2 thyroid gland function Bone mineralization

Typical effects of thyroid hormones in the body

energymetabolism: consume O2 in tissue producing heat

Growth and development of body

metabolism: sugar → energy (SYMPTOMS OF VERY ACTIVE PERSON) weight loss, warm, energetic, agitation, sleep disorder, tremor

nervous system: Development

Myocardium: Stimulates B adrenergic receptors increaseing O2 consumption

T3 is 10 times more potent then T4

Terminology

-thi- = thyroid homrone antagonist

HYPOthyroidism: Decreased thyroid function and reduced hormone levels. → Hormone replacement therapy. Caused by autoimmune thyroiditis, hyperthyroidism, thyroid gland surgery, medications (lithium, amiodarone)

Hyperthyroidism: Increased thyroid function and increased hormone levels. caused by graves (bazedovs) diease, nodular toxic goiter. The characteristic symptoms of hyperthyroidism are the opposite of those of hypothyroidism. Surgical treatment, radioactive iodine therapy or thyrostatic drug therapy applied as a cure. More energy heat/weight loss/tachycardia

Toxicology of thyroid hormone preparations

overdose of thyroid horomes

Mild/moderate intoxication cause tachycardia, tremor, anxiety, feeling of heat, agitiation, sleep disorders

severe intoxication cause: supraventricular tachycardia, hyperthermia, hypertension, seuzure, coma

Treatment: symptomatic (beta blockers)

Levothyroxine

Synthetic form of T4

Converts to T3 → stimulates intracellular thyroid receptors → nuclear DNA → gene expression → protein syntheisis

Indicaiton: hypothyroidism, autoimmune (hashimoto) thyroiditis. Replacement therapy after thyroidectomy

SE: Tachycardia, Malabsorbiton if combined with other drugs, Toxic if overdoed

Thiamazole (methimazole)

Antithyroid agent

Inhibit thyroid peroxidase (interfering with iodine and tyronine structure) reducing synthesis of (MIT,DIT) T3/T4

Indication: hyperthyroism (graves/bazedovs diease)
SE: Dont give to pregnant, allergic skin reaction, agranulocytosis

thia - thyroid → antagonist

Propylthiouracil

Antithyroid agent

Inhibits thyroid peroxidase → inhibit T3 / T4 synthesis
Inhibit iodothyonine deiodinase → inhibit T4 to T3 convertion

Indication: hyperthyroism (graves/bazedovs diease)
SE: Dont give to pregnant, allergic skin reaction, agranulocytosis

can be used during 1 trimester

bone mineral metabolism

important minerals: Ca2+ and phosphates

Regulated by: PRH (paraphyroid hormone) and Vitamin D

Bone remodling receptor/signal: RANK and OGG (by osteoblast)

Terminology

Osteoporosis is a chronic, progressive, multifactorial skeletal disease. Decreased bone mineral density BMD or bone mass loss (brittle bones).

Osteoporosis: Treatment drugs: bisphosphonates, RANKLinhibitors, * estrogens / androgens ( All are antiresorptives → reduce bone resorption)

secondary osteoporosis caused by prologed use of medications (glucocorticoids, loop diuretics, proton pump inhibitors). Inadequate bone mineralization. called rickets in children. called osteomalacia (soft bones) in adults.

Renal osteoporosis: Cronic renal disase (GFR<30) → bad vitaminD/Ca absorbtion (hypocalcaemia). → Bone demineralization → Decreased Ca levels causes increased phosphate levels (hyperphosphatemia)

Bisphosphonates (BP): BPbinds to bone hydroxyapatite crystals and inhibits bone resorption. In combination with calcium, BP provides sustained osteoclast inhibition and apoptosis

PTH FORM BONES: Calcitrol, Teriparatide
Reduce bone broken down and reabsorbed: alendronic/zolendronic acid, Denosumab

Alendronic acid, Zoledronic acid

Bisphosphonates

Anti BONE reabsorbtive (less bone is reabsorbed)

Drug combination:
NSAID → GIT irritation
antacids → intefere absorption

weekly, take in morning 30 min before first meal with water, have to be vertical (cause GI trackt irritation)

Indication: osteoprosis (postmenopause, andropause)
bone tumor metastases (oncogenic hypercalcaemia)
secondary osteoporosis (glucocorticoid indused osteoporisis)

SE: hypocalcaemia (arrhythmia, neurological symptoms seizures, tetany)

Denosumab

RANKLinhibitors

(suppresses osteoclast formation) (osteoclast break down bone)

Indication: osteoprosis (postmenopause, andropause)
bone tumor metastases (oncogenic hypercalcaemia)
secondary osteoporosis (glucocorticoid indused osteoporisis)

SE: hypocalcaemia (arrhythmia, neurological symptoms seizures, tetany)

Teriparatide

Osteoanabolic agents
parathyroid hormone (PTH) analogues/agonist

promote bone formation

Indication:
Severe osteoporosis (in post-menopause, andropause)
Secondary osteoporosis (glucocorticoid-induced osteoporosis)

Contraindicaiton: hypercalcemia

Calcitriol

Active vitamin D form. non selective intracellular vitamin D receptor agonist

Regulates bone mineralization/orestoclast differentiation/Ca & phosphate homeostasis
reducaes PTH synthesis

↑ Ca2+and↑PO4 absorption

Indication: Prevents rickets (secondary osteoporosis in children), osteoporosis, renal osterodystorphy, hypocalcaemia

Side effect: hypercalcaemia, calcification of organs

Precursor of Vitamin D (Ergocalciferol, Cholecalciferol)

Cinacalcet

Allosteric modulator of Calcium sensitive receptor for parathyroid cells (CaSR). By increasing the sensitivity of CaSR to extracellular Ca2+, decreases PTH secretion- an antiparathyroid agent

Antisecretory action

Indication: Primary and secondary hyperparathyroidism

SE: hypocalcaemia