Thyroid and antithyroid drugs. Hypothalamic and pituitary hormones Flashcards
Hyperthyreosis (symptoms and Causes)
- Symptoms • Subjective symtoms: nervosity, anxiety, insomnia, tremor, palpitations, heat intolerance, increased GI motility • Objective symptoms: weight loss, increased glucose, tachiarrhythmias, hair loss, cholesterin reduced, wet and warm skin; in case of Basedow: exophtalmus, pretibial edemas 2. Causes Immunological (Graves’ disease) • TSH-receptor-antibodies stimulate the thyroid gland Multinodular goiter (Thyroid adenoma) • nodules grow up and secrete thyroid hormone autonomously Hypersecretion of thyroid stimulating hormone • pituitary adenoma, T3-resistent Thyroid cancer (rare)
Tx of Hyperthyeosis
- Thyrostatics -Thioamides : inhibitors of peroxidase enzyme - Inhibitors of iodine uptake - Iodine (high dose) : Inhibition of release of thyroid hormones 2. Surgery 3. Radioiodine
2 Thioamides
Thiamazol (methimazol) (A12) Propylthiouracil (PTU) (A12)
Thioamides Mode of action
-Blockade of Thyroid-Peroxidase (both functions) -onset - 1-4 weeks (first the previously synthesized hormones will be released)
Thioamides Pharmacokinetics
– metabolism: oxidation and glucuronid conjugation – half life of thiamazol: 4-6 h, but duration of action: 24 h – half life of propylthiouracil: 2 h, - 6x daily – all cross the placenta, propylthiouracil has lower amount in breast milk
Thioamides Adverse effect
- maculopapular pruritic rash, fever – agranulocytosis, (leukopenia) – usually first 2-6 weeks – allergy – hypothyreosis
Iodine treatment in case of hypertyreosis
- Iodine in high dose (>5mg/d) inhibits the organification, the release of T4 and T3. (mechanism of action is not clear)
- onset: 24 h. max.: 10-15 d; after that gradual decrease in the effects • Radioiodine therapy • 131I – β emission
- selective uptake into the thyroid gland • treatment of Graves’ disease, adenomas and iodine storing cancers
- adverse effect: hypotyreosis (80%) • duration of the treatment: 5-14 d, onset: 10-12 weeks • contraindications: children, pregnancy
Hypothyreosis (symptoms and Causes)
- Causes Immuntyreoditis (Hashimoto), postoperative, drug-induced 2. Subjective symptoms disabilty, weakness, lethargy, devolution, fatigue, feeling cold, poor memory, constipation less frequently: mental depression, weight gain, cardiac problems, hair loss, poor appetite, joint pain 3. Objective symptoms dry skin, hoarseness, slow speech, dry and rough hair, bradycardia, delayed relaxation of tendon reflexes less frequently: swelling of the tongue, cardiomegaly, hypertension, myxedema
Thyroid hormones used in case of hypothyroidism
Levothyroxine (T4) (A12) Liothyronine (T3) (Not in the list) Iodine (A12)
Levothyroxine (T4) (A12)
- Oral, IV - Converted to T3 in target cells, liver, kidneys - Maximum effect is seen after 6-8 weeks of therapy - Hypothyroidism -Side effects: symptoms of thyroid excess
Liothyronine (T3) (Not in the list)
- Oral, IV - 10X more potent than T4 - Hypothyroidism; used in case of deiodinase enzyme deficiency (T4 cannot be converted to T3) -Side effects: symptoms of thyroid excess
Iodine (A12)
- Essential mineral nutrient, intake with diet - Daily requirement 150 μg - Iodine salt preparation (KI) for replacement therapy - Oral - Dietary iodine deficiency (endemic goiter) - Thyrotoxicosis crisis (high dose suppresses the gland) -Side effects: cutaneous and mucus membrane irritation, allergic reaction, hypo-/hyper- thyroiditis
Propylthiouracil (PTU) (A12)
- Oral - Duration of action 6-8 h’ - Requires 3-4 weeks for onset of activity (delayed action since the release of preformed thyroid hormones is not affected) - Hyperthyroidism - Used during pregnancy and lactation -Side effects: skin rash, nausea, vasculitis, agranulocytosis, liver dysfunction, hypothyroidism, drug-induced lupus
Thiamazol (methimazol) (A12)
- Oral - Duration of action 24 h’ - Requires 3-4 weeks for onset of activity (delayed action since the release of preformed thyroid hormones is not affected) - No effect on deiodinase enzyme - Hyperthyroidism - Preferred generally (administered once per day) -Side effects: skin rash, nausea, vasculitis, agranulocytosis, liver dysfunction, hypothyroidism, drug-induced lupus, teratogenic
Thyrotoxic crisis (thyroid storm)
Rare condition, presents as a life-threatening exacerbation of hyperthyroidism, accompanied by fever, delirium, seizures, coma, vomiting, diarrhea, and jaundice. Mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as 30%, even with treatment.
Thyrotoxic crisis is usually precipitated by acute illness (stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.
Management:
- PTU or methimazole (IV bolus, high dose)
- Potassium-iodide solution (IV)
- β-blockers to control tachycardia and adrenergic symptoms (IV)
- Glucocorticoids to control ophthalmopathy (IV)
Myxedema coma
Rare condition, life-threatening exacerbation of hypothyroidism.
Presentation:
- Hypothermia
- Hypoglycemia
- Hypotension
- Altered mental status
Management:
- Thyroid hormones (IV)
- Glucocorticoids (pituitary-adrenal axis is impaired in severe hypothyroidism)
- Supportive management
- Elimination of triggering event (if possible)
Hormones releasing from Anterior pituitary
- Growth hormone (GH)
Controls growth and glucose metabolism
Mediated via the somatomedins - ACTH
Acts on the adrenal gland to stimulate the release of cortisol - Gonadotropins
Luteinizing hormone ( ovulation, secretion of sex hormones
Follicle stimulating hormone ( development of follicles
and sperm cells - Prolactin stimulates breasts to develop milk
- TSH
- Melanocyte stimulating hormone
Enhances synthesis of melanin
All the anterior pituitary hormones are under the control of a
hypothalamic hormone , and with the exception of prolactin
Hormones releasing from Posterior pituitary
- Antidiuretic hormone (vasopressin)
Causes the retention of fluid in the urine
Combats dehydration - Oxytocin
•Causes lactation
•Contractions during child birth
2 Growth Hormone (GH) (not in the list)
- Somatropin (somatotropin)
- Recombinant form of human GH
- Subcutaneous injection
- GH deficiency – dwarfism (genetic, developmental, acquired)
- Increased final adult height in children with conditions associated with short stature (Prader-Willi syndrome, Turner syndrome)
- Idiopathic short stature
- AIDS-associated wasting
- Malabsorption syndromes in patients who have undergone bowel intestinal resection
Side effects: pseudotumor cerebri, slipped capital femoral epiphysis, edema, hyperglycemia, scoliosis, risk of asphyxia in severely obese patients with Prader-Willi syndrome and upper airway obstruction or sleep apnea
- Asellacrin
- human GH, is available for parenteral use (IM).
- Side effects : diabetes, antibodies againts the drug
2 GH antagonists (1 in the list)
Octreotide (A12) , Lanreotid (not in the list)
Inhibit the release of GH, insulin, glucagon, gastrin
- Parenteral administration
- Regular formulation – inject 2-4 times daily
- Slow-release formulation – inject every 4 w’
Indications
- Acromegaly (pituitary adenoma), gigantism
- Endocrine tumors (carcinoid, gastrinoma, glucagonoma, insulinoma, VIPoma)
- Control of bleeding from esophageal varices
Side effects: GI disturbances, steatorrhea (due to impaired pancreatic secretion), gall stone, cardiac conduction abnormalities
2 Hyperprolactinemia treatment drugs
Bromocriptin (A12) , Cabergoline (not in the list)
Dopamine D2 receptor agonist
- Suppresses pituitary secretion of prolactin and GH (to lesser extent)
- Oral
- Indications : hyperprolactinemia , Parkinson disease, stop of lactation
- Acromegaly (effective only in high doses)
Side effects : nausea, vomiting, dizziness, neuropsychiatric symptoms
Adrenocorticotrop hormone (ACTH, corticotropin)
-Main actions
- mineralocorticoids, glucocorticoids , androgen
- Cortisol changes according to circadian rhythms
- Side effects: allergy, salt and water retention
corticotrophin (ACTH) analogue
Tetracosactrin (Not in the list)
-synthetic, less allergy, long term application, cortisol
effects
-Diagnostic purpose: differentiation of Cushing syndrome and increased
ACTH synthesis
-Parenteral administration
Follicle Stimulating Hormone: (FSH)
Mode of Action
- Interacts with specific receptors (present in the
plasma membrane of ovaries and testes). - Released during the follicular phase of the menstrual
cycle and is required for the proper development of
the ovarian follicles. - In males is responsible for the maturation of the
germinal elements of the testis and stimulates
spermatogenesis
Luteinizing Hormone : (LH)
Mode of Action
- In females, LH is required to stimulate oestrogen
production and for the production of progesterone by
the corpus luteum of the ovary and is essential for
ovulation - Very similar to hCG produced in placanta
- In males, more precisely called interstitial cell
stimulating hormone Leydig cells stimulates
testosterone biosynthesis
hMG (Gestyl)
Human menopausal gonadotropin (HMG) is isolated from the urine of
postmenopausal women. It is rich in LH and FSH.
- Uses: Used to treat infertility in women who fail to ovulate despite the
presence of potentially functional ovaries.
- -Dose: 75 IU is given parenterally for 9 -12 consecutive days to stimulate
ovarian follicular growth and to prime the ovaries to ensure responsiveness
to the subsequent administration of Human Chorionic Gonadotrophin
- (hCG) which exhibit biological activity similar to that of hCG
hCG (Pregnyl)
HCG is a hormone produced by human placenta and excreted in the urine of
pregnant women.
Uses:
- For the induction of ovulation when injected after priming of ovaries with
HMG. - To stimulate descent of the testis in male patients with cryptorchidism in
whom no anatomical obstruction. - Hypogonadism that is secondary to pituitary failure.
Oxytocin (A12)
Oxytocin receptor agonist
- IV
- Induction and augmentation of labor
- Control of uterine hemorrhage after delivery
Side effects: fetal distress, placental abruption, uterine rupture, fluid retention, hypotension
Desmopressin (A12)
–V 1 Gq ) VSMC → vasoconstriction
–V 2 Gs ) renal tubule → ↑ water resorbtion
- Synthetic analogue of ADH (peptide)
- Prolonged half-life and duration of action compared to endogenous ADH
- IV, intranasal, oral, subcutaneous
- Central diabetic insipidus
- Hemophilia A – factor VIII deficiency
- Von-Willebrand disease
Side effects: GI disturbances, headache, hyponatremia, allergic reaction
Drugs affecting ADH hormone antagonists
- Lithium (A31)
- Tolvaptan (B23)
competitive vasopressin receptor 2
(V2) antagonist
Indications:
Hyponatremia
Syndrome of in appropiate ADH
secretion
