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Clinical Pharmacology > SA Endocrine 2 (Thyroid) > Flashcards

SA Endocrine 2 (Thyroid) Flashcards

1
Q

Iodine

A
  • Taken up by thyroid tissue (TSH dependent)

- Iodine –> iodide bound to tyrosine on the TG molecule by thyroid peroxidase

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2
Q

Thyroglobulin

A
  • precursor protein made by thyroid follicular cells
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3
Q

Thyroglobulin -

A

After iodine is bound to tyrosine on TG molecule by thyroid peroxidase, it is converted to T3 and T4

  • Only 20% T3 made in thyroid; 80% made from T4 in tissues as needed
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4
Q

T3 and T4 negative feedback

A
  • negative feedback on TRH in the hypothalamus and TSH in the pituitary
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5
Q

Thyroid hormone basics

A
  • Active in most cells in the body
  • Increases metabolic rate
  • Catabolic effects (muscle and adipose)
  • cardiac inotropic and chronotropic
  • Stimulates erythropoiesis
  • Regulates cholesterol synthesis/degradation
  • Normal growth of the neurologic/skeletal system (mental alertness and peripheral nerves in adults)
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6
Q

Thyroid hormone basics

A
  • Most thyroid hormone is protein bound (99%)
  • Only free form (non protein bound) is active and enters cells
  • Free T3 or T4
  • T3 is more biologically active than T4
  • Most T3 produced peripherally from T4
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7
Q

Primary hypothyroid

A
  • Potential antibody formation against thyroglobulins and/or thyroid hormones
  • Thyroid tissue destruction resulting in decreased T3 and T4 production
  • Loss of negative feedback to pituitary gland
  • Increase in TSH production (~70%)
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8
Q

Thyroid stimulating hormone (TSH) or Thyrotropin Alfa (thyrogen - rhTSH) Indication

A
  • Gold standard hormone used for diagnosis of hypothyroid

- Recombinant human product

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9
Q

MOA of TSH

A
  • Increases iodine uptake by thyroid glands and increases production/secretion of thyroid hormones
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10
Q

TSH stimulation use

A
  • Evaluates the thyroid gland’s ability to respond to TSH and produce thyroid hormones
  • Useful for differentiating hypothyroidism from non-thyroidal illness
  • In non-thyroidal illness you have decreased TSH
  • Normal thyroid gland, so in non-thyroidal illness it should decrease
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11
Q

Adverse effects of TSH

A
  • Hypersensitivity (human product)
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12
Q

Cost of TSH

A
  • VERY $$$$
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13
Q

Levothyroxine

A
  • T4
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14
Q

Levothyroxine indication

A
  • Treatment of choice for hypothyroidism
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15
Q

Route of Levothyroxine

A

PO

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16
Q

Dosage of Levothyroxine

A
  • dose is must higher than in people because dogs have a higher 1st pass metabolism
  • Human pharmacists may question our dose
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17
Q

Levothyroxine cautions

A
  • Hypoadrenocorticism, cardiac disease, diabetes mellitus

- Consider dose reduction

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18
Q

Adverse effects of levothyroxine

A
  • Start with 1/2 dose in dogs with heart disease as it will increase myocardial oxygen demand
  • Can develop hyperthyroidism
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19
Q

Drug interactions of Levothyroxine

A
  • Many! Check before using
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20
Q

Other considerations for levothyroxine

A
  • Food may decrease bioavailability
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21
Q

Liothyronine MOA

A
  • Direct hormone replacement of T3
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22
Q

Cautions of Liothyronine

A
  • Not recommended
  • More expensive than T4
  • Does not increase T4 concentrations
  • T3 is produce as needed by tissues so could overdose some tissues
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23
Q

Indications of Liothyronine

A
  • Again, in general, don’t use
  • Use when there is no response to T4 administration suspected due to poor GI absorption
  • T3 has better GI absorption than T4
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24
Q

Thyroid extracts/dessicated thyroid Source

A
  • Most often porcine (Armour thyroid)
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25
Q

Thyroid extracts/dessicated thyroid

A
  • Powdered thyroid glands collected at slaughterhouses
  • Contain T4 and T3 in 4:1 ratio
  • Less expensive than synthetic T4
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26
Q

Indications for thyroid extracts/dessicated thyroid

A
  • Not recommended
  • Potential for allergies/sensitivities
  • Variability from batch to batch
  • Variation in shelf life
  • Difficulty in maintaining proper regulation with T4/T3 content
27
Q

Hyperthyroid overview

A
  • Usually benign nodule develops in thyroid gland (can be bilateral)
  • Thyroid nodule produces excessive amounts of T4
  • Negative feedback suppresses TSH production
  • Normal thyroid tissue atrophies and stops producing thyroid hormones
28
Q

Liothyronine for hyperthyroidism

A
  • Administered as part of the T3 suppression test for hyperthyroidism
  • Should inhibit TSH production
  • If TSH decreases, then T4 will decrease
  • Following T3 administration, T4 should be <50% baseline in normal cats, but there will be minimal suppression in hyperthyroid cats
  • Usually takes about 3 days, have to give a pill over 3 days
29
Q

Methimazole Indication

A
  • Drug of choice for hyperthyroidism
30
Q

MOA Methimazole

A
  • Inhibits thyroid peroxidase (therefore inhibits iodide binding to tyrosine to form T3 and T4
31
Q

Dosing Routes of Methimazole

A
  • Oral tablets - good bioavailability
  • Transdermal (compounded)
  • Dose adjusted every 2-3 weeks as needed based on CBC/Chem/UA/Total T4 levels
32
Q

Transdermal methimazole

A
  • Great
  • Compounded
  • Must be in pluronic lecithin organogel (PLO)
  • Fewer GI side effects
  • May take longer to see maximum effects
33
Q

Cautions with transdermal methimazole

A
  • Can be transferred to people or other pets
34
Q

Adverse effects of methimazole

A
  • Most are generally reversible
  • GI upset (reduce dose, divide dose, switch to transdermal)
  • Neutropenia/thrombocytopenia in 3-9% (monitor CBC and discontinue the drug if needed)
  • Facial excoriation in 2-3% (pruritus and erythema and discontinue drug if needed)
  • Hepatotoxicity (monitor biochemistry panel/liver enzymes and discontinue drug if noted)
  • Renal decompensation (cats already have underlying renal disease, and hyperthyroidism will increase GFR. Treating will decrease GFR to unmask renal disease)
35
Q

Drug interactions of methimazole

A

– Needed doses of some medications may change once the cat has become euthyroid

  • Diabetic may need less insulin
36
Q

How long does it take to suppress T4 concentration with Methimazole?

A

1-3 weeks

37
Q

Carbimazole Indication

A
  • Hyperthyroid
38
Q

Carbimazole MOA

A
  • Pro-drug converted to methimazole
39
Q

Carbimazole adverse effects

A
  • fewer GI effects
40
Q

Carbimazole availability in the US

A
  • Not available in the US
41
Q

Stable iodine (iodide) or potassium iodate MOA

A
  • Large amounts of iodide given over 1-2 weeks may inhibit organification of thyroid hormone
  • Wolff-Chaikoff effect
42
Q

Indication of stable iodine

A
  • Could be used for hyperthyroid
  • Only useful for short term control (1-3 weeks)
  • Will not achieve complete remission
43
Q

Adverse effects of Stable iodine

A
  • GI upset

- Tastes bad - give in gel cap

44
Q

I-131 (radioactive iodine) indication

A
  • Treatment of hyperthyroid
45
Q

I-131 MOA

A
  • Concentrated in hyperfunctional thyroid cells as they take up iodine to make thyroid hormone
  • Beta particles destroy the tissue that takes up I-131
  • Function of the normal thyroid tissue is suppressed and not producing hormone so it is preserved
46
Q

Other considerations of I-131

A
  • Must be administered by trained personnel in designated facilities
  • Cats are quarantined after administration until radiation levels diminish (1 week to 3 weeks)
47
Q

Amlodipine Indication with Hyperthyroid

A
  • Hypertension
48
Q

Beta blockers indication

A
  • Sympathetic overdrive with hyperthyroid

- e.g. propanolol, atenolol

49
Q

Diabetes insipidus (Central)

A
  • Partial or complete deficiency of ADH production

- Congenital, neoplasia, trauma

50
Q

Diabetes insipidus (Nephrogenic)

A
  • Defect in nephron causing lack or impaired renal tubular responsiveness to ADH
51
Q

Primary Nephrogenic Diabetes Insipidus

A
  • Congenital
52
Q

Secondary Nephrogenic Diabetes Insipidus

A
  • Conditions affecting ADH binding and function (hyperadrenocorticism, neoplasia, glucocorticoids, hyperaldosteronism, pyometra, hypercalcemia, etc.)
53
Q

Desmopressin acetate (DDAVP) MOA

A
  • Synthetic analog of vasopressin (ADH)

- Replaces ADH

54
Q

Indications for Desmopressin acetate (DDAVP)

A
  • Used for treatment of Central DI

- Used for differentiation of central DI from nephrogenic DI

55
Q

Route of DDAVP

A
  • Nasal solution given as an eye drop of SC

- 1 Drop in the conjunctival sac that can increase up to 4 drops

56
Q

Adverse effects of DDAVP

A
  • Uncommon - ocular irritation if given conjunctivally
57
Q

Oral Bioavailability of DDAVP

A
  • Low
58
Q

Cost of DDAVP

A
  • $$$ Expensive
59
Q

Concentrations of nasal solution of DDAVP

A
  • Be sure to get correct concentration of nasal solution as several products are available
60
Q

Thiazide diuretics (chlorothiazide, hydrochlorothiazide) MOA

A
  • Work in the early distal tubule to inhibit Na/Cl cotransporter
  • Causes enhanced excretion of Na and water
61
Q

Thiazide diuretics and DI

A
  • Reduces clinical PU/PD
  • mechanism not well understood with several proposed theories (inhibit distal sodium resorption, volume contraction, increased proximal tubular sodium and water resorption)
62
Q

Route for thiazide diuretics

A
  • Oral
63
Q

Drug interactions for thiazide diuretics

A
  • Many! Check before giving

Clinical Pharmacology (7 decks)

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