Myasthenia Gravis Sarcoidosis

Thyroid Disease

Alsean Bryant

P4 PharmD Candidate

Preceptor: P. Ghazvini, PharmD

Medicine I & II Rotation

Chief Complaint: SOB and weakness

• History of Present Illness

– FC is a 61 y.o. AA female who presents to the emergency department stating that she has not been in her usual state of health. She has been SOB, gradually becoming weaker, and having more anxiety and depressive symptoms since February. The patient states that she has also been swelling all over her body much more than usual. The patient also has a history of myasthenia gravis (MG) and normally receives intravenous immune globulin (IVIG) for treatment. However, due to a nationwide shortage of IVIG, FC missed her last dose and developed a MG flare which included weakness of lower extremities and double vision. She has been admitted for management and possible plasmapheresis.

Review of Symptoms• Positive for mild chest pain

relieved by albuterol

• Anxiety/ depression

• Blurred vision

• Generalized weakness

• SOB

• Increasing generalized swelling

Physical Exam

• 2+ pitting edema bilaterally in lower extremities

• Mild pain to palpation of lower extremities

• Small blisters and vesicles on right and left shins

Past Medical History

• Hypertension• Hyperlipidemia• Uncontrolled diabetes mellitus• Chronic Obstructive Pulmonary Disease• Morbid obesity• Chronic pain• Chronic renal insufficiency• Myasthenia gravis• Hypothyroidism • Sarcoidosis• Migraines• Obstructive sleep apnea with Pickwickian syndrome• History of pacemaker with removal secondary to endocarditis• History of pulmonary embolism in 2009• History of breast cancer status post mastectomy in 2005

• Past Surgical History– Mastectomy– Appendectomy– Cholecystectomy– Hysterectomy– Tonsillectomy– Bilateral knee and right shoulder surgery

• Social History– Lives with immediate family– Does not smoke cigarettes – No history of tobacco use– Occasional drinking

• Family History– Was not given

Home Medications

• Combivent inhaler, 1-2 puffs Q6H• ASA 81mg QD• Cardizem CD 240mg QD• Sinemet 25/100mg, 1 tab QD• Vitamin B12 1000mcg, 1 tab QD• Insulin NPH 60u in AM and 50u in PM• Synthroid 137mcg QAM• Prednisone 30mg QD• Zocor 40mg QD• TriCor 145mg QD• KCl 20mEq QD• Vicodin 5/500mg Q6H PRP• Phenergan 12.5mg, 1-2 tab QD• Calcium with vitamin D, 1 tab TID

Allergies:

• Celebrex• Codeine• Flagyl• Percodan• Percocet

Admitting Labs: 03-12-10

LAB VALUE RANGE LAB VALUE RANGE

Na 140 136-144 Ca 9.4 8.2-10

K 5 3.5-5.1 TSH 0.459 0.34-5.6

Cl L 100 101-111 TG H 394 <150

CO2 32 22-32 LDL H 203 <100

BUN H 40 8-20 HDL L 41 50-70

SrCr H 1.4 0.44-1.03 WBC H 12.8 4-10.5

Glucose H 401 70-99 RBC L 3.99 4.2-5.4

BUN:Cr H 29 5-24 HGB L 11.6 12.5-16

Ht (in) Wt (lb) BMI

61 337 ?

Vital Signs

Temp 98.5

BP 150/69

HR 98

RR 18

O2 Sat. 94%

Assessment and Plan

• MG exacerbation – steroid treatment continued until seen by neurologist to be placed on IVIG therapy

• SOB secondary to COPD versus OSA – treated with Xopenex. Received O2 via nasal cannula to maintain saturations.

• OSA – BiPAP/CPAP at nighttime and supplemental O2 during the day

• Heart failure secondary to OSA

• Sarcoidosis – stable. Progressive in nature

• Hypothyroidism – treated with Synthroid

• Dyslipidemia – continue home med of TriCor

• COPD – pt uses home O2. Received Xopenex nebulizer treatments prn

Assessment and Plan Cont.

• Anxiety – Ativan PRN

• Constipation – stable

• Unstable DM – sliding scale insulin and NPH insulin QAM/PM

• Chronic pain – home medication of Vicodin, Norco 5/325mg 1-2 tab Q6H PRP

• Vesicles on lower extremities – culture and herpes culture of bullae on right leg along with Gram stain

• Chronic renal insufficiency – spot check urine sodium and urine creatinine. Cr is 1.4 and BUN 35 – hydrate and recheck values

• DVT prophylaxis with Fragmin 7500u Q24H

• GI prophylaxis – Nexium 40mg Q24H

• Mild ulceration over buttocks, particularly right side – Nystatin topical 100,000u/g cream applied BID

Hospital Medications

See Word Document

Discharge Summary

• MG flare-up: Pt underwent a total of 7 plasmapheresis, which she tolerated very well. She was also treated with steroids. Her symptoms improved significantly

• OSA with pickwickian syndrome: On admission, pt was recommended to use CPAP overnight to help with her respiration which she refused because it was uncomfortable. On morning of 3/22, pt was found to be in respiratory distress, likely secondary to CO2 narcosis. Because of this, pt was transferred to ICU for close monitoring. An arterial blood gas (ABG) was done and it showed a pH of 7.28, pCO2 of 51.4, and pO2 of 81. She was placed on BiPAP and observed in the ICU. Two days after being monitored in the ICU, pt was doing better and breathing well on room air. Repeated ABG showed a pH of 7.41, pCO2 of 45, and pO2 of 80. Pt was transferred back to regular floor for further monitoring.

Discharge Summary Cont.

• Pt constantly refused CPAP because of it being uncomfortable. Towards the end of the hospitalization on 3/25, pt underwent an overnight pulse oximetry to evaluate the need for a sleep study. The studies showed that the pt had significant hypoxemia overnight. Upon discharge, the pt was told that she needs to follow up with pulmonary in 2 weeks to get a sleep study.

• Uncontrolled DM: Throughout the hospitalization, the pt had uncontrolled high sugars. She was receiving NPH insulin 60u QAM and 50u QPM. She was also receiving IGMO sliding scale high coverage. Additionally, pt was receiving prednisone 20mg daily for her MG. Even with this grade of insulin coverage, her sugars remained uncontrolled. In part, this was because pt was not compliant with her diet. The pt was recommended to follow strict diet consisting of 1800kcal with a carbohydrate count.

Discharge Medications

• Combivent inhaler, 1-2 puffs Q6H• ASA 81mg QD• Cardizem CD 240mg QD• Insulin NPH 60u in AM and 50u in PM• Insulin IGMO sliding scale• Synthroid 137mcg QAM• Prednisone 30mg QD• Zocor 40mg QD• TriCor 145mg QD• Calcium with vitamin D, 1 tab TID• Cymbalta 20mg QD

Myasthenia Gravis

• Latin and Greek origin

• Neuromuscular transmission disorder between neurons and muscles

• Age Onset– Women < 40 years old– Men > 60 years old

• Causes

– Acquired immunologic abnormality directed against the postsynaptic acetylcholine receptor (AchR) complex

– Genetic abnormalities producing a structural abnormality at the neuromuscular junction

– Thymus abnormalities – hyperplastic changes indicative of active immune response

Clinical Presentation

• Muscle weakness– Ptosis, facial expression, dysarthria, gait,

hands, arms, shortness of breath, difficulty swallowing

• Factors that worsen symptoms– emotional upset, systemic illness, drugs

affecting neuromuscular transmission

Diagnosis

• Medical history, physical or neurological exams– Change in eye movements or muscles weakness

without altered ability to feel

• Blood test – immune molecules or AchR antibodies

• Endrophonium Chloride (Tensilon) Test

• Electormyography– Repetitive Nerve Stimulation– Single Fiber Stimulation

• Computed Tomography (CT) of thymus

• Pulmonary Function Test – myasthenia crisis

CT of Thymus

Pharmacological Treatment

• Anticholinesterases– Neostigmine Bromide (Prostigmine®)– Pyridostigmine Bromide (Mestinon®)

• Immunosuppressants– Prednisone (Deltasone®)– Azathioprine (Imuran®)– Cyclosporine A – only in patients intolerant or

unresponsive to azathioprine therapy (side effect profile, drug interactions)

• High-dose intravenous immune globulin (IVIG)

Medication DosesDrug Formulation Dose MP

Pyridostigmine Bromide (Mestinon)

60 mg tab180 mg ER tab60 mg/5 mL syrup5 mg/mL injection

Syrup/Conventional tab- range from 1-25 tab or tsp/dayER- 1-3 tab QD or BID with at least 6 H between doses

Neostigmine Bromide (Prostigmine)

15mg tab1:1000 injection1:2000 injection1:4000 injection

15-325mg/day; SQ/IM 1mL of 1:2000 (0.5mg); individualize subsequent doses

Prednisone (Deltasone) 2.5, 5, 10, 20, 50mg tab Inpatient: Begin 20mg then increase by 5mg Q2-3 days, max 50mg/dayOutpatient: Begin 5mg (see above)

Weight; BP; glucose;

Azathioprine (Imuran) 50mg tab Initial: 2.5-3mg/kg/dayMaintenance: 1.5-2.5mg/kg/day

Hct; WBC; platelets; LFTs

Cyclosporine A (Sandimmune, Neoral)

25, 50mg capsules, soft gelatin for microemulsions

Oral soln for microemulsion 100mg/mL

2.5mg/kg BID Renal fxn; BP; serum levels

Mycophenolate mofetil (CellCept)

500mg tab250mg capsule200mg/mLoral suspension

1g BID Renal insufficiency

IVIG 2g/kg (over 2-5 days)

Other Treatment Modalities

• Plasmapheresis

• Thymectomy– Reduces symptoms in approximately 70%

of patients

Adverse Effects

• Anticholinesterases– SLUD effects, fasciculations

• Corticosteroids– Weight gain, fluid retention, HTN, diabetes, increased

risk for infections, osteoporosis

• Azathioprine– Flu-like symptoms or GI disturbances occur in 10%,

usually within first few days of tx– Hepatitis– Myelosuppression– Monitoring parameters?

Medications that may exacerbate weakness and trigger MG crisis

• Quinidine

• Aminoglycosides

• Beta blockers

• Succinylcholine chloride

• Magnesium sulfate

Sarcoidosis

• Multisystem granulomatous inflammatory disease

• Most commonly found in lungs and lymph nodes

• Women > Men

• African descent > Caucasian

• Age– Peak 20-29 and >50 years old

Causes

• Dysregulation of immune system– Accumulation of monocytes, macrophages, and

activated T-lymphocytes

• Infectious agents

• Vitamin D dysregulation– Conversion of vitamin D to active form

• Memory loss, metallic taste, irritability, fatigue

• Thyroid disease– Women have higher risk

Signs and Symptoms

• Fatigue unchanged by sleep• Weight loss• Aches and pains• Shortness of breath• Knee swelling• Cutaneous: rashes, small

bumps• Cardiac: conduction

abnormalities → fatal ventricular arrhythmias

• Patchy hair loss• May cause atelectasis

Pharmacologic Treatment

• Predisone (Deltasone®)

• Azathioprine (Imuran®)

• Methotrexate (Trexall®)

Thyroid Disease

Thyroid Hormone: The Basics

• Thyroid Hormone– In children is responsible for growth and development– In adults it maintains metabolic stability

• Formation (Organification)– Takes place in the thyroid cells

• Coupling– Combining the monoiodotyrosine ( MIT ) with diiodotyrosine

(DIT)– MIT + DIT = T3– DIT + DIT =T4

• Hormones are released by proteolysis into the bloodstream

• Thionamide drugs inhibit thyroid peroxidase and therefore block thyroid hormone synthesis.

Thyroid Hormone: The Basics Cont.

• T3 and T4 are highly protein bound

• Unbound initiates responses and regulates thyroid stimulating hormone (TSH)– TSH stimulates growth and function of thyroid

• T4 - Secreted only from the thyroid

• T3 - Secreted from the thyroid and produced when T4 is catalyzed in the peripheral tissues.

• Potency: T3 > T4

Diagnostic Tests

• Total T4: Measures both bound and unbound T4 serum levels, this is the standard initial screening test.

• Free T4: Measures unbound T4 in the serum & is the most accurate reflection of thyrometabolic status

• Total T3:Measures the bound and unbound T3 serum levels.

• TSH: Measures the serum concentrations of thyroid stimulating hormone

• TRH Stimulation Test: Measures the ability of injected TRH to simulate the pituitary to release TSH

• Antithyroid antibodies: Measures the anitbody titers against thyroglobulin and TSH receptor.

• Radioactive Iodine Uptake Test: Detects the ability of the thyroid gland to trap and concentrate iodine.

HYPERthyroidism: Signs and Symptoms

• Heat Intolerance• Palpitations• Pruritis• Dyspnea on exertion• Weight loss with

hyperphagia• Diarrhea• Tremors• Weakness• Urinary frequency• Nocturia• Restlessness

• Warm, smooth moist skin

• Onycholysis (loosening of the nail bed)

• Thinning of the Hair• Lid Retraction and Lag• Tachycardia• Atrial Fibrillation • Hyperactive Reflexes• Cognitive impairment

HYPERthyroidism: Treatment Modalities

• Surgery

• Antithyroid medications

• Radioactive Iodine (RAI)

• Goals of therapy are;– Eliminate excess thyroid hormone– Minimize the symptoms and the long-term

effects of hyperthyroidism.

HYPERthyroidism: Antithyroid Meds

• Classified as thionamides

• MOA: Impairs the processes of organification and coupling and therefore decrease the production of T3 and T4

• May also exert immunosuppressive actions

• Treatment may continue for one to two years

• Common ADEs:– Pruritis, rash, arthralgias, fever, sore throat, mouth

ulcers, nausea

• Serious ADEs:– Agranulocytosis, liver disease and lupus like syndrome

HYPERthyroidism: Antithyroid Meds

Characteristic Propylthiouracil Methimazole

Mechanism of Action

Decrease thyroid hormone biosynthesis, Decrease peripheral conversion of T4 to T3 (at high doses)

Decrease thyroid hormone biosynthesis,

Dose Initial:300-400 mg in 3 divided dosesMaintenance dose: 100-150 mg in 3 divided doses

Initial: 15-60 mg in three divided dosesMaintenance: 5-15 mg daily

Time to euthyroidism Months Weeks

Agranulocytosis Idiosyncratic Dose dependent ( > 30 mg daily)

Monitoring Parameters

Baseline Free T4 then monthlyBaseline CBC then every 3-6 months

Baseline Free T4 then monthly

HYPERthyroidism: Antithyroid Meds• Radioiodine

– Treatment of Choice– Cheap and effective– Administered as I131 orally– MOA: Incorporated into the thyroid gland where β-emissions

produces radiation thyroiditis and fibrosis.– Euthyroid occurs in 6-18 weeks– Dose depends on

• Size of the goiter• Physician preference

– May give high dose = thyroid ablation therapy– May give low dose = conservative to prevent

hypothyroidism– Tapering of gluccocorticosteroids and smoking cessation is

recommended prior to therapy.– Patients allergic to iodine should not receive I131.– Patient should avoid physical contact with other persons especially

pregnant women for at least one week.– Women should not conceive and men should not father children for

at least 6 months following therapy

HYPERthyroidism: Antithyroid Meds

• Beta Blockers– Treat symptoms of anxiety, tremor and palpitations prior to obtaining

euthyroidism– Propranolol and Nadolol have added benefit of inhibiting the peripheral

conversion of T4 to T3– Patients may require higher doses due to resistance– Taper and discontinue after euthyroidism is achieved– Verapamil and Diltiazem may be used as alternative therapy if Beta-

Blockers are contraindicated

• Radiation Thyroiditis– Increase in the symptoms of hyperthyroidism following radioiodine therapy.– Peaks 10-14 days after treatment– Antithyroid medications may be used in the elderly or cardiac patients to

induce euthyroidism and decrease the risk of acute thyroiditis• Stop 1-2 days prior to therapy and restart 3-5 days after therapy.• May decrease the effectiveness of the radioiodine therapy.

HYPOthyroidism: Signs and Symptoms

• Weakness• Fatigue• Lethargy• Decreased Energy• Cold Intolerance• Dry Skin• Decreased

Sweating• Decreased Tendon

Reflexes

• Difficulty Concentrating

• Constipation• Weight Gain• Hair Loss or

Changes • Arthralgia• Depression• Anorexia

HYPOthyroidism: Treatment Modalities

• Goals of therapy include– Restore normal thyroid hormone

concentrations in tissues– Provide symptomatic relief– Prevent neurological deficits

• Two types of products– Natural Thyroid Hormone– Synthetic Thyroid Hormone

HYPOthyroidism: Natural Thyroid Hormone

• Armour Thyroid– T4:T3 combination– Desiccated beef or pork thyroid gland

• Problems– Unpredictable hormonal stability

• Advantages– Cheap

HYPOthyroidism: Synthetic Thyroid Hormone – Levothyroxine • DRUG OF CHOICE

– What are some of the brand and generic names??

• T4 only

• Advantages– Chemically Stable– Relatively Inexpensive– Free of antigenecity– Uniform potency between brands– Once daily dosing

• Drug Interactions– How should it be administered?– Clearance is increased by rifampin, phenytoin and

carbamazepine. What do all of these have in common?

HYPOthyroidism: Synthetic Thyroid Hormone Cont.

• Liothyronine– T3 only– Short half life– Rapid onset

• Liotrix– T4:T3– Attempts to mimic the bodies natural

production of thyroid hormone.– Major limitation is cost– Lack of therapeutic rationale

Dosing Guidelines

• TSH should be evaluated every 4-6 week until normal levels are obtained and then every 6 to 12 months.

• Therapy may be interrupted for several days without metabolic consequences.

• Signs and symptoms of excessive dosing: tachycardia, nervousness, tremors, palpitations

Initial Dose Increase dose by

Patient < 60 0.05-0.1 mg/d 0.05 mg every 4-6 weeks

Patient > 60 0.025-0.05 mg/d 0.025 mg every 4-6 weeks

Preexisting Cardiac Disease

0.0125-0.025 mg/d

0.0125 mg every 4-6 weeks

Summary

• Pharmacists play an integral role on healthcare team– Medication experts

– Clinical: understand lab values

– Drug interactions

– Consolidate drug therapy

– Medication Therapy Management

– Patient role in effective and quality care

– 5 P’s

Any Questions