Endocrine Pharmacology Flashcards
Goal of Tx for canine hypothyroidism
Replace hormone the body is not producing
- Liothyronine: T3
- LEVOTHYROXINE: T4 (soloxine)
Levothyroxine requires ____(more/less)____ frequent dosing & has ___(higher/lower)___ risk of causing thyrotoxicosis (excessive T4 levels) than liothyronine
less, higher (I think)
Levothyroxine pharmacologic considerations
- Must be given for rest of pt life
- Monitored by measuring T4 levels
- Thyro tabs are the only vet approved
-Drugs that may interfere with T4 levels: phenobarbital, zonisamide, sulfonamides, lucocorticoids, phenylbutazone, quinidine
Goal of Tx in hyperthyroidism in cats
-stop excessive hormone productions
Pharmacologic tx options for feline hyperthyroidism
- Thioureylenes
- Iodides
Thioureylenes- Methimazole & Carbimazole
- inhibit thyroid hormone synthesis
- Consistently efficacious
- Side effects uncommon and most are manageable
Thioureylenes– PTU (propylthiouracil)
- inhibit thyroid hormone synthesis
- inhibit conversion of T4 -> T3 in tissues
- also efficacious
- Higher incidence of serious side effects
Iodides and Iodinated contrast agents
- Inhibit thyroid hormone synthesis
- inhibit release of pre-formed hormone
- Inhibit T4> T3 conversion in periphery (contrast agents)
- Efficacy is variable and often transient
Clinical signs of acute hypocalcemia
Hyperesthesia/pawing at the face, tremors, progressing flaccid paralysis, seizures, hyperthermia, bradycardia
Pariparturient hypocalcemia
Milk fever, eclampsia
- sudden increase in calcium usage, patient can’t adapt rapidly enough
- acute
Acute Hypocalcemia RoA
- Oral vs IV (parenteral for emergencies)
- Parenteral ca options: Ca gluconate or Ca chloride
Acute Hypocalcemia, calcium RoA contraindications
-Ca Chloride is caustic: NO SQ/IM
-Ca Gluconate: dilute if giving Sq, IV IS BEST
Ca is incompatible with some fluids/drugs
-Rapid IV admin of Ca can cause arrhythmias (monitor ECG!)
Chronic Hypocalcemia (HypoPTH): oral Ca options
Ca Carbonate and Ca propionate: gi tract must be able to absorb calcium
Hypoparathyroidism results in inability of the body to convert _____ to it’s active form ________
Vit D –> Calcitrol
No PTH –> the GIT can’t absorb Ca
Biggest potential side effect of calcitriol is
hypercalemia
Hypoglycemia can be managed with (3 things)
1) Diet: Frequent, small carb meals
2) Dextrose 50% sol’n: Mucosal absorption is decent, no dextrose SQ, IV no more than 5%
3) Glucagon hormone: IV, not common
Chronic hypoglycemia goal and tx options (2)
Address the cause and if not alter the glucose produced and used
- diet
- Corticosteroids: prednisone
Hyperglycemia
- Doesn’t require therapy
- Diabetes mellitus (DM)- insulin deficiency
Oral hypoglycemic agents
- CAUSE hypo, don’t Tx hyper!
- Glipzide(glucotrol): sulfonylurea – only effective in ~30% of cats; may accelerate B-cell loss
- Only useful in type II diabetes where pancrease can still secrete some insulin (CATS ONLY)
Oral hypoglycemic agents MoA
Stimulate insulin secretion by the pancreatic B-cells (blocking K channels)
-also increase tissue sensitivity to insulin
T/F: all insulin are inectible and similar potency (except detemir)
TRUE
Regular Insulin/Humulin-R/Crystalline/Neutral Insulin
- short acting
- IV, IM, SQ
- Commonly used for hosp pt not eating
- Duration: Short to long term mgmt
NPH (Isophane), Lente, Vetsulin/Caninsulin
- SQ only
- Intermediate acting insulin
- Protamine or zinc are added to delay absorption and extend clinical effect
- good for starting insulin
- not adequate control in felines
Protamine zinc/PZI, Glargine, & Detemir
- SQ only
- Long acting insulin
- Glargine: forms microprecipitate in physiologic pH, very gradual absorption (flat curve)
- Prozinc: may have shorter duration than the rest; Long acting (particularly in cats)
- Determir: has much higher potency in dogs (4x), requires special dosing and may be difficult to dose in smol doggos
Two types of corticosteroids
1) glucocorticoids
2) mineralcorticoids
Glucocorticoid general info
- produced by zona fasciculata
- cortisol in the endogenous hormone
- regulated by hypo/pitu through CRH and ACTH
Prednisone, dexamethason, triamcinolone, hydrocortisone are all ______
glucocorticoids
Clinical uses of glucocorticoids
- Diagnostics: low dose dexamethason suppression test, HDDS
- Physiologic replacement therapy: Addisons (Hypoadrenocorticism)
- Anti-inflammatory: allergies
- Immunosuppressive: immune mediated dz
Glucocorticoids pharmacokinetics
Generally well absorbed orally or paraenterally
- Protein bound: transcortin, albumin
- Some must be hydrolyzed: pred, cortisone, methylpred
Salt/Soluble Esters
- Na succinate, Na phosphate
- Steroid is soluble = suitable for IV admin
- onset may be faster but duration is unchanged
Insoluble esters (pivalate, acetate, acetonide)
- Less souble, takes longer to absorb
- Delayed onset, longer duration
- Opaque suspensions- NOT FOR IV USE
- Methylprenisolone acetate (depomedrol)
Side effects of glucocorticoids- short term (delayed wound healing)
- Not serious
- lab changes (stress leukogram, decrease thyroid)
- pu/pd/polyphagia
- fetal abnormalities, abortion
Side effects of glucocorticoids- long term
- increased susceptibility to infection
- skin changes (hyperpigmentation, thinning, alopecia)
- collagen dz (cruciate injury), delayed wound healing
- hypertension, thromboembolic dz
- iatrogenic Adison
- Myopathy, calcinosis cutis, osteoporosis
Mineralcorticoids
- Zona glomerulosa
- Aldosterone is the endogenous hormone
- regulate Na+ retention/K+ excretion by the kidney
- Monitor K/Na
Two mineral corticoids:
1) Fludrocortisone (florinef) orally BID
2) DOCP: Parenterally (IM,Sq)
Cushings disease is aka
Hyperadrenocorticism
Hyperadrenocorticism cause
-Excess glucocorticoid produced (fn adrenal mass, fn pituitary mass)
Mitotane (lysodren)
Adrenal gland tissue
cytotoxic to cells of the fasciculate
- narrow therapeutic index
- caution with owner handling
- start with high dose (induction) then reduce to lower dose for maintenance
- monitor adrenal function with ACTH
- adverse effects related to oversuppression
Trilostane (Vetoryl)
Prod of glucocorticoids
- inhibit 3B-hydroxysteroid dehydrogenase in the cortisol production pathway
- most commonly used drug to tx Cushings and other endocrine dermatopathies
- Narrow therapeutic index
- Monitored with ACTH
- Dosed BID, start w/ low
Ketoconazole
prod of glucocorticoids
- inhibit enzymes in the steroid synthesis pathway
- potential for hepatotoxicity
- potent hepatic microsomal enzyme inhibitor
Pergolide
Prod of ACTH by pituitary
- dopamine agonist
- will suppress production of ACTH and thus reduce cortisol production
- used to tx pituitary pars intermedia dysfunction (PPID) in horses
Selegiline
Prod of ACTH by pituitary
- inhibits MAO-B which results in increased dopamine
- It is labeled for tx of canine cognitive dysfunction, sometimes used to attempt to tx Cushing’s
Addison’s is aka
Hypoadrenocorticism
Hypoadrenocorticism
- Deficient production of glucocorticoids +/- mineral corticoids
- Usually caused by chronic destruction of adrenal gland
Typical Addisons
-Pt lacking BOTH gluco and mineral corticoids, therefore require prednison and either DOCP or Fludrocortisone
Atypical Addisons
-lacking just the glucocorticoid therefore they only need prednisone therapy
Iatrogenic adrena insufficiency
- if EXOGENOUS glucocorticoids are used chronically then stopped abruptly pt may suffer insufficient adrenal output (chronic neg feedback)
- Or adrenal glands may be damaged through excessive action of drugs used to tx hyperadrenocorticism (mitotane, trilostane)
