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3. Clin Pharm 2 > Thyroid and Anti-thyroid > Flashcards

Thyroid and Anti-thyroid Flashcards

1
Q

synthesis and secretion of thyroid hormones - steps

A
  1. cellular uptake of iodide by follicular cells (sodium-iodide symporters)
  2. oxidation of iodide to iodine, rapid iodination of tyrosine residues on thyroglobulin molecules to form mono-iodo-tyrosine and di-iodo-tyrosine by the enzyme thyroid peroxidase that is present as an integral membrane protein on the apical membrane of each thyrocyte (organification)
  3. coupling of iodine residues on thyroglobulin molecules (also carried out by thyroid peroxidase), storage as colloid in the follicular lumen
    > couple can yield T3 (mono+di) or T4 (di+di)
  4. resorption of colloid found in the follicular lumen into the thyrocyte at the apical lumen by endocytosis, then into lysosomes
  5. proteolysis of thyroglobulin by lysozymes,
  6. release into bloodstream
    <><>
    binding of thyrotropin (TSH) from the anterior pituitary to its receptor on the thyrocyte stimulates the steps in synthesis and release of the hormones by each thyrocyte in the gland
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2
Q

T4:T3 is released in what ratio

A

§T4:T3 is released in a ~4:1 ratio by thyroid

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3
Q

what proportion of thyroid is bound to Thyroid Binding Globulin

A

§ Circulate bound to Thyroid Binding Globulin; ~99%

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4
Q

elimination half-life of T4 and T3 in dog

A

§ Elimination half-life: T4 (12-16 hrs) vs T3 (5-6 hrs)

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5
Q
  • Peripheral conversion of T4 to T3 by what enzyme?
  • why bother with this?
  • is T4 or T3 more potent?
  • T4 acts as what?
A

§ Peripheral conversion of T4 to T3 by 5’-deiodinase (mainly in liver)
§ Maintains intracellular control over T3 production
§ T3 has 3-10x the biologic potency as T4
§ T4 acting as a prohormone

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6
Q

hypothyroidism
- dogs cats horses: in which is it common vs rare

A

§ Common in dogs, rare in cats, horses

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7
Q

primary vs secondary hypothyroidism
- which is more common?
- causes?

A

Primary (thyroid-based)-most common form
§ Acquired (nearly all)
> lymphocytic thyroiditis; ~50% of primary cases
> idiopathic follicular atrophy
> neoplastic destruction
§ Congenital
> disorders of dyshormonogenesis, iodine deficiency
<><><><>
Secondary (pituitary-based)-rare
§ Acquired
> pituitary masses
§ Congenital
> dwarfism, dyshormonogenesis, receptor defects

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8
Q

most common cause of primary hypothyroidism

A

lymphocytic thyroiditis, ~50% of primary cases

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9
Q

clinical signs of hypothyroidism

A

Manifest as a slowing of bodily functions:
§ CNS, cardiovascular and energy metabolism
<><><><>
§ Weight gain (obesity)
§ Lethargy, weakness, unwillingness to exercise
§ Cold intolerance/heat seeking
§ Dermatology
> poor coat quality, alopecia, seborrhea,
> hyperpigmentation
> 2° pyoderma and pruritus
§ Bradycardia
§ Abnormal estrous, infertility, lack of libido

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10
Q

hypothyroidism therapy
- drug of choice? why?

A

§ L-thyroxine (T4) is drug of choice for replacement therapy in clinical hypothyroidism regardless of cause
§ T4 almost always indicated for the life of the dog once diagnosed with hypothyroidism
<><><><>
Advantages:
§ Longer half-life allows for once daily dosing
§ T4 is main circulating thyroid hormone versus T3
§ Easily monitored in plasma
§ T4 does not bypass cellular regulatory process
controlling the production of T3 from T4

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11
Q

advantages of giving T4 instead of T3 for hypothyroid therapy

A

§ Longer half-life allows for once daily dosing
§ T4 is main circulating thyroid hormone versus T3
§ Easily monitored in plasma
§ T4 does not bypass cellular regulatory process
controlling the production of T3 from T4

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12
Q

synthetic preparations of T4 available

A

Several synthetic preparations available
§ Thyro-Tabs®, Leventa®- licensed in dogs
§ 0.1-0.8 mg tablets, oral solution (1 mg/mL)
§ a daily total dosage of 20 μg/kg is indicated that can
be given once daily, or divided and given twice daily

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13
Q

dosing regimen for T4 therapy
- consideration for once or twice daily dosing

A

Dividing the daily dosage can be beneficial regarding T4 pharmacokinetics in early treatment, with once daily dosing following stabilization of the patient; owner compliance can be a concern with twice daily dosing

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14
Q

how to monitor T4 therapy
- when to start?
- what should T4 levels be at different T4 doses
- monitoring for first months vs later
- brand change?

A

§ Monitoring requires time for resolution of clinical signs
> Usually monitor ~4 weeks after therapy begun
> Ideally; T4 in reference range prior to dosing and high normal 4-6 hours after once daily dosing; twice daily dosing can be checked anytime
<><>
§ Monitoring every ~8 weeks recommended for the first 6-8 months
> T4 metabolism changes as metabolic rate normalizes
> Subsequently monitor 1-2X a year
<><>
§ If brand is changed; monitor serum levels at 4-8 weeks after switching

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15
Q

T4 therapy for hypothyroidism
- when will we see clinical improvement?
- what will we see?

A

§ Clinical improvement should be evident in 1-2 weeks
> Increased activity level
§ Weight loss evident in ~8 weeks
§ Normal hair coat may take months

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16
Q

T3 for hypothyroidism
- forms we can get
- possible adverse outcome
- recommended?
- dosing timing and why
- who gets this therapy
- bioavailability

A

§ Available as tablet and powder for injection
§ Increased chances of iatrogenic hyperthyroidism
> use is not recommended
§ Shorter half-life requires 3X daily dosing; owner compliance concerns § T3 therapy reserved for individuals not responding to T4
> GI absorption problems with T4
> T3 has almost 100% bioavailability

17
Q

what is Liotrix? what does it treat? pros and cons?

A

§ Mixture of T4/T3 in a 4:1 ratio
§ Mimics physiologic release of hormones in humans
§ Expensive; rarely used
§ May predispose to iatrogenic hyperthyroidism

18
Q

what is myxedema?
how to treat?

A

§ Myxedema: severe hypothyroidism-medical emergency
§ IV route for T4 (T3?) as poor GI absorption likely
§ Loading dose may be needed
§ Other supportive care as needed

19
Q

what is the most common endocrine disease in cats

A

Elevated thyroid hormones: thyrotoxicosis
(hyperthyroidism)

20
Q

causes of hyperthyroidism

A

§ Functional adenomatous hyperplasia of the thyroid gland > Usually both lobes of the thyroid
§ Rarely functional adenocarcinomas

21
Q

clinical signs of hyperthyroidism

A

n Weight loss
n Polyphagia
n PU/PD
n Tachycardia, +/- cardiac abnormalities
n Hyperactivity
n Diarrhea
<><>
n Palpable goitre (enlargement of thyroid) possible in some cats

22
Q
  • Drugs Used to Control Hyperthyroidism
  • Drugs Used to Control Clinical Signs of Hyperthyroidism
  • Drugs Used to Cure Hyperthyroidism
A

CONTROL:
- Methimazole
- Iodine (Potassium iodide)
- Iopanoic acid
<><>
CONTROL SIGNS:
- Beta-Blockers > propranolol
<><>
CURE:
- Radioactive iodine therapy > Its ^131

23
Q

Thioureylene antithyroid drugs
- what is their purpose and effect?
- example?

A

§ Are non-curative !! §Control hyperthyroidism only !!
- Methimazole

24
Q

methimazole
- what is this drug for?
- how does it work?
- uses
<><>
- dosing
- monitoring

A

§ Drug accumulates in thyroid gland
§ Inhibits thyroid peroxidase
> Organification and iodo-tyrosine coupling
§ Does not affect preformed T4 and T3 in thyroid
<><>
§ Uses include……
§ Chronic medical management
§ Patient stabilization prior to…….
> Surgery
> Radioactive Iodine therapy
<><>
Dosing:
- (1.25, 2.5 or 5.0 mg coated tablets)
§ Label recommends 2.5 mg/cat q 12 hrs
§ Titrate upward in 2.5 mg increments based on T4
§ Total dose not to exceed 20 mg (10 mg q 12hr)
<><>
Monitoring:
§ Plasma half life is 4-6 hrs
§ Intrathyroidal residence time ~20 hrs in humans
§ Assess T4 levels at 4 weeks, 3 months and 6 months, if on chronic therapy
§ Relapse of hyperthyroidism upon discontinuation
§ in plasma T4 levels after 24-72 hrs
§ Discontinue methimazole 2 weeks before I131 therapy …… uptake for 9 days ?

25
Q

methimazole dosing in cat
- label reccomendation?
- can we change it over time?

A

§ Label recommends 2.5 mg/cat q 12 hrs
§ Titrate upward in 2.5 mg increments based on T4
§ Total dose not to exceed 20 mg (10 mg q 12hr)

26
Q

methimazole monitoring:
- plasma half life
- how long does it stay in thyroid
- how often should we check T4
- what happens if we stop

A

§ Plasma half life is 4-6 hrs
§ Intrathyroidal residence time ~20 hrs in humans
§ Assess T4 levels at 4 weeks, 3 months and 6 months, if on chronic therapy
§ Relapse of hyperthyroidism upon discontinuation
§ in plasma T4 levels after 24-72 hrs

27
Q

if a cat is on methimazole and will undergo I 131 therapy, when should we stop methimazole?

A

§ Discontinue methimazole 2 weeks before I131 therapy

28
Q

methimazole adverse effects (6)

A

§ Transient lethargy, vomiting and anorexia; often resolves even with continued therapy; can persist in some cases
§ Positive ANA; chronic treatment or doses of drug above 15 mg/day
§ Agranulocytosis and thrombocytopenia
§ Facial/neck pruritus and excoriation; glucocorticoids can help but discontinuation of drug often required for complete resolution
§ Hepatotoxicity is a serious adverse effect generally requiring permanent discontinuation of drug
§ Post-treatment renal failure !! > common in cats, rapid drop in renal GFR

29
Q

how common is post-treatment renal failure for methimazole in cats? what happens?

A

§ considered common (17-38%) in cats
§ rapid drop in renal GFR
§ can occur with all treatments

30
Q

purpose of a methimazole trial for a cat? when do we need this?

A
  • avoid post-treatment renal failure
    <><>
    “methimazole trials” recommended
    § few published data for guidance; anecdotal
    § cats with adequate urine specific gravity (>1.035) don’t need trials ??
    § how long to run the trial……..30 days ?
    § make sure to check T4 levels during the trial !!
    > usually 1 week after start trial
    > want cat euthyroid for a month and not just on drug
    § evaluate blood work every 2 weeks
31
Q

methimazole admin route options
- considerations for owner compliance?
- efficacy?

A

§ Long term oral methimazole administration can be limited by owner
compliance in some cases
<><>
§ Transdermal methimazole is available thru compounding pharmacies and can offer an alternative to cats with oral administration of methimazole and GI upset
> formulated in lipoderm at 50 mg/mL
> poor absorption reported after single dosing
> chronic dosing showed comparable efficacy results to oral dosing at 4 weeks

32
Q

iodine for hyperthyroidism
- what form
- what does it do?
- when do we use it?
- when should we avoid?

A

§ Potassium iodide
§ Rapid and short-lived reduction in hormone release
§ Used short-term pre-operativey in preparation for surgery
§ Contraindicated prior to radioiodine therapy

33
Q

Iopanoic acid
- use

A

for control of hyperthyroidism
- Replaced ipodate (radiocontrast agent) as an alternative to methimazole therapy, but only useful for acute medical management and not long term

34
Q

Drugs Used to Control Clinical Signs of Hyperthyroidism

A

Beta-Blockers
§ Propranolol

35
Q

propranolo uses?
- what does it do
- can be used with what other drugs? why?
- uses

A
  • controls clinical signs of hyperthyroidism
    § Symptomatic control of tachycardia, hypertension
    and prevent possible arrhythmias
    § Can be used in combination with iodine or methimazole
    § Ensure a more rapid and effective response
    § Used to stabilize patient for surgery or radioiodine therapy
36
Q

what drug is used to cure hyperthyroidism? Is it a good treatment option?

A

Radioactive iodine therapy
§ I131 is generally considered the safest and most effective therapy for hyperthyroidism

37
Q

I 131 for hyperthyroid
- what does it do?
- how might we prep for this treatment
- how do we administer I 131? How does it work?
- when do we see changes in T4 / T3?
- precautions?
<><>
- complication and solution

A
  • radioactive iodine therapy to cure hyperthyroidism
    <><>
    § Use of methimazole prior to stabilize patient??
    § I131 given IV or SC
    > High uptake by thyroid
    > Emission of gamma and ß-rays; latter produces local tissue destruction
    > Serum T4 and T3 commonly normalize by ~1-2 weeks
    > Need special facilities to administer isotope and precautions
    § Hypothyroidism is an uncommon complication that will require T4 supplementation
    § Cat is hospitalized while isotope is eliminated
38
Q

can we give I 131 at home?

A

No
§ Cat is hospitalized while isotope is eliminated

3. Clin Pharm 2 (12 decks)

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