Posterior Pituitary Hormones: Dr

Posterior pituitary hormones: Dr. Entisar Al-Mukhtar

 Vasopressin & oxytocin, they are not regulated by RHs.  Synthesized in the hypothalamus, transported to Hormones of the Posterior the posterior pituitary & released in response to Pituitary high plasma osmolarity or parturition. Desmopressin DDAVP Oxytocin PITOCIN  Both Hs are susceptible to proteolytic cleavage. Vasopressin (ADH) PITRESSIN  Given IV & have very short half-lives. Drugs Affecting the Thyroid Iodine and potassium iodide Oxytocin LUGOL’S SOLUTION  Extracted from animal posterior pituitaries. Liothyronine CYTOMEL Levothyroxine LEVOXYL,  stimulate uterine contraction to induce or SYNTHROID reinforce labor. Methimazole TAPAZOLE  Given as IV injection for labor induction & as Propylthiouracil (PTU) nasal spray to induce milk ejection. Liotrix THYROLAR  HT, uterine rupture, water retention, & fetal death have been reported. Note: Oxytocin is contraindicated in abnormal fetal presentation, fetal distress, and premature births.  Its antidiuretic & pressor activities are very much lower than vasopressin.

Vasopressin (antidiuretic hormone"ADH")  Structurally related to oxytocin.  Has both antidiuretic & vasopressor effects.  Binds to the V2 receptor in the kidney, increasing water reabsorption.  Its major use is to treat diabetes insipidus.  Also used in the management of cardiac arrest & in controlling bleeding due to esophageal varices.  Other effects of vasopressin are mediated by the V1 receptor, which is found in liver, vascular smooth muscle (causing constriction), & other tissues. Major toxicities are water intoxication & hyponatremia. Abdominal pain, tremor, and vertigo can also occur.  Used cautiously in patients with coronary artery disease, epilepsy & asthma.

Desmopressin  A modified vasopressin, that has minimal activity at the V1 receptor, thus it is largely free of pressor effect.  Preferred for diabetes insipidus & nocturnal enuresis. 1

 It is longer-acting than vasopressin.  Administered intranasally or orally. [Note: nasal spray should not be used for enuresis due to reports of seizures in children using this formulation.].  Local irritation may occur with nasal spray.

Thyroid Hormones (THs)  Thyroid gland facilitates normal growth & maturation by maintaining a level of metabolism in the tissues that is optimal for their normal function.  THs include →Triiodothyronine (T3; the most active form) & thyroxine (T4).  inadequate secretion of THs (hypothyroidism) results in bradycardia, poor resistance to cold & mental & physical slowing (can cause mental retardation and dwarfism in children. Whereas excess secretion of THs (hyperthyroidism) can cause tachycardia & cardiac arrhythmias, body wasting, nervousness, tremor & heat intolerance. Thyroid hormone synthesis and secretion The thyroid gland is made up of multiple follicles that consist of a single layer of epithelial cells surrounding a lumen filled with thyroglobulin (storage form of TH).

 Thyroid function is controlled by TSH ( thyrotropin), TSH generation is governed by the hypothalamic TRH  cAMP mediates TSH action & stimulates iodide (I–) uptake. The peroxidase oxides I– to iodine (I2) this step followed by iodination of tyrosines on thyroglobulin (Abs against thyroid peroxidase are diagnostic for Hashimoto thyroiditis).  Condensation of two diiodotyrosine residues results in T4, whereas condensation of a monoiodotyrosine residue with a diiodotyrosine residue generates T3.  By proteolytic cleavage of the thyroglobulin THs are released. Mechanism of action  Both T4 & T3 must dissociate from thyroxine-binding globulin (TBG) prior to entry into cells.  In the cell, by deiodinases T4 is deiodinated to T3, which enters the nucleus & attaches to & activates specific receptors, promoting the formation of RNA & subsequent protein synthesis, which is responsible for T4 effects.

Pharmacokinetics  Both THs are well absorbed given orally. Food, Ca & AL (in antacids) can decrease the absorption of T4 (but not of T3). Hypothyroidism  Usually results from autoimmune destruction of the gland or the peroxidase & is diagnosed by elevated TSH.  It is treated with levothyroxine (T4), which is given once daily (long half-life). Steady state is achieved in 6 to 8 weeks.  As T4 is better tolerated and has a longer half-life than T3 preparations [ T3 (liothyronine) or T3/T4 combination products (liotrix)] thus, it’s the preferred.  Toxicity is directly related to T4 levels, results in nervousness, heart palpitations & tachycardia, heat intolerance & unexplained weight loss.  Phenytoin, rifampin & Phenobarbital accelerate metabolism of the THs.

Hyperthyroidism (thyrotoxicosis)  Associated with a number of disease states, including Graves disease, toxic adenoma, and goiter.  TSH levels are reduced (due to negative feedback).  Hyperthyroidism is treated by decrease the synthesis and/or release of additional hormone either by (1) removing part or all of the thyroid gland (2) inhibiting THs synthesis (3) blocking THs release. 1. Removal of part or all of the thyroid:  Either surgically or by using radioactive iodine (131I).

 Younger patients are treated with the isotope without prior pretreatment with methimazole, which should be given to elderly patients.  Most patients become hypothyroid and require treatment with levothyroxine.

2. Inhibition of TH synthesis:  Propylthiouracil (PTU) & methimazole are thioamides, they concentrated in the thyroid & inhibit both oxidative processes (essential for iodination of tyrosyl groups) & condensation (coupling) of iodotyrosines to form T3 & T4.  PTU can blocks the conversion of T4 to T3.  Note: Since thioamides affect synthesis rather than release of THs, their clinical effects may be delayed (3–4weeks) until thyroglobulin stores are depleted.  Comparing to PTU, methimazole has a longer half-life (once-daily dosing) and a lower incidence of adverse effects. However, PTU is recommended during the first trimester of pregnancy due to a greater risk of teratogenic effects with methimazole.  PTU has been associated with hepatotoxicity and, rarely, agranulocytosis.

3. Blockade of TH release:  A pharmacologic dose of iodide inhibits the iodination of tyrosines (“acute Wolff- Chaikoff effect”), but this effect lasts only a few days.  The more important effect of iodide is the inhibition of THs release from thyroglobulin (mechanisms not yet understood).  Today, iodide is rarely used as the sole therapy. However, it is employed to treat potentially fatal thyrotoxic crisis (thyroid storm) or prior to surgery, (decreases the vascularity of the thyroid gland).  Iodide is not useful for long-term therapy, because the thyroid ceases to respond to the drug after a few weeks.  Iodide is administered orally.  Adverse effects → sore mouth & throat, swelling of the tongue or larynx, rashes, mucous membranes ulcerations & metallic taste. Thyroid storm: Treated as hyperthyroidism, but with higher doses & more frequently.  Β-blockers lacking sympathomimetic activity eg. metoprolol or propranolol are effective in blunting the widespread sympathetic stimulation.  Diltiazem is an alternative to β -blockers in patients with severe HF or asthma.  Other agents include PTU, iodides, iodinated contrast media (which rapidly inhibits the conversion of T4 to T3) & glucocorticoids (to protect against shock).