Review function of HPA axis

The key elements of the HPA axis are...

It contains neuroendocrine neurons which synthesize and secrete vasopressin and corticotropin-releasing hormone (CRH)

CRH and vasopressin stimulate the _________ to secrete adrenocorticotropic hormone (ACTH), once known as corticotropin

It produces glucocorticoid hormones (mainly cortisol in humans) in response to stimulation by ACTH. Glucocorticoids in turn, act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle

Cortisol produced in the adrenal cortex works by _____ to inhibit both the hypothalamus and the pituitary gland

When cortisol inhibits the hypothalamus and pituitary, it reduces the secretion of______ and _____, and also directly reduces the cleavage of_______ into___ and ______.

Epinephrine and norepinephrine (E/NE) are produced by the _____through sympathetic stimulation and the local effects of cortisol (_____ enzymes to make E/NE).

Epinephrine and norepinephrine (E/NE) will _____ give feedback to the _____ and _____ the breakdown of proopiomelanocortin (POMCs) into ACTH and β-endorphins.

Drugs of the Anterior Pituitary

-These agents used to ↓ production of gonadal steroids—androgen & estrogen -Prescribed for use in prostate cancer, endometriosis & precocious puberty

-CI—pregnancy & breastfeeding -AE—in women, hot flushes, sweating, decreased libido, depression & ovarian cysts -AE—in men, bone pain [initially], edema. gynecomastia, diminished libido, metabolic bone disease

Corticotropin releasing hormone [CRH] stimulates release of _____from pituitary

Stress ______; cortisol ______

MOA of Corticotropin releasing hormone [CRH]

Discuss ACTH's limited medical use

AE of Corticotropin releasing hormone [CRH]

Growth hormone releasing hormone [GHRH] stimulates release of ____; is inhibited by ______.

This hormone stimulates cell proliferation, bone growth, lean muscle mass production, skin thickness and ↓ adiposity

MOA of Growth hormone releasing hormone [GHRH]

Used to treat GH deficiency in children; growth failure in Prader-Willi, HIV wasting & adults with documented low GH; used off label as “antiaging” hormone

Somatotropin given ____; stimulates _____ in the liver

AE of Growth hormone releasing hormone [GHRH]

CI of Growth hormone releasing hormone [GHRH]

Somatostatin (GHRH) binds to receptors that suppress____ & ____ release; this hormone also suppress release of ______, ________ & _____.

Used to treat acromegaly & s/e of carcinoid tumors, _____ & ______are the synthetic versions of Somatostatin—depot injections given q4 weeks

AE of Octreotide & Lanreotide

Hypothalamus releases GnRH in pulsed fashion to stimulate release of____&____ from anterior pituitary

Continuous release of ____ [thru use of synthetic versions] causes down regulation of the receptors & inhibits release of the gonadotropins

These regulate our gonadal steroid production. Used as prescriptions in infertility

Obtained from urine of post-menopausal women, contains both FSH & LH. Can be used exogenously in fertility treatments.

Placental hormonal found in the urine of pregnant women. Acts like LH in fertility therapies.

FSH obtained from postmenopausal women that has no LH in it, and is also used to treat infertility

FSH products made by DNA recombinant technologies—for infertility

Made by DNA recombinant therapy identical to hCG—used in fertility therapies. These are given IM over 5-12 days—the ovarian follicle grows & matures. A round of hCG follows—ovulation then occurs.

AE Choriogonadotropin α

Stimulates & maintains lactation; yet it ↓ sexual drive & reproductive functions, its secretion is inhibited by dopamine acting at D2 receptors

______& all antipsychotics that act as dopamine ______ will increase the secretion of prolactin

Hyperprolactinemia causes ____ & _____.

For ↑ prolactin [not related to drugs], we prescribe _____ or _____.

Posterior pituitary hormones are not regulated by regulator or releasing hormones—they are made in the_____, then transported to the _______ & released in response to specific physiological changes [such as ∆ in plasma osmolarity]

How are the hormones of the Posterior Pituitary (Oxytocin & Vasopressin) adminstered?

Used to stimulate uterine contraction & to induce labor. Also causes milk ejection by contracting myoepithelial cells around the mammary alveoli.

Has both antidiuretic & vasopressor effects. In kidney it works to ↑ H2O permeability & reabsorption in collecting tubules. Used to treat diabetes insipidus. Can also be used in cardiac arrest & to ↓ bleeding in esophageal varices.

AE of antidiuretic hormone [ADH]

Analog of ADH that has minimal renal effects—used largely as a pressor. Longer acting than ADH; used for DI and nocturnal enuresis. Given PO or nasally [no longer given nasally for enuresis in children r/t ↑ risk of seizures.

-Regulates protein, fat and carbohydrate metabolism -Regulates cell metabolic rate -Regulates body heat production -Maintains growth hormone secretion and skeletal muscle maturation -Affects CNS development (fetal through 2 years of age) -Maintains cardiac rate, force and output -Maintains secretion of GI tract -Affects RR and oxygen utilization

Measures your thyroid-stimulating hormone. This is usually the first test most providers recommend.

Your pituitary gland makes TSH. It travels to your thyroid gland, stimulating it to produce thyroid hormones ___&____

This test serves as “early warning system” – often occurring before the actual level of thyroid hormones in the body becomes too high or too low

Indicates that the thyroid gland is not making enough thyroid hormone (primary hypothyroidism)

Usually indicates that the thyroid is producing too much thyroid hormone (hyperthyroidism)

Measures the amount of triiodothyronine in your blood. This hormone is one of two main hormones that your thyroid makes. Most useful in screening, diagnosis, and monitoring of hyperthyroidism

Measures the amount of thyroxine in your blood. Thyroxine is the other main type of hormone that your thyroid makes. Tests measuring free T4 – either a free T4 (FT4) or free T4 index (FTI) – more accurately reflect how the thyroid gland is functioning when checked with a TSH

The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine.

Is characterized by increased thyroid hormone synthesis and secretion from the thyroid gland

Refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source

Anti-thyroid medications include...

Are used in symptomatic thyrotoxicosis and Grave's disease

Is a common finding in people with hyperthyroidism

Most common cause of hyperthyroidism - immune system disorder that results in the overproduction of thyroid hormones

Symptoms include: Anxiety and irritability, A fine tremor of the hands or fingers, Heat sensitivity and an increase in perspiration or warm, moist skin, Weight loss, despite normal eating habits, Enlargement of the thyroid gland (goiter), Change in menstrual cycles, Erectile dysfunction or reduced libido, Frequent bowel movements, Bulging eyes, Fatigue, Thick, red skin usually on the shins or tops of the feet, Rapid or irregular heartbeat (palpitations), Sleep disturbance

Grave's disease treatment options:

Happens when your thyroid gland releases a large amount of thyroid hormone in a short amount of time. It’s a rare complication of hyperthyroidism. This condition is a medical emergency and is life-threatening

Having a high fever — a temperature between 104 degrees to 106 degrees Fahrenheit is common, Having a rapid heart rate (tachycardia) that can exceed 140 beats per minute, Feeling agitated, irritable and/or anxious, Delirium, Congestive heart failure, Loss of consciousness.

Antithyroid medication (thionamides) to stop your thyroid from making new thyroid hormones, Iodine solution to stop your thyroid from releasing thyroid hormone, Beta-blockers to manage your symptoms, Bile acid sequestrants to prevent your gut from reabsorbing thyroid hormone, Acetaminophen and cooling blankets to lower your temperature, Respiratory treatment, such as supplemental oxygen.

Undergoes hepatic metabolism with no active metabolites. Renal excretion is < 10%. The elimination half-life is approximately 5—9 hours. However, the intrathyroidal residence of this thioamide drug is roughly 20 hours, and the duration of action 40 hours, which allows once-daily dosing some patients.

Rash, pruritis, and arthralgia; associated with agranulocytosis and hepatotoxicity

Interactions with Methimazole

Greater risk of teratogenic effects in the first trimester of pregnancy

Preferred over PTU because of longer ½ life and once-daily dosing, and lower incidence of adverse effects

What is the thioamide drug? -Absorption: 75% -Distribution: 80 to 85% of the drug is bound to plasma proteins (lipoproteins and albumin are the major binding proteins), Vd 0.4 L/kg -Onset: 24 to 36 hours are necessary for a significant therapeutic effect. -Duration: 12 to 24 hours. -Half-life elimination: approximately 1 hour.

Rash, pruritis, and arthralgia; associated with agranulocytosis and hepatotoxicity (more severe with this drug), and more severe forms of liver injury (including acute liver failure)

Interactions with Propylthiouracil

Recommended during the first trimester of pregnancy due to a greater risk of teratogenic effects with methimazole

BMI between 25-29.9

BMI of 30 or more

BMI of 40 or more

Childhood overweight is being at or above _____of weight for age

Childhood obesity is a BMI at or above the _____ for a specific age

AHA, ACC and Obesity Society [2015] state that weight loss intervention is indicated for:

These are approved for short term use only [90 days] and include Diethylpropion [Tenuate] and Phentermine [Adipex-P]

Both agents ↑ norepinephrine [Phentermine also ↑ dopamine] & both inhibit the reuptake of NE [+/- Dp]; this ↑ in NE ↓appetite

Phentermine is excreted in kidney; Diethylpropion is metabolized in the liver, the active metabolites are excreted in kidney—these metabolites have a 4-8 hour ½ life

Controlled substances [S IV] b/c of potential for dependence; common SE—dry mouth, HA, insomnia, constipation; can ↑ BP

-Avoid in those with uncontrolled BP, CV disease, arrhythmias, CHF or stroke hx -Contraindicated with other sympathomimetics [Sudafed, excess caffeine, etc.] & MAO inhibitors

-Pentatonic acid ester that inhibits gastric and pancreatic lipases, ↓ breakdown of fat -↓ fat absorption by 30%; main mechanism of weight loss—this loss of calories

List Anorexiants

List Lipase Inhibitors

Taken with food that contains fat; minimal absorption; excreted in feces

Oily spotting, gas, interferes with absorption of fat soluble vitamins [A, E, D, K & β carotene]

Pregnancy, chronic malabsorption, cholestasis

Serotonin Agonists

-Selectively binds to 2C serotonin receptor [5-HT2c] -Previous drugs of this class caused valve disease—thought to be linked to their effect on 5-HT 2B receptors

With 5HT-2c receptor activation, stimulates pro-opiomelanocortin neurons, which activate melanocortin receptors, causing a ↓ in appetite

Metabolized in liver—inactive metabolites are eliminated in the urine [not recommended in severe renal impairment]

Nausea, headache, dry mouth, constipation, lethargy

-Rarely, mood changes and SI -Caution with use of other serotonergic agent—SNRIs, SSRIs, MAOIs—because of risk of NMS -Monitor patient for development of valvular heart disease—assess for new or ∆ in murmur -Avoid prescribing this agent in patients with hx of CHF, those with hx of known valve problems

-For weight loss—exact MOA is unknown -Naltrexone antagonizes various opioid receptors, while Bupropion inhibits neuronal uptake of NE & dopamine

Combination Agents