Pharmacotherapy of Thyroid Medications Exam 1 Flashcards
clinical presentation of hyperthyroidism
- Nervousness
- Sweating
- Palpitations
- Fatigue / weakness
- Oligomenorrhea
- Loss of libido
- Emotional lability
What are signs / symptoms upon a physical exam that could denote hyperthyroidism?
- high blood pressure
- high heart rate
- thyroid palpitation and auscultation to determine size, nodularity and vascularity
- eye exam
What are lab abnormalities with hyperthyroidism?
- Low TSH
- High TT4
- High FT4
- High TT3
What are additional tests that can be done to confirm hyperthyroidism?
- thyrotropin receptor antibodies
- radioactive iodine uptake
- measurement of thyroidal blood flow on ultrasonagraphy
What are the treatment options for hyperthyroidism?
- Thioamides
- Potassium Iodide
- Beta Blockers
- Radioactive Iodine (RAI)
- Surgery (Thyroidectomy)
Thioamides indication
- mild hyperthyroidism
- preoperative preparation for thyroidectomy
- pretreatment for RAI in elderly or patients with cardiac disease
- elderly
- thyroid storm
- Grave’s disease
- pregnancy
Thioamides MOA
Inhibits synthesis of thyroid hormones by inhibiting coupling of MIT and DIT and formation of T3 and T4; propylthiouracil also inhibits the peripheral conversion of T4 to T3
Thioamides monitoring
- complete blood count (CBC) to evaluate neutropenia and
- liver function test (LFT) due to hepatotoxic risk
- T3, T4, and TSH 4 weeks after initiation and at 8 week intervals until euthyroid levels achieved, then every 6 months
Thioamides adverse effects
- rash
- arthralgias
- drowsiness
- flulike symptoms
- abdominal pain
- GI intolerance in 4-5% of
patients - edema
- headache
Thioamides severe adverse effects
- Agranulocytosis
- Hepatotoxicity
- Fever
- Pneumonitis
- DO NOT rechallenge the patient if any of this occurs
Thioamides severe adverse effects: Agranulocytosis
- fever, malaise, gingivitis, oropharyngeal infection, and granulocyte count <250mm3
- more common in patients >40 yoa who are receiving MMI doses >40mg/day or PTU doses >400mg/day
- typically occurs during 1st three months of therapy
- after stopping therapy, improvement seen withing a few days to a few weeks
Thioamides severe adverse effects: Hepatotoxicity
Typically occurs during 1st three months of therapy
Thioamides advantages
- Noninvasive
- lower initial cost (~$45-90)
- low risk of permanent hypothyroidism and lifelong treatment
- avoidance of surgery and radioactivity exposure
Thioamides disadvantages
- Low cure rate
- adverse drug reactions
- drug adherence
Thioamides pearls
- PTU is preferred in 1st trimester of pregnancy or lactation
- PTU drug of choice in thyroid storm because of the earlier onset of action
- Effect can be delayed by weeks since is blocks production of new hormones
- Clinical improvement usually seen within 3 months
- Discontinue therapy after 12-18 months if values normalize
Potassium Iodide indication
- Preparation for surgery
- quickly attain euthyroid state in patients severely thyrotoxic with cardiac compromise
- to inhibit thyroid hormone release following RAI
Potassium Iodide MOA
Inhibits secretion of thyroid hormone
Potassium Iodide monitoring
Thyroid function (T3, T4, TSH) 6 weeks after initiation and every 8 weeks until euthyroid and then annually
Potassium Iodide adverse effects
- Hypersensitivity reactions
- salivary gland swelling
- “iodism” (metallic taste, burning mouth and throat, sore teeth and gums)
- stomach upset
- diarrhea
- gynecomastia
Potassium Iodide contraindications
- Hypersensitivity
- nodular thyroid condition with heart disease
Potassium Iodide advantages
Rapid and effective in severe thyrotoxicosis and rapid onset (24-48 hours)
Potassium Iodide disadvantages
Maximal effect is only sustained for 10-15 days
Beta Blockers indication
- Adjunct therapy for relief of symptoms of palpitations, anxiety, tremor and heat tolerance
- adjunct therapy for Grave’s disease, toxic nodules, preparation for surgery
- used in thyroid storm
Beta Blockers MOA
Inhibits beta adrenergic receptors and partially inhibits peripheral conversion of T4 to T3 at high doses
Beta Blockers adverse effects
- Hypotension,
- bradycardia
- fatigue
Beta Blockers contraindications
- Uncompensated heart failure
- severe hyperactive airway disease
Beta Blockers advantages
- Symptomatic relief
- rapid onset (hours)
- useful in acute thyrotoxic states
Beta Blockers disadvantages
- Does not correct hyperthyroidism
- variable tolerability of beta blockers
Beta Blockers pearls
Alternative to beta blocker if cannot be used is diltiazem 120mg every 8 hours or clonidine 150mcg twice daily
Beta Blockers used for hyperthyroidism
- Propranolol
- Nadolol
- Atenolol
- Metoprolol tartrate
Radioactive Iodine (RAI) indication
- Grave’s disease
- toxic autonomous nodules
- toxic multinodular disease
- comorbidities increasing surgical risks
- planning a pregnancy in the future
- liver disease
- thyroid ablation
Radioactive Iodine (RAI) MOA
Disrupts hormone synthesis by incorporating into thyroid hormones and thyroglobulin -> cellular necrosis and breakdown of follicles
Radioactive Iodine (RAI) adverse effects
- Metallic taste
- chest pain
- neck soreness and swelling
- nausea
- vomiting
- hives
- pruritus
- tachycardia
Radioactive Iodine (RAI) contraindications
- Pregnancy
- lactation
- thyroid cancer
Radioactive Iodine (RAI) monitoring
FT4 and TT3 1-2 months and every 4-6 weeks after RAI until euthyroid, then annual thyroid function test
Radioactive Iodine (RAI) advantages
- “Cures” hyperthyroidism
- more immediate results
- avoids surgery
- avoids A/E with drug therapy
Radioactive Iodine (RAI) disadvantages
- High risk of subsequent hypothyroidism with lifelong therapy
- can take up to 1 year for hyperthyroidism to resolve
- pregnancy must be deferred for 6-12 months
- increase risk of breast cancer
Radioactive Iodine (RAI) pearls
- Treat with thioamides prior to RAI ablation in the elderly and patients with cardiac disease because preformed thyroid hormone will be released causing a transient increase in thyroid hormone levels
- Can treat with potassium iodide 1-48 hours prior to RAI to help inhibit thyroid hormone release after RAI
- If patient had thioamides and relapses, recommendation is to treat with RAI
Surgery (Thyroidectomy) indication
- Large thyroid gland >80g
- severe ophthalmopathy, lack of remission on antithyroid drugs, pregnant women, intolerant of thioamides, thyroid malignancies, liver disease, or refuses RAI
Surgery (Thyroidectomy) procedure
- Propylthiouracil (PTU) or methimazole (MMI) until euthyroid (usually 6-8 weeks). Then therapy is stopped.
- Potassium iodide at 50-100mg 3x/day for 10-14 days prior to surgery to decrease the vascularity of the gland and decrease thyroid blood flow.
- Propranolol can be administered preoperatively and 710 days after surgery to main a pulse rate <90 beats/min
Surgery (Thyroidectomy) complications
- Hypothyroidism (49%)
- hypoparathyroidism (3.9%)
- vocal cord abnormalities (5.4%)
Surgery (Thyroidectomy) monitoring
- After surgery: Calcium, parathyroid hormone
- 6-8 weeks post surgery: TSH
- Annually: TSH
Surgery (Thyroidectomy) advantages
- Rapid
- effective
- “cures” hyperthyroid
- useful in patients with large goiter
- avoids radioactivity exposure and long-term A/E with thioamides
Surgery (Thyroidectomy) disadvantages
- Invasive
- potential complications
- cost
- permanent hypothyroidism (0.6-17.9%)
- lifelong treatment with T4
- pain/scarring
Clinical presentation: thyroid storm
- decompensated thyrotoxicosis
- high fever (>103F)
- tachycardia
- tachypnea
- afib
- CHF
- dehydration
- delirium
- coma
- nausea
- vomiting
- diarrhea (symptoms may persist up to 8 days)
Precipitating factors: thyroid storm
- infection
- trauma
- surgery
- RAI treatment
- withdrawal from antithyroid drugs
Thyroid Storm Treatment
- PTU or MMI
- Potassium iodide
- Propranolol or esmolol
- Hydrocortisone or dexamethasone
clinical presentation of hypothyroidism
- intolerance to cold
- constipation
- muscle ache / weakness
- hair loss
- depression
- weight gain
What are lab abnormalities with hypothyroidism?
- High TSH
- Low TT4
- Low FT4
- Low TT3
When should patients with high TSH be treated?
when TSH levels >5 mIU/L with symptoms or >10 mIU/L without symptoms
What is one thing to note about lab values when considering hypothyroidism?
Some patients will have low-normal FT4 level at first (compensated hypothyroidism) but as the disease progresses, the level will drop below normal
What are the treatment options for hypothyroidism?
- Levothyroxine
- Liothyronine
- Liotrix / Thyrolar
- Natural desiccated thyroid hormone
Levothyroxine counseling
Ingestion with food can impair absorption; take at least 30-60 minutes before food or 4 hours after last meal of the day
Levothyroxine adverse effects
- Heart failure
- angina
- MI
- arrhythmia
- anxiety
- dyspnea
Levothyroxine advantages
- Stable
- pure
- predictable potency
- inexpensive
Levothyroxine disadvantages
Not therapeutically bioequivalent, stay within the same brand
Levothyroxine dosing categories
- Uncomplicated adult <50
- > 50 without CVD or < 50 and CVD
- > 50 and CVD
- Severe hypothyroidism
- Subclinical hypothyroidism
Levothyroxine dosing: Uncomplicated adult <50
- 1.6 mcg/kg/day
- Dose titration by 25 mcg every 6-8 weeks; usual doses < 200 mcg/day
Levothyroxine dosing: > 50 without CVD or < 50 and CVD
- 25-50 mcg/day
- Dose titration by 12.5-25 mcg/day every 6-8 weeks as tolerated
Levothyroxine dosing: > 50 and CVD
- Initial 12.5-25 mcg/day
- Dose titration by 12.5-25 mcg/day every 4-6 weeks as tolerated
Levothyroxine dosing: Severe hypothyroidism
- Initial 12.5-25 mcg/day
- Dose titration by 25 mcg every 2-4 weeks as tolerated
Levothyroxine dosing: Subclinical hypothyroidism
1 mcg/kg/day
Levothyroxine monitoring
Check TSH levels 6-8 weeks until normalized and 8-12 weeks after dosage change; yearly thereafter
Levothyroxine pearls
- May need to lower dose in elderly patients or patients who have lost a significant amount of weight
- Dose will need to be increased in pregnancy
- Category >50 yoa and CVD – patients can be very sensitive to the CV effects of therapy – replace very slowly
Liothyronine brand names
- Cytomel
- Triostat
Liothyronine adverse effects
- Arrhythmia
- tachycardia
- hypotension
Liothyronine advantages
- Stable
- pure
- predictable dosing
- rapid onset (hours)
Liothyronine disadvantages
- Greater potential for cardiac A/E
- multiple daily dosing
- higher cost
Liothyronine monitoring
- T3
- TSH
- heart rate
- blood pressure
- 8 weeks after initiation and dose change and then yearly
Liotrix (Thyrolar)
Levothyroxine/Liothyronine T3T4
Liotrix adverse effects
- Increased blood pressure
- arrhythmia
- anxiety
- alopecia
- changes in menstrual cycle
- weight loss
- thyrotoxicosis with high T3
Liotrix advantages
- Stable
- pure
- predictable potency
Liotrix pearls
- Trials have shown that the combination is no better than T4 monotherapy
- not recommended in pregnancy
Liotrix monitoring
- T4
- TSH
- heart rate
- blood pressure
- 8 weeks after initiation and dose change and then yearly
Natural / Desiccated Thyroid adverse effects
Allergic reaction
Natural / Desiccated Thyroid pearls
Not recommended by the American Association of Clinical Endocrinologists because variable amount of iodine, thyroid hormones and potency
Natural / Desiccated Thyroid monitoring
- T4
- TSH
- heart rate
- blood pressure
- 8 weeks after initiation and dose change and then yearly
clinical presentation of myxedema coma
- Decompensated hypothyroidism with symptoms
- hypothermia
- delirium
- coma
Myxedema coma treatment options
- IV levothyroxine 300-500 mcg followed by 75100 mcg IV until patient stabilizes and can take oral therapy
- Hydrocortisone 100 mg Q8H until adrenal suppression is ruled out
Warfarin and thyroid abnormalities scenarios
- hyperthyroidism require less warfarin (increased warfarin catabolism)
- hypothyroidism require more warfarin (decreased warfarin catabolism)
Digoxin and thyroid abnormalities scenarios
- hyperthyroidism require more digoxin (resistant to digoxin)
- hypothyroidism require less digoxin (increased sensitivity to digoxin)
Insulin and thyroid abnormalities scenarios
Insulin degradation can be delayed leading to lower insulin doses
What can impair absorption of levothyroxin?
- Taking the medication with food
- Cholestyramine
- Calcium carbonate
- Sucralfate
- Aluminum hydroxide
- Ferrous sulfate
- Histamine blockers
- Proton pump inhibitors
- Dietary fiber supplements
What can you do to optimize levothyroxin absorption based on the factors that can decrease absorption?
Separate drug administration by 4 hours
What are the causes of drug-induced thyroid disease?
- lithium
- amiodarone
Drug-induced thyroid disease: Lithium
- chronic lithium inhibits release of thyroid hormone
- lithium induced goiter can cause hypothyroidism
- most patients with lithium induced hypothyroidism have a prior history of thyroid dysfunction, positive thyroid antibodies or a strong family history of thyroid disease
- monitor: baseline thyroid function tests and recheck every 6 months
Drug-induced thyroid disease: Amiodarone
- Can cause hypo- or hyperthyroidism because of its high iodine content
Drug-induced thyroid disease: Amiodarone Hypothyroidism
- may occur at any point and not dose related
- normal FT4 and elevated TSH
- treat with levothyroxine
Drug-induced thyroid disease: Amiodarone Hyperthyroidism
- occurs early / suddenly
- elevated hormone level and undetectable TSH
- Type I and Type II
Drug-induced thyroid disease: Amiodarone Hyperthyroidism Type I
- Patients have underlying risk factors for thyroid disease (multinodular goiter) and is related to iodine load (large amounts of thyroid hormone are produced in response to load)
- Treatment: Methimazole and Potassium
Drug-induced thyroid disease: Amiodarone Hyperthyroidism Type II
- Direct destructive type of thyroiditis causing excess release of thyroid hormone
- Treatment: beta blockers, corticosteroids
