thyroid , antithyroid , parathyroid & calcium...
TRANSCRIPT
Thyroid , antithyroid , parathyroid & Calcium metabolism
Suharti K SuhermanDept. of Pharmacology & TherapeuticMedical Faculty, Univ. of Indonesia
Thyroid secreted by thyroid gland → source of 2 different type of hormones :
a. tetraiodothyronine (T4) & triidothyronine (T3)
essential for normal growth & b. calcitonin secreted by parafollicular
cells
Synthesis unique & complex - TH are synthesized & stored as AA residues
of thyroglobulin = a protein component of thyroid follicular colloid
Thyroid H the only hormone that contains iodine 2 important functions :* in developing phase determinants
of normal development espsl CNS devepl.
* in adult it maintains metabolic homeostasis affecting the function of all organ
• Steps of thyroid h synthesis & secretion 1 - uptake or active transport of I- – by the gland 2 - oxidation of iodide & iodination of tyrosyl residues
in thyroglobulin 3 - coupling of iodotyrosine molecules within
thyroglobulin to form T4 & T3 4 - proteolysis of thyroglobulin, with release of
free iodothyronines & iodotyrosines into the circulation
5 – deiodination of iodotyrosines within the thyroid cell
6 – intrathyroidal conversion of T4 to T3 as well as in peripheral tissue
** thyroid H in the circulation is bound in thyroxine –
binding globulin (TBG) major carrier of TH
T4 is also bound to TB prealbumin a small number is bound to albumin or free
**degradation & excretion :eliminated slowly from the body t½ 6–8 dayshyperthyroidism shortened to 3 – 4days hypothyroidis 9 – 10days
pregnancy ↑ binding to TBG retarded clearence
** metabolism liver
Factors that alter binding of Thyroid to TBG
↑ Binding ↓ Binding estrogen glucocort clofibrate androgen
5–fluorouracil salicylates tamoxifen mefenanic acid
SERM phenytoin, carbarmazepin
Treatment Hypothyroidism• levothyroxine Na (L-T4) tablet & as
lyophilized powder for inj, replacement dose 0.05 – 0.2 mg/d with a mean of about 0.125 mg/d;
• Liothyronine Na (L-T3) tab & injectable form mixture of L-T4 & L-T3 = Liotrix
• L-T4 prefer for thyroid replacement longer duration of action, 50 – 80% of the dose is absorbed
• blood level is easily monitored by FT4 & TSH serum level
• T1/2 7 days once daily
• Side effects : allergic reactions, signs of hyperthyroidis
• Drugs interactions: # cholestyramin,iron,calcium,Al (OH)3
& soy product interfere L-T4 absorption
# phenytoin, carbamezepin & rifampin ↑ biliary excretion of L-T4 often necessary ↑ the dose
# pregnant woman/oral contracept the dose of levothyroxine need to be ↑ due to ↑ serum TBG induced by estrogen
Hyperthyroidism antithyroid
• propylthiouracil ( PTU), methimazole & carbimazol (a carbethoxy derivative of
methimazole it inhibits thyroglobulin to form T4 & T3 within the thyroid gland
• PTU , but not methimazole, block peripheral conversion T4 to T3
PTU Methim• plasma prot binding --- 75%.........nil• plasma t1/2 ……………75 min…..4–6 hrs• concentrated in thyroid…yes…….yes• metab in severe liver disease…………..normal…….⇓ kidney disease………..normal…….normal* dosing frequency……..1- 4 x/d…..1–2 x/d
transplacental/ breast milk………………low……… ↑.
Side effects
• Skin rash ( 3% & 7%)• Agranulocytosis ( 0.44 & 0.12% )
Parathyroid & vit D• a polypeptide hormone, regulates plasma
Ca++ by affecting boneformation & resorption, renal Ca++ excretion/ reabsorption, & calcitriol synthesis ( indirectly regulates GI calcium absorption
• importance role in calcium metabolism • secreted by parathyroid gland Ca++
plasma = the most powerful regulator for its secretion
• Ca++ plasma is low PTH secretion ↑ , if the hypocalcemia is sustained hypertrophy & hyperplasia of the gland
Fig-1 .Whole body daily turnover of calcium
Fig-2 .Calcium homeostasis & its regulation by PTH & 1.25-dihydroxyvitamin D.
• effects on bone PTH ↑ bone resorption , ↑ Ca++ delivery to the extracellular fluid
• the cellular terget for PTH is the osteoblast
• it recruits osteoclast precursors to form new bone remodeling units (fig-3)
• Effects on kidney
Fig-3 Bone remodeling sequence in healthy subjects
Other fac tor to bone s treng th : bone turn over
Calcitonin• hormone produced by parafollicular C cells• A single chain peptide hormone IM /
nasal spray• Postmenopausal oeteoporosis calcitonin
inhibit osteoclast activity in bone resorption osteoklast ↑ BMD = Bone Mineral Density)
enough intake Calcium cukup & vitamin D
• Preparations : synthetic salmon calcitonin nasal spray 50 IU 2x/ day or injection ampul 50 IU 1 x / 2 days
• Adverse reactions : nausea, flushing, dose-dependent
Calcitriol• active metabolite of vit. D3• synthesized by the kidney from its
precursor 25-OH cholecalciferol
• Its productions per day ± 0,5 – 1,0 µg ↑ in pregnancy during bone
development • Normal fuction ↑ GI absorption of
Ca++ & regulates bone mineralisation
• Osteoporotic postmenopausal woman calcitriol ↓ bone resorption
• cegah hilangnya massa jaringan • tulang, tetapi pembentukan tulang • tidak berubah• Dosis : 0,25 ug 1 x / 2 x / hari dapat
menyebabkan hiperkalsemia & hiperkalsiuria
OK dosis awal dimulai 0.25mg/h -- setelah itu dapat di ↑ 0.5 mg/h monitor kadar Ca++• Adverse reactions : hypersens