January 27, 2023


Pharmacology of drugs used in treatment   of pituitary and thyroid disorders, so let’s get  right into it. joined at the base of the brain,   the key players in the endocrine system.   “the master gland” due to its function to control  the secretion or inhibition of hormones.   hormones are the most potent chemical

Messengers  in our bodies, telling the body what to do and   when. that’s why imbalanced or poorly functioning  hormones can cause a variety of medical problems.   now, the “master” pituitary gland consists of an  anterior lobe, which contains specialized cells   that produce and secrete hormones in response  to

Hormones released from the hypothalamus,   neuronal projections extending from the   so as you can see, hypothalamic hormones  can be broadly classified into two groups.   that act on the anterior pituitary gland   such as thyrotropin-releasing hormone (trh)   that stimulates specialized endocrine cells called 

Thyrotrophs (t) to release thyroid stimulating   hormone (tsh), which in turn stimulates thyroid  gland to produce and release thyroid hormones;   the next one is gonadotropin-releasing hormone  (gnrh) that stimulates gonadotrophs (g) to   release follicle-stimulating hormone (fsh) and  luteinizing hormone (lh), which in turn

Stimulate   the reproductive functioning of the ovaries and  testes; the next one is corticotropin-releasing   hormone (crh) that stimulates corticotrophs (c) to  release adrenocorticotropic hormone (acth), which   produce and secrete certain steroid hormones;   the next one is growth hormone-releasing hormone  (ghrh)

That stimulates somatotrophs (s) to release   growth hormone (gh), which in turn stimulates  the liver and other tissues to produce growth   stimulants called insulin-like growth factors;  and lastly we have two inhibiting hormones   that is growth hormone-inhibiting hormone (ghih),  which inhibits somatotrophic cell release

Of   growth hormone, and prolactin-inhibiting hormone  (pih), which is simply the neurotransmitter   now, moving on to the second group  transported down the axons of the same neurons  that synthesize them to the posterior pituitary   from where they’re released into the circulation.  which acts primarily on the kidney

To regulate  water balance in the body; and oxytocin, which   all right, so as you can see, hormones produced   a crucial role in regulating metabolism,   of that, many drugs have been developed   order to treat various endocrine disorders.   so, now let’s take a closer look at how these  drugs work to produce

Their therapeutic effects,   to gain better understanding of the mechanism   the mechanism by which thyroid hormones are   is the functional unit of thyroid gland.   intrafollicular colloid and follicular cells,   production of thyroid hormones. the recipe for   making thyroid hormones calls for two principle 

Called thyroglobulin, which is synthesized in the  rough endoplasmic reticulum of follicular cell,   and then is secreted into the colloid; the second  ingredient is an iodide, which is actively pumped   into the cell by sodium-iodide symporter, and  then is passively transported into the colloid   along with thyroglobulin. in

The colloid, with  the help of an enzyme called thyroid peroxidase,   iodide (i-) is oxidized to iodine (i0) and hormone  synthesis begins with the addition of iodine   molecules in a process called iodination.   and the entire complex re-enters the follicular  cell. back inside the cell, proteolytic enzymes   thyroid

Molecules, thyroxine known as t4   where they quickly bind to carrier  now, free extracellular t4 and t3 enter the  target cell through transporter proteins. once   has greater biological activity than t4,   2 abbreviated d1 and d2 that catalyze the   intracellular levels of the active hormone.   as d3) serves to

Inactivate t4 by converting   therefore limiting the amount of t4 that can   be used to form t3. in the final step, t3 moves  to the nucleus and binds to the thyroid hormone   with the retinoid x receptor (rxr) to induce   transcription of target genes known as thyroid  response elements. this leads to synthesis of  

Now, the drugs used in treatment of thyroid  disorders can be generally divided into two   treat the condition in which there is inadequate   hypothyroidism. medications used to treat   is a synthetic version of t4, liothyronine,   which is a synthetic combination of t4 and t3,   natural thyroid hormone prepared from

Dried   now, moving on to the second group that includes   there is overproduction of thyroid hormones,   known as hyperthyroidism. medications used to  treat hyperthyroidism include propylthiouracil   thyroid peroxidase that is required for   coupling of iodotyrosines in thyroglobulin   propylthiouracil also

Inhibits deiodinase 1  all right, now that we discussed drugs  move on to our next pharmacological target that is  gonadotropin-releasing hormone receptor (gnrhr).   so, the hypothalamic hormone, gnrh, is released  and transported to the anterior pituitary   receptors expressed by the pituitary gonadotrophs.   under various

Physiological conditions,   and fsh. in order to modulate the gnrh effects  for therapeutic purposes, a number of gnrh analogs   or upregulate the secretion of lh and fsh.   are more potent and have longer half-life  than natural gnrh. they produce an initial   results in increased secretion of lh and fsh,   followed

By downregulation and inhibition of the  pituitary-gonadal axis. in comparison to gnrh   agonists, gnrh antagonists such as degarelix,  elagolix, ganirelix and cetrorelix promptly   suppress pituitary gonadotropin by competitively  blocking gnrh-receptor, thereby avoiding the   initial stimulatory phase of the agonists. the 

Resulting suppression of lh and fsh in turn leads   to profound inhibition of estrogen and androgen  synthesis, which makes these agents effective   on the other hand, the deficiency of both lh  and fsh as a result of hypothalamic or pituitary   disease can cause infertility or subfertility both  in men and women. to address

This problem, variety   of pharmaceutical preparations of lh and fsh have  been developed to stimulate spermatogenesis in men   and to induce follicle development and ovulation  in women. these preparations include menotropins,   which consist of a purified mixture of lh and fsh;  urofollitropin, which is a purified form of

Human   fsh; follitropin, which is a form of recombinant  human fsh; lutropin, which is a recombinant   form of human lh; and choriogonadotropin alfa,  which is a recombinant form of human chorionic   produced by the placenta during pregnancy   that shares structural similarities with lh and  thus binds to and activates

The same receptor.  all right, moving on to our next pharmacological  so, the main action of adrenocorticotropic hormone  (acth) on the adrenal cortex is to stimulate the   androgen hormones. specifically, inside the   cells of the adrenal cortex, stimulation by acth  activates cholesterol side-chain cleavage enzyme,   the

Precursor of all adrenocortical hormones  including mineralocorticoids, glucocorticoids,   diseases affecting adrenal gland can be divided   into disorders of hormone deficiency and disorders  of hormone excess. addison’s disease is the   classic example of adrenocortical insufficiency  characterized by inadequate secretion of

Cortisol,   for adrenocortical insufficiency involves   replacing the missing hormone aldosterone with  the synthetic analog such as fludrocortisone,   synthetic analogs such as hydrocortisone or   prednisone. on the other hand, cushing’s syndrome  is the example of excessive cortisol production.   involves either

Stopping corticosteroid   adrenal tumor is identified, medications such as   ketoconazole, mitotane and metyrapone can be used  to inhibit enzymes involved in cortisol synthesis.  also called somatotropin. so, growth is a very  complex process that requires coordinated action   of several hormones. growth hormone, although 

It has largely indirect effect on growth,   the growth process. the pituitary secretes   growth hormone in response to the hypothalamus  releasing growth-hormone releasing hormone and   the stomach releasing ghrelin. the major role of  the growth hormone in stimulating body growth is   secrete insulin-like growth factor-1

(Igf-1).   cartilage cells, resulting in bone growth, as   well as formation of new proteins particularly in  skeletal muscle cells, resulting in muscle growth.   directly bind to its receptors on target cells   such as fat cells, causing them to break down  triglycerides and suppresses their ability   now,

Deficiency in growth hormone can lead to   developmental disorders such as growth retardation  or dwarfism. to treat these disorders, a synthetic   somatotropin can be injected into the body to  compensate for insufficient levels of growth   hormone. in addition to that, pediatric patients  with growth failure and severe igf-1

Deficiency   somatotropin, can be treated with a recombinant   human igf-1 product called mecasermin. now, the  body’s primary mechanism of regulating growth   hormone is to release growth hormone-inhibiting  hormone also known as somatostatin. somatostatin   secreted from the hypothalamus simply inhibits  the pituitary

Gland’s secretion of growth hormone.   secretion, which can lead to gigantism in   forms of somatostatin can be used to reduce   such agents are octreotide and lanreotide,   which work by binding to somatostatin receptors  located on the surface of different cell types   now let’s move on to discussing drugs that 

Affect prolactin secretion. so, the secretion   of prolactin is regulated by dopamine, which is  secreted by hypothalamic dopaminergic neurons   into the anterior pituitary via portal vessel.  dopamine that is released by these neurons   causing inhibition of prolactin secretion.   include either insufficient prolactin

Levels,   excessive prolactin levels, which results   in galactorrhea and infertility. two types of  drugs can be used to treat these disorders.   antagonist such as metoclopramide, which works   by blocking d2 receptors from being stimulated,  thereby increasing prolactin secretion. the second   type includes

Dopamine receptor agonists such as  bromocriptine and cabergoline, which stimulate d2   all right, finally before we end, let’s briefly   discuss pharmacology of the posterior pituitary  hormones that is anti-diuretic hormone also known   to the first hormone, when there’s a change in   plasma osmolality, volume, or

Redistribution of  blood, osmoreceptors located within hypothalamus   atria, and caro-tids stimulate the release   of vasopressin into the circulation. vasopressin  action is mediated primarily by binding to the   v2 receptors (v2r) on cells in the distal tubules  and collecting ducts of the kidney, which in turn  

Stimulates insertion of water-permeable channels  called aquaporins into the luminal membrane.   osmotic gradient and the urine to become more   concentrated. in addition to that, vasopressin  can act directly on blood vessels by binding   smooth muscle to cause vasoconstriction.   now, in terms of therapeutic options,

We have  natural vasopressin available in injection form   as well as synthetically modified selective v2  receptor agonist called desmopressin (ddavp) that   is also available in oral and nasal formulations.  vasopressin and desmopressin are treatments of   choice for diabetes insipidus, certain bleeding  disorders and

Nocturnal involuntary urination.   associated with increased vasopressin levels   which work mainly by blocking v2 receptors  thereby effectively correcting hyponatremia   now, moving onto our last hormone that is  oxytocin. so, oxytocin has been best known for   its roles in female reproduction. for instance,  in the

Late stage of pregnancy, stretching of   tissues in the uterus and cervix causes local  stretch receptors to send nerve impulses to the   hypothalamus, which in turn causes the pituitary  to secrete oxytocin into the circulation.   oxytocin then travels to the uterus and causes  the muscles in uterine walls to contract,  

Thereby bringing the baby downwards, stretching  the cervix even more, and repeating the cycle   until birth occurs. after the birth, oxytocin  release is stimulated by the suckling of an infant   at the breast, which again, triggers the synthesis  and release of the oxytocin into the circulation.   this time, oxytocin travels

To the breast where  it stimulates receptors in the cells of the   that results in forcing milk down the duct.   oxytocin can be administered to induce labor   and with that i wanted to thank you for watching,   and as always stay tuned for more.

Transcribed from video