the neoplastic indications for CCNU in dogs and cats?
CETL and non-epitheliotropic lymphoma
MCT
Histiocytic sarcoma
How often is CCNU dosed in dogs?
q21-28 days
What medication might you consider giving to a dog who is being treated with lomustine any why?
Denamarin – has a protective effect against CCNU-induced hepatotoxicity
Where are CCNU antitumor metabolites produced?
Liver
During what part of the cell cycle is methotrexate active?
S phase
What is the MOA of vincristine?
Binds to tubulin –> disrupts mitotic spindle during mitosis
What is the MOA of amphotericin B?
Binds to sterols (i.e. ergosterol) in plasma membrane –> pores form –> leakage of intracellular enzymes
Besides ergosterol, what other component of the cell membrane can amphotericin B bind to (thus resulting in side effects)?
Cholesterol (binds to any sterols)
How does amphotericin B lead to potential nephrotoxicity?
Binds to cholesterol in renal tubules and renal epithelial cells –> pores form –> nephrotoxicity
What is the MOA of nystatin?
Binds to ergosterol in cell membrane –> pore forms –> leakage of intracellular ions
Which is more toxic, nystatin or amphotericin B?
Nystatin (this is why it isn’t used systemically)
What is the MOA of terbinafine?
Inhibits squalene epoxidase so that squalene cannot be converted to lanosterol (and therefore cannot be converted to ergosterol)
What is the MOA of azoles?
Inhibit 14-a-demethylase so that lanosterol cannot be converted to ergosterol
What is the MOA of echinocandins (i.e. caspofungin)?
Inhibit Beta-(1,3)-glucan synthase –> lack of formation of Beta-(1,3)-glucan in fungal cell wall
What is the benefit of echinocandin antifungals over other antifungal drugs
Less potential for mammalian cell toxicity because Beta-(1,3)-glucan synthase is absent in mammalian cells
What is the MOA of griseofulvin?
Binds to tubulin –> inhibits microtubule formation –> reduced fungal cell mitosis
What is the MOA of flucytosine?
Converted to 5-FU –> acts as antimetabolite by competing with uracil –> inhibits pyrimidine metabolism –> reduced RNA and protein synthesis
What is the antifungal MOA of lufenuron?
Disrupts chitin and chitosan synthesis in fungal cell walls
What class of drug is amphotericin B?
Polyenes
What class of drug is terbinafine?
Allylamines
Is griseofulvin fungistatic or fungicidal?
Fungistatic
What fungal organisms are the primary indication for griseofulvin?
Dermatophytes (ineffective against most other fungi)
Should griseofulvin be given with or without food?
With (fatty meal)
Is griseofulvin a cytochrome p450 inhibitor or inducer?
Inducer (increases metabolism of other p450 drugs)
What antifungal has been associated with development of TEN and erythema multiforme?
Griseofulvin
Is griseofulvin-induced myelotoxicity dose-dependent?
No, idiosyncratic
What cat breeds may be more susceptible to griseofulvin-related idiosyncratic drug rxns?
Persians
Himalayans
Abysinnians
Siamese
Why is flucytosine usually combined with amphotericin B?
High likelihood of resistance to flucytosine
What fungal organisms are the primary indication for flucytosine use?
Aspergillus
Candida
Cryptococcus
What enzyme is responsible for converting flucytosine to 5-FU?
Cytosine deaminase
Why is flucytosine less toxic to mammalian cells than fungal cells?
Mammalian cells are lacking cytosine deaminase which is responsible for converting flucytosine to 5-FU
What are the primary SE of flucytosine?
Myelosuppression
Nephrotoxicity
Cutaneous drug eruptions
GI upset
Hepatotoxicity
CNS signs
A pregnant animal requires the use of a systemic antifungal medication. Which one is safe to use?
Terbinafine
What class of drugs is nystatin?
Polyenes
Besides fungi, what other organism is amphotericin B effective against?
Leishmania
True or false: Amphotericin B is highly effective against dermatophytes
False
Is amphotericin B fungistatic or fungicidal?
Fungicidal at high concentrations
Fungistatic at low concentrations
What are the main SE of amphotericin B?
nephrotoxicity (cats more sensitive)
Non-regenerative anemia
Anorexia
Through which mechanism do penicillins cause an adverse drug reaction?
Hapten hypothesis (B- and T-cells activated)
What are the 4 mechanisms of drug allergy?
Hapten hypothesis
Danger theory
Pharmacological interaction concept
Viral reactivation
What 2 drugs have been associated with pruritus as a CADR in cats?
Spironolactone
Methimazole
What type of hypersensitivity is involved in pruritus caused by a CADR?
Type I
Type IV
What type of hypersensitivity is urticaria and edema?
Type I
What type of hypersensitivity is a PF-like CADR?
Type II
What type of hypersensitivity is a vasculitis CADR?
Type III
What type of hypersensitivity is a fixed drug eruption?
Type IV (cell mediated cytotoxic response)
What %BSA is affected in an EM drug reaction?
<10%
What type of hypersensitivity is Sweet’s syndrome?
Type IV
What breed has been associated with superficial suppurative necrolytic dermatitis and what is the causative agent?
Miniature schnauzers
Natural shampoos
