PHCL 554 Cardiovascular Pharmacology Douglas Larson, Ph.D. 626-0944 [email protected].
Thyroid Disorders PHCL 442 Hadeel Al-Kofide MS.c.
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Transcript of Thyroid Disorders PHCL 442 Hadeel Al-Kofide MS.c.
Thyroid Disorders
PHCL 442
Thyroid Disorders
PHCL 442
Hadeel Al-Kofide MS.c
Topics to be coveredTopics to be covered
• Thyroid physiology
• Hypothyroidism
• Hyperthyroidism
Thyroid PhysiologyThyroid Physiology
HypothyroidismHypothyroidism
• Causes
• Clinical presentation
• Goals of therapy
• Treatment options
• Monitoring
• Special considerations
CausesCauses
• Primary:
Autoimmunue disease: Genetic, more common in female
Iatrogenic destruction of thyroid: Example: in surgey
Drug induced: example: Iodine & lithium
• Secondary:
Due to deficiency in TSH or TRH
Hypothyroidism
Clinical PresentationClinical Presentation
• Increase weight
• Loss of appetite
• Cold intolerance
• Headache
• Muscle cramps & pain
• Weakness, tiredness & fatigue
• Dyspnea
• Constipation
Hypothyroidism
Symptoms
Clinical PresentationClinical Presentation
• Thin brittle nails
• Puffiness of face & eyelid
• Yellowish skin
• Thinning of outer eyebrow
• Peripheral edema
• Bradycardia
• Hypertension
Hypothyroidism
Physical Findings
Clinical PresentationClinical Presentation
• High TSH
• Low T3 & T4
• Positive antibodies
• Anemia (decrease Hct & Hgb)
Hypothyroidism
Laboratory
Goal of TherapyGoal of Therapy
• Normalize thyroxin level
• Provide symptomatic relief
• In a child, or infant we want to maintain normal growth &
development
Hypothyroidism
TreatmentTreatment
1) Natural thyroid products: Desiccated thyroid (T3 & T4)
• Problems with these preparations is that they can cause severe
allergy
• There is no bioequivalence: different content from batch to
batch
• It losses its potency by time
Hypothyroidism
NO more used
TreatmentTreatment
2) Triiodothyroxine (T3)
• Not recommended for routine use due to:
Short acting given 4 times a day
Because this drug contains the active form T3 this can cause
fast supra-physiological levels then soon go back to normal &
so on (fluctuation)
This is considered a major problem specially in elderly
patients & patients with cardiac problems
Hypothyroidism
TreatmentTreatment
2) Triiodothyroxine (T3)
• Used only in the following situations:
Myxedema coma
Patients with impaired conversion from T4 to T3
Hypothyroidism
TreatmentTreatment
3) Liotrix (T3 & T4)
• Combination of T4 & T3 (4:1)
• It has same disadvantages of any preparation containg T3
• Expensive
• Not commonly used
Hypothyroidism
TreatmentTreatment
4) Levothyroxine
• Drug of choice in hypothyroidism
• Advantages:
Stability & uniform potency
Low cost
No allergy
Long half life (7 days so can give once daily)
Hypothyroidism
TreatmentTreatment
4) Levothyroxine
• Due to problems in drug absorption we advice patients to take it
on empty stomach (at least 60 minutes before meals)
• Cholestyramine, sucralfate, aluminum containing antacid can
decrease absorption so must space between them
• Also it is affected by enzyme inducers & inhibitors (ex:
rifampicin)
• Dose: 1.6 – 1.7 mcg/kg/day
Hypothyroidism
MonitoringMonitoring
• Improvement in symptoms
• Improvement in lab findings
• Improvement will start in 2-3 weeks but maximum effect after
4 -6 weeks
• Monitor patients for TSH, T3 & T4 every 6-8 weeks
Hypothyroidism
Special ConsiderationsSpecial Considerations
Pregnancy:
• Usually pregnant women require larger doses of thyroxine,
around 20-50% increase in dose
• After delivery can go back to usual dose
Hypothyroidism
Special ConsiderationsSpecial Considerations
Subclinical hypothyroidism:
• Normal T3 & T4 but high TSH
• Only mild symptoms
• Look at each patient individually then it depends if you will treat
him or not
• Patients with TSH more than 10 mIU/L must be given thyroxine
even in the absence of symptoms
Hypothyroidism
Special ConsiderationsSpecial Considerations
Myxedema coma:
• The end stage of long standing uncorrected hypothyroidism
• It can lead to coma, hypoxia & psychosis
• Mortality from 60-70%
• Treatment of choice: could use products with T3 (fast action)
but better is IV L-thyroxine 400-500 mcg
Hypothyroidism
HyperthyroidismHyperthyroidism
• Causes
• Clinical presentation
• Goals of therapy
• Treatment options
• Monitoring
• Special considerations
CausesCauses
1) Graves’ disease:
• Autoimmune disease: the presence of antibodies affecting
TSH
• All gland is hyperactive producing large amounts of thyroid
hormone
• Ocular symptoms common in graves’ disease
Hyperthyroidism
CausesCauses
2) Other causes:
• Tumors: could be benign or malignant
• Thyroditis: inflammation (may be due to viruses)
• Drug induced: exogenous thyroid hormone replacement
Hyperthyroidism
Clinical PresentationClinical Presentation
• Heat intolerance
• Weight loss with increased appetite
• Palpitation
• Nervousness
• Tachycardia
• Hypertension (but here due to increase sympathetic tone)
Hyperthyroidism
Symptoms
Clinical PresentationClinical Presentation
• Diarrhae (due to increased GI activity)
• Tremor
• Weakness
• Fatigue
• Amenorrhea in female
Hyperthyroidism
Symptoms
Clinical PresentationClinical Presentation
• Exophthalmos: lid lag, lid retraction, chemosis, conjunctivitis,
periorbital edema, & loss of extraorbital movement
• Thinning of hair
• Moist skin
Hyperthyroidism
Physical Findings
Clinical PresentationClinical Presentation
• Increase T3 & T4
• Increased Free T3 & T4
• Low TSH
• Thyroid receptor antibodies (TPO antibodies)
• Increase liver enzymes
• Radioactive iodine uptake, how?
Hyperthyroidism
Laboratory
Goals of TherapyGoals of Therapy
• Decrease amount of thyroid hormone
• Improve symptoms of the disease
Hyperthyroidism
Treatment ModalitiesTreatment Modalities
• Surgery
• Drugs
• Radioactive iodine
Hyperthyroidism
SurgerySurgery
Treatment of choice in:
1. Suspected malignancy
2. Patients with goiter with difficulty of breathing
3. Contraindications to other modalities (ex: pregnancy)
4. Failure to respond to medications
Hyperthyroidism
SurgerySurgery
• Subtotal thyroidectomy: avoid risk of hypothyroidism, but
risk of recurrent hyperthyroidism
• If hyperthyroidism occurred after surgery, do not do it again
but use other treatment modalities
Hyperthyroidism
SurgerySurgery
• Advantages: Quick & no lag time
• Disadvantages: expensive, complications
• Before surgery must be in euthyroid state, because with
surgical manipulation there may be release of high amount of
thyroid hormones leading to severe hyperthyroidism (thyroid
storm)
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
1. Propylthiouracil
2. Methimazole
• Mechanism of actions:
They inhibit thyroid hormone synthesis
They also suppress autoantibody synthesis
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Methimazole: drug of choice because only one tablet is
requires, less expensive & no bitter taste
• Propylthiouracil: needs 7 tablets 2-3 times/day, but it is safer
in pregnant & lactation; have the advantage of inhibiting
converting T4 to T3 so decreasing the active form & this is
an advantage for patients with thyroid storm
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Monitoring therapy:
1. Baseline FT4 & TSH before treatment then measure every 4-6
weeks, then when normal every 3 months, if normal for 2 times
then measure yearly
2. They can cause agranulocytosis: make baseline WBC &
differentials before treatment & during therapy
3. Liver function test
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Duration of therapy: 1- 2 years but patients may need it for
life, so duration of treatment depends on individual patient
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Side effects:
1. Rash: if mild continue therapy but give antihistamine or
topical steroids. If more severe rash change to other
thioamide (cross allergy is uncommon)
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Side effects:
2. Hepatitis: Increase in liver function test, with propylthiouracil
it is not dose related but with methimazole doses more than 40
mg increase risk of hepatitis. If liver functioned increased early
in therapy then went to normal can continue on same treatment
but if kept increasing then must DC the drug
Hyperthyroidism
Drugs used in HyperthyroidismDrugs used in Hyperthyroidism
Thioamides:
• Side effects:
3. Agranulocytosis: decrease in neutophils, usually develops
within the first 3 months of treatment. Tell the patient to
watch for symptoms such as: unexplained fever, blue like
symptoms & sore throat
Hyperthyroidism
Radioactive IodineRadioactive Iodine
• The only organ which traps iodine (advantage)
• This radioactive iodine causes death of cells
• Minimum side effects because don’t go to other sites in the
body
• Before treatment patient must be in euthyroid state (use
drugs)
Hyperthyroidism
Radioactive IodineRadioactive Iodine
Treatment of choice in:
• Patients failed other treatment modalities
• Debilitated patient (or patients with poor surgical candidates)
• Recurrent hyperthyroidism after surgery
Contraindication:
• Pregnancy
Hyperthyroidism
Radioactive IodineRadioactive Iodine
Advantages:
• Safe, effective treatment, painless & economic
Disadvantage:
1. Takes long time 10-12 months for total affect to appear
2. Patients fear from radiation
3. Patients will have hypothyroidism
Hyperthyroidism
Radioactive IodineRadioactive Iodine
Advantages:
• Safe, effective treatment, painless & economic
Disadvantage:
1. Takes long time 10-12 months for total affect to appear
2. Patients fear from radiation
3. Patients will have hypothyroidism
Hyperthyroidism
Beta-BlockersBeta-Blockers
• Because increase sympathetic activity, beta-blockers may help in
reducing symptoms
• Propranolol have the advantage of inhibiting the conversion of T4
to T3 (useful in thyroid storm)
Advantages:
1. Used as adjunct to surgery & radioactive iodine to control
symptoms
2. In pregnant women until she delivers to control symptoms
Hyperthyroidism
Iodinated Contrast MediaIodinated Contrast Media
• Effective short term treatment
• They have the advantage of inhibiting the conversion of T4 to
T3
• Used in: Pre-surgery& after radioactive iodine (not before)
• Not used in: pregnancy
• Must give with it thioamides (need around 8 weeks to work)
Hyperthyroidism
Monitoring Therapy in HyperthyroidismMonitoring Therapy in Hyperthyroidism
• T3, T4 & TSH: every 4-6 weeks then every months then
yearly
• Watch signs & symptoms of hypothyroidism (specially after
surgery or radioactive iodine)
Hyperthyroidism
Pregnancy & HyperthyroidismPregnancy & Hyperthyroidism
• Hyperthyroidism can happen during early pregnancy &
symptoms decrease after 2nd or 3rd trimester
• So at this stage patients may not take their medication so after
delivery there will be exacerbation leading to thyroid storm
• Treatment of choice: surgery or thioamides
Hyperthyroidism
Thyroid StormThyroid Storm
• Acute onset of fever, tachycardia, tachypnea, confusion,
psychosis & coma
• Mortality rate can reach 50%
• Needs acute & immediate treatment
• Treatment: Please look at table 49-11 at applied therapeutics
Hyperthyroidism
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