Endocrine Pharmacology Flashcards
What is the endocrine system? What are the 7 major organs in this system?
group of organs/glands that release hormones into circulation to regulate various physiological functions
- hypothalamus
- pituitary gland
- parathyroid glands
- thyroid glands
- adrenal glands
- ovaries/testes
- pancreas
What is the origin, transport, target, action, duration, and response of hormones?
ORIGIN = endocrine glands
TRANSPORT = blood
TARGET = distal and local organs
ACTION = slow
DURATION = short and long-lived
RESPONSE = involuntary
What is the origin, transport, target, action, duration, and response of neurotransmitters?
ORIGIN = neurons of NS
TRANSPORT = neurons
TARGET = local receptors on neurons
ACTION = fast
DURATION = short-lived
RESPONSE = voluntary and involuntary
In what 3 ways do hormones and neurotransmitters overlap?
- chemicals with specific functions
- have receptor sites in target cells
- regulate each other with feedback systems
What are the 3 main examples of neurohormones?
- noradrenaline
- dopamine
- oxytocin
have characteristics of both hormones and neurotransmitters
What hormones are released by the 6 organs of the endocrine system?
- hypothalamus - GnRH
- pituitary gland - GH, ACTH, TSH, LH, FSH, PRL, ADH, oxytocin
- thyroid - thyroxine, triiodothyronine, PTH
- pancreas - insulin, glucagon
- adrenal gland - adrenalin, corticosteroids
- ovary/testicles - testosterone, estrogen, progesterone
What do hormones do? What are 5 specific functions?
control the functions of all organs by affecting diverse processes of growth and development, reproduction, sexual characteristics, temperature, and hunger
- send chemical signals all over the body
- play a role in the development on bones and muscles
- necessary in bodily changes, like puberty
- control metabolism
- aid in the upkeep of homeostasis
What are the 3 classifications of hormones? What are they made of? What are some examples?
STEROIDS - lipids (easily pass cell membrane)
- cholesterol, progesterone, testosterone, estrogen, cortisol
AMINES - tyrosine
- thyroxine, catecholamines, melatonin
PEPTIDES/PROTEINS - linked amino acids (charged and water-soluble, harder time crossing cell membrane and bind to surface receptors)
- insulin, oxytocin, vasopressin (ADH), GH
How are drugs used to treat hormonal imbalances?
drugs that produce hormone-like effects (agonists) can treat endocrine hypofunction
drugs that inhibit hormone synthesis or block receptors (antagonists) can treat endocrine hyperfunction
What does the pituitary gland do? What 7 hormones does it produce?
regulates other glands such as the thyroid, adrenal glands, ovaries, testes, and breasts by releasing hormones that regulate and control other hormones
- GH - stimulates growth and repair
- ACTH - stimulates adrenal glands to produce corticosteroids
- TSH - stimulates thyroid to secrete thyroxine
- ADH - controls water retention by the kidneys
- oxytocin - uterine contraction, milk production
- LH and FSH - reproductive functions
- PRL - stimulates the breasts to produce milk
What are 3 possible causes of decreased hormone release by the pituitary gland?
- hypopituitarism (pituitary dwarfism)
- acquired growth hormone deficiency
- neoplasia
What 3 diseases result from hypersecretion of pituitary hormones?
- acromegaly - excess GH
- Cushing’s syndrome - excess ACTH increases cortisol from adrenal glands
- galactorrhea - excess PRL
What causes diabetes insipidus?
vasopressin (ADH) deficiency or vasopressin receptor abnormality
What is Cushing’s disease? How does it compare in dogs and cats? What are some symptoms?
increased cortisol typically caused by a benign tumor in the pituitary gland causing an increase in ACTH release
affects 80-90% of dogs and is less common in cats
- weight gain
- fatigue
- hypertension
- diabetes
- premature osteoporosis
What is galactorrhea?
lactation without pregnancy
(can occur in males)
How does growth hormone signaling occur?
- GH or growth inhibitors bind to tyrosine kinase receptors on the membrane of cells
- receptors dimerize and undergo transphosphorylation
- this activates JAK/STAT signaling
- receptors in the nucleus then bind to DNA and cause the transcription of insulin growth factor-1, which causes cell growth/division
What drug is used as an agonistic growth hormone agent? What are the 2 results?
GH (somatotropin)
- promotes the growth of all body tissues (bone, muscle, mammary glands)
- promotes lipolysis
What growth hormone agent is typically used in dairy cattle? What does it do?
Sometribove (Posilac), bovine somatotropin (bST)
promotes milk production
What drug is used as an antagonistic growth hormone agent? What does it do? How?
somatostatin
inhibits pituitary gland secretion of GH and TSH
binds to somatostatin receptors in cells of the stomach, intestine, and pancreas
What are the adrenal glands? What are the 3 steps to their activation?
homeostatic organs that regulate reactions to stress
- stimuli (trauma, stress, chemicals) cause the hypothalamus to release corticotropin-releasing hormone (CRH)
- CRH stimulates the pituitary gland to release ACTH
- ACTH stimulates the adrenal glands to proliferate and produce corticosteroids
What are the 2 main classes of endogenous corticosteroids? What other 2 hormones are produced by the adrenal glands?
- glucocorticoids - metabolism and immunity; cortisol
- mineralocorticoids - sodium and water retention; aldosterone
- adrenaline (EPI)
- androgens
What is Addison’s disease?
adrenal dysfunction - hypoadrenocorticism caused as a result of insufficient adrenaline, cortisol, and aldosterone secretion most common in yount to middle-aged dogs and occasionally in horses
What is Cushing’s disease?
adrenal dysfunction - hyperadrenocorticism in dogs caused by the overproduction of cortisol due to hypersecretion of ACTH from the pituitary gland
What are tumors of the adrenal glands called? What do they commonly cause?
pheochromocytoma - dogs and cats
excessive production of catecholamines, resulting in hypertension
What are corticosteroids? What effects do they have?
class of steroid hormones that are synthetic analogs of cortisol produced by adrenal glands
- CNS
- cardiovascular
- skeletal muscle
- blood cells and lymphoid tissue
- immunological
- anti-inflammatory, immunosuppressive
- metabolism
- electrolytes, water balance
What is the cellular mechanism of action of glucocorticoids?
- bound to corticosteroid-binding globulin
- disassociates and binds to glucocorticoid receptor within the cell
- enters nucleus and binds to either pGRE or nGRE
- binding to pGRE causes the production of anti-inflammatory proteins, gluconeogenesis, and muscle, fat, and connective tissue catabolism
How are short-acting corticosteroids used? What are 3 examples?
treats pruritus and inflammation associated with allergy
- hydrocortisone
- cortisone
- fludrocortisone (MC)
How are intermediate-acting corticosteroids used? What are 4 examples?
long-term control of allergies, chronic inflammation, immunosuppression, and lymphoma control
- prednisone
- prednisolone
- methylprednisolone
- triamcinolone
How are long-acting corticosteroids used? What are 4 examples?
used topically to treat inflammation and pruritus associated with allergy
- dexamethasone
- betamethasone
- paramethasone
- flumethasone
What drug class has one of the most widespread and potent immunosuppressant anti-inflammatory effects?
glucocorticoids
- decrease T and B cells, eosinophils, basophils, and monocytes
- decrease neutrophil migration to tissues
- decrease macrophage production of TNFα, IL, plasminogen activator, IFNγ
- inhibits phospholipase A2, so arachidonic acid is not available
- effects on COX-2 decreases prostaglandin production
- decreases histamine release by mast cells
- inhibits hair and skin growth
What is a common result of insufficient or excessive glucocorticoid activity?
increase susceptibility to infections - immunosuppressant!
How do glucocorticoids affect metabolism?
- increase lipogenesis
- increase glucose metabolism
- increase protein breakdown
What 4 actions do glucocorticoids have on electrolytes and water balance?
- reduce ADH secretion
- increase excretion of Na+ and water
- calcium-mediated hypokalemia leading to increased PTH secretion
- promotes osteoblast apoptosis
3 + 4 = osteoporosis
How do glucocorticoids affect the CNS, respiratory system, and skeletal muscle?
CNS - stimulation leading to euphoria
RS - bronchodilation, decrease histamine, bradykinin, and prostaglandins, induce decongestion of airways
SM - maintains function
How do glucocorticoids affect the cardiovascular system?
- increase vasomotor responses and myocardial contractions
- increases epinephrine synthesis
- increase expression of α and β adrenergic receptors
- facilitate angiotensin system
- promotes the breakdown of bradykinin, a vasodilator
- decreases capillary permeability
How does long-term usage of corticosteroids affect the animal?
effects similar to Cushing’s disease
- muscle wasting
- osteoporosis
- fat redistribution to the face (moon face), trunk, back
- red, swelling
- diabetes
- acne, hair loss
- increased platelets
- GI ulceration
Why is it not recommended to abruptly stop taking corticosteroids?
negative feedback mechanisms result in symptoms similar to Addison’s disease
- anorexia
- nausea, vomiting
- weight loss
- lethargy
- joint and muscle pain
- postural hypotension
- low BP
What are the most common adverse effects of corticosteroids in dogs and cats?
DOGS = hepatotoxicity
CATS = congestive heart failure
What are the 2 replacement therapies used for hypoadrenocorticism?
(Addison’s disease)
- deoxycorticosterone pivalate suspension
- fludrocortisone
What 4 adrenal steroid inhibitors are used to control hyperadrenocorticism?
(Cushing’s disease)
- mitotane
- trilostane
- ketoconazole
- selegiline
What is Mitotane? What is its mechanism of action?
irreversible corticosteroid inhibitor used for Cushing’s disease and adrenal neoplasms
cytotoxic to the zones of the adrenal cortex that secrete all endogenous steroids EXCEPT aldosterone
What is the main result of the long half-life of Mitotane?
easy chance of overdose, converting from hyperadrenocorticism to hypoadrenocorticism
What is Trilostane? What is its mechanism of action?
synthetic steroid analog that acts as an adrenal steroid inhibitor for treatment of Cushing’s in dogs
competitive inhibitor of an enzyme that is essential for corticosteroid synthesis
In what animals is Trilostane contraindicated? Why?
pregnant animals
inhibits progesterone synthesis
What is Ketoconazole? What is its mechanism of action?
adrenal steroid inhibitor used to treat Cushing’s in dogs resistant to mitotane and as a palliative therapy in dogs with cancer metastasis
reversible inhibition of cytochrome P450 enzymes involved in steroid synthesis
What is Selegiline? What is its mechanism of action?
adrenal steroid inhibitor used to treat pituitary-dependent hyperadrenocorticism and canine cognitive dysfunction
inhibits MAO-B, causing an increase of dopamine, which blocks ACTH to lower cortisol levels
