Neuroendocrine Obesity Pharm

100問 • 2年前

問題一覧

Review function of HPA axis

A major neuroendocrine system at controls reactions to stress and regulates many body processes, including digestion, immune responses, mood and emotions, sexual activity, and energy storage and expenditure. It is the common mechanism for interactions among glands, hormones, and parts of the midbrain that mediate the general adaptation syndrome (GAS)

The key elements of the HPA axis are...

The paraventricular nucleus of the hypothalamus, anterior lobe of the pituitary gland, and the adrenal cortex

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

Paraventricular nucleus of the hypothalamus

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

Anterior lobe of the pituitary gland

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

Adrenal cortex

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

Negative feedback

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

CRH and vasopressin; proopiomelanocortin (POMC) into ACTH and β-endorphins.

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

adrenal medulla; upregulation

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

positively; pituitary; increase

Drugs of the Anterior Pituitary

Leuprolide, Goserelin, Nafarelin, and Histrelin

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

Leuprolide, Goserelin, Nafarelin, and Histrelin

-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

Leuprolide, Goserelin, Nafarelin, and Histrelin

Corticotropin releasing hormone [CRH] stimulates release of _____from pituitary

ACTH

Stress ______; cortisol ______

↑ release of ACTH; ↓ ACTH release

MOA of Corticotropin releasing hormone [CRH]

Hypothalamus releases CRH to stimulate ACTH in the anterior pituitary to convert cholesterol to pregnenolone in the adrenal cortex, which results in the synthesis of adrenal steroids and adrenal androgens

Discuss ACTH's limited medical use

Mainly to help differentiate Addison’s disease from 2⁰ adrenal failure [caused by a pituitary issue]

AE of Corticotropin releasing hormone [CRH]

None with short term use; with longer use s/e similar to using steroids chronically

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

GH; Somatostatin

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

Growth hormone releasing hormone [GHRH]

MOA of Growth hormone releasing hormone [GHRH]

GH effects exerted directly on its target organs, yet some effects mediated through insulin like growth factors 1 & 2

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

Growth hormone releasing hormone [GHRH]

Somatotropin given ____; stimulates _____ in the liver

SQ or IM; IGF-1

AE of Growth hormone releasing hormone [GHRH]

Edema, arthralgias, ↑ risk of DM

CI of Growth hormone releasing hormone [GHRH]

Children with closed epiphyses, those with diabetic eye disease, patients with Prader-Willi that are obese

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

GH & TSH; insulin, glucagon & gastrin

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

Octreotide & Lanreotide

AE of Octreotide & Lanreotide

Diarrhea, abdominal pain, gas, nausea & steatorrhea

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

FSH & LH

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

GnRH

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

FSH/LH

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

hMG

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

hCG

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

Urofollitropin

FSH products made by DNA recombinant technologies—for infertility

Follitropin [α & β]

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.

Choriogonadotropin α

AE Choriogonadotropin α

Ovarian enlargement & possible hyperstimulation

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

Prolactin

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

Metoclopramide; antagonists

Hyperprolactinemia causes ____ & _____.

galactorrhea & hypogonadism

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

Bromocriptine or Cabergoline

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]

hypothalamus;posterior pituitary

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.

Oxytocin

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.

Antidiuretic hormone [ADH]

AE of antidiuretic hormone [ADH]

H2O intoxication & low Na+

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.

Desmopressin [DDAVP]

-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

Principal function/actions of the thyroid gland

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

TSH (thyroid-stimulating hormone)

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

T3 and T4

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

TSH (thyroid-stimulating hormone)

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

High TSH level

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

Low TSH level

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

T3 (or free T3) (triiodothyronine)

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

T4 (or free T4) (thyroxine)

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.

Clinical presentation and therapy for hypothyroidism

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

Hyperthyroidism

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

Thyrotoxicosis

Anti-thyroid medications include...

Methimazole and propylthiouracil

Are used in symptomatic thyrotoxicosis and Grave's disease

Beta blockers (propranolol)

Is a common finding in people with hyperthyroidism

A high level of T-4 and a low level of TSH

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

Graves disease

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

Grave's disease treatment options:

Beta-blockers (propranolol and metoprolol), Antithyroid medications (methimazole and propylthiouracil), Radioiodine therapy, and thyroidectomy

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

Thyroid storm

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.

Common symptoms of Thyroid Storm

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.

Medications and treatment therapies for Thyroid Storm

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.

Pharmacokinetics of Methimazole

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

Side Effects/Adverse Effects of Methimazole

Interactions with Methimazole

May interact with blood thinners and digoxin

Greater risk of teratogenic effects in the first trimester of pregnancy

CI for Methimazole

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

Dosing Considerations for Methimazole

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.

Pharmacokinetics of Propylthiouracil

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)

Side Effects/Adverse Effects of Propylthiouracil

Interactions with Propylthiouracil

May interact with blood thinners and digoxin

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

Dosing Considerations for Propylthiouracil

BMI between 25-29.9

overweight

BMI of 30 or more

obese

BMI of 40 or more

severe obesity

Childhood overweight is being at or above _____of weight for age

85th percentile

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

95th percentile

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

-BMI >25 and 1 or more CV weight related risk factor or condition -BMI >/= to 30, regardless of the presence of cardiometabolic risk factors -Waist circumference is a significant parameter that should be assessed in all overweight/obese patients -In the US, the cutoff is 40 inches for men and 35 inches for women [for Asian Americans the cut off is 5” less]

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

Anorexiants

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

MOA of Anorexiants

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

Pharmacokinetics of Anorexiants

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

AE of Anorexiants

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

Anorexiants

-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

MOA of Orlistat [Xenical/Alli]

List Anorexiants

Diethylpropion [Tenuate] Phentermine [Adipex-P]

List Lipase Inhibitors

Orlistat [Xenical/Alli]

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

Pharmacokinetics of Lipase Inhibitors

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

AE of Lipase Inhibitors

Pregnancy, chronic malabsorption, cholestasis

CI for Lipase Inhibitors

Serotonin Agonists

Lorcaserin [Belviq]

-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

Serotonin Agonists

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

MOA of Serotonin Agonists

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

Pharmacokinetics of Serotonin Agonists

Nausea, headache, dry mouth, constipation, lethargy

AE of Serotonin Agonists

-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

Considerations for Serotonin Agonists

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

Naltrexone ER/Bupropion ER [Contrave]

100

Combination Agents

Naltrexone ER/Bupropion ER [Contrave]

Patho Renal

Two Clean Queens · 100問 · 2年前

Patho Renal