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Pharmacology II > EndoPharm 1 > Flashcards

EndoPharm 1 Flashcards

1
Q

What does the endocrine system encompass?

A

The Endocrine system encompasses a group of organs/glands that release hormones into circulation for regulating various physiological functions.

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2
Q

Why are the hypothalamus & pituitary gland important for regulating the endocrine system?

A

Pg is part of hypothalamus. Very small, does a lot.
Hypo regulates the endocrine system

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3
Q

What is the difference in origin between hormones and neurotransmitters?

A

Endocrine glands vs. neurons of the NS

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4
Q

What is the difference in the FORM of transport between hormones and neurotransmitters?

A

Blood vs. neurons

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5
Q

What is the difference in the DISTANCE of targets between hormones and neurotransmitters?

A

distal and local organs vs local receptors on neurons

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6
Q

What is the difference in onset of action between hormones and neurotransmitters?

A

Slow (up to a few days) vs. fast (up to miliseconds)

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7
Q

What is the difference in duration of effect between hormones and neurotransmitters?

A

Short and long lived vs. short lived

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8
Q

What is the difference in response between hormones and neurotransmitters?

A

Involuntary vs. voluntary and involuntary

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9
Q

What do hormones and neurotransmitters have in common?

A
  1. Chemicals
  2. Functions
  3. Receptor sites in target cells
  4. Regulate each other
  5. Feedback system
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10
Q

What chemicals are considered neurohormones? What does this mean?

A

**Noradrenaline (norepi), dopamine, oxytocin are all called neurohormones. Possess characteristics of both neurotransmitters and hormones.

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11
Q

What does the adrenal gland produce?

A

Adrenalin, corticosteroids

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12
Q

What does the pituitary gland produce?

A

Major producer of endocrine system.

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13
Q

What do the testicles and ovaries produce?

A

Sex hormones, testosterone, estrogen, progesterone

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14
Q

What does the brain produce?

A

Gonadotropin-releasing hormone (GnRH)

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15
Q

What does the pancreas produce?

A

Insulin, glucagon

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16
Q

What does the thyroid produce?

A

Thyroid hormones, thyroxine, triiodothyronine, parathyroid hormone

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17
Q

What are the functions of hormones?

A

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

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18
Q

How are hormones classified?

A

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.

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19
Q

ACTH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. Corticotrophin
  2. Pituitary gland
  3. Adrenals
  4. Stimulates the adrenal gland to produce a hormone called cortisol.
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20
Q

Thyrotropin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. TSH/Thyroid stimulating hormone
  2. Pituitary gland
  3. Thyroid
  4. Stimulates the thyroid gland to secrete its own hormone, which is called thyroxine
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21
Q

LH & FSH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. Gonadotrophins
  2. Pituitary gland
  3. Ovaries (females), testes (males)
  4. Controls reproductive functioning and sexual characteristics. Stimulates the
    ovaries to produce estrogen and progesterone and the testes to produce
    testosterone and sperm.
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22
Q

Prolactin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. PRL
  2. Pituitary gland
  3. Mammary glands
  4. 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.
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23
Q

Growth Hormone
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. GH
  2. Pituitary gland
  3. All cells in the body
  4. Stimulates growth and repair. Research is currently being carried out to identify the functions of GH in adult
    life.
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24
Q

ADH
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. Vasopressin
  2. Pituitary gland
  3. Kidneys
  4. Controls the blood fluid and mineral levels in the body by affecting water retention by the kidneys.
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25
Q

Oxytocin
1. Is also called?
2. Is produced by which organ?
3. Targets which organ(s)?
4. Function?

A
  1. N/A
  2. Pituitary gland
  3. Uterus, mammary glands
  4. Affects uterine contractions in pregnancy and birth and subsequent release of breast milk
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26
Q

Cortisol
1. Is produced by which organ?
2. Function?

A
  1. Adrenals
  2. 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
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27
Q

Thyroxine
1. Is produced by which organ?
2. Function?

A
  1. Thyroid
  2. Thyroxine controls many body functions, including heart rate, temperature and metabolism. It also plays a role in the metabolism of calcium in the body
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28
Q

Estrogen
1. Is produced by which organ?
2. Function?

A
  1. Ovaries
  2. 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.
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29
Q

Progesterone
1. Is produced by which organ?
2. Function?

A
  1. Ovaries
  2. 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
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30
Q

Testosterone
1. Is produced by which organ?
2. Function?

A
  1. Testes
  2. Testosterone is responsible for the characteristics of the masculine body. Testosterone is essential for the production of sperm and also acts to strengthen bones.
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31
Q

List the types of hormonal imbalances in animals.

A

❖ Pituitary Disorders
❖ Adrenal Dysfunction
❖ Thyroid/Parathyroid Disorders
❖ Disorders of Endocrine Pancreas
❖ Disorders of Reproductive System
❖ Uterine dysfunction and infections

“Patted U”

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32
Q

Drugs that produce __________-like effects, meaning they are ____________, have important therapeutic value for the treatment of endocrine _____-function

A

hormone, agonists, hypo

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33
Q

Drugs that _______ the hormone synthesis or _____ receptors can be used for the treatment of endocrine ______-function

A

inhibit, block, hyper

These are antagonists that either block the receptor or replace the hormone action.

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34
Q

Endocrine Drugs come in different classifications such as:

A

❖ 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

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35
Q

What is the function of the pituitary gland?

A

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.

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36
Q

What is the function of GH?

A

GH: stimulates growth and repair

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37
Q

What is the function of ACTH?

A

ACTH : stimulates adrenal glands to produce corticosteroids

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38
Q

What is the function of TSH?

A

TSH: stimulates thyroid gland to secrete thyroxine

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39
Q

What is the function of ADH (vasopressin)?

A

ADH (vasopressin): controls water retention by the kidneys

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40
Q

What is the function of oxytocin?

A

Oxytocin: uterine contraction and milk production

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41
Q

What is the function of LH & FSH?

A

LH & FSH: control reproductive functions

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42
Q

What is the function of PRL?

A

PRL: stimulates the breasts to produce milk

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43
Q

List three common pituitary disorders that occur in dogs and cats.

A

❖ Hypopituitarism (pituitary dwarfism)
❖ Acquired growth hormone (GH) deficiency
❖ Neoplasia

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44
Q

Acromegaly results from excess of?

A

GH

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45
Q

Cushing’s syndrome results from excess of?

A

ACTH (Increase in cortisol)
ACTH is important to act on adrenal glands –> release cortisol.

Excess ACTH can result in excess GH too.

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46
Q

Galactorrhea results from excess of?

A

PRL
This condition results in inappropriate mammary gland development and lactation without pregnancy. Can happen in both males and females.

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47
Q

Diabetes insipidus results from?

A

vasopressin deficiency or vasopressin receptor abnormality

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48
Q

Cushing’s disease affects what % of dogs?

A

80-90%

49
Q

Is Cushing’s disease common in cats?

A

Occurs less in cats

50
Q

What are the symptoms of cushing’s disease?

A

Symptoms:
weight gain
Fatigue
Hypertension
Diabetes
Premature osteoporosis

51
Q

Galactorrhea is defined as? Occurs in what sex?

A

Lactation without pregnancy
Can happen in males, but mainly females.

52
Q

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.

A
53
Q

Growth hormone signaling
Growth pathway

A

Growth factors promote cell division

54
Q

Growth hormone signaling
Growth inhibition pathway

A

Factors stop cells from growing

55
Q

Explain the process occurring in this image.

A
  • 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 GF at plasma membrane and then phosphorylates + activates JAK/STAT signaling. Receptor + peptide go into nucleus and bind to DNA to specific GH sequencing. DNA –> then transcribes different target genes. In this case it is insulin GF.

56
Q

What is Somatotropin? What is its function?

Name the two GH agents, we use as drugs, as an agonist (hypo)

A

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

Sometribove (PosilacTM) OR bovine somatotropin (bST) is used in dairy cattle to promote milk production

Used in “hypo” situations. Used as an agonist.

57
Q

Name the two GH agents, we use as drugs, as an antagonist (hyper)

A

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.

58
Q

Adrenal glands serve as a ?
What maintains homeostasis?

A

homeostatic organ, regulating reactions to stress
A negative feed-back mechanisms maintains homeostasis

59
Q

Stimuli (trauma, chemicals, stress) cause the hypothalamus to release ?

A

corticotropin-releasing hormone (CRH)

60
Q

CRH stimulates the pituitary gland to release?

A

ACTH

61
Q

ACTH stimulates the adrenal glands to ?

A

proliferate (trophic effect) and to produce corticosteroids

62
Q

Glucocorticoids are ________ and ________ system related. List two examples.

A

metabolism, immune
➢ Cortisol
➢ Corticosterone

63
Q

Mineralocorticoids are involved in _______ and _______ retention. List two examples.

A

sodium, water

➢ Aldosterone
➢ Deoxycorticosterone

64
Q

Glucocorticoids and mineralocorticosteroids are?

A

Endogenous corticosteroids

65
Q

Adrenaline and androgens?

A
66
Q
A
67
Q

Define addison’s disease.

A

❖ 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.

68
Q

Define Cushing’s disease.
What may be the result of this?

A

❖ 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

69
Q

Define Pheochromocytoma.
What does this cause?

A

❖ Pheochromocytoma (tumors of adrenal gland) in dogs and cats can cause excessive production of catecholamines, resulting in hypertension

70
Q

Corticosteroids are a class of steroid hormones that are ?

A

synthetic analogs of cortisol produced by glands that are used for therapeutic purposes.

71
Q

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

A
72
Q

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

A
73
Q

List the short-acting corticosteroids.

A

➢ Hydrocortisone (cortisol)
➢ Cortisone
➢ Fludrocortisone (MC)

74
Q

What are short-acting corticosteroids used to treat? How quickly do they act?

A

used to treat pruritus and inflammation associated with allergy

< 12 hrs

75
Q

List the intermediate-acting corticosteroids.

A

➢ Prednisone
➢ Prednisolone
➢ Methylprednisolone
➢ Triamcinolone

76
Q

What are intermediate-acting corticosteroids used to treat? How quickly do they act?

A

used for the long-term control of allergies, chronic inflammation, immunosuppression, and lymphoma control

12-36 hrs

77
Q

List the long-acting corticosteroids.

A

➢ Dexamethasone
➢ Betamethasone
➢ Paramethasone
➢ Flumethasone

78
Q

What are long-acting corticosteroids used to treat? How quickly do they act?

A

used topically to treat inflammation and pruritus associated with allergies

36-72 hrs

79
Q

Glucocorticoids have one of the most widespread and potent ?

A

immunosuppressant anti-inflammatory effects of any drug class

80
Q

Glucocorticoids function to?
▪ Decrease which cells?
▪ Decrease _______ migration into tissues
▪ Macrophages produce less
▪ Phospholipase A2 is inhibited, so __________ _____ is not available to produce inflammatory _________ and _________
▪ Effects on COX-__ decreasing prostaglandin production
▪ Decrease ________ release by mast cells
▪ ____ and ____ growth is inhibited

A
  1. T and B cells, eosinophils, basophils, and monocytes
  2. neutrophil
  3. TNFα, interleukins, plasminogen activator, interferon γ
  4. arachidonic acid (AA), prostaglandins, leukotriens
  5. 2
  6. histamine
  7. Hair, skin
81
Q

Insufficient or excessive glucocorticoid activity can?

A

increase susceptibility to infections

82
Q

Glucocorticoids increase?
Increase _________ and ______ metabolism
Increase ______ breakdown
Increase ________ responses and ________ contractions
Increase _______ synthesis
Increase expression of α- and β- ________Rs

A

lipogenesis, glucose
protein
vasomotor, myocardial
epinephrine
adrenergic

83
Q

Glucocorticoids facilitate? Promote?

A

Facilitate the angiotensin system
Promote the breakdown of bradykinin, a vasodilator

84
Q

Glucocorticoids decrease?

A

Decrease capillary permeability

85
Q

How do glucocorticoids act on electrolytes and water balance?

A
  • Reduce ADH (vasopressin) secretion
  • Increased excretion of Na+ and H2O
  • Ca++ - mediated hypokalemia leading
    to increase PTH secretion
  • Promote osteoblasts apoptosis

Last two –> osteoperosis

86
Q

How do Glucocorticoids act on the brain?

A

Stimulate the CNS leading to euphoria

87
Q

How do Glucocorticoids act on the lungs?

A

Cause bronchodilation
Decrease histamine, bradykinin, prostaglandins
Induce decongestion of the airways

88
Q

How do Glucocorticoids act on skeletal muscle?

A

Maintain skeletal muscle function

89
Q

What are the adverse effects of Corticosteroid use?

A
  • 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
90
Q

What are the adverse effects of Corticosteroids in dogs specifically?

A

Hepatotoxicity in dogs

91
Q

What are the adverse effects of Corticosteroids in cats specifically?

A

Congestive heart failure in cats

92
Q

The long-term use of Corticosteroids has effect like ?

A

in Cushing’s Syndrome (pituitary adenoma secreting ACTH)

93
Q

Should you stop using Corticosteroids abruptly? Explain.

A

No –> negative feedback mechanisms.
Causes:
* Anorexia
* Nausea/vomiting
* Weight loss
* Lethargy
* Joint and muscle pain
* Postural hypotension
* Low blood pressure

94
Q

Abruptly stopping Corticosteroids resembles?

A

Addison’s disease

95
Q

Corticosteroid therapy serves as?

A
  1. Replacement Therapy for hypoadrenocorticism (Addison’s disease)
  2. Adrenal Steroid Inhibitors to control hyperadrenocorticism
    (Cushing’s disease or adrenal gland carcinoma)
96
Q

List two examples of replacement therapy for hypoadrenocorticism.

A

➢ Deoxycorticosterone pivalate suspension
➢ Fludrocortisone: has high mineralocorticoid and glucocorticoid potency

97
Q

List four examples of adrenal steroid inhibitors to control hyperadrenocorticism.

A

➢ Mitotane
➢ Trilostane
➢ Ketoconazole
➢ Selegiline

98
Q

Mitotane (LysodrenR) functions as?

A

an irreversible corticosteroid inhibitor

99
Q

What is Mitotane’s (Lysodren) mechanism of action?

A

Cytotoxic to the zones of adrenal cortex that secrete
all endogenous steroids except aldosterone

100
Q

What is Mitotane’s (Lysodren) PK?

A

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

101
Q

What is Mitotane’s (Lysodren) used for?

A

Cushing’s syndrome and adrenal neoplasms

102
Q

What are the adverse effects of Mitotane’s (Lysodren)?

A

Lethargy, weakness, ataxia, anorexia, vomiting, or diarrhea
Hepatotoxicity
Mitotane-induced hypoadrenocorticism (fludrocortisone replacement therapy)

103
Q

Trilostane (ModrenalR) functions as?

A

a synthetic steroid analog

104
Q

What is Trilostane (ModrenalR) mechanism of action?

A

Competitive inhibitor of an enzyme that is essential for corticosteroid
synthesis

105
Q

What is Trilostane (ModrenalR) PK?

A

PO: absorption through GI tract in dogs (peak levels in 2 hrs)
Liver metabolism, urine/feces excretion
Plasma t1/2 is ~1 hr

106
Q

What is Trilostane (ModrenalR) used for?

A

In dogs for treatment of Cushing’s syndrome

107
Q

What are the adverse effects of Trilostane (ModrenalR) ?

A

Lethargy, anorexia, vomiting, electrolyte abnormalities, and diarrhea

108
Q

What are the contraindications of Trilostane (ModrenalR) ?

A

Pregnant animals (inhibits progesterone synthesis )

109
Q

Ketoconazole functions as?

A

blocks production of adrenal steroids

110
Q

What is Ketoconazole’s mechanism of action?

A

Reversible inhibition of cytochrome P450 enzymes that are involved in steroid synthesis

111
Q

What is Mitotane’s (Lysodren) PK?

A

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

112
Q

What is Ketoconazole used for?

A

to treat hyperadrenocorticism in dogs that are resistant to mitotane and
as palliative therapy in dogs with cancer metastasis

113
Q

What are the adverse effects of Ketoconazole?

A

Anorexia, vomiting, and/or diarrhea are the most common
Hepatotoxicity
Reproductive disturbances (due to inhibition of sex hormones)
Drug-drug interaction

114
Q

Selegiline (AniprylR) functions as?

A

Monoamine Oxidase Inhibitor (MAOI)

115
Q

What is Selegiline (AniprylR) mechanism of action?
What is the caveat with using this drug?

A

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.

116
Q

What is Selegiline (AniprylR) PK?

A

rapid absorption
liver metabolism to active metabolites
urine excretion

117
Q

What is Selegiline (AniprylR) used for?

A

▪ For treatment of the pituitary-dependent hyperadrenocorticism
▪ For treatment of canine cognitive dysfunction syndrome

118
Q

What are the adverse effects of Selegiline (AniprylR) ?

A

GI: Vomiting diarrhea
CNS : restlessness, repetitive movements, or lethargy;
salivation, anorexia
Diminished hearing/deafness, itching, licking,
shivers/shakes/trembles (rare)

Pharmacology II (27 decks)

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