12. Thyroid and antithyroid drugs. Hypothalamic and pituitary hormones Flashcards
Growth hormone analogue
not on the list
Somatropin (GH)
Mecasermin (IGF-1)-> recombinant
GH antagonist
Somatostatin analogue:
Ocreotide
(Leutrotide)
-inhibtis GH, insulin, glucagon, gastrin release
Receptor antagonist:
(Pegvisomant)
FSH and LH analogues
not on the list
- follitropin-alpha - recombinant form of FSH
- Menotropin -> FSH and LH, infertility men
- human chorionic gonadotropin (hCG) -> agonist of LH-receptor
- Lutropin -> recombinant LH
GnRH analogue
Goserelin
(leuprorelin)
intermittend application: FSH++, LH++
long application: FSH–, LH–
GnRH antagonist
Degarelix
Ganirelix
Prolactin
Dopamine-Receptor2 agonist:
Bromocriptine
- suppresses PL and GH (less)
(Cabergoline)
controlled ovulation
- Inhibit endogenous FSH and LH
GnRH agonist, Goserelin
or antagonist, degarelix - FSH, follicular development
(follitropin alpha) - LH, final oocyte development
(hCG or Lutropin)
Posterior pituitary hormones
oxytocin - agonist
oxytocin-receptor antagonist: (Atosiban)
Vasopressin:
V2-agonist: Desmopressin (Centeal diabetes insipidus)
V1+2-agonist: Vasopressin
V1+2-antagonist: (Conivaptan)- Syndrom of inappropriate ADH secretion (SIADH)
Hypothyroidism therapy
levothyroxine (T4)
(liothyronine (T3)) -> deionidase enzyme deficiency
Iodine (thyrotoxicosis + dietery insufficiency)
Antithyroid drugs (hyperthyroidism therapy)
Thioamines:
- inhibits thyroid peroxidase+ inhibits deiodinaseenzyme in periphery
1. Propylthiouracil (PTU), may cause lupus, vasculitis agranulocytosis
(2. Methimazole) -> (aplasia cutis), teratogenic, lupus, vasculitis agranulocytosis
(thiamazole?)
Iodide salts: - inhibits tyrosine iodination+ thyroid hormone release, reduces size and vascularity (Lugal solution) (Potassium iodide) -thyroid storm, thyroidectomy
Radioactive iodine: I131- hyperthyroidism (destruction by radiation)
Anion inhibitors:
- competitive inhibitors for iodine transport- reduce Iodine uptake
(1. Thiocyanate)
(2. Perchlorate) - iodine induced Hyperthyroidism
ß-blocker:
inhibit peripheral conversion (deiodinase enzyme)
Propanolol- control thyroid storm , tachycardia, other cardiac abnormalities
Corticosteroids: Hydrocortisone Methylprednisolone - inhibits deiodinase enzyme - Thyroid storm -baselow eyes -control opthalmopathy
Somatropin (somatotropin)
GH analogue
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
Mecasermin
not on the list
GH analogue
Recombinant form of human IGF-1
- Subcutaneous injection
- Replacement therapy in IGF-I deficiency
- Growth retardation in patients not responsive to
exogenous GH (ex. Laron dwarfism)
Side effects:
hypoglycemia,
intracranial hypertension, increased liver enzymes
- Octreotide
GH release inhibitor
Somatostatin analogues
(- Lantreotide)
Inhibit the release of GH, insulin, glucagon, gastrin
- Parenteral administration
- Regular formulation – inject 2-4 times daily
- Slow-release formulation – inject every 4 w’
- 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
Pegvisomant
not on the list
GH receptor antagonist
- Subcutaneous injections
- Long-acting
- Acromegaly
Side effects: increased liver enzymes
Follitropin-α
not on the list
Recombinant form of human FSH
- Parenteral
- Controlled ovarian stimulation
(induce follicle development – 2nd stage) - Male infertility
Side effects: ovarian hyperstimulation syndrome, multiple pregnancies in women, gynecomastia in men, headache, depression, edema in both sexes
Menotropin
not on the list
FSH and LH activity
- Parenteral
- Extract of the urine of postmenopausal
women - Male infertility
Human chorionic gonadotropin (hCG)
not on the list
Agonist of LH receptors
- Parenteral
- Controlled ovarian stimulation (3rd stage - oocyte maturation)
- Male infertility
Side effects: ovarian hyperstimulation syndrome, headache, depression, edema
Lutropin
not on the list
Recombinant form of human LH
- Parenteral
- Controlled ovarian stimulation (3rd stage - oocyte maturation)
- Male infertility
Side effects: ovarian hyperstimulation syndrome, headache, depression, edema
Goserelin
Leuprolide
Synthetic peptide with GnRH agonist activity
- Parenteral
- Long-acting
- Increased LH and FSH secretion with
intermittent administration; reduced LH and FSH secretion with prolonged continuous administration - Ovarian suppression in women undergoing controlled ovulation induction (1st stage)
- Ovarian suppression in endometriosis, leiomyoma
- Central precocious puberty
- Blockade of endogenous puberty in transgender or
gender-variant early pubertal adolescents - Advanced prostate cancer
Side effects: headache, nausea, injection site reactions, symptoms of hypogonadism with continuous treatment
Degarelix
Ganirelix
GnRH antagonists
- Parenteral
Degarelix:
- Advanced prostate cancer
Side effects:
nausea,
headache
Ganirelix:
- Ovarian suppression in women undergoing controlled ovulation induction (1st stage)
Side effects:
nausea,
headache
Degarelix:
- Advanced prostate cancer
Side effects:
nausea,
headache
Bromocriptine
Dopamine D2 receptor agonist
(Cabergoline)
- Suppresses pituitary secretion of prolactin and GH (to lesser extent)
- Oral
- Prolactin-secreting adenoma
- Acromegaly (effective only in high doses)
Side effects:
GI disturbances,
orthostatic hypotension, headache,
psychiatric disturbances, vasospasm and pulmonary infiltrates in high doses
Oxytocin
Posterior pituitary hormone
Oxytocin
Mediates uterine contraction via activation of oxytocin receptors (OXTR) – Gq-coupled mechanism
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
Atosiban
Oxytocin receptor antagonist
- IV
- Not approved in all countries
- Tocolytic agent (relax uterine contraction, suppress preterm labor)
Side effects:
increased rates of infant death
Vasopressin
V1, V2 agonist
- Peptide hormone
- IV, intranasal, oral, subcutaneous
- Control bleeding due to esophageal varices or colon diverticula (effect on V1 receptors → vasoconstriction)
- Central diabetic insipidus (effect on V2 receptors)
Desmopressin
Selective V2 agonist
- 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
Conivaptan
not on the list
V1, V2 antagonist
- IV
- SIADH
- Offset fluid retention (hyponatremia or heart failure)
Side effects:
infusion site reaction, osmotic demyelination syndrome due to rapid Na+ correction
Levothyroxine
Levothyroxine (T4)
Synthetic thyroid hormones, used in the management of hypothyroidism.
- Activation of nuclear receptors results in gene expression, RNA formation, protein synthesis and subsequent physiological response
- 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 on 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
- 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)
Antithyroid drugs
Used in the management of thyroid gland hyperactivity.
Thioamides
- Inhibit thyroid peroxidase activity
- Inhibit peripheral conversion of T4 to T3 (deiodinase enzymes)
- 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
Methimazole
not on the list
Antithyroid drugs
Used in the management of thyroid gland hyperactivity.
Thioamides
- Inhibit thyroid peroxidase activity
- Inhibit peripheral conversion of T4 to T3 (deiodinase enzymes)
- 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 daily)
Side effects:
skin rash,
nausea,
vasculitis,
agranulocytosis,
liver dysfunction,
hypothyroidism,
drug-induced lupus,
teratogenic ('aplasia cutis')
Iodide salts
not on the list
- Inhibit tyrosine iodination
- Inhibit thyroid hormone release
- Reduce the size and vascularity of hyperplastic thyroid gland
Lugol’s solution
(iodine + potassium iodide)
Potassium iodide
(saturated solution)
- Oral
- Onset of action within 2-7 days
- Effect may be transient (the gland may “escape” the iodide blockage
after several weeks of treatment) - Thyroid storm
- Preparation for surgical thyroidectomy
- Toxicity is generally rare
Radioactive iodine
not on the list
- Radiation-induced destruction of thyroid parenchyma
I131
- Oral
- Not to be used during pregnancy and lactation
- Hyperthyroidism
Side effects:
pharyngitis,
hypothyroidism
Anion inhibitors
- Competitive inhibitors of iodide transporter – reduce the uptake of iodide by the thyroid gland
Thiocyanate (SCN-)
Perchlorate (ClO4-)
- Unpredictable effect
- Rarely used clinically
- Iodide-induced hyperthyroidism
Side effects: aplastic anemia
β-blockers
- Inhibit peripheral conversion of T4 to T3 (deiodinase enzymes)
- Control the tachycardia and other cardiac abnormalities of severe thyrotoxicosis
Propranolol
- Oral
- Rapid onset of activity
- Thyroid storm
Side effects: bronchospasm, AV block, hypotension, bradycardia
Corticosteroids
- Inhibit peripheral conversion of T4 to T3 (deiodinase enzymes)
- Control thyroid ophthalmopathy (seen with Graves’ disease)
Hydrocortisone Methylprednisolone
- Oral or parenteral
- Moderate to severe thyroid ophthalmopathy
- Thyroid storm
Thyrotoxic crisis (thyroid storm)
Rare condition, presents as a life-threatening exacerbation of hyperthyroidism, accompanied by: 1. fever, 2. delirium, 3. seizures, 4. coma, 5. vomiting, 6. diarrhea, and 7. 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)
1st line:
Propanolol
Propylthiouracil or methimazole
hydrocortisone
2nd line
Potassium-iodide solution (IV), Lugol solution or sodium iodide
Lithium carbonate
L-Carnitine
support therapy:
- depolarising electrolyte solution
- Paracetamol
- Phenobarbital
- Furosemide and ACE-inhibitors in case of cardiac failure
selected cases:
- assisted mechanical ventilation case of hypoxemia
- cooled mattresses and cold blankets in case of hyperthermia (if body temperature > 40°C)
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)
