Upload
vachhani-nirav
View
674
Download
2
Tags:
Embed Size (px)
DESCRIPTION
Citation preview
Phamacotherapeutical management of
Thyroid DysfunctionPresented by:Mr. Nirav S. VachhaniM.Pharm Pharmacology (Sem-2)
Guided by:
Dr. Rina H. GokaniS. J. Thakkar pharmacy college, Rajkot.
Thyroid
2
Introduction:The thyroid gland was described by Galen and
was named "glandulae thyroidaeae" by Wharton in 1656.
The thyroid gland is the source of two fundamentally different types of hormones.
The iodothyronine hormones include1. Thyroxine (T4) and2. 3,5,3’-triiodothyronine (T3)
They are essential for normal growth and development and play an important role in energy metabolism.
3
Anatomy:
4
Physiology:Biosynthesis of Thyroid Hormones :
5
Regulation of Thyroid Function :
6
The ratio of T4 and T3 secreted :- 10:1Approximate Values for Thyroid Hormone Plasma Concentrations and Various Kinetic Parameters.
T4 T3
Plasma concentration
Total 7.77 mg/dL 0.14 mg/
dL
Free 1.554 ng/dL 0.389
ng/dL
Total hormone in free
form
0.02% 0.3%
Plasma half-life 6.7 days 0.75 days
Volume of distribution 10 L 40 L
Metabolic clearance rate 1.1 L/day 24 L/day
Total production rate 85.47
mg/day
33.6
mg/day
From thyroid secretion 100% 20%
7
Actions of Thyroid Hormones :
8
Evaluation of Thyroid Diseases:
Thyroid Function test :commonly in use for estimating the iodine, TBG, free T4 and free T3 concentrations are as follow:
• Protein-bound iodine:It is a measure of organically bound iodine in blood (normal 4-8 ug/dl: myxoedema 2ug/dl; thyrotoxicosis 10-12 ug/dl).
• Serum T4:It is measured by radio-immuno assay (normal 5-12 ug/dl). Serum T3 assay can also be done (normal 80-180 ng/dl).
9
• Serum TBG:
It is measured by radio-immuno assay or immuno electrophoresis, and the ratio of T4 to TBG is used as an index of free hormone activity.
• Free thyroxine index and effective thyroxine ratio:
These are calculated from the serum T4 and serum TBG level. There is a good correlation between these values and free T4 levels. Direct free T4 measurement are tedious and difficult.
• Scintillography:
The radio iodine uptake by the gland is recorded photographically and scanned.
10
• T3 suppression test:
In the standard test, the pretreatment radioactive iodine uptake (RAIU) is determined. Then T3 (as Cytomel) 25 ug tid, is given for 7-10 days. On the last day a repeat RAIU is performed. In a normal person the RAIU will be suppressed by 50% or less of the original value. Whereas in Graves’ disease there is no suppresion as the thyroid is functioning autonomously.
Clinical history and physical examination :
11
Thyroid Imaging :• Radioactive imaging• Ultrasound waves• CT/MRI scan
12
Diseases of the Thyroid :Two significant functional disorders characterized by distinct clinical syndromes are :
I. Hyperthyroidism :Associated with excessive release of
Thyroid hormones.
II. Hypothyroidism :Associated with Thyroid hormone
deficiency.
13
1) Hyperthyroidism :The term hyperthyroidism is restricted to those conditions in which thyroid hormone production and release are increased due to gland hyper function.
The condition is more frequent in females and is associated with rise in both T3and T4 levels in blood, though the increase in T3 is generally greater than that of T4.
Etiopathogenesis :Primary : Graves’ disease
Toxic multi-nodular goiterToxic adenoma
Secondary : TSH hyper secretion by a pituitary tumor
14
Clinica
l manife
statio
n :
Mainly referable to1.Hypermetabolic state
2.Over activity of the sympathetic nervous system
15
Diagnosis :Autonomous thyroid function
Low TSH Elevated T3 / T4
Thyroid scan diffuse elevated iodine uptake
Thyroid ultrasound
16
Treatment :Choices:1. Antithyroid drugs2. Radioactive iodine therapy3. Surgery
Choice depends on:1. Age2. Severity of the disease3. Size of the gland4. Coexistent pathology (Ophthalmoplegia)5. Other factors:
Patient’s preferencePregnancy
17
1. Antithyroid drugs : Propyl thiouracil (PTU) = 100-300 mg TID Methimazole (Tapazole) = 10-20 mg TID then OD Carbimazole = 40 mg OD
MOA : Inhibits the organic binding of iodine and coupling of
iodotyrosine PTU can also lower conversion of T4 to T3; it can
also decrease thyroid autoantibody levels.
18
Disadvantages of these drugs :Crosses the placenta --> inhibits fetal thyroid
function
Excreted in breast milk
Side effects:Skin rashesFeverPeripheral neuritisPolyarthritisGranulocytopenia (reversible)
19
2. Radioactive Iodine Therapy :MOA :
131I is taken up and trapped
Emission of α-particle
Destroy thyroid tissue
Advantages :i. Avoidance of surgery (no injury to nerve /
parathyroid gland)ii. Reduce cost & ease of treatment
20
Disadvantages :i. Lifelong thyroxin replacement therapyii. Slower correction of hyperthyroidismiii. Higher relapse rateiv. Adverse effect of ophthalmopathyv. Development of Hypothyroidism after thyroid
ablation
Suitable for :i. Small or moderate size goiterii. Relapse after medical and surgical therapyiii. Antithyroid drug and surgery are contraindicated
Contraindicated :i. Pregnant / breast feedingii. Ophthalmopathy (progression of eye signs)iii. Young age (children/adolescence)
----> Infertility / carcinoma21
3. Thyroid Surgery : Mainly Suitable for :
i. Young patientii. With Graves’ ophthalmopathyiii. Pregnant
Advantages :i. Immediate cure of the diseaseii. Low incidence of hypothyroidismiii. Potential removal of coexisting thyroid
carcinoma Disadvantages :
i. Complication ---> nerve injury (1%) and hypoparathyroidism (13% transient/ 1% permanent).
ii. Hematomaiii. Hypertrophic scar formation 22
2) Hypothyroidism :
Hypothyroidism is a hypometabolic clinical state resulting from either
i. Inadequate production of thyroid hormones for prolonged periods,
ii. From resistance of the peripheral tissues to the effects of thyroid hormones (rarely).
Depending on whether the hypothyroidism arises from an intrinsic abnormality in the thyroid or results from hypothalamic or pituitary disease, divided into primary and secondary categories.
23
Causes of hypothyroidism :
Primary
Postablative (after surgery or radioiodine therapy)
Primary idiopathic hypothyroidism
Hashimoto thyroiditis*
Iodine deficiency*
Congenital biosynthetic defect (dyshormonogenetic goiter)*
Secondary
Pituitary or hypothalamic failure (uncommon)
24
Clinica
l manife
statio
n :
Mainly referable to1.Cretinism
2.Myxoedema
25
Cretinism :A cretinism is a child with severe hypothyroidism present at birth or developing within first two years of postnatal life.
Clinical features :• Impaired development of skeletal system & CNS• Severe mental retardation• Coarse facial features• A protruding tongue• Umbilical hernia
26
Treatment of Cretinism :Iodine only if iodine deficiency is the cause.Levothyroxine (T4): Average dose 1.6 ug/kg Age > 50-60 or cardiac disease:
must start at a low dose (25 ug/d) Recheck thyroid hormone levels every 4-6 weeks
after a dose change Aim for a normal TSH level
Liothyronine (T3): Tablet (Cytomel®) : 5-10 ug/d (starting)
: 25 ug/d (maintenance) Injection (Triostat®) : 50-100 ug
27
Myxoedema :
Myxoedema coma is a rare syndrome that represents the extreme expression of severe, long-standing hypothyroidism.
Common precipitating factors include :
1. Pulmonary infections,
2. Cerebrovascular accidents,
3. Congestive heart failure
Clinical features :• Hypothermia, which may be profound;• Respiratory depression• Unconsciousness• Dry & rough skin
28
Treatment of Myxoedema :
Levothyroxine500 mg/day
Livothyronine75 mg/day
Other Rewarming with blankets Correction of hyponatremia Treatment of the precipitating incident
29
Parathyroid
30
Introduction: The parathyroid glands are usually 4 in number:
1. The superior pair derived from the 3rd branchial pouch
2. Inferior pair from the 4th branchial pouch of primitive foregut
31
Anatomy:
composed of solid
sheets and cords of
parenchymal cells
32
Regulation of Parathyroid Function :
33
Actions of Parathyroid Hormones :
34
Diseases of the Parathyroid :
The major parathyroid disorders are its functional disorders:
1. Hypoparathyroidism
2. Hyperparathyroidism
35
1) Hypoparathyroidism :When the parathyroid glands do not secrete sufficient PTH, the osteocytic reabsorption of exchangeable calcium decreases and the osteoclasts become almost totally inactive.
As a result, calcium reabsorption from the bones is so depressed that the level of calcium in the body fluids decreases.
When the parathyroid glands are suddenly removed, the calcium level in the blood falls from the normal of 9.4 mg/dl to 6 to 7 mg/dl within 2 to 3 days.
36
Aetiology:Most common cause : Surgery for thyroid diseases
Neck exploration
Adenoma
Clinical manifestation:Most of due to Hypocalcaemia
Increased neuromuscular excitablity
Major symptoms
• Numbness around mouth• Muscle spasm• Irritability• Cataract• Positive chvostek’s sign• Positive trousseau’s sign 37
Treatment:For sever, acute treatment:
10% calcium gluconate IV injection
For chronic treatment:
PTH therapy (not currently practised)
Maintenance treatment:
Vitamin D preparations
38
Drug Preparations Activity
Ergocalciferol
( calciferol, vitamine
D2)
Calciferol injection 7.5 mg
(3000000 units/ml)
Calciferol tablets 250µg
(10000 units) and 1.25mg
(50 000 units)
Calcium and ergocalciferol
tablet (2.4 mmol of calcium
+ 400 units of
ergocalciferol)
Requires renal
and hepatic
activation
Colecalciferol
( vitamin D3)
• A range of preparation
containing calcium (500-
600mg) and colecalciferol
(200-440 units)
Requires renal
and hepatic
activation
39
Alfacalcidiol
(1α-
hydroxycolecalciferol)
Alfacalcidiol capsule
250ng, 500ng and 1µg
Alfacalcidiol injection
2µg/ml
Requires hepatic
activation
Calcitriol (1, 25 –
dihydroxycolecalcifero
l)
Calcitriol capsule
250ng and 500 ng
Calcitriol injection
1µg/ml
Active
Dihydrotachysterol • Dihydrotachysterol oral
injection 250mg/ml
Requires hepatic
activation
40
2) Hyperparathyroidism :
Hyperparathyroidism is the clinical state that results from increased production of PTH by the parathyroid gland.
Hyperparathyroidism is further categorized as follow:
1. Primary Hyperparathyroidism
2. Secondary Hyperparathyroidism
3. Tertiary Hyperparathyroidism
41
I. Primary Hyperparathyroidism:Aetiology:
Cause of primary hyperparathyroidism is a tumor of one of the parathyroid gland.
Much more frequently in women.
Common causes:
Parathyroid adenomas 80%
Carcinoma of parathyroid 2-3%
Primary hyperplasia 15%
Clinical features: Elevated levels of parathyroid hormone Hypercalcaemia Hypercalciuria Kidney stones 42
II. Secondary Hyperparathyroidism:
In secondary hyperparathyroidism, high levels of PTH occur as a compensation for hypocalcemia rather than as a primary abnormality of the parathyroid glands.
Etiology:Chronic renal insufficiency
Vitamin D deficiency
Intestinal malabsorption syndromes
Clinical features:Mild hypocalcaemiaRenal osteodystrophySoft tissue calcification 43
III.Tertiary Hyperparathyroidism:
Tertiary hyperparathyroidism is a complication of secondary hyperparathyroidism in which hyper function in spit of removal of the cause of secondary hyperplasia.
Possibly, hyperplastic nodule in the parathyroid gland develops which becomes partially autonomous and continue to secrete large quantities of parathyroid hormone without regard to the needs of the body.
44
Treatment of Hyperparathyroidism:
(i) Surgical removal of the diseased gland.
(ii) Intravenous saline infusion to correct dehydration.
(iii) Intravenous infusion of 0.1 M solution of basic sodium phosphate to promote calcium excretion.
(iv) Isotonic sodium sulphate and sodium chloride administered intravenously to induce calciuresis.
(v) Disodium edetate (EDTA). It chelates calcium, but is too toxic for routine use. In an emergency 50 mg/kg in 500 ml saline may be given intravenously.
(vi) Mithramycin. It is a cytotoxic agent and reduces serum calcium levels. In an emergency 25 mcg/kg/day may be given IV for 3 to 4 days.
45
(vii) Calcitonin 5 to 25 mcg/kg may be of therapeutic value, but experience with this agent is limited.
(viii) Glucocorticosteroids may be tried. They are claimed to be effective in hypercalcaemia of vitamin D therapy.
(ix) Haemodialysis may be of value when all other measures have failed.
Thus, effective pharmacotherapy for hyperparathyroidism is not available. Mainly the treatment is operative.
46
Summery:The thyroid gland is the source of two fundamentally
different types of hormones.
1. Thyroxine (T4) and
2. 3,5,3’-triiodothyronine (T3)The ratio of T4 and T3 secreted :- 10:1The evaluation of Thyroid function is maninly done by
Thyroid function test.Diseases of Thyroid include
1. Hyperthyroidism
2. HypothyroidismTreatment of these include
1. Antithyroid drugs
2. Radioactive iodine therapy
3. Surgery 47
Parathyroid :• The Parathyroid gland gland derived from 3rd and 4th bronchial pouch.• The gland mainly secrets the Pararthyroid hormone.• The main action of PTH on the Kidney, Bone and Small intestine.• There are two main diseases related to PTH.
1)Hypoparathyroidism
2)Hyperparathyroidism• Treatment:
48
• HypothyroidismErgocalciferolColecalciferolAlfa CalciferolCalcitriolDihydrotachysterol
• HyperparathyroidismSurgeryIV infusin of NaPO4Disodium EdetateMithramycineCalcitonin
References:
49