Meds Flashcards
What is drug class and mechanism of action of frusemide?
- loop diuretic
- inhibits Na+/K+/2Cl cotransporter
What is frusemide used for?
Oedema - pulmonary or ascites, assoc with cardiac insufficiency/CHF and acute, non-inflam tissue oedema
- hypercalcaemia
- Systemic hypertension
- Oliguric AKI
- prevention of sterile haemorrhagic cystitis secondary cyclophosphamide
What is drug class and mechanism of action of frusemide?
- loop diuretic
- inhibits Na+/K+/2Cl cotransporter
What is torsemide used for?
- CHF management
What is drug class and mechanism of action of sildenafil?
Vasodilator and phosphodiesterase 5 inhibitor
inhibits cGMP specific PD5 => NO mediated vasodilation within the pulmonary vascular smooth muscle
What is sildenafil used for?
- reduce pulmonary hypertension with primary cardiac, respiratory or HW
- slow cardiac remodeling with MMVD
- congenital MO
- Eisenmengers syndrome
What is drug class and mechanism of action of Spironolactone?
Aldosterone antagonist - potassium sparing diuretic
Aldosterone is competitively inhibited by spironolactone in the distal renal tubules with resultant increased excretion of sodium, chloride, and water, and decreased excretion of potassium, ammonium, phosphate, and titratable acid.
What is spironolactone used for?
- CHF for cardioprotective and potassium sparing diuretic
- ascites
What is drug class and mechanism of action of Hydrochlorothiazide?
Thiazide diuretic
acts on cortical diluting segmen of nephron and interfers with the transport of sodium ions across renal tubular epithelium.
What is hydrochlorothiazide used for?
Nephrogenic diabetes insipidus
- hypertension
- CaOx urolith prevention
- hypoglycaemia
- Diuretic for CHF
- ascites
- Hypermagnesemia
- antihypertensive
What is drug class and mechanism of action of Nitroglycerin?
Venodilator and afterload reducer
relaxes predominantly venous smooth muscle + dose related arteriole effect via formation of NO
What is nitroglycerin used for?
vasodilator in acute CHF
What is drug class and mechanism of action of hydralazine?
Vasodilator - semicarbazide-sensitive amine oxase inhibitor - alters Ca++ metabolism to reduce contraction. more impact on arterioles than veins.
Increase CO and decrease systemic vascular resistance
What is hydralazine used for?
- Afterload reducer for CHF
- Antihypertensive
What is drug class and mechanism of action of Prazosin?
Alpha 1 adrenergic blocker
Selective, competative inhibition of post-synaptic a1-adrenergic receptors. directly relaxes smooth muscle on both arterial and venous
What is prazosin used for?
- Reduce sympathetic tone to treat functional urethral obstruction and idiopathic vesico-urethral reflex dyssynergia or urethral spasm
- dysuria with prostatic carcinoma
- hypertension
- adjunctive treatment of heart failure
What is drug class and mechanism of action of benazepril?
ACE-i
What is benazepril used for?
- CHF
- hypertension
- CKD
- Proteinuria
What is drug class and mechanism of action of Pimobendan?
Inodilator - positive iontrop and vasodilatory effects
Inhibits PDE-III and increases intracellular calcium sensitivity
What is pimobendan used for?
- CHF in dogs secondary to DCM or degen AV valve insuff
- Preclinical (stage B2) MMVD and DCM
- Pulmonary arterial hypertension
- non-obstructive HCM with left ventricular systolic dysfunction and CHF in cats
What is drug class and mechanism of action of Amlodipine?
Calcium channel blocker (L-type)
inhibits volutage gated calcium channels in cardiac and vascular smooth muscle.
kindeys - Ltype are found in the afferent arterialos.
What is Amlodipine used for?
- Systemic arterial hypertension
- afterload reduction in refractory CHF
What is drug class and mechanism of action of Nitroprusside?
Vasodilator - arterial and venous
provides intracellular NO => increased cGMP => inhibits vascular smooth muscle contration.
What is nitroprusside used for?
- acute/severe hypertension inc phaeo
- acute CHF
- dobutamine for refractory CHF
When should nitroprusside not be used?
- compensatory hypertension eg AV shunts, coarctation of the aorta, cushing’s reflex.
- inadequate cerebral circulation or emergency surgery if the patient is near death
- hypoT4 or low sodium
- undiluted
- geriatric, renal , liver.
What is drug class and mechanism of action of Diltazem?
Calcium channel blocker - benzothiazeprines
Class IV antiarrhythmic
weak negative ionotrope
act on nodal cells to prolong refractory period and slow conduction.
What is diltiazem used for?
- SVT (originate above the AV node), Afib
- systemic hypertension
- pulmonary hypertension
When should diltazem not be used?
- hypothension
- sinus node dysfunction
- high grade AV block
- sick sinus syndrome
- pulonary congestion or oedema
- acute myocardial infarction
- old, liver, renal - use with care
What is drug class and mechanism of action of dobutamine?
Beta adrenergic inontrope
direct B1 and mild B2 and alpha 1 adrenergic effects
mild chronotropic, arrhtymogenic and vasodilatory effects. increase cardiac output and work.
What is dobutamine used for?
- shock
- CHF
- hypotension during GA
When should dobutamine not be used?
- subaortic stenosis
- insufficient blood volume
- vent tachyarrhythmia or afib. use digoxin first for afib.
What is drug class and mechanism of action of dopamine?
Adrenergic/dopaminergic ionotrope
acts directly and indirectly on alpha and beta receptors
lower dose = β1 effects, exerting positive cardiac inotropic activity (eg, increased contractility, cardiac output, heart rate);
a CRI of 10 – 15 µg/kg/min IV will have both β1 and α1 effects,3-6 although α1 effects (eg, increased systemic and pulmonary vascular resistance, increased venous return) predominate in a dose-dependent fashion.
what is dopamine used for?
- correct hypotension assoc with low Cardiac output in patient with shock after adequate fluid replacement or peripheral vasodilation
- CHF
- hypotension under GA
When should dopamine not be used?
- phaeo
- V-fib
- uncorrected tachyarrhythmia
- occlusive vascular disease
- oliguric AKI
What is drug class and mechanism of action of digoxin?
Cardiac glycoside
thought to increase the availability of Ca++ to myocardial fibers and inhibit Na+/K+ ATPAse withincrease intracallual Na+ and decreased K+
- increase myocardial contraction (+ve ionotrope)
- decrease conduction velocity through AV node and prolong refractory period.
What is digoxin used for?
- CHF
- Afib or flutter (+diltiazem)
- SVT
When should digoxin not be used?
- Vfib
- digitalis intoxication
- 3rd degree AV block
+/- cats with HCM
- don’t give extravascular
- care with complex arrhythmia and subaortic stenosis.
What is drug class and mechanism of action of mitoxantrone?
Antineoplastic - antitumour antibiotic.
Binds DNA and inhibits both DNA and RNA synthesis via inhibition of RNA and DNA polymeraizses and topoisomerase II
not cell phase specific, but most active in S-phase
What is mitoxantrone used for?
- UCC/TCC and AGASAC
- cardiac sparing/post max dose of doxorubicin
- rescue lymphoma
- mammary/renal adenocarcinoma
- SCC
- thyroid or prostate carcinoma
- fibroid sarcoma
When should mitoxantrone not be used?
- myelosuppression
- infection
What is melphalan used for?
- Multiple myeloma
Which agents are alykylating chemo drugs? and what is their mechanism of action?
Alykylating agents:
- melphalan
- cyclophosphamide
- Chlorambucil
- meclorethamine (mustargen)
- Ifosfamide
covalent binding of alkyl groups to cellular macromolecules = > cross link DNA
What is the drug class and mechanism of action for Cyclophosphamide?
Alykylating agent
covalent binding of alkyl groups to cellular macromolecules = > cross link DNA
What is cyclophosphamide used for?
- Multiagent chemo for lymphoma
- bone marrow abalation prior to BM transplantion
- Sarcoma
- Mammary carcinoma
- metronomic chemo
Which agents are alykylating chemo drugs? and what is their mechanism of action?
Alykylating agents:
- melphalan
- cyclophosphamide
- Chlorambucil
- meclorethamine (mustargen)
- Ifosfamide
- CCNU
- procarbazine
- Dacarbazine (DTIC)
- Streptozocin
covalent binding of alkyl groups to cellular macromolecules = > cross link DNA
What is Ifosfamide used for?
- sarcomas including feline injection site sarcoma
What is the drug class and mechanism of action for chlorambucil?
Alykylating agent + immunosuppressant
covalent binding of alkyl groups to cellular macromolecules = > cross link DNA
What is chlorambucil used for?
- chronic lymphocytic leukaemia
- T-cell lymphoma
- Waldenstrom’s macroglobulinaemia
- Feline low grade/small cell GI lymphoma
- metronomic chemo for bladder TCC
- multiple myeloma
- MCT
- cutaneous plasmacytosis
- Polycythemia vera
- Ovarian adenocarcinoma.
- HSA
- immunosuppression for IBD, IMHA, non-erosive arthritis, immune med skin disease
What is chlorambucil used for?
Round tumours:
- chronic lymphocytic leukaemia
- T-cell lymphoma
- Waldenstrom’s macroglobulinaemia
- Feline low grade/small cell GI lymphoma
- multiple myeloma
- MCT
- cutaneous plasmacytosis
- Polycythemia vera
Other
- metronomic chemo for bladder TCC
- Ovarian adenocarcinoma.
- HSA
- immunosuppression for IBD, IMHA, non-erosive arthritis, immune med skin disease
What is the drug class and mechanism of action for chlorambucil?
Alykylating agent + immunosuppressant
covalent binding of alkyl groups to cellular macromolecules = > cross link DNA
What is the drug class and mechanism of action for Lomustine (CCNU)?
Nitrosourea - alkylating agent
DNA-DNA or DNA to protein cross links.
What is the drug class and mechanism of action for Lomustine (CCNU)?
Nitrosourea - alkylating agent
Cell cycle non-specific
DNA-DNA or DNA to protein cross links.
What is CCNU used for?
- CNS neoplasia
- MCT
- histocytic sarcoma
- rescue lymphoma
metronomic chemo
What is the drug class and mechanism of action for Streptozocin?
Nitrosourea - alkylating agent
cell cycle non-specific
DNA-DNA or DNA to protein cross links.
What is streptozocin used for?
- insulinoma
does have activity against gram +ve and gram -ve but cytotoxicity prevents this from being useful.
What is the drug class and mechanism of action for Dacarbazine?
Alkylating agent
methylates the O6 and N7 positions of guanine, thereby ceasing DNA replication elongation and causing DNA double-strand break
not cell phase specific
What is dacarbazine used for?
- on own or + Dox or CCNU for relapsed lymphoproliferative disease
- With dox +/- vinc for HSA
- STS
- Histiocytic sarcoma
- melanoma
What is the drug class and mechanism of action for Procarbazine?
Alkylating agent
inhibit protein, RNA, and DNA synthesis. Procarbazine is auto-oxidized into hydrogen peroxide, which may also directly damage DNA.
What is procarbazine used for?
in combination therapy for lymphoma +/- relapse:
- MOPP (mechlorethamine, vincristine, procarbazine, prednisone)
- MPP (mechlorethamine, procarbazine, prednisone),
- LOPP (lomustine, vincristine, procarbazine, prednisone),
- BOPP (bendamustine, vincristine, procarbazine, prednisone)
What antitumour antibiotics are there? what is their mechanism of action?
Doxorubicin
Mitoxantrone
Actinomycin D
Bleomycin
DNA intercalation, interfering with topoisomerases, and other mechanisms. These drugs usually exhibit cross-resistance with others in their class and with drugs in some other classes, particularly mitotic inhibitors, and they are substrates for the multidrug resistance (MDR) pump
What is the drug class and mechanism of action for Doxorubicin?
Antitumour antibiotic
Inhibition of DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis by inhibiting DNA and RNA polymerases and impairing topoisomerase II, as well as through generation of free radicals
Doxorubicin alters transcription and replication by intercalating with DNA base pair
What is doxorubicin used for?
- lymphoma
- HSA
- OSA
- histiocytic sarcoma
- feline injection site sarcoma
- mammary carcinoma
- Thryoid carcinoma
- Colonic adenocarcinoma
What adverse effects should be noted with doxorubicin?
- anaphalaxis
- extravasation (cold compress + dexrazonaxane)
- cardiotoxicity with both acute and cumulative exposure => transient arrhythmia and DCM => CHF
- nephrotoxicity in cats.
What is the drug class and mechanism of action for Actinomycin D (Dactinomycin)?
Antitumour antibiotic
Bind DNA => inhibit transcription this inhibiting RNA and protien synthesis
What is Acintomycin D used for?
Mulitagne protocol for dogs with lymphoma/lymphoprolif disease as relapse or dox substitute
- bone and STS
- Carcinomas
- Gram +ve and gram -ve bacteria = some fungi
- some immunosuppressant
- some hypocalcaemic activity.
What is the drug class and mechanism of action for Bleomycin?
Bleomycin has both a DNA binding site and a site that binds to the ferrous form of iron. By serving as an electron acceptor from the ferrous ion to an oxygen atom in the DNA strand, bleomycin cleaves DNA and causes cellular apoptosis.
Resistance to bleomycin can result from reduced cellular uptake of the drug, reduced ability to damage DNA, increased rates of DNA repair by the cell and drug inactivation by the enzyme bleomycin hydrolase
What is Bleomycin used for?
lymphomas, oral squamous cell carcinomas, teratomas, nonfunctional thyroid tumors acanthomatous ameloblastoma
may be used intralesional +/= electrophemealization.
gram-negative and gram-positive bacteria and some fungi; however, its cytotoxicity to eukaryote cells prevents it from being clinically useful as an antimicrobial drug.
What drugs are antimetabolite chemo drugs? what is their mechanism of action?
- Cytosine arabinoside
- Methotrxate
- Gemcitabine
- 5-Fluorouracil
- Rabacfosadine
inhibit the use of cellular metabolities in the course of cell growth and division.
What is the drug class and mechanism of action for Cytosine arabinosine?
Antimetabolite and immunosuppressant.
Competes with deoxycytidine triphosphate to inhibit DNA polymerase, resulting in inhibition of DNA synthesis.
Specific to the S phase of the cell cycle (DNA synthesis) and blocks cell progress from the G1 phase to the S phase.
What is cytosine arabinosine (cytarabine) used for?
rescue lymphoma in DMAC protocol (dexamethasone, melphalan, actinomycin-D, Ara-C)
lymphoreticular neoplasia
leukaemia
CNS lymphoma
MUO
What are the different lymphoma protocols?
- DMAC: dexamethasone, melphalan, actinomycin-D, Ara-C)
- MOPP: (mechlorethamine, vincristine, procarbazine, prednisone)
- MPP: (mechlorethamine, procarbazine, prednisone),
- LOPP: (lomustine, vincristine, procarbazine, prednisone),
- BOPP: (bendamustine, vincristine, procarbazine, prednisone)
- CHOP: (cyclophosphamide, doxo, vinc, pred)
- COP: (cyclophosphamide, vinc, pred)
What is the drug class and mechanism of action for methotrexate?
Antimetabolite
folate analog that inhibits the enzyme dihydrofolate reductase, thus depleting reduced folate pools required for purine and thymidylate biosyn-thesis
What is methotrexate used for?
rarely used. used to be for lymphoprolif neoplasia in multi agent protocols.
Some immunosuppressant effect but limited.
What is the drug class and mechanism of action for Gemcitabine?
Antimetabolite chemo
inhibition of DNA synthesis through incorperationi into the DNA strand => inhibition of DNA polymerase => new DNA strand termination
S-phase killing cells undergoing DNA synthesis and inhibiting cell progression to GA/S boundary
What is gemcitabine used for?
- radiosensitizer but not well tolerated.
- with piroxicam in TCC
no benefit noted in lymphoma, OSA, mammary carcinoma or hepatocellyar carinoma.
What is the drug class and mechanism of action for 5 Fluorouracil (5-FU)?
Antimetabolite chemo
incorporated into RNA and DNA interfering with synthesis and function.
The 5-FU metabolite FdUMP is an inhibitor of thymidylate synthetase, leading to depletion of thymidine 5′-monophosphate and thymidine 5′-triphosphate. The alterations in thymidine and deoxyuridine phosphate pools caused by thymidylate synthetase inhibition, effects on DNA synthesis and integrity, and effects on RNA synthesis and processing
What is 5-fluorouracil used for?
- organ epithelial cell tumours - hepatic, pancreatic, renal, mammary +
- GIT adenocarcinoma
- AGASAC
- nasal adenocarcionma
- solar induced SCC
- mammary tumours (+ doxo and cyclophosphamide)
* NOT CATS*
What is the drug class and mechanism of action for Rabacosadine?
Antimetabolite chemo
- guanine nucleotide analog
=> potent, chain-terminating inhibitor of the major deoxyribonucleic acid (DNA) polymerases
inhibits proliferation of mitogen-stimulated lymphocytes and lymphoma/leukemia cell lines
Inhibit DNA synthesis => S-phase arrest and apoptosis
What is rabacosadine used for?
single agent for
- cutaneous T- cell,
- relapsed B-cell,
- multiple myeloma
+ dox => multicentric lymphoma (dog)
What are the antimicrotubule agents and how do they work?
Paclitaxel
Docetaxel
Part of the vinc alkaloids
interference with the polymerization or depolymerization of the microtubules that play critical roles in cell function and division
=> chromosome segregation during mitosis, leading to mitotic arrest.
What is the drug class and mechanism of action for Paclitaxel and Docetaxel?
Antimicrotuble agents. part of vinc alkaloids
alteration in microtubule function causes an abnormal organization of spindle microtubules involved in chromosome segregation during mitosis, leading to mitotic arrest.
What are Paclitaxel and Docetaxel used for?
Mammary carcinoma
SCC
What are the vinc alkaloids? what is their mechanism of action?
- vinblastine
- vincristine
- vindesine
- vinorelbine
bind to a distinct site on tubulin and inhibit microtubule assembly. This inhibition of microtubule function leads to a disruption in the mitotic spindle apparatus resulting in metaphase arrest and cytotoxicity.
What is the drug class and mechanism of action for Vinblastine?
Vinc alkaloid - antimicrotubule chemo
bind to a distinct site on tubulin and inhibit microtubule assembly. This inhibition of microtubule function leads to a disruption in the mitotic spindle apparatus resulting in metaphase arrest and cytotoxicity.
What is vinblastine used for?
- lymphoma rescue or instead of vinc if significant GI adverse effects
- Carcinoma
- MCT
- splenic tumours
- UCC/TCC
What is the drug class and mechanism of action for Vincristine?
Vinc alkaloid - antimicrotubule chemo
bind to b- tubulin and inhibit microtubule assembly. This inhibition of microtubule function leads to a disruption in the mitotic spindle apparatus resulting in metaphase arrest and cytotoxicity.
+ amino acid metabolism interference => purine synthesis CAC and urea formation
What is vincristine used for?
lymphoma/haematopoietic neoplasia (CHOP/COP) - however cats had less side effects with vinblastine so may use this instead of vinc for CHOP
HSA
- transmissible veneral tumours.
some immuno suppressant activity + induces thrombocytosis => IMT
What is the drug class and mechanism of action for Vinrelbine?
Vinc alkaloid - antimicrotubule chemo
bind to b- tubulin and inhibit microtubule assembly. This inhibition of microtubule function leads to a disruption in the mitotic spindle apparatus resulting in metaphase arrest and cytotoxicity.
+ amino acid metabolism interference => purine synthesis CAC and urea formation
What is vinrelbine used for?
- bronchoalveolar or primary pulmonary carcinoma
- histiocytic sarcoma
- MCT
- palliative rescue for TCC
What are the platinum chemo drugs? what is their mechanism of action?
Carboplatin
Cisplatin (not in cats)
Covalent binding of DNA through displacement reaction resulting in bifunctional lesion and inter or intrastrand crosslinks.
What is carboplatin used for?
Sarcomas:
- OSA
melanoma
Carcinomas:
- SCC
- AGASAC
- intestinal
- prostatic
- mesothelioma
- carcinomatosis
- pulmonary
- nasal
- ovarian
Radiation sensitization.
What is cisplatin used for?
NOT CATS
generally use carbo instead as less side effects.
OSA SCC TCC ovarian cacinoma nasal carcinoma Thyroid adenocarcinoma
intracavitary for neoplastic pulmonray effusion
clsplatin impregnated beads for intralesional treatment
with electrochemotherapy for MCT, sarcomas and injection site sarcoma in cats (injected into margins not given systemically).
What is the mechanism of action of cisplatin?
intra- and interstrand DNA cross-linking that causes single- and double-stranded DNA breakage, impairs DNA replication, RNA transcription and protein synthesis, leading to cell death and inhibition of tumor growth
What is the drug class and mechanism of action for hydroxyurea?
Antineoplastic
interfere with DNA synthesis without interfering with RNA or protein synthesis
S phase inhibitor and nay arrest cekks at G1-S border
What is hydroxyurea used for?
- bone marrow disorders:
- polycythaemia vera
- granulocytic leukaemia
- MCT
- meningioma
What is the drug class and mechanism of action for L-asparaginase?
anti-neoplastic
depletion of circulating l-asparagine leads to inhibition of protein synthesis in tumor cells lacking l-asparagine synthetase, causing induction of apoptosis
most effective in the post mitotic G1 cell phase.
What is L-asparaginase used for?
initial induction or at relapse of lymphoprolif disorders. develops resistance.
Which are the tyrosine kinase inhibitors and what is their mechanism of action?
Toceranib
mastinib
imatinib mesylate
small-molecule inhibitors that block, receptor tyrosine kinases (RTKs) expressed on the cell surface by acting as competitive inhibitors of adenosine triphosphate (ATP) binding
+ anti-angiogenic effect through inhibition of VEGFR and PDGFR
+ KIt (Stem cell growth factor)
induce cell cycle arrest and apoptosis in canine tumor cell lines expressing activating mutations in KIT.
What is toceranib used for?
Patniak grade II or III, recurrent cutaneous MCT +- regional LN mets.
- heart base tumours sarcoma - carcinoma - melaonma - multidrug resistant lymphoma - multiple mylepma
What is the drug class and mechanism of action of prednisolone?
Class - glucocorticoid.
induce killing of hematopoietic cancer cells through interaction with the glucocorticoid receptor328 and the induction of apoptosis.3
What is pred used for?
1) replacement or supplementation (eg, relative adrenal insufficiency associated with septic shock) for glucocorticoid deficiency secondary to hypoadrenocorticism,
2) anti-inflammatory agent,
3) immunosuppression,
4) antineoplastic agent
What are the effects of pred?
Cardiovascular system:
- reduce capillary permeability and enhance vasoconstriction, increased blood volume=>increased blood pressure.
Cells: inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lymphocytes, and the cellular response to mediators of inflammation
CNS: lower the seizure threshold, alter mood and behavior, diminish response to pyrogens, stimulate appetite, and maintain α-rhythm.
Endocrine:
- suppress the release of corticotropin (ACTH)
- reduces release of TSH, FSH, prolactin, and LH + T3-T4
- increased PTH
- reduce ADH effect on renal tubules => diuresis
- inhibit osteoblast function.
- inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin.
Fluid and electrolyte balance:
- increase renal K+/Ca++ loss and NaCl reabsorption => increase ECF
GI tract and hepatic system:
- increase the secretion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation.
- reduce Fe and Ca++ absorbed
- increase fat absorbed.
Hepatic: increased fat and glycogen deposits in hepatocytes and increased (ALT), (GGT) and (ALP).
Hematopoietic system:
- increase circ PLT, neutrophils, and RBCs, but platelet aggregation is inhibited.
- Decreased amounts of lymphocytes (peripheral), monocytes, and eosinophils due to sequester these cells into the lungs and spleen
- involution of lymphoid tissue.
- inhibit neutrophil, macrophage, and monocyte migration; reduce production of interferon; and inhibit phagocytosis, chemotaxis, antigen processing, and intracellular killing.
- antagonize the complement cascade
- MCT reduced and histamine synthesis is suppressed.
Metabolic effects: Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (eg, abdomen), and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxidation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver).
Musculoskeletal:
muscular weakness, atrophy, and osteoporosis.
inhibited bone growth via growth hormone and somatomedin inhibition, increased calcium excretion, and inhibition of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited.
Skin: Thinning and skin atrophy.
Hair follicles can become distended and alopecia may occur.
What is the drug class and mechanism of action of
Beta adrenergic blocker
- relatively specific for B1
- Minimal B2 at recommended doses.
When is atenolol used?
- ventricular hypertrophy
- tachyarrhythmia including SVT, VPCs
- HCM/OHCM
+ mexiletine for ARVC
+/- systemic arterial hypertension, HCM and aortic/pulmonary stenosis
When should atenolol not be used?
- brady arrhythmias
with caution in patients with:
- CHF, CKD and sinus node dysfunction as is a negative ionotrope
- DM as can causes hyper/hypoglycaemia or mask signs of hyperT4 or hypoglycaemia.
What drugs are Beta blockers?
B1 selective:
- atenolol
- esmolol
- metoprolol
nonselective B blockers:
- carvediol,
- propranolol
- sotolol
What are the cardiac effects of B1 blockade?
Negative ionotrope
negative chronotrope
=> reduced HR + slow AV conduction
=> reduced CO, BP and myocardial O2 demands.
What are the effects of B2 blockade on CV and Resp system?
bronchospasm
peripheral vasodilation => hypotension.
What class is Esmolol and when should it be used?
ultrashort acting Beta (1) blocker - class II antiarrhythmic. - neg ionotroph and chronotrope => reduce HR, work , CO and BP
increases sinus cycle length, slow av node conduction and prolongs sinus recovery time.
For:
- SVT
- to see if Beta blocker therapy is needed
- under GA and risk of hypertension.
- hyperdynamic R vent outflow tract obstruction post balloon valvuloplasty for pulmonary valve stenosis.
When should esmolol not be used?
- Overt CHF
- second or 3rd degree AV blood
- sinus bradycardia
- cardiogenic shock
- bronchoconstriction
- DM
What class is metopralol and when should it be used?
second generation, Beta 1 blocker
used for:
- SVT or Afib for rate control
- VPC
- systemic hypertension
- HCM
When should metopralol not be used?
- unstable/overt CHF
- sensitive to beta blockers
- second or third degree AV block
- sinus bradycardia
care in:
- liver disease
- bronchospasm - less than propranolol so used more.
- CHF
- hyperT4
- DM
- sinus node dysfunction
What class is Carvediol and when should it be used?
nonselective B blocker
selective alpha 1 blocker
negative ionotrope
Class II antiarrhythmic
used fro :
- DCM to attenuate pacing induced DCM
- reduce Afib induction
When should carvediol not be used?
- unstable/overt CHF
- bronchial asthma
- sensitive to beta blockers
- second or third degree AV block
- sick sinus syndrome (unless paced)
- sinus bradycardia/severe brady cardia
- cardiogenic shock
What class is Propranolol and when should it be used?
nonspecific B blocker
selective alpha 1 blocker
negative ionotrope
Class II antiarrhythmic
used fro :
- short term management of thyrotoxicosis or phaeo
- hypertension
- B2 agonist toxicity (albuterol/terbutaline)
generally use other ones
When should propranolol not be used?
- unstable/overt CHF (unless secondary to tachyarrhythmia responsive to B blocker)
- bronchial asthma
- sensitive to beta blockers
- second or third degree AV block
- sick sinus syndrome (unless paced)
- sinus bradycardia/severe bradycardia
care in:
- liver/renal disease
- digitalis toxicity
- DM
- first degree AV blocks
- sinus node dysfunction
What class is Sotolol and when should it be used?
Non selective B blocker Potassium channel blocker (class III antiarrhythmic) - prolongs repolarization and refractoriness without affecting conduction
used for:
- long term oral management of ventricular tachycardia +/- mexiletine including ARVC, german shep with inherited arrhythmia and ventricular tachycardia that is refractory to IV antiarrhythmics.
- supraventricular tachycardia inc accessory pathway mediated reciprocating tachycardia, atrial-flutter and a cat with SVT
When should Sotolol not be used?
- unstable/overt CHF (unless secondary to tachyarrhythmia responsive to B blocker)
- bronchial asthma
- sensitive to beta blockers
- second or third degree AV block
- sick sinus syndrome (unless paced)
- sinus bradycardia/severe bradycardia
- hypokalaemic bradycardia
- long QT syndrome
- cardiogenic shock
care in:
- liver/renal disease
- digitalis toxicity
- DM
- first degree AV blocks
- sinus node dysfunction
What class is amidarone and when should it be used?
Class III antiarrhythmic (K+ channel inhibitor)
+ blocks Na+ and Ca++ channels
+ block B adrenergic receptors.
=> prolongs myocardial AP duration and refractory period.
only used when less toxic compounds not available.
- Cardioversion from Afib to sinus rhythm
- refractory arrhythmia wiht systolic dysfucntion.
+ itraconazole => treat trypanosoma cruzi (Chagas) due to disruption of calcium homeostasis, sterol production, and blockade of the protease cruzipain
When should amidarone not be used?
- unstable/overt CHF
- second or third degree AV block
- sick sinus syndrome
- sinus bradycardia/severe bradycardia esp if syncope
- cardiogenic shock
- iodine sensitivity
Care with thyroid disease - can cause hyper or hypothyroidism
can cause histamine reactions, pulmonary fibrosis, corneal deposits, thrombocytopenis, hepatotoxic, coombs +ve
What class is procainamide and when should it be used?
Class 1a antiarrhythmic
Procainamide prolongs the refractory times in both the atria and ventricles, decreases myocardial excitability, and depresses automaticity and conduction velocity
- negative inotrope but CO maintained.
- some anticholinergic effects
Used for
- SVT with wide QRS complex
- A-fib
- VPC
- V-tach
- tachycardias that cannot be confirmed to be supraventricular or ventricular in origin due to wide QRS.
When should procainamide not be used?
- myasthenia gravis
- hypersensitivity
- torsade de pointes
- 2nd or 3rd degree AV block (unlesss paced)
with caution in dogs with
- cardiac glycoside intoxication
- hepatic/renal disease
- CHF
- DCM
- subaortic stenosis
- patients susceptible to tachyarrhythmic -induced sudden death.
- SLE?
What class is triamterene and when should it be used?
K+ sparing diuretic
- distal renal tubule, triamterene inhibits the reabsorption of sodium in exchange for hydrogen and potassium ions
- doesn’t competitively inhibit aldosterone
- increases excretion of sodium, calcium, magnesium, and bicarbonate; urinary pH may be slightly increased.
- Serum concentrations of potassium and chloride may be increased
alternative to spironolactone
infrequently used
When should triamterene or amiloride not be used?
- anuria
- severe progressive renal disease
- severe hepatic diseas
- hypersensitivity
- pre-exisiting hyperkalaemia
- concurrent therapy with another potassium sparing agent
- potassium supplementation.
What class is amiloride and when should it be used?
K+ sparing diuretic
- blocks epithelial sodium channel the late distal tubule, connecting tubule and collecting duct => reduced absorption of Na+ and reduced excretion of K+
alternative to spironolactone.
What is the mechanism of action of vasopressin?
- acts through at least 5 different receptors (3 subtypes: V1, V2, V3; the oxytocin receptor; and the purinergic P2 receptor) to maintain serum osmolality.
- V2 receptors, vasopressin promotes the renal reabsorption of solute-free water in the distal convoluted tubules and collecting duct
- vasopressin V1 receptor stimulation and blockade of K+ -sensitive ATP channels can cause smooth muscle contraction = > vasoconstriction of capillaries and small arterioles in particular => decreased blood flow.
When is vasopressin used?
- diagnostics as part of water depreviation test.
- treatment for central DI
- CPR - can improve myocardial perfusion with no pulse.
- increase BP SIRS/sepsis associated hypotension.
When should vasopressin not be used?
- vascular disease
- seizure disorders
- heart failure
- asthma
- extravasation necrosis possible.
What is the mechanism of action of desmopressin?
Similar to vasopressin but more antidiuretic and less vasopressor properties.
+
dose depending increase in vWF and factor VIII
When should desmopressin be used?
- Diagnosis and treatment of central DI
- peroperatively in dogs with type 1 vWF diseases to increase vWF
- surgical adjunct to reduce LN involvement and mets of canine mammary carcinoma (controversoal)
When should desmopressin not be used?
- Hypersensitivity to it
- nephrogenic DI
- hyponaturaemia
- Type IIb (=> PLT aggregation and thrombocytopenia) , type III (not efffective) or platelet-type (pseudo) vWF disease
What is the class and mechanism of action of chlorpropamide?
- Sulfonylurea + antidiabetic agent.
- antidiuretic activity: potentiating vasopressin’s effects on the renal tubules =/- increased ADH secretion
- lowers BG but not sure how maybe by stimulating the beta cells in the pancreas to secrete additional endogenous insulin + increased peripheral sensitivity to insulin
What is chlorpropamide used for?
Diabetes insipidus with partial ADH deficiency
possible DM?
When should chlorpropamide not be used?
- severe burns/trauma/infection
- hypoglycaemia or diabetic coma
- ketosis/ketoacidosis/other acidic condistion
with care:
- adrenal/pituitary insufficiency
- thyroid, cardia, renal, hepatic function impairment.
- fluid retention.
What is Tolvaptan and when could it be used?
Selective, competitive ADH V2 antagonist
used to treat hyponatraemia assoc with CHD, cirrhosis and SIADH
what is stomatotropin and when could it be used?
Hormone
- hypo-pituitary dwarfism
- growth hormone responsive dermatosis/alopecia X
When should stomatotropin not be used?
hypersenstivity to it
can cause DM and acromegaly.
What is medroxyprogesterone and when is it used?
Synthetic progrestin
* adverse effects - consider others first
- sexually dimorphic behaviour problems including roaming, inter-male aggression, spraying, mounting etc when castration is not effective/possible
- feline psychogenic dermatitis
- alopecia X
- young german shepard dwarfs
- short term treatment of benign prostatic hypertrophy
When should medroxyprogresterone not be used?
- puberty
- pregnancy
- pseudo pregnancy
- dioestrus
- prolonged cycle unless cystic ovarian disease is confirmed nad surgery, gnrh or hCG are not options
- DM
What is L-thyroxine and when is it used?
Synthetic T4
Treatment of hypothryoidism
When should Thyroxine not be used?
- acute myocardial infarction
- thyrotoxicosis
- untreated adrenal insufficiency (hypoA)
care/lower dose with:
- cardiac disease
- DM
- treated hypoA
- geriatrics
What is Octreotide and lanreotide and when is it used?
Long acting stomatostatin analog
- inhib synthesis and secretion of insulin, glucagon, secretin, GH, gastrin and motilin.
used for:
- gastrinoma
- management of hyperinsulinaemia with insulinoma
Not effective at reducing GH levels or enhancing insulin sensitivity in cats with acromegaly
Use with caution in billary tract disorders.
What is pasireotide and when is it used?
Multireceptor ligand stomatostatin (growth hormone inhibitory hormone) analogue
decreases IGF-1 and improves insulin sensitivity in cats
What is the mechanism of action of Cabergoline?
Ergot alkaloid-derived dopamine (D2) receptor agonist
- Direct inhibitory effect on the secretion of prolactin from the anterior pituitary gland.
- induces estrus by dopamine agonist effects on GnRH secretion rather than its effects on prolactin.
What is Cabergoline used for?
- pyometra
- inducing and synchronizing oestrus
- Primary or secondary anoestrus
- Mastitis
- Pseudopregnancy
- pregnancy termination in the second half of pregnancy
- prior to mammary tumour surgery
- reduce post-spay aggression when spay occurs in the luteal phase.
When should Cabergoline not be used?
- during pregnancy (unless a termination is wanted)
- hypertension
- hypersensitivity to it or bromocriptine
- pregnant women or hepatic disease.
What is the mechanism of action of Selegiline/L-Deprenyl?
Monoamine oxidase inhibitor
For hyperA:
In the hypothalamus, corticotropin-releasing hormone (CRH) acts to stimulate the production of ACTH in the pituitary, and dopamine acts to inhibit the release of ACTH. As dogs age, there is a tendency for a decrease in dopamine production that can contribute to the development of PDH
- dopamine is metabolized by monoamine oxidase-B (MAO-B) and selegiline irreversibly inhibits MAO-B, dopamine concentrations can be increased at receptor sites after selegiline administration.5 In theory, this allows the concentration of dopamine and CRH to be in balance in the hypothalamus, thereby reducing the amount of ACTH produced and, ultimately, cortisol
What is Selegiline/L-Depreny used for?
- Canine cognitive dysfunction
- chronic anxiety or noise phobisa (+benzo or B-blocker)
- maybe pituitary dependant hyperA but not really effective.
When should Selegiline/L-Depreny not be used?
- HyperA that is not pituitary dependant
- aggression
- with some drugs => Serotonin syndrome
What drugs are associated with serotonin syndrome?
Monoamine oxidase inhibitors:
- selegiline
- amitraz
- linezolid
- methylene blue
- SSRis inc fluoxetine
- tricyclic antidespressants - clomipramine, amitryptyline
- opioids
- mirtazapine
- tramadol
- trazodone
What is the mechanism of action of Aglepristone?
Progesterone receptor antagonist
- Synthetic steroid that competitively antagonizes progesterone at the P4 progesterone receptor
- Progesterone is necessary for maintaining pregnancy, thus aglepristone binding to P4 receptors of the uterus, terminates pregnancy or induces parturition
for pyometra => pening of the cervix and resumption of myometrial contractility
Also binds to glucocorticoid receptors but without glucocorticoid activity
What is Aglepristone used for?
- pregnancy temination (+/- additional medication for cats)
- induce partuition
- pyometra
- mammary hyperplasia in cats
When should Aglepristone not be used?
During pregnancy unless for termination or induction of parturition.
- unwell, Dm or liver/renal disease
- hypoA
- COPD or CV disease esp bacterial endocarditis.
What is the mechanism of action of methimazole and carbimazole?
- Carbimazole is the prodrug of methimazole
- inhibits thyroid peroxidase and interferes with iodine incorporation into tyrosyl residues of thyroglobulin, thereby inhibiting thyroid hormone synthesis.
- inhibits iodinated tyrosyl residues from coupling to form iodothyronine
- doesn’t effect already circ thyroid hormones
Has antiVitamine K activity => increased risk of bleeding
When should methimazole/Carbimazole be used?
- treatment of feline hyperthyroidism
When should methimazole/carbimazole not be used?
- Hypersensitive to methimazole or carbimazole or PEG
- autoimmune disease
- primary liver disease
- renal failure
- haematological disorders or coagulopathies
- DM
What is the mechanism of action of propylthiouracil?
PTU inhibits the enzyme thyroperoxidase, which facilitating iodine’s addition to tyrosine residues on the hormone precursor thyroglobulin, thus preventing Tg synthesis
Also inhibits enzyme 5’-deiodinase (tetraiodothyronine 5’ deiodinase), which converts T4 to the more active form T3 (methimazole doesn’t do this)
more side effects so not used any more.
What are the different types of insulin and their duration of action in dogs?
- Regular crystaline
- IV
- IM 4-6h
- SC 6-8h - Lispro - IV
- NPH/humulin - 6-12h
- Lente/caninsulin - 8-14h
- PZI - 10-16h
- Glargine 8-16h
- Detemir 8-16h
What are the different types of insulin and their duration of action in cats?
- Regular crystaline
- IV
- IM 4-6h
- SC 6-8h - Lispro - IV
- NPH/humulin - 6-10h
- Lente/caninsulin - 8-12h
- PZI - 10-14h
- Glargine 8-16h
- Detemir 8-16h
When should you use PZI instead of NPH/Humulin or Lente/Caninsulin in dogs?
If they are poorly controlled with a shorter acting insulin as PZI has a longer duration of effect.
When should you use glargine in dogs?
If NPH/Humulin or Lente/Caninsulin have too short a duration of effect
If detemir has too long a duration of effect
Can be considered first line but generally not.
What insulin should be used first line in cats?
Glargine or maybe PZI
Lente/NPH often have too short duration of effect for q12h dosing
What does detemir bind to, to slow release?
Albumin
What insulins are commonly used to treat DKA?
IV insulin such as regular crystaline or Lispro
What is Toujeo? When is it useful?
long acting, higher dose glargine insulin
useful for difficult to manage or acromegalic diabetic cats.
What are sulfonylureas?
Antidiabetic drug class.
- lowers blood glucose concentrations in both diabetic and nondiabetic patients.
- stimulate beta cells in the pancreas to secrete additional endogenous insulin + increase peripheral sensitivity to insulin and reduce the production of hepatic basal glucose.
Which drugs are sulfonylureas?
Chlorpropamide
Glimepiride
Glipizide
What is glipizide and what is it used for?
sulfonylurea antidiabetic drug that increase existing pancreatic beta cell function and improves insulin sensitivity
used in cats with type II diabetes provided there is existing beta cell function present.
generally still recommended to use insulin concurrently or initially
not in hypoglycaemia, DKA or other ketosis.
What is Glimepiride and what is it used for?
medium to long acting secretagogue sulfonylurea antidiabetic drug that increase existing pancreatic beta cell function and improves insulin sensitivity
used in cats with type II diabetes (non-insulin dependent DM) provided there is existing beta cell function present. Less side effects than glipizide,
generally still recommended to use insulin concurrently or initially
not in hypoglycaemia, DKA or other ketosis or allergic to sulphonamides
What is Chlorpropamide and what is it used for?
sulfonylurea antidiabetic drug that increase existing pancreatic beta cell function and improves insulin sensitivity
=> used in cats with type II diabetes provided there is existing beta cell function present.
+ also has antidiuretic activity => potentiates ADH effects on renal tubules and may stimulate ADH release
=> for Diabetes insipidus
What is metformin and what is it used for?
Anti-hyperglycaemia
- increases insulin’s peripheral ability for cells to uptake glucose
- decreases hepatic glucose production,
- decrease intestinal absorption of glucose.
does not stimulate insulin production or release from the pancreas and, therefore, does not cause hypoglycemia.
Used in type II/non-insulin dependent DM, predominantly in cats but could also be used in dogs.
not with iodinated contrast or acidosis
What is Acarbose and what is it used for?
oral antidiabetic drugs.
- Competitively inhibits pancreatic α-amylase and α-glucosidases found in the small intestine.
=> delays digestion of complex carbohydrates
=> glucose absorbed in lesser amounts lower in the GI tract.
=> decreases blood glucose and insulin requirements during the postprandial hyperglycemic phase
may be used in non-insulin dependant DM (predom cats + dogs)
+/- in Insulin dependent DM (type 1) as an adjunct treatment
+/- used when insulin activity peaks too soon.
What class is Exenatide and what is its mechanism of action?
- glucagon-like peptide-1 (GLP-1)–receptor agonist,
- incretin mimetic
- increases glucose-dependent insulin synthesis and secretion,
- increases pancreatic endocrine β-cell proliferation and survival,
- inhibits glucagon secretion (without impeding glucagon secretion in response to hypoglycemia).
- improves insulin sensitivity in muscles
- reduces hepatic gluconeogenesis.
requires adequate mass of functional pancreatic endocrine β cells.
What is Exenatide used for?
Adjunctive treatment of uncomplicated DM in cats, esp newly diagnosed with glargine insulin
When should Exenatide not be used?
- DKA
- monotherapy for type 1 DM
- pancreatitis due to exenatide
- drug induced IMT due to exenatide
- hypersensitivity,
- severe GI disease,
- severe or end-stage renal disease,
- medullary thyroid carcinoma,
- multiple endocrine neoplasia syndrome type 2
What are GLP-1 receptor agonists and what is their mechanism of action?
Exenatide
Liraglutide
Activate GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses that are both glucose-dependent-with a consequent low risk for hypoglycemia
- increases glucose-dependent insulin synthesis and secretion,
- increases pancreatic endocrine β-cell proliferation and survival,
- inhibits glucagon secretion (without impeding glucagon secretion in response to hypoglycemia).
- improves insulin sensitivity in muscles
- reduces hepatic gluconeogenesis.
What is the class and mechanism of action of Diazoxide?
Direct vasodilator/hyperglycaemic
vasodilatory effect on the smooth muscle in peripheral arterioles + reduces peripheral resistance and blood pressure.
hyperglycemic:
- inhibiting pancreatic insulin secretion, (decrease the intracellular release of ionized calcium, thus preventing release of insulin from beta cell insulin granules)
- stimulating hepatic gluconeogenesis and glycogenolysis
- stimulating the beta-adrenergic system to cause epinephrine release and inhibit tissue use of glucose.
What us diazoxide used for?
hypoglycaemia secondary to hyperinsulin secretion (insulinoma) if refractory to pred and diet managment
What should diazoxide not be used?
functional hypoglycaemia
hypoglycaemia secondary to insulin overdose
Can cause Na++ and H2O retention - use with care
What is Phenytoin and what is it’s mechanism of action?
Anticonvulsant and anti-dysrhythmic
Anticonvulsant actions: caused by the promotion of sodium efflux from neurons, thereby inhibiting the spread of seizure activity in the motor cortex.
Antiarrhythmic - Group 1B: depresses phase 0 slightly and can shorten the action potential. Its principle cardiac use is in the treatment of digitalis-induced ventricular arrhythmias.
- can inhibit insulin and vasopressin (ADH) secretion
What is phenytoin used for?
Digoxin induced ventricular arrhythmia
not really used as an antiarrhythmic
When should phenytoin not be used?
- Cats
- 2nd or 3rd degree heart block,
- Sinoatrial block,
- Adams-Stokes syndrome,
- sinus bradycardia.
What is trilostane and its mechanism of action?
Adrenal Steroid Synthesis Inhibitor
- competitive inhibitor of 3-β hydroxysteroid dehydrogenase
- reduces synthesis of cortisol, aldosterone, and adrenal androgens. Inhibition is reversible and apparently dose dependent
What is trilostane used for?
- pituitary dependent hyperA
- Adrenal dependant hyperA
- Alopecia x
dogs and cats
When should trilostane not be used?
- hypoadrenocorticism
care with
- liver/renal disease
- anaemia
What is Mitotane and its mechanism of action?
Antineoplastic
severe, progressive necrosis of the zona fasciculata and zona reticularis.
adrenal cytotoxic agent, it apparently can also inhibit adrenocortical function without causing cell destruction
Mostly spares zona glomerularis so generally aldosterone secretion is not significantly affected
What is mitotane used for?
- pituitary dependent hyperA
- palliative treatment of adrenal carcinoma
When should mitotane not be used?
- cats
- sick patients
- addison’s
- patients without clinical and lab findings of pituitary dependent hyperA.
care with
- liver/renal disease
- DM
- potential for hypoA
What is ketoconazole and its mechanism of action?
imidazole antifungal
- generally fungistatic but can be fungicidal
inhibits a fungal cytochrome P450-dependent demethylation enzyme that produces ergosterol in the cell membrane
Anti-inflam by inhibition of 5-lipooxygenase
Suppress T-lymphocyte proliferation
inhib Vit D activation
steroid synthesis inc testosterone and cortisol is directly inhibited by blocking several P450 enzyme systems
What is ketoconazole used for?
Others usually recommended but Antifungal for: - Blastomyces dermatitidis, - Coccidioides immitis, - Cryptococcus neoformans, - Histoplasma capsulatum, - Microsporum spp, - Trichophyton spp. \+ higher doses for Aspergillus spp and Sporothrix
Historically for hyperA and prostatic carcinoma
Reduce cost of other drugs that req CYP450 inc cyclosporine.
When should ketoconazole not be used?
- Cats
- hypersensitivity
- liver disease
- thrombocytopenia
- stressful events
- care with other drugs associated with CYP450 metabolism
what is bromocriptine and what is it used for?
Dopamine agonist/prolactin inhibitor.
use cabergoline now.
- acromgealy in cats
- oestrus induction in dogs
- treatment of pseudo pregnancy
- pregnancy termination
- pyometra
What is melatonin and its mechanism of action?
Pineal gland hormone
What is melatonin used for?
Hair loss:
- alopecia X
- canine pattern baldness
- recurrent flank alopecia
- post clipping alopecia
- follicular disorders inc follicular dysplasia
Brain assoc:
- sleep cycle disorders
- cognitive dysfunction
- phobias and anxiety
others:
- idiopathic vaculolar hepatopathy
- prologning interoestur period in queens
- reversible reduction in sperm quantity and quality in male cats.
- not for use in sexually immature animals.
What is metyrapone and its mechanism of action?
Adrenal steroid inhibitor
- inhibiting hydroxylation of 11-deoxycortisol to cortisol in the adrenal cortex.
- suppress synthesis of aldosterone, and cause a mild natriuresis
- ACTH production can increase as the negative feedback mechanism is inhibited but may be overridden in time.
When is metyrapone used?
- cats with hyperA prior to adrenalectomy + reduce insulin requirement.
- need to monitor BGs
What is the difference between cosyntropin and endogenous corticotropin? What is their mechanism of action
Cosyntropin is not as immunogenic as endogenous corticotropin (ACTH) due to difference in C-terminal.
Both can be used for ACTH stim test but cosyntropin is more available.
ACTH stimulates the adrenal cortex (principally the zona fasciculata) to stimulate the production and release of glucocorticoids/cortisol.
ACTH release is controlled by corticotropin-releasing factor (CRF), activated in the hypothalamus via a negative feedback pathway, whereby either endogenous or exogenous glucocorticoids suppress ACTH release.
What is Fludrocortisone and it’s mechanism of action?
Mineralocorticoid + glucocorticoid
Mineralocorticoids increase sodium reabsorption at the renal distal tubule and enhance potassium and hydrogen ion excretion in the collecting tubule
What is fludrocortisone used for?
- HypoA
When should fludrocortisone not be used?
- systemic fungal infections
risk of glaucoma/cataracts + immunosuppression
Care with:
- renal/cardiac disease (fluid retention + elyte imbalance + hypertension)
- recent intestinal anastamosis,
- GI ulcers
- osteoporosis
- Myasthenia gravis
What is Desoxycorticosterone Pivalate and its mechanism of action?
DOCP - mineralocorticoid
acts on the renal distal tubule, where it increases the reabsorption of sodium. Mineralocorticoids also enhance potassium and hydrogen ion excretion in the collecting tubules.
What is Desoxycorticosterone Pivalate used for?
HypoA in dogs (limited info in cats)
more effective at reducing renin than fludrocortisone
When should Desoxycorticosterone Pivalate not be used?
- IV
- hyperesensitivity to it
- hypoA crisis that is not rehydrated
- CHF
- liver failure
- oedema
What is hydrocortisone?
Glucocorticoid with intermediate mineralocorticoid activity.
When should hydrocortisone be used?
- Acute adrenal insufficiency/HypoA crisis
- critical illness assoc corticosteroid insufficiency
When should hydrocortisone not be used?
- systemic fungal infection unless used for replacement therapy for dogs with hypoA
- idiopathic thrombocytopenia
What tests does hydrocortisone interfere with? What could be used instead
- ACTH stim: do test before or 24h after last dose of hydrocortisone. * dex does not cross react
- used for LDDST/HDDST
- suppress TSH => reduced T3 and T4.
- Reduces uptake of I131
- increase serum cholesterol + neuts
- reudce serum potassium and lymphocytes.
What is phenoxybenzamine and its mechanism of action?
- α-adrenergic Antagonist (nonselective),
- Vasodilator
- noncompetitively blocks the α-adrenergic response to circulating epinephrine or norepinephrine;
- greater affinity for α1-receptors than α2-receptors.
- increases cutaneous blood flow
- block pupillary dilation, lid retraction, and nictitating membrane contraction
Whatis phenoxybenzamine used for?
- urethral hypertonus
- urethral obstrucion
- hypertension associated with phaeo
When should phenoxybenzamine not be used?
- hypotension
- glaucoma
Caution with:
- CHF/cardiac disease
- renal disease
- cerebral/coronary arteriosclerosis
What is metirosine and what is it used for?
Anti-hypertensive drug
It inhibits the enzyme tyrosine hydroxylase and, therefore, catecholamine synthesis,
=> depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body.
thus alleviate symptoms related to catecholamine excess, including hypertension, headache, tachycardia, constipation, and tremor - eg with pheochromocytoma.
What is pamidronate and its mechanism of action?
IV bisphosphonate
- inhibit bone resorption and do not inhibit bone mineralization via binding to hydroxyapatite crystals.
- impede osteoclast activity, and induce osteoclast apoptosis
When is pamidronate used?
- hypercalcaemia inc
- idiopathic,
- assoc with malignancy
- Vit D toxicicity
- palliative pain management of osteolytic bone cancer
When should pamidronate not be used?
hypersensitivity to it, other bisphosphonates or mannitol
care with reduced renal function, juvenile animals, healing bone fractures.
What is calcitonin and its mechanism of action?
Osteoclast inhibiting hormone.
- inhibiting osteoclastic bone resorption.
- reduces tubular reabsorption thus increases excretion of calcium, phosphate, sodium, magnesium, potassium, and chloride,
- increases jejunal secretion of water, sodium, potassium, and chloride (not calcium).
What is calcitonin used for?
Control hypercalcaemia
pain that originates from the bone
When should calcitonin not be used?
Hypersensitivity
- young animals
- hypocalcaemia
What is calcitriol and its mechanism of action?
Vit D3 analogue
- enhance calcium absorption from the GI tract,
- promote reabsorption of calcium by the renal tubules,
- increase the rate of accretion and resorption of minerals in bone.
Unlike other forms of vitamin D, calcitriol does not require renal activation for it to be effective.
What is calcitriol used for?
+ oral calcium therapy for long term management of hypocalcaemia assoc with primary hypoPTH or secondary renal hypoPTH
- CKD (dogs = survival benefit, cats = weak evidence)
- MCT (may potentiate some chemo drugs)
- refractory dermatopathies (primary idiopathic seborrhea)
When should calcitriol not be used?
- hypercalcaemia
- vit D toxicity
- sensitive to effects of Vit D
- hyperphosphataemia (tissue mineralization)
- CaOx urate producers
- GIT disease with malabsorption.
What is Edetate Calcium Disodium (CaEDTA), its mechanism of action and use?
Heavy metal chelator for lead and zinc toxicity.
- The Calcium in CaEDTA can be displaced by divalent or trivalent metals to form a stable, water-soluble complex that is excreted in the urine (lead and zinc).
- CaEDTA also binds cadmium, copper, iron, and manganese, but does not facilitate removal of those metals from the body.
- CaEDTA is relatively ineffective for use in treating mercury, gold, or arsenic toxicities.
What is alendronate and its mechanism of action?
Bone resorption inhibitor
- Binds to bone hydroxyapatite, inhibits osteoclast function and thereby reduces bone resorption.
- promoting apoptosis and inhibiting osteoclastogenesis, angiogenesis, and cancer cell proliferation (in osteogenic tumours)
What is alendronate used for?
- refractory hypercalcemia inc idiopathic hyperCa++
- bone pain,
- osteosarcoma treatment adjunct
- feline tooth resorption
When should alendronate not be used?
- hypocalcaemia
- Upper GI effects inc oesophagitis/ulcers
- query severe renal disease
What is Ergocalciferl and its mechanism of action?
Vit D2
req hydroxylation in liver to 25-hydroxyVit D, then activeted in kidneys to 1,25 -dihydroxyvit D
- enhance calcium and phosphate absorption from the GI tract,
- promote reabsorption of calcium by the renal tubules,
- increase the rate of accretion and resorption of minerals in bone
What is ergocalciferol used for?
Calcitriol recommended first
- hypocalcaemia assoc with hypoPTH (+ calcium)
When should ergocalciferol not be used?
- hypercalcemia,
- vitamin D toxicity,
- malabsorption syndrome,
- abnormal sensitivity to the effects of vitamin D.
- *hyperphosphatemia.
- kidney dysfunction - may not be able to activate it.
What is cyclosporine and its mechanism of action?
Calcineurin inhibitor - selective immunosuppressant, primarily of CMI
- binds to T-cell cyclophilin and blocks calcineurin-mediated T-cell activation.
- inhibit cytokine production and release (including IL-2 and interferon-gamma => affect function of eosinophils, mast cells, granulocytes, and macrophages)
- inhibit antigen-presenting functions of the dermal immune system.
- increase thromboxane production.
When can cyclosporine be used?
- atopic dermatitis + other skin disease (eosinophilic, neutrophilic, ulcerative dermatosis of nose, alopecia areata etc)
- perianal fistula/anal frunculosis
off label:
- IMHA + pure red cell aplasia (c)
- IMT or thrombocytopenia purpura (c)
- allograft transplant rejection
- Chronic enteropathy/IBD
- idiopathic chronic hepatitis
- sebaceous adenitits
- steroild nodular paniculitis
- sterile granuloma/pyogranuloma complex,
- refractory cases of juvenile sterile granulomatous dermatitis and lymphadenitis (ie, juvenile cellulitis)
- vasculitis,
- reactive histiocytic disorders,
- pemphigus foliaceus (controversial results),
- lupus erythematosus complex,
- MUO
- erythema multiforme,
- uveodermatologic syndrome
- chronic stomatitis (c)
- feline asthma
When should cyclosporine not be used?
- neoplasia
- FIV/FeLV
Caution:
- infectious disease (only if benefit outweighs risk)
- DM
- renal disease
- toxo
- MDR1/ABCB1-1delta mutation?
- Vaccination - reduced response = used killed.
What is leflunomide and what is its mechanism of action?
selective Immunomodulator/immunosuppressant
Pyramidine synthesis inhibitor
- inhibits autoimmune T-cell proliferation and autoantibody production by B cell
- prevents formation of (rUMP), => decreased DNA and RNA synthesis, inhibition of cell proliferation, and G1 cell cycle arrest primarily in lymphocytes
- antiviral
- tyrosine kinase inhibiting properties,
- antiplatelet effect
What is leflunomide used for?
- IMHA
- IMT
- Evans
- pancytopenia
- IMPA and rheumatoid arthritis
- IBD/CE
- systemic and cutaneous reactive histiocytosis
- GME
- vasculitis
- transplant rejection
When should leflunomide not be used?
- hypersensitivity
- liver/renal
care with:
- severe immunodeficiency
- bone marrow dysplasia
- active infection
- with other immunosuppressants or durgs known to be hepatotoxic.
Who long do different immunosuppressants take to work?
IVIG: “rapid”
Pred: up to 1-2 weeks. generally reported less than 1 week
Mycophenolate: 2 days to 2 weeks.
Cyclosporine: 3-7 days. reported up to 2 weeks
Leflunomide: 1-3 weeks
Azathioprine: lag period of 1 week. up to 3-5 weeks for clinical immunosuppression
What drugs are recommended as second line immunosuppressant for IMHA?
- Cyclosporine
- mycophenolate
- azathioprine
INI with these - use leflunomide or IVIG (salvage option)
What is IVIG and its mechanism of action?
Immune serum
B-cells produce IG, thus IVIG Abs act to:
- antimicrobial or antitoxin neutralization
- anti-idiotypic antibodies that neutralize autoantibodies;
- negative feedback and down-regulation of antibody production; binding to CD5, IL-1a, IL-6, TNF-alpha, and T-cell receptors;
- suppressing pathogenic cytokines and phagocytes.
What is IVIG used for?
Canine only
- IMHA
- IMT
- Evans
- Immune med dermatopathies (erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis, other cutaneous drug reactions)
Not used as a first line - only in refractory.
When should IVIG not be used?
- cats
- prior hypersensitivity to human albumin
Risks:
- hypercoag state (eg IMHA)
- renal dysfunction, AKI, osmotic nephrosis
- increase BP
- local reaction
- Vol overload
- anaphalaxis
What is mycophenolate and its mechanism of action?
Selective immunosuppressant (IMPDH inhibitor) => inhibits guanosine synthesis (purine)
- noncompetitively, but reversibly, inhibits inosine monophosphate dehydrogenase (IMPDH) (Esp type 2 in activated lymphocytes)
- lack of guanosine => proliferation of B and T cells is inhibited.
+ suppress Ab formation
=> inhibition of both CMI and humoral immune response
What is mycophenolate used for?
Dog +/- cats?
- IMHA (D+C)
- Aplastic anaemia
- IMT
- glomerulonephritis
- myathenia gravis
- MUO
- pemphigus foliaceous/immune med skin disease
When should mycophenolate not be used?
- SARDs (not effective)
- maybe IBD due to GIT side effects
- renal dysfunction
care:
- lymphoma
- serious infections.
- pappilomatosis
What is azathioprine and its mechanism of action?
Non-specific immunosuppression.
Purine antagonist
- antagonizes purine metabolism
=> breaks in DNA and RNA
=> termination of the replication process.
Cellular metabolism may become disrupted by the drug’s ability to inhibit coenzyme formation. - interferes with CD28 costimulation of T lymphocytes by converting the costimulatory signal from CD28 to trigger apoptosis
- greater activity on delayed hypersensitivity and cellular immunity than on humoral antibody responses.
- Clinical response to azathioprine may not be observed for up to 5 weeks.
When is azathioprine used?
used in combo with pred.
- no large scale studies on its use
- IMHA
- other autoimmune diseases
+ cyclosporine to prevent renal allograft rejection in dogs
When should azathioprine not be used?
- cats (myelosuppression)
- hypersensitivity, renal/liver disease
=> increased risk of infection or neoplasia
What is flucytosine and its mechanism of action?
Antifungal
- metabolite competes with uracil
=> interfere with pyrimidine metabolism
=> prevent RNA and protein synthesis.
+ inhibits thymidylate synthesis => inhibits DNA synthesis.
What is flucytosine used for?
Cryptococcus
Candida
penetrates CNS
- must be used with other antifungals as develops resistance quickly.
- synergistic with amphotericin B
When should flucytosine not be used?
Must use with another antifungal as will develop resistance rapidly on own.
Use extreme caution in:
- dogs (drug assoc skin disease)
- renal impairment
- pre-exisiting BM depression
- haematological diseases
- those recieving bone marrow suppressants
What is amphotericin B and its mechanism of action?
Systemic antifungal (polyene macrolide antibiotic) Fungistatic => fungicidal
- binding to sterols (primarily ergosterol) in the fungal cell membrane and altering the permeability of the membrane, allowing intracellular potassium and other cellular constituents to leak out.
- Mammals have cholesterol in their cells so can be affected but less so than ergosterol.
What is amphotericin B used for?
most severe systemic fungal disease including:
- Blastomyces spp,
- Aspergillus spp,
- Paracoccidioides spp,
- Coccidioides spp, Histoplasma spp,
- Cryptococcus spp,
- Mucor spp,
- Sporothrix spp.
- lipsomal form can be used to treat leishmaniasis (not recommended => resistance) and naegleria protozoa
When should amphotericin B not be used?
- not severe, life-threatening, progressive disease that is unresponsive to other antifungals.
- not indicated by antifungal susceptibility results.
- renal disease
What are the different formulations of amphotericin B and what is the benefits of them?
- Amphotericin B deoxycholate (conventional formulation)
- Amphotericin B lipid complex (ABLC, Abelcet), a suspension of amphotericin B complexed with two phospholipids. The most extensively evaluated in dogs, shown in one study to be safe and effective in dogs at a cumulative dosage of 8-12 mg/kg.
- Amphotericin B cholesteryl sulfate complex (Amphotec). This is a colloidal dispersion, also called ABCD (amphotericin B colloidal dispersion).
- Liposomal complex of amphotericin B encapsulated in a lipid bilayer (L-AmB, AmBisome)
- lipid and cholesteryl formulations of amphotericin B are commonly used in people, but experience is limited in veterinary medicine due to cost. The advantage over traditional formulations is that these forms can be given at higher doses with greater efficacy and less toxicity.
What is griseofulvin and its mechanism of action?
Antifungal for dermatophytes only
- disrupts the structure of the cell’s mitotic spindle, arresting the metaphase of cell division, and inhibiting nucleic acid synthesis.
- concentrated in skin, hair, nails, fat, skeletal muscle, and the liver.
only new hair/nail growht is resistant to dermatophytes
What is griseofulvin used for?
Dermatophytosis only:
- Trichophyton,
- Microsporum,
- Epidermophyton
concentrated in skin, hair, nails, fat, skeletal muscle, and the liver.
only new hair/nail growht is resistant to dermatophytes
When should grizeofulvin not be used?
- Cats with FIV
- kittens
- liver failure
- pregnancy
Which drugs are azole antifungals?
What are their uses?
Ketoconazole Itraconazole Fluconazole Voriconazole Posaconazole
What is the mechanism of action of azole antifungals?
what limits their efficacy?
- inhibits a fungal CYP450-dependent demethylation enzyme that produces ergosterol in the fungal cell membrane.
=> weakened cellular membranes
=> increased membrane permeability, leakage of cellular contents and impairing uptake of purine and pyrimidine precursors.
-high lipophilicity and poor solubility
=> limits GI absorption unless the medication is administered with food to stimulate stomach acids to aid in lipid dissolution.
thus => Antacids, H2 blockers and PPIs can decrease GI absorption
What is itraconazole and its mechanism of action?
tri-Azole antifungal
- inhibits a fungal CYP450-dependent demethylation enzyme that produces ergosterol in the fungal cell membrane.
=> weakened cellular membranes
=> increased membrane permeability, leakage of cellular contents and impairing uptake of purine and pyrimidine precursors.
\+ Antifinlamf - suppression of Tlymph prolif, - inhib of Ca++-dependent inflam by Neut, - inhib of leukotriene B4
When is itraconazole used?
- dermatophytosis in cats due to microsporium canis
- non life threatening mycosis that DO NOT involve the CNS including:
- aspergillosis,
- cryptococcal meningitis
- blastomycosis
- coccidioidomycosis
- sporotrichosis,
- histoplasmosis
- candida (+ terbinafine)
can cross into the eye/brain if inflam but ?? better for crypto than others
+
- Trypanosoma cruzi (+amidarone)
- fungal osteomyelitis,
- onychomycosis,
- Malassezia spp dermatitis
adjunctive for:
- pythiosis,
- lagenidiosis,
- zygomycosis,
- phaeohyphomycosis,
- hyalohyphomycosis.
When should itraconazole not be used?
- hypersensitivity to it or other azoles
Caution with:
- cardiac (slight neg ionotropic effect)
- liver/renal
- a/hypoclohydria
- other meds that inhib cytochrome P450 pathway.
What is fluconazole and its mechanism of action?
tri-Azole antifungal
- inhibits a fungal CYP450-dependent demethylation enzyme that produces ergosterol in the fungal cell membrane.
=> weakened cellular membranes
=> increased membrane permeability, leakage of cellular contents and impairing uptake of purine and pyrimidine precursors.
+
Antifinlamf
- reduce IL4
- inhib of leukotriene B4
When is fluconazole used?
- CNS fungal infections.
- urinary fungal infections
- blasto
- histoplasmosis
- skin/nail with candida, dermatophytes and malassezia (but ketoconazole or itraconazole may be better)
When should fluconazole not be used?
- hypersensitivity to it or other azoles
- receiving drugs that both prolong the QT interval and are metabolized by cytochrome P450 3A4
Care with
- hepatotoxicity
- renal
What is voriconazole and its mechanism of action?
Second gen triazole
- inhibits a fungal CYP450-dependent demethylation enzyme that produces ergosterol in the fungal cell membrane.
=> weakened cellular membranes
=> increased membrane permeability, leakage of cellular contents and impairing uptake of purine and pyrimidine precursors. - also inhibits 24-methylene dehydrolanosterol demethylation in molds such as Aspergillus spp giving it more activity against these fungi
What is voriconazole used for?
- CNS fungal infection
- blasto
- crypto
- Aspergillus
- Candida
- Trchosporon
- Fusarium
When should voriconazole not be used?
- cats (unless last resort for aspergillus)
- given with food
- hyperesnsitivity to it or other azoles
- hepatic
- arrhythmia prone
What is posaconazole and its mechanism of action?
Second gen triazole
- inhibits a fungal CYP450-dependent demethylation enzyme that produces ergosterol in the fungal cell membrane.
=> weakened cellular membranes
=> increased membrane permeability, leakage of cellular contents and impairing uptake of purine and pyrimidine precursors. - also inhibits 24-methylene dehydrolanosterol demethylation in molds such as Aspergillus spp giving it more activity against these fungi
- delayed release tablets had better absorption than oral suspension
What is posaconazole used for?
- cats
- trypanosoma crusi
- aspergillosis,
- cryptococcus
- sporotrichosis,
- coccidioidomycosis,
- blastomycosis,
- histoplasmosis,
- zygomycosis,
- mucormycosis.
- Candida
When should pozaconazole not be used?
Not well known in animals but in people
- hypersensitivity to the drug or any component in the suspension,
- concomitant use with:
- HMG-CoA reductase inhibitors (eg, atorvastatin, simvastatin),
- sirolimus,
- ergot alkaloids,
- CYP3A4 substrates that can prolong QT interval (eg, pimozide, quinidine).
+ decrease dose with renal disease but not hepatic.
Which antifungals are useful for CNS infections?
- fluconazole
- flucytosine
- Amphoteracin B
- voriconazole
What is Terbinafine and its mechanism of action?
allylamine antifungal,
- inhibits synthesis of ergosterol
=>block enzyme squalene monooxygenase (ie, squalene 2,3-epoxidase),
=> inhibits the conversion of squalene to sterols (especially ergosterol) and causes accumulation of squalene.
=> both effects are antifungal.
not mediated by cytrchorme P-450 enzs
What is terbinafine used for?
Fungicidal
- dermatophytes inc Microsporum spp, Trichophyton spp
Fungistatic
- yeasts (eg, Candida spp, malassezia
- Aspergillus spp,
- Blastomyces dermatitidis,
- Coccidioidomyces immitis,
- Histoplasma capsulatum,
- Sporothrix schenckii,
- Cryptococcus neoformans.
- pythiosis (+ other antifungal)
When should terbinafine not be used?
- hypersensitive to it
- liver disease
- as sole drug for pythiosis
What is milbemycin and what is it used for?
Macrolide antiparasitic
- heartworm prevention
- hoockworm
- adult round worm (Toxocara and toxascaris)
- whipworm (trichuris vulpis)
- demodex and sarcoptes (off label)
- angiostrongylus vasorum (+spinosad - dogs)
- lungworm (Cats)
What is ivermectin and what is it used for?
Avermectin antiparaciticide
used for:
- Heartworm prevention - larvae/microfilaricide
(+doxycycline as an adulticide pretreatment. Can be used as slow kill but not recommended… maybe in cats to reduce worm burden)
- hookworms
- ectoparasites: demodex sarcoptes, cheyletiellosis, nasal mites, otodectes
***MDR1/ABCB1 risk of CNS toxicity
What is moxidectin and what is it used for?
milbemycin-class, macrocyclic lactone antiparasitic
- Prevention of heartworm inc circ microfilaria
- doxycycline => Slow kill for heartworm (not recommended)
- hookworms (Ancylostoma caninum, Uncinaria stenocephala),
- roundworms (Toxocara cati),
- whipworms (Trichuris vulpis).
+ imidcloprid
- fox lungworm (Crenosoma vulpis)
- Feline aelurostrongylosis (Aelurostrongylus abstrusus)
- Ocular Thelazia callipaeda (eyeworm)
- Demodex
** safe for MDR1/ABCB1 mutation dogs
What is selemectin and what is it used for?
Avermectin atiparaciticide
- fleas (Ctenocephalides felis),
- prevention of heartworm disease (Dirofilaria immitis) but NOT adult HW or circulating microfilaria
- ear mites (Otodectes cynotis)
- sarcoptic mange (Sarcoptes scabiei)
- tick infestations (Dermacentor variabilis).
- nasal mites
- cheletiellosis
In cats:
- hookworms (Ancylostoma tubaeforme)
- roundworms (Toxocara cati)
- ear mites
What is melarsomine and its mechanism of action?
Arsenical antiparasitic
- mechanism of action not known
- 90% to 99% effective in killing adult and L5 larvae of Dirofilaria immitis
- The 2-dose method kills only ≈90% of adult worms whereas the 3-dose method kills 98%
What is melarsomine used for?
Stabilized class 1 (mild), 2 (moderate) and 3 (severe) heartworm disease caused by immature to mature adult infection for dirofilaria immitis.
What is the recommended protocols for melasomine use in heartworm in dogs?
Adulticide therapy
- Macrocytic lactone Day 0, 30, 60, 90 + ongoing (prior to melarsomine) + exercise restriction (+/- antihistamine and pred tapering dose over the first month if symptomatic)
- Doxycycline for 4 weeks (Day 1-30) then month break before melarsomine (eliminate Wolbachia)
- Melarsomine - 3 doses: days 60, 90 and 91 post starting ML
Caval syndrome:
- surgical removal of worms first
When should melarsomine not be used?
- Cats
- Class 4 (caval syndrome) heartworm disease
- if can’t be given via deep IM injection.
*must exercise restrict afterwards.
What is unfractionated heparin and its mechanism of action?
Anticoagulant
- acts on coagulation factors in both the intrinsic and extrinsic coagulation pathways.
- combines with antithrombin,
=> inactivate factor Xa and prevent the conversion of prothrombin to thrombin.
+ inactivates factors IX, X, XI, XII
Also - inactivates thrombin,
- blocks fibrinogen to fibrin
- prevents the formation of stable fibrin clots (inhib factor XIII).
does not lyse clots but it can prevent the growth of existing clots
What is unfractionated heparin used for?
During treatment of:
- immune-mediated hemolytic anemia (IMHA),
- pulmonary thromboembolism,
- other thromboembolic diseases,
- occasionally during the hypercoagulable state of disseminated intravascular coagulation (DIC) (not recommended any more - blood products prefered)
- reduce incidence of developing macrovascular thromboembolism in high-risk patients
When should unfractionated heparin not be used?
- severe thrombocytopenia
- factor depletion
- uncontrolled bleeding
- given IM (=> haematoma)
- DIC???
What is dalteparin and enoxaparin and its mechanism of action?
-LMW (fractionated) heparin anticoagulant
- binds to and accelerating antithrombin III, => enhance the inhibition of factor Xa and thrombin.
More selective than unfractionated heparin => minimal impact on PT, TT and aPTT)
enoxaprin has a shorter duration of action esp in cats (q6h dosing)
What is daleparin and enoxaparin used for?
- prophylaxis or treatment of thromboembolic disease
- maybe angina
When should dalteparin or enoxaparin not be used?
- hypersensitive to it, heparin, or pork products.
- major bleeding
- heparin-induced thrombocytopenia,
- thrombocytopenia
- renal dysfunction (drug accumulation)
- those getting epidural anesthesia or with increased risk for hemorrhage.
- give SC only (not IM/IV)
What is Aspirin and its mechanism of action?
antiplatelet agent + NSAID
- inhibits cyclooxygenase (COX-1, prostaglandin synthetase), thereby reducing prostaglandin and thromboxane (TXA2) synthesis.
- platelets can’t make more COX => irreversibile inhibition of platelet aggregation.
When should aspirin be used?
- offset cyclosporine-induced thromboxane synthesis
- IMHA
- Antiplatelet antithrombotic (long duration of action in cats)
- not used as often as clopidogrel appears to be safer and more effective
+
- Analgesia
- antipyretic
- anti-inflam
When should aspirin not be used?
- hypersensitivity reactions to aspirin or other salicylates
- GI erosions and ulcerations
- concurrent pred/NSAIDs
- haemorrhagic disorders
- asthma
- renal insufficiency
Care with:
- cats
- hypoalbuminaemia
- liver/renal failure
What is clopidogrel and its mechanism of action?
a platelet aggregation inhibitor
- metabolized and then selectively binds and irreversibly alters platelet surface ADP receptor, P2Y12,
=> reduced activation
+ inhibits full activation of the glycoprotein GPIIb/IIIa complex (which is responsible for platelet binding to fibrinogen and integration into clots)
What is clopidogrel used for?
preventio of thromboembolic disease
- arterial TE
- may improve pelvic limb circ after FATE
Possibly in dogs with hypercoag conditions:
- IMHA
When should clopidogrel not be used?
- hypersensitive
- actie bleeding
- inherited thrombocytopathias
- surgery (unless at high risk for thrombosis)
What is rivaroxaban and its mechanism of action?
Factor Xa inhibitor - anticoagulant/antithrombotic
- inhibitor of activated clotting factor X (FXa) and prothrombinase activity.
- Unlike heparins, its anticoagulant effect does not require a cofactor. It indirectly inhibits platelet aggregation induced by thrombin.
When is rivaroxaban used?
prevent or treat thromboembolic disease in dogs and cats
prefered over unfractionated heparin
When should rivaroxaban not be used?
- allergy
- uncontrolled bleeding
- renal/ hepatic disease +/- coagulopathy
- bleeding disorders
- coagulopathies
- epidurals
What is streptokinase?
- firinolytic/thrombolytic medication that breaks down clots.
Stimulates conversion of plasminogen to plasmin=> degrades fibrin clots
- needs to be used within 6h of clot formation.
don’t use if
- uncontrolled bleeding
- hypertension
- prev intracranial haemorrhage or any other serious intracranial pathology.
What is tissue plasminogen activator?
- thrombolytic = break down clots
catalyses conversion of plasminogen to plasmin=> degrades fibrin clots
What is pyrimethamine and its mechanism of action?
Folic acid inhibitor/anti-protozoal drug
- inhibits dihydrofolate reductase, which catalyzes the conversion of dihydrofolic acid to tetrahydrofolic acid.
=> reduced folic acid impairs protozoal production of proteins and nucleic acids. - binds to protozoal dihydrofolate reductase more than the mammalian enzyme.
-has in vitro activity against T gondii; adding sulfadiazine can synergistically enhance activity
What is pyrimethamine used for?
- Hepatozoon americanum
- toxoplasma (+/- sulfonamides or clindmycin)
- neospora
When should pyrimethamine not be used?
- pre-exisiting folate deficiency
- hypersensitivity
Care with cats, seizures, liver/renal
What is clindamycin used for?
Protozoa:
- Toxo
- neospora
- sarcocystis
- amercan hepatozoonosis
What is Azithromycin used for?
Protozoa: (+ atovaquone)
- Babesia
- Cytauxzoonosis
What is atovaquone used for?
Protozoa: (+ azithromycin)
- Babesia
- Cytauxzoonosis
What is Decoquinate used for?
Protozoa:
- American hepatozoon
- sarcocystisis
What is Azithromycin used for?
Protozoa: (+ atovaquone)
- Babesia
- Cytauxzoonosis
What is atovaquone used for?
Protozoa: (+ azithromycin)
- Babesia gibsoni/conradae
- Cytauxzoonosis
maybe toxo and pneumocystis
What is Ponazuril used for?
Protozoa:
- Toxo
- Neospora
- Isospora
What is imidocarb dipropionate used for?
Protozoa:
- Large babesia infections
- Hepatozoon
Can be used for small babesia and feline cytauxzoon but more effective agents are available.
What is Amprolium and what is it used for?
Thiamine analogue
Intestinal coccidiosis
*can get CNS signs from thiamine deficiency
What is Ponazuril and what is it used for?
Triazine antiprotozoals
- predominantly against apicomplexan coccidial infections.
- in apicomplexan protozoa, act on a plastid-like chloroplast organelle (the apicoplast) that contains a small circular genome and operates key biochemical pathways.
=> may inhibit metabolic enzymes or decrease pyrimi-dine synthesis within the apicoplast.
Protozoa:
- Toxo
- Neospora
- Isospora
What is toltrazuril and what is it used for?
Triazine antiprotozoals
- predominantly against apicomplexan coccidial infections.
- in apicomplexan protozoa, act on a plastid-like chloroplast organelle (the apicoplast) that contains a small circular genome and operates key biochemical pathways.
=> may inhibit metabolic enzymes or decrease pyrimi-dine synthesis within the apicoplast.
Protozoa:
- Hepatozoon (as effective as TMS/clinda/pyrimethamine)
- Isospora
- Toxo
- Neospora
- Isospora
What is Metronidazole and what is it used for?
Nitroimidazole => causes free radical damageto parasite DNA.
Parasitic/protozoa:
- giardia (fenbendazole prefered)
What is tinidazole and what is it used for?
5-nitroimidazole that has amoebicidal, giardicidal, trichomonicidal, and anaerobic bactericidal activity
- Giardia
What is ronidazole and what is it used for?
Nitroimidazole => causes free radical damageto parasite DNA.
- Tritrichomonas foetus
What is nitozoxanide and what is it used for?
Nitazoxanide is a nitrothiazolyl-salicylamide derivative
- inhibits the pyruvate-ferredoxin/flavodoxin oxidoreductase enzyme-dependent electron transfer reaction needed for anaerobic metabolism
- Cryptosporidium spp.,
- Giardia spp.,
- Sarcocystis neurona,
- some anaerobic bacteria,
- Helicobacter spp.,
- Campylobacter jejuni.
What is Paromycin and what is it used for?
Aminoglycoside antibiotic
Protozoa:
- enteric est cryptosporidium
- not in cats
What is doxycycline and what is it used for?
Parasite/protozoa:
- combination treatment for babesia and HW/woolbacia
What is sodium stibogluconate and what is it used for?
Antimony compound - selectively inhibit the leishmanial enzymes required for glycolytic and fatty acid oxidation.
Leishmania
- dont use in dogs with pre-existing cardiac arrhythmias, or significantly impaired renal function
What is N-methylglucamine antimoniate (meglumine antimoniate, Glucantime) and what is it used for?
Pentavalent Antimony compound - selectively inhibit the leishmanial enzymes required for glycolytic and fatty acid oxidation.
Leishmania (+/- allopurinol = synnergy + reduced drug resistance)
possibly in cats as well.
What is allopurinol and what is it used for?
Purine analog + xanthine oxidase inhibitor.
- stop urate and dissolve stones in dogs (not from PSS though)
- treat leishmania +/- trypanosoma
=> inhibit the enzyme xanthine oxidase, which is responsible for the conversion of oxypurines (eg, hypoxanthine, xanthine) to uric acid
thus treatment and prevention of recurrent uric acid and hyperuricosuiric CaOx stones in dogs (Esp dalmations).
* doesn’t dissolve urate uroliths in dogs with portovasc anomalies.
Purine analogue
=> inhibits Leishmania spp activity by limiting available purines.
=> Allopurinol is taken up by the protozoa and metabolized into a toxic compound (4-amino-pyrazole-pyrimidine), which incorporates into the parasite’s RNA, causing death
=> treat Leishmania
+/- trypanosomiasis
