EndoPharm 1 Flashcards
What does the endocrine system encompass?
The Endocrine system encompasses a group of organs/glands that release hormones into circulation for regulating various physiological functions.
Why are the hypothalamus & pituitary gland important for regulating the endocrine system?
Pg is part of hypothalamus. Very small, does a lot.
Hypo regulates the endocrine system
What is the difference in origin between hormones and neurotransmitters?
Endocrine glands vs. neurons of the NS
What is the difference in transport between hormones and neurotransmitters?
Blood vs. neurons
What is the difference in target between hormones and neurotransmitters?
distal and local organs vs local receptors on neurons
What is the difference in action between hormones and neurotransmitters?
Slow (up to a few days) vs. fast (up to miliseconds)
What is the difference in duration of effect between hormones and neurotransmitters?
Short and long lived vs. short lived
What is the difference in response between hormones and neurotransmitters?
Involuntary vs. voluntary and involuntary
What do hormones and neurotransmitters have in common?
- Chemicals
- Functions
- Receptor sites in target cells
- Regulate each other
- Feedback system
What chemicals are considered neurohormones? What does this mean?
**Noradrenaline (norepi), dopamine, oxytocin are all called neurohormones. Possess characteristics of both neurotransmitters and hormones.
What does the adrenal gland produce?
Adrenalin, corticosteroids
What does the pituitary gland produce?
Major producer of endocrine system.
What do the testicles and ovaries produce?
Sex hormones, testosterone, estrogen, progesterone
What does the brain produce?
Gonadotropin-releasing hormone (GnRH)
What does the pancreas produce?
Insulin, glucagon
What does the thyroid produce?
Thyroid hormones, thyroxine, triiodothyronine, parathyroid hormone
What are the functions of hormones?
Hormones control the functions of all the organs. They affect diverse processes of growth and development, reproduction and sexual characteristics, temperature, hunger.
▪ Sending chemical signals to everywhere in the body
▪ They play a role in the development of bones and muscles
▪ They are necessary for bodily changes such as puberty
▪ They control metabolism
▪ They aid in the upkeep of homeostasis
How are hormones classified?
Structure determines hormone function.
Hormones can be steroids, amines, peptides/proteins
Sterorids are lipophillic. Drugs that can mimic or counter them also have to be lipophillic. Cross cell membrane easily and induce action. Recpetors are in cytoplasm or nucleus of the cell.
Peptides are AA linked togeher. Charged, water soluble, have a hard time crossing cell membrane. Rely on receptors on cell surface of target cell.
ACTH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- Corticotrophin
- Pituitary gland
- Adrenals
- Stimulates the adrenal gland to produce a hormone called cortisol.
Thyrotropin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- TH
- Pituitary gland
- Thyroid
- Stimulates the thyroid gland to secrete its own hormone, which is called thyroxine
LH & FSH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- Gonadotrophins
- Pituitary gland
- Ovaries (females), testes (males)
- Controls reproductive functioning and sexual characteristics. Stimulates the
ovaries to produce estrogen and progesterone and the testes to produce
testosterone and sperm.
Prolactin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- PRL
- Pituitary gland
- Mammary glands
- Stimulates the mammary glands to produce milk. This hormone is secreted
in large amounts during pregnancy and breast feeding, but is present at all times in both males and females.
Growth Hormone
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- GH
- Pituitary gland
- All cells in the body
- Stimulates growth and repair. Research is currently being carried out to identify the functions of GH in adult
life.
ADH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- Vasopressin
- Pituitary gland
- Kidneys
- Controls the blood fluid and mineral levels in the body by affecting water retention by the kidneys.
Oxytocin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?
- N/A
- Pituitary gland
- Uterus, mammary glands
- Affects uterine contractions in pregnancy and birth and subsequent release of breast milk
Cortisol
1. Is produced by which organ?
2. Targets which organ(s)?
3. Function?
- Pituitary gland
- Adrenals
- Cortisol promotes normal
metabolism, maintains blood sugar levels and blood pressure, provides resistance to stress and acts as an anti-inflammatory agent. It also plays a part in regulation of fluid balance in the body
Thyroxine
1. Is produced by which organ?
2. Targets which organ(s)?
3. Function?
- Pituitary gland
- Thyroid
- Thyroxine controls many body functions, including heart rate, temperature and metabolism. It also plays a role in the metabolism of calcium in the body
Estrogen
1. Is produced by which organ?
2. Targets which organ(s)?
3. Function?
- Pituitary gland
- Ovaries
- Estrogen facilitates growth of the tissues of the sex organs and other tissues related to reproduction. Estrogen also acts to strengthen bones and has a protective effect on the heart.
Progesterone
1. Is produced by which organ?
2. Targets which organ(s)?
3. Function?
- Pituitary gland
- Ovaries
- Progesterone promotes the
changes in the uterus that occur in preparation for the implantation of a fertilized ovum and prepares the
breasts for milk production
Testosterone
1. Is produced by which organ?
2. Targets which organ(s)?
3. Function?
- Pituitary gland
- Testes
- Testosterone is responsible for the characteristics of the masculine body. Testosterone is essential for the production of sperm and also acts to strengthen bones.
List the types of hormonal imbalances in animals.
❖ Pituitary Disorders
❖ Adrenal Dysfunction
❖ Thyroid/Parathyroid Disorders
❖ Disorders of Endocrine Pancreas
❖ Disorders of Reproductive System
❖ Uterine dysfunction and infections
“Patted U”
Drugs that produce __________-like effects, meaning they are ____________, have important therapeutic value for the treatment of endocrine _____-function
hormone, agonists, hypo
Drugs that _______ the hormone synthesis or _____ receptors can be used for the treatment of endocrine ______-function
inhibit, block, hyper
These are antagonists that either block the receptor or replace the hormone action.
Endocrine Drugs come in different classifications such as:
❖ Growth Hormone drugs
❖ Corticotropin (ACTH), Corticosteroids, and Inhibitors
❖ Gonadotropins
❖ GnRH and Analogs
❖ Anti-Diabetic Agents
❖ Thyroid Hormone and Anti-Thyroid Agents
❖ Agents for the Treatment of Hypocalcemia
❖ Sex Steroids
❖ Uterine Contractants and Drugs to Induce Luteolysis
❖ Milk Production Enhancer
What is the function of the pituitary gland?
Pituitary gland is an endocrine gland, about the size of a pea, that is connected and regulates other glands such as thyroid, adrenals, ovaries and testes, breasts by releasing hormones that regulate and control other hormones.
Anterior PG is highly vascularized.
What is the function of GH?
GH: stimulates growth and repair
What is the function of ACTH?
ACTH : stimulates adrenal glands to produce corticosteroids
What is the function of TSH?
TSH: stimulates thyroid gland to secrete thyroxine
What is the function of ADH (vasopressin)?
ADH (vasopressin): controls water retention by the kidneys
What is the function of oxytocin?
Oxytocin: uterine contraction and milk production
What is the function of LH & FSH?
LH & FSH: control reproductive functions
What is the function of PRL?
PRL: stimulates the breasts to produce milk
List three common pituitary disorders that occur in dogs and cats.
❖ Hypopituitarism (pituitary dwarfism)
❖ Acquired growth hormone (GH) deficiency
❖ Neoplasia
Acromegaly results from excess of?
GH
Cushing’s syndrome results from excess of?
ACTH (Increase in cortisol)
ACTH is important to act on adrenal glands –> release cortisol.
Excess ACTH can result in excess GH too.
Galactorrhea results from excess of?
PRL
This condition results in inappropriate mammary gland development and lactation without pregnancy. Can happen in both males and females.
Diabetes insipidus results from?
vasopressin deficiency or vasopressin receptor abnormality
Cushing’s disease affects what % of dogs?
80-90%
Is Cushing’s disease common in cats?
Occurs less in cats
What are the symptoms of cushing’s disease?
Symptoms:
weight gain
Fatigue
Hypertension
Diabetes
Premature osteoporosis
Galactorrhea is defined as? Occurs in what sex?
Lactation without pregnancy
Can happen in males, but mainly females.
On a molecular level, GHS is a Ligand-specific signaling pathway that controls gene expression, specifically insulin growth factor 1. GH is a peptide hormone which is soluble and has a hard time crossing the membrane. Tyrosine kinase receptors on cell surface help GH enter cells/blood. Able to perform its various functions this way.
Growth hormone signaling
Growth pathway
Growth factors promote cell division
Growth hormone signaling
Growth inhibition pathway
Factors stop cells from growing
Explain the process occurring in this image.
- Growth factor and growth inhibitors bind receptors on the membranes of the cells and activate downstream signaling
- Receptors usually interact with one another or dimerize before become activated
- Activated receptors process signaling pathways inside cells to nucleus and DNA
- Activation is carried out by transfer molecules called phosphates from one to other
- Proteins that perform phosphorylation are called Kinases
- Accumulation of certain proteins for growth or inhibition
TK binds and phosphorylates JAK/STAT signaling pathway –> nucleus —> binds DNA seq –> transcribes target genes, one of which is insulin growth factor.
Name the two GH agents, we use as drugs, as an agonist (hypo)
E.g.: Somatotropin, a type of GH, exists in both natural and synthetic forms. Natural in animals, different name in humans (Somatropin).
▪ Promotes growth of all body tissues (bone, muscle, and mammary gland)
▪ Promotes lipolysis
Used in “hypo” situations. Used as an agonist.
Sometribove (PosilacTM) OR bovine somatotropin (bST) is used in dairy cattle to promote milk production
Used in “hypo” situations. Used as an agonist.
Name the two GH agents, we use as drugs, as an antagonist (hyper)
Somatostatin (natural and synthetic GH inhibitory peptides) inhibits the pituitary gland’s secretion
of GH and TSH. Somatostatin binds to somatostatin receptors in cells of stomach, intestine, and pancreas
Synthetic drugs are better - why? improved stability, reduce hepatic clearance longer half life.
Adrenal glands serve as a ?
What maintains homeostasis?
homeostatic organ, regulating reactions to stress
A negative feed-back mechanisms maintains homeostasis
Stimuli (trauma, chemicals, stress) cause the hypothalamus to release ?
corticotropin-releasing hormone (CRH)
CRH stimulates the pituitary gland to release?
ACTH
ACTH stimulates the adrenal glands to ?
proliferate (trophic effect) and to produce corticosteroids
Glucocorticoids are ________ and ________ system related. List two examples.
metabolism, immune
➢ Cortisol
➢ Corticosterone
Mineralocorticoids are involved in _______ and _______ retention. List two examples.
sodium, water
➢ Aldosterone
➢ Deoxycorticosterone
Glucocorticoids and mineralocorticosteroids are?
Endogenous corticosteroids
Adrenaline and androgens?
Define addison’s disease.
❖ Addison’s disease (hypoadrenocorticism) is caused as a result of insufficient adrenaline, cortisol, and aldosterone secretion. It is seen most in young to middle-aged dogs and occasionally in horses.
Define Cushing’s disease.
❖ Cushing’s Disease (hyperadrenocorticism) in dogs is caused by an overproduction of cortisol. Hypersecretion of ACTH from pituitary gland (tumor) may result in an overactive adrenal gland
Define Pheochromocytoma.
❖ Pheochromocytoma (tumors of adrenal gland) in dogs and cats can cause excessive production of catecholamines, resulting in hypertension
Corticosteroids are a class of steroid hormones that are ?
synthetic analogs of cortisol produced by glands that are used for therapeutic purposes.
Corticosteroids
▪ CNS effects
▪ Cardiovascular effects
▪ Skeletal muscle effects
▪ Effects on blood cells and lymphoid tissue
▪ Immunologic effects
▪ Anti-inflammatory and immunosuppressive effects
▪ Effects on intermediary metabolism
▪ Actions on electrolytes and water balance
Glucocorticoids are bound to CBG in the blood, when free they enter through the cell membrane (lipophillic) and bind to its receptor in the nucleus. Estrogen receptor, androgen, glucocorti, and mineralcor = nuclear receptors.
Bind to receptors –> dimerization –> bind to specific sequencing DNA and have different transcrption of different genes, depends on + GRE or negative GRE. Whichever it binds to –> different proteins are produced.
When binds to positive = bottom left
When binds to negative = bottom right
List the short-acting corticosteroids.
➢ Hydrocortisone (cortisol)
➢ Cortisone
➢ Fludrocortisone (MC)
What are short-acting corticosteroids used to treat? How quickly do they act?
used to treat pruritus and inflammation associated with allergy
< 12 hrs
List the intermediate-acting corticosteroids.
➢ Prednisone
➢ Prednisolone
➢ Methylprednisolone
➢ Triamcinolone
What are intermediate-acting corticosteroids used to treat? How quickly do they act?
used for the long-term control of allergies, chronic inflammation, immunosuppression, and lymphoma control
12-36 hrs
List the long-acting corticosteroids.
➢ Dexamethasone
➢ Betamethasone
➢ Paramethasone
➢ Flumethasone
What are long-acting corticosteroids used to treat? How quickly do they act?
used topically to treat inflammation and pruritus associated with allergies
36-72 hrs
Glucocorticoids have one of the most widespread and potent ?
immunosuppressant anti-inflammatory effects of any drug class
Glucocorticoids function to?
▪ Decrease T and B cells, eosinophils, basophils, and monocytes
▪ Decrease neutrophil migration into tissues
▪ Macrophages produce less TNFα, interleukins, plasminogen activator, interferon γ
▪ Phospholipase A2 is inhibited, so arachidonic acid (AA) is not available to produce inflammatory prostaglandins and leukotriens
▪ Effects on COX-2 decreasing prostaglandin production
▪ Decrease histamine release by mast cells
▪ Hair and skin growth is inhibited
Insufficient or excessive glucocorticoid activity can?
increase susceptibility to infections
Glucocorticoids increase?
Increase lipogenesis and glucose metabolism
Increase protein breakdown
Increase vasomotor responses and myocardial contractions
Increase epinephrine synthesis
Increase expression of α- and β-adrenergic Rs
Glucocorticoids facilitate? Promote?
Facilitate the angiotensin system
Promote the breakdown of bradykinin, a vasodilator
Glucocorticoids decrease?
Decrease capillary permeability
How do glucocorticoids act on electrolytes and water balance?
- Reduce ADH (vasopressin) secretion
- Increased excretion of Na+ and H2O
- Ca++ - mediated hypokalemia leading
to increase PTH secretion - Promote osteoblasts apoptosis
Last two –> osteoperosis
How do Glucocorticoids act on the brain?
Stimulate the CNS leading to euphoria
How do Glucocorticoids act on the lungs?
Cause bronchodilation
Decrease histamine, bradykinin, prostaglandins
Induce decongestion of the airways
How do Glucocorticoids act on skeletal muscle?
Maintain skeletal muscle function
What are the adverse effects of Corticosteroid use?
- Muscle wasting
- Osteoporosis
- Fat redistribution into the face (moon faces), trunk, back
- Red and swollen
- Diabetes risk
- Acne, hair loss
- Increased platelets (thrombosis)
- GI ulceration
What are the adverse effects of Corticosteroids in dogs specifically?
Hepatotoxicity in dogs
What are the adverse effects of Corticosteroids in cats specifically?
Congestive heart failure in cats
The long-term use of Corticosteroids has effect like ?
in Cushing’s Syndrome (pituitary adenoma secreting ACTH)
Should you stop using Corticosteroids abruptly? Explain.
No –> negative feedback mechanisms.
Causes:
* Anorexia
* Nausea/vomiting
* Weight loss
* Lethargy
* Joint and muscle pain
* Postural hypotension
* Low blood pressure
Abruptly stopping Corticosteroids resembles?
Addison’s disease
Corticosteroid therapy serves as?
- Replacement Therapy for hypoadrenocorticism (Addison’s disease)
- Adrenal Steroid Inhibitors to control hyperadrenocorticism
(Cushing’s disease or adrenal gland carcinoma)
List two examples of replacement therapy for hypoadrenocorticism.
➢ Deoxycorticosterone pivalate suspension
➢ Fludrocortisone: has high mineralocorticoid and glucocorticoid potency
List four examples of adrenal steroid inhibitors to control hyperadrenocorticism.
➢ Mitotane
➢ Trilostane
➢ Ketoconazole
➢ Selegiline
Mitotane (LysodrenR) functions as?
an irreversible corticosteroid inhibitor
What is Mitotane’s (Lysodren) mechanism of action?
Cytotoxic to the zones of adrenal cortex that secrete
all endogenous steroids except aldosterone
What is Mitotane’s (Lysodren) PK?
PO: absorption through GI tract
Distribution: occurs to all tissues in the body and stored in the fat
A very long plasma t1/2 ranging 18-159 days (human data)
***As a result of long and variable t1/2 of mitotane, it would be very easy to overdose the animal, which would convert from hyperadrenocorticism to hypoadrenocorticism
What is Mitotane’s (Lysodren) used for?
Cushing’s syndrome and adrenal neoplasms
What are the adverse effects of Mitotane’s (Lysodren)?
Lethargy, weakness, ataxia, anorexia, vomiting, or diarrhea
Hepatotoxicity
Mitotane-induced hypoadrenocorticism (fludrocortisone replacement therapy)
Trilostane (ModrenalR) functions as?
a synthetic steroid analog
What is Trilostane (ModrenalR) mechanism of action?
Competitive inhibitor of an enzyme that is essential for corticosteroid
synthesis
What is Trilostane (ModrenalR) PK?
PO: absorption through GI tract in dogs (peak levels in 2 hrs)
Liver metabolism, urine/feces excretion
Plasma t1/2 is ~1 hr
What is Trilostane (ModrenalR) used for?
In dogs for treatment of Cushing’s syndrome
What are the adverse effects of Trilostane (ModrenalR) ?
Lethargy, anorexia, vomiting, electrolyte abnormalities, and diarrhea
What are the contraindications of Trilostane (ModrenalR) ?
Pregnant animals (inhibits progesterone synthesis )
Ketoconazole functions as?
blocks production of adrenal steroids
What is Mitotane’s (Lysodren) mechanism of action?
Reversible inhibition of cytochrome P450 enzymes that are involved in
steroid synthesis
What is Mitotane’s (Lysodren) PK?
PO: bioavailability in dogs is variable, GI absorption
Peak plasma concentration in 1-4 hrs
> 85% bound to plasma proteins
Liver metabolism; bile/feces excretion
t1/2 in dogs is 1-6 hrs
What is Trilostane (ModrenalR) used for?
to treat hyperadrenocorticism in dogs that are resistant to mitotane and
as palliative therapy in dogs with cancer metastasis
What are the adverse effects of Trilostane (ModrenalR) ?
Anorexia, vomiting, and/or diarrhea are the most common
Hepatotoxicity
Reproductive disturbances (due to inhibition of sex hormones)
Drug-drug interaction
Selegiline (AniprylR) functions as?
Monoamine Oxidase Inhibitor (MAOI)
What is Selegiline (AniprylR) mechanism of action?
Selective. Only inhibits MAO-B
Important in dopamine levels.
Alos inhibits ACTH. Dopamine inverse relationship with ACTH. Increase dopa, decrease ACTH –> inhibits sitmulation of adrenal glands.
Not all parts of pg are stimulated by ACTH. Only those stimulated by ACTH can be inhibited. Caveat in use of selegiline for cushings: 85% have PG tumors, only 20
% of them have tumors in part of gland where ACTH is dependent on dopamine.
What is Selegiline (AniprylR) PK?
rapid absorption
liver metabolism to active metabolites
urine excretion
What is Selegiline (AniprylR) used for?
▪ For treatment of the pituitary-dependent hyperadrenocorticism
▪ For treatment of canine cognitive dysfunction syndrome
What are the adverse effects of Selegiline (AniprylR) ?
GI: Vomiting diarrhea
CNS : restlessness, repetitive movements, or lethargy;
salivation, anorexia
Diminished hearing/deafness, itching, licking,
shivers/shakes/trembles (rare)
