Endocrine Pharmacology, Pt. 2 Flashcards

1
Q

What are mineralocorticoids responsible for? What 3 are most common?

A

regulate electrolytes and water balance

  1. aldosterone
  2. deoxycorticosterone pivalate (DOCP)
  3. fludrocortisone (aldosterone analog)
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2
Q

What are the main actions of mineralocorticoids in the kidneys, brain, and heart?

A

KIDNEYS: increases Na+ reabsorption in to the blood and excretion of K+ and H+ into the urine

BRAIN: stimulates the production of ADH (vasopressin)

HEART: enhances renin-angiotensin-aldosterone system to increase Na++ and blood pressure (hypertension)

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3
Q

What is the cellular mechanism of action of mineralocorticoids?

A

mineralocorticoids bind to intracellular MR and is transported into the nucleus where it binds to HRE and induces DNA transcription

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4
Q

What is the mineralocorticoid affinity for MR?

A

deoxycorticosterone > corticosterone (rodents) > aldosterone > cortisol (mammals)

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5
Q

What corticosteroid is able to bind to both mineralocorticoid and glucocorticoid receptors?

A

fludrocortisone

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6
Q

What are the 2 results of aldosterone deficiency?

A
  1. decreased Na+ and Cl- concentration —> decreased ECF volume —> decreased blood volume —> cardiac dysfunction
  2. increased K+ in ECF —> cardiac toxicity —> arrhythmia —> cardiac death

(all lead to death)

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7
Q

What 3 aldosterone agonists are used to treat aldosterone deficiency?

A
  1. aldosterone
  2. deoxycorticosterone
  3. fludrocortisone (aldosterone analog)
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8
Q

What are the 3 functions of aldosterone agonists?

A
  1. increase Na+ resorption into the blood
  2. promote excretion of K+ and H+ into the urine
  3. regulate blood pressure
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9
Q

What are aldosterone agonists commonly used to treat?

A

Addison’s (hypoadrenocorticism) in dogs and cats

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10
Q

What is the main result of aldosterone excess?

A

reabsorption of excess Na+ and water from renal tubules increases arterial blood pressure, leading to pressure diuresis

excretion of Na+ and water in the urine causing hypokalemia, muscle weakness, spasms, paralysis, and decreased ECF

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11
Q

What is spironolactone? How does it work? What 2 effects does it have?

A

aldosterone agonist that acts as a competitive antagonist

  1. decreases Na+ reabsorption and K+ excretion
  2. has effects on RAAS
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12
Q

What is canrenone?

A

aldosterone antagonist that is a diuretic metabolite of spironolactone

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13
Q

What is eplerenone? Why is it unique?

A

aldosterone antagonist that binds the MR (not PR or AR)

specificity for MR gives it a more specific effect

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14
Q

What 3 things are aldosterone antagonists used to treat?

A
  1. hypertension
  2. CHF
  3. other conditions where the body retains excess fluid (edematous state)
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15
Q

Glucocorticoid vs. mineralocorticoid effects:

A

some conditions require both effects

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16
Q

What stimulates the thyroid gland to excrete its hormones?

A
  • hypothalamus releases thyroid-releasing hormone (TRH)
  • this stimulated the pituitary gland to release thyroid-stimulating hormone (TSH, thyrotropin)
  • this stimulates the thyroid to release triiodothyronine (T3) and thyroxine (T4)
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17
Q

What body functions do T3 and T4 control?

A
  • heart rate
  • temperature
  • metabolism (Ca++)
  • brain development
  • bone maintenance
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18
Q

What ion is an essential component of T3 and T4?

A

iodine - correct functioning of thyroid relies of the proper supply from the diet

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19
Q

How do T3 and T4 compare? How do they become active?

A

T3 = more biologically active form that has a high binding affinity to TH receptor

T4 = inactive form that has a higher binding affinity to plasma proteins and converts into T3 on cell entry

diodinase enzymes convert inactive T4 into active T3

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20
Q

How do T3 and T4 compare in plasma protein binding? What 3 plasma proteins are used for transport?

A

T3 = 0.3% unbound (active!)
T4 = 0.03% unbound (inactive!)

  1. thyroxine-binding protein (70%)
  2. transthyretin/pre-albumin (<15%)
  3. albumin (15%)
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21
Q

How does protein-binding affinity of T4 compare amount animal species?

A

PROTEIN-BOUND = primates > goats > horses > dogs > cats, rodents, birds

FREE = cats, rodents, birds > dogs > primates, horses, goats

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22
Q

What 4 genomic effects does T3 have? 1 non-genomic effect?

A
  1. metabolic rate (enzymes, fat, protein, gluconeogenesis)
  2. neurological development (myelination, neuron signaling)
  3. skeletal development (bone formation and remodeling)
  4. muscle development
  • TR metabolites may be coupled to Na+ channels, Na+,K+ ATPase to affect electrolyte balance
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23
Q

What are the 2 thyroid disorders? What animals are they most common in?

A
  1. HYPOthyroidism - insufficient production of thyroxine (T4), most common in dogs and horses
  2. HYPERthyroidism - production of excess thyroxine (T4), resulting in an increased metabolic rate most common in adult cats
24
Q

Why are anti-thyroid agents only recommended for treater hyperthyoidism in cats?

A

hyperthyroidism in other species is most commonly caused by adenocarcinoma

25
Q

What 2 thyroid agents are recommended to treat hypothyroidism? Which is preferred?

A
  1. levothyroxine (T4)
  2. levothyronine (T3)

T4 —> maintains higher TH activity in the brain compared to T3

26
Q

What is methimazole? How does it work?

A

anti-thyroid agent that suppresses the synthesis of T3 and T4

27
Q

What is ipodate? How does it work?

A

anti-thyroid agent that inhibits the conversion of T4 into T3 by binding to deiodinases and blocks T3 receptors to inhibit the action of TSH

28
Q

How is radioactive iodine (Na131I) used as an anti-thyroid agent? What are the 2 main uses? Adverse effect?

A

emits β-particles and X-rays to destroy thyroid follicles

  1. hyperthyroidism in cats
  2. thyroid adenocarcinoma in cats and dogs

hypothyroidism can be induced by treatment

29
Q

What is the main function of the parathyroid? What hormones does it release?

A

maintains calcium homeostasis

PTH - induces calcium release into the blood
calcitonin - blocks calcium release into the blood

30
Q

What are 5 functions of calcium?

A
  1. bone growth and remodeling
  2. secretion (exocytosis)
  3. stabilization of membrane potential
  4. enzyme cofactor (factor IV)
  5. intracellular second messenger
31
Q

How is calcium concentration in the blood controlled?

A
  • PTH induces release into blood
  • vitamin D makes PTH more effective
  • calcitonin opposes PTH
32
Q

What are 3 functions of PTH?

A
  • decreased calcium in blood causes the increased release of PTH, leading to….
  1. increased bone resorption by osteoclasts to release calcium
  2. increased renal calcium reabsorption
  3. increased calcium absorption in the small intestine
33
Q

What are the 2 functions of calcitonin?

A
  1. decrease bone resorption by inhibiting osteoclasts and stimulating osteoblasts
  2. decrease renal reabsorption of calcium
34
Q

What are the 2 parathyroid disorders? In what animals are they most common?

A
  1. HYPOparathyroidism - insufficient PTH secretion, leading to hypocalcemia, characterized by neuromuscular excitability, bradycardia, and convulsions in dogs and cats
  2. HYPERparathyroidism - overproduction of PTH, leading to hypercalcemia in dogs and horses
35
Q

What is a common cause of hyperparathyroidism in horses?

A

nutritional secondary hyperparathyroidism - grazing exclusively on grasses containing high levels of oxalate

36
Q

What is calcium gluconate? How does it work? How is it used?

A

agent to treat hypocalcemia by regulating important cellular functions associated with calcium-mediated events

used to treat animals with symptomatic hypocalcemia

37
Q

What is dihydrotachysterol (DHT)? How does it work? How is it used?

A

vitamin D2 analog that mobilizes calcium from bone, increases intestinal absorption, and reduces calcium loss in urine (also controls phosphorus levels)

treats hypocalcemia secondary to hypoparathyroidism or severe renal disease in small animals

38
Q

What is calcitriol? How does it work? How is it used?

A

vitamin D3 metabolite that increases plasma calcium and controls phosphorus levels

treats hypocalcemia secondary to hypoparathyroidism or severe renal disease in small animals

39
Q

How does calcitriol compare to dihydrotachysterol (DHT)?

A

shorter duration

40
Q

What part of the pancreas has endocrine function? What 3 cells are found here? What do each do?

A

Islet of Langerhans

  1. α-cells: produce glucagon, which converts glycogen into glucose to increase its concentration in the blood
  2. β-cells: produce insulin, which converts glucose into glycogen to decrease its concentration in the blood
  3. δ-cells: produce somatostatin (STOP)
41
Q

What is the function of insulin?

A

regulates normal cellular lipid and carbohydrate metabolism and glucose absorption by all cells in the body

DECREASES blood glucose

42
Q

In what 5 ways does insulin decrease blood glucose?

A
  1. increases glycogen synthesis
  2. increases the uptake of amino acids and protein synthesis
  3. decreases hepatic glycogenolysis
  4. decreases gluconeogenesis
  5. increases glucose transport into muscle cells and adipocytes via GLUT4 activation and translocation
43
Q

What is diabetes? What are the 2 types?

A

too much glucose in the blood

  1. TYPE I = D. juvenile - no insulin production; insulin dependence, permanent
  2. TYPE II = D. mellitus (elderly) - non-functioning insulin receptor, insulin resistance, diabetic remission possible
44
Q

What is the mechanism of action of insulin?

A
  • high blood glucose levels activates insulin
  • insulin then binds to a membrane insulin receptor (insulin = protein, unable to cross)
  • this activates a signaling pathway that activates GLUT 4 (+ GLUT1) on the cell membrane
  • glucose from the blood leaves and enters the cell
  • glucose is synthesized into glycogen
45
Q

What are the 2 disorders of the endocrine pancreas? What are the most common causes of each?

A
  1. hyperglycemia (hypoinsulinemia) - most common in dogs and cats; diabetes mellitus
  2. hypoglycemia (hyperinsulinemia) - insulin overdose
46
Q

When is hyperglycemia usually able to be diagnosed?

A

late-stage - β-cells have mostly been destroyed

(hypoinsulinemia)

47
Q

What are the 3 most common causes of diabetes mellitus?

A
  1. deficiency of insulin secretion from the pancreas
  2. decreased glucose uptake into cells
  3. increased hepatic glucose production
48
Q

What are the 3 most common symptoms of diabetes mellitus?

A
  1. excessive excretion of urine (polyuria)
  2. excessive thirst (polydipsia)
  3. excessive hunger (polyphagia)
  • high blood glucose (hyperglycemia), glucosuria, fatigue
49
Q

How does diabetes mellitus compare in dogs and cats?

A

DOGS = female, middle-aged, Type I; typically caused by pancreatitis, immune attack, breed, or lifestyle

CATS = male, older (geriatric), Type II; typically caused by pancreatitis, pancreatic amyloidosis, insulin resistance, or high blood glucose damaged cells

50
Q

How is diabetes mellitus diagnosed? What are the 3m ost common treatments?

A
  • history/PE: lethargy, PD/PU, polyphagia, weight loss, cataracts
  • high blood sugar
  • glucosuria
  • ketones in urine
  1. insulin
  2. dietary manipulation - manage obesity (low carbohydrates in cats, high fiber in dogs)
  3. treat concurrent illness - withdraw medications causing insulin resistance
51
Q

What is the structure of insulin like? How does itcompare across species?

A

51 amino acids, with 2 peptide chains (21 aa, and 30 aa) joined by disulfide linkages

amino acid sequence varies among species - more changes between species = more adverse effects if given to another species

52
Q

What are the 5 available insulin treatments in dogs and cats?

A
  1. Regular - short duration
  2. rNPH - intermediate-acting
  3. Lente (Vetsulin) - long-acting
  4. rPZI - long-acting
  5. insulin analogs - long-acting
53
Q

What is the preferred insulin treatment? From what species does it originate?

A

Lente - Vetsulin = porcine insulin zinc suspension

54
Q

How is blood glucose monitored in dogs and cats?

A

Alpha TRAK glucometer

DOG = blood from ear, gums, elbow, or foot pads
CAT = blood from ear

55
Q

What are the 2 most common adverse effects of insulin?

A
  1. hypoglycemia - insulin shock, CNS disturbances, convulsions, coma
  2. insulin resistance - insulin antibodies may attenuate response to treatment (most common in cats) + excessive secretion of hyperglycemic hormones including stress hormones
56
Q

What is metformin? What are its 3 mechanisms of action?

A

antihyperglycemic (NOT hypoglycemic - does not stimulate insulin secretion)

  1. decreases glucose absorption in the GI tract
  2. decreases glucose output from the liver
  3. increases insulin receptor sensitivity
57
Q

What is metformin used to treat in cats and dogs?

A

CATS = non-insulin dependent DM

DOGS = DM caused by obesity or resistance to insulin