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BIOL2049 S2 > Endocrine pharmacology > Flashcards

Endocrine pharmacology Flashcards

1
Q

LO

A
  • Describe the role of corticotrophin and adrenal steroids.
  • Describe the role of the hypothalamic pituitary axis
  • Describe the female reproductive system and contraceptive drugs.
  • Describe the endocrine pancreas and the control of blood glucose
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2
Q

Lecture content

A
  • Overview of the endocrine system; the role of the hypothalamic pituitary axis
  • Corticotrophin and adrenal steroids
  • The female reproductive system and contraceptive drugs
  • The endocrine pancreas and the control of blood glucose
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3
Q

Which label represents the pituitary gland?

A

b

a is the hypothalamus

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4
Q

What hormone is produced when stressed?

A

If stressed, you have an increased level of cortisol as the limbic system connected to hypothalamus which is connected to anterior and posterior pituitary which is involved in hormone production

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5
Q

Which of the following statements is false…

  1. The anterior and posterior pituitary have the same embryological origin
  2. The pituitary stalk contains a portal blood supply
  3. The release of hormones from the anterior pituitary is controlled by releasing factors
  4. There is a region in the pituitary called the intermediate lobe
A

1 is false

The pituitary is an organ of dual origin. The anterior lobe (adenohypophysis) is derived from oral ectoderm and is epithelial in origin, whereas the posterior lobe (neurohypophysis) derives from the neural ectoderm.

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6
Q

Tell me the relationship between the hypothalamus and the anterior and posterior pituitary glands

A
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7
Q

How does the hypothalamus signal to the anterior pituitary?

Explain the feedback loops and draw the diagram

A
  • RF travel in portal blood supply and act on anterior pituitary
  • The loop has a negative feedback loop; once hormones released from anterior pituitary they can feedback and act on receptors on the anterior or in the hypothalamus to inhibit the further release of the RF or the hormone (controls the amount of hormone circulating the body at any one time)- provides for homeostasis
  • Control from posterior pituitary doesn’t contain RF
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8
Q

What are releasing factors?

A

releasing factors (RF) are hypothalamic hormones

Most are Neuropeptides (sequences of AA)- the clue to their role is in their name

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9
Q

Give some examples of neuropeptides

A
  • Growth hormone-releasing factor (GHRF)
  • Somatostatin (GH inhibiting factor)
  • Thyrotrophin-releasing hormone (TRH)- 3 AA long
  • Corticotrophin-releasing factor (CRF)
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10
Q

give an example of a hypothalamic hormone that isnt a neuropeptide

Tell me its sequence from release to target

A

DOPAMINE – this is a catecholamine not a neuropeptide

a precursor for noradrenaline in the brain

it inhibits prolactin release

released from the hypothalamic neurones –> portal blood supply where its –>released form the anterior pituitary –> inhibits prolactin release

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11
Q

Tell me the cells of the anterior pituitary and their function

A
  • Lactotrophs- release prolactin
  • Somatotrophs- release GH
  • Corticotrophs- release corticotrophin and control cortisol levels
  • Gonadotrophs- control hormones to do with gonads and reproduction
  • Thyrotrophs- release TSH
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12
Q

How does the hypothalamus signal to the posterior pituitary?

A
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13
Q

Tell me the posterior pituitary hormones, where the cells they are secreted from are located and the major functions of the hormone?

A
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14
Q

Summary of pituitary hormones

A
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15
Q

Tell me some disorders fo the hypothalamic-pituitary axis

A

Growth hormone

Thyroid hormone

Diabetes insipidus

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16
Q

What type of hormone is GH and what does this mean?

A

GH = Anabolic hormone (builds up body tissue and builds muscle by stimulating AA uptake into muscle)

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17
Q

Tell me some of the major functions of GH?

A
  • Stimulates amino acid/protein uptake into muscle.
  • Stimulates IGF-1 (insulin-like growth factor-1) release from liver. IGF-1 is a somatomedin- anabolic
  • IGF-1 especially important in growth of skeleton and cartilage
  • (GH inhibits glucose uptake)- increases circulating levels of glucose in body. Works in an antagonistic fashion to insulin (Diabetes can be a side effect to levels of GH)
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18
Q

Tell me some disorders that can occurs from GH secretion?

A

In childhood: Altered growth/stature (could be too much or too little) e.g., gigantism due to excessive GH in adulthood and dwarfism if too little GH

In adulthood: ↑GH Acromegaly (enlargement in soft tissues)

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19
Q

Tell me some different treatmenrs for the GH insufficiency pituitary dwarfism

A
  1. Injection human recombinant GH (Somatropin)
  2. Injection of human recombinant IGF-1 (Mecasermin) –

abnormal GH receptor Laron’s dwarfism: typically caused by mutations in the GH receptor which is located on the liver so can no longer produce IGF-1

GHRF–> acts via anterior pituitary –> GH –> Liver –> IGF1

  1. Sermorelin is a GHRF analogue- used a diagnostic and also to increase growth in children.

Can treat with GHRF as would predict to see an increase in GH and if there isn’t then there’s an issue in the anterior pituitary. But if do see an increase then could be due to issue with GHR. Can be used as a diagnostic to look at how levels differ (think about signaling cascade to thing about how treatments and diagnostic regiments work)

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20
Q

What is acromegaly?

A

Excess of GH

Growth of soft tissues especially around the jaw and ears

mild hyperglycaemia (Hyperglycaemia is the medical term for a high blood sugar (glucose) level)

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21
Q

Tell me about the treatment for acromegaly?

A

The goal of treatment is to restore the pituitary gland to normal function, producing normal levels of growth hormone. Treatment may include removal of the tumor, radiation therapy, and injection of growth hormone blocking drugs. Left untreated, acromegaly can lead to worsening diabetes mellitus and hypertension.

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22
Q

What does thyroid hormone have a key role in?

A

metabolism and development

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23
Q

What does thyroid hormone increase?

A
  • lipid, carbohydrate and protein metabolism
  • oxygen consumption
  • heat production
  • basal metabolic rate

uncoupling oxidative phosphorylation to bring about calorigenic effect

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24
Q

What does the thyroid gland produce and tell me about this?

A

Thyroid glands produce: Thyroxine (T4= prohormone) & Triiodothyronine (T3). Both are tyrosine-based hormones which means they contain tyrosine

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25
Q

What does the production of thyroid hormone require?

A

iodine

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26
Q

What does the thyroid hormone target?

A

Target cells contain thyroid hormone nuclear receptor (TR)

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27
Q

Tell me a condition that comes about due to a lack of iodine in the diet

Tell me the treatment for it

A
  • Non-toxic goitre (= Derbyshire neck)
  • Childhood iodine deficiency= cretinism
  • Hyperplasia from lack of thyroid hormones: negative feedback from TH to TRH and TSH stopped. This increases the TSH levels and decreases that to thyroid gland

TRH –> TSH –> acts on thyroid gland –> TH

TH inhibits TSH and TRH via negative feedback loop

  • Simple treatment
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28
Q

Give two examples of hypothyroidism?

What types of diseases are these?

A
  • Myxoedema
  • Hashimoto’s disease/ Hashimoto’s thyroiditis most common

=autoimmune disease

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29
Q

What are some symptoms of hypothyroidism?

A

Symptoms: fatigue/depression/weight gain/cold intolerance

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30
Q

Name a hyperthyroid disease?

A

Graves’ disease (diffuse toxic goitre)- often autoimmune

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31
Q

Give some examples of hyperthyroidism

A

Symptoms: anxiety/ hyperactivity/ Weight loss/goitre/bulging eyes/ tachycardia/sweating

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32
Q

Cascade for thyroid T3 and T4

A
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33
Q

What is the structure of Thioureylenes?

A

-S=C-N-

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34
Q

Give some examples of Thioureylenes

A

Eg carbimazole, methimazole. Inhibit iodination of tyrosine

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35
Q

What is Protirelin and what is it used for?

A

Protirelin- synthetic TRH, used diagnostically to test functionality of anterior pituitary to produce thyrotrophin/TSH

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36
Q

How does Thioureylenes inhibit thyroperoxidase?

A
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37
Q

Tell me disorders of the hypothalamic posterior pituitary axis and treatment?

Tell me the hormones involved

A
  • Antidiuretic hormone/Vasopressin
  • (involved in blood volume and osmolarity control)
  • ↓ADH Diabetes insipidus; treatments with hormone analogues
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38
Q

Learning outcomes checklist

A
  • Describe the role of the hypothalamic pituitary axis

We have covered:

  • how hormones are released from the pituitary gland- giving specific examples.
  • conditions associated with pituitary hormone imbalance and what interventions are possible.
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39
Q

Practice essay question

A

Outline the role of the hypothalamus in regulating tropic hormone release from the anterior pituitary. (70%) Using a named specific example of an endocrine disorder, show the importance of a pharmacological intervention in the above system. (30%)

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40
Q

Adrenal gland hormones

A
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41
Q

Name some hormones produced by adrenal glands

A

Adrenal cortex

  • Aldosterone
  • Androgens
  • Cortisol
42
Q

What is aldosterone?

What does it act on?

What ions does it effect and what effect does it cause?

A
43
Q

What does aldosterone regulate?

A

regulates water and electrolyte balance

44
Q

Tell me the regulation of aldosterone secretion?

A
  • ↓ extracellular fluid
  • Activates kidney release of renin
  • Renin convert Angiotensin to Ang I then
  • ACE converts to Ang II
  • Ang II acts on adrenal cortex to stimulate aldosterone production
45
Q

When aldosterone is released it creates more Na+ retention, what does it increase?

A
46
Q

What is cortisol?

A

The bodys major glucocorticoid hormone

47
Q

Tell me three functions of cortisol?

A
  1. metabolic
  2. actions on tissues and organs
  3. anti-inflammatory and immune response
48
Q

Tell me the metabolic function of cortisol on skeletal muscle, adipose and liver

A
49
Q

Tell me the action of cortisol on tissues and organs

A
50
Q

Tell me the anti-inflammatory and immune responses of cortisol

A
51
Q

Adrenal steroids: synthesis of aldosterone and hydrocortisone

A
52
Q

All steroid hormones are made from what?

A

Cholesterone

53
Q

What is the first step in Steroidogenesis (production of steroid hormones)?

A

Conversion of Cholesterol into Pregnenolone first step in STEROIDOGENESIS (production of steroid hormones)

54
Q

What does ACTH and Angiotensin II increase?

A

Pregnenolone production

55
Q

Whats made from Pregnenolone?

A

From Pregnenolone both Aldosterone and Cortisol (and the Sex Steroids) are made.

56
Q

What does 17a-hydroxylase convert aldosterone precursors into?

A

cortisol precursors

57
Q

Aldosterone production from corticosterone is stimulated by what?

A

Angiotensin II

58
Q

What is the final enzyme synthesis of cortisol?

A

11-b-hydroxylase

59
Q

Name two diseases of the adrenal glands?

A
60
Q

What are the signs and symptoms of Cushing’s syndrome?

What is it caused by?

A

= signs and symptoms associated with cortisol excess

Often caused by excessive steroid medication

61
Q

Whats cushing’s disease?

A

A type of cushings syndrome

62
Q

What is Cushing’s diseased caused by?

What does it lead to?

A
  • Caused by CRH or ACTH excess
  • Leads to excessive cortisol secretion
63
Q

What are the symptoms of Cushing’s disease?

A
64
Q

What are the treatments of Cushing’s disease and why are they used?

A
  • Aminoglutethimide: decreases synthesis of all steroid hormones (blocks actions of P450scc)
  • Metyrapone: 11-b-hydroxylase inhibitor
    *
65
Q

Whats another treatment of Cushing’s disease?

A
66
Q

What is often the main causes of Addison’s disease?

A

The primary kind is known as Addison’s disease. It is rare. It is when the adrenal glands don’t make enough of the hormones cortisol and aldosterone

Secondary adrenal insufficiency occurs when the pituitary gland doesn’t make enough of the hormone ACTH

67
Q

Is Addison’s disease autoimmune and if it is what does it destroy?

A
68
Q

When someone has addison’s disease there is an adrenal gland deficiency. A decrease in glucocorticoids and mineralocorticoids can lead to what?

What is a decrease in these hormones due to?

A
69
Q

Tell me some clinical uses of corticosteroids?

A

Uses of an anti-inflammatory or immunosuppressant

  • Replacement therapy for AD-
  • Rheumatoid arthritis
  • Asthma
  • Chronic Obstructive Pulmonary disease (COPD)
  • Lupus
  • Allergic rhinitis (hay fever)
  • Ulcerative colitis
  • Eczema
  • Psoriasis
  • Multiple sclerosis
  • Often used in cancer therapy- various reasons….e.g.hodkins lymphonma the corticosteroid can decrease lymphocyte production
70
Q

Examples of corticosteroid medication

A
71
Q

Name some corticosteroid medication…

A
72
Q

LO checklist

A
  • Be able to describe the actions of cortisol and aldosterone.
  • Be able to describe how steroid hormones are made from cholesterol.
  • Be able to describe what Addison’s disease and Cushing’s Syndrome are.
  • Be able to describe why cortisol and corticosteroids can have unwanted actions.
  • Appreciate the drug choices available for corticosteroids
73
Q

Tell me the function of the hypothalamus in the female reproductive system and what it acts on?

Tell me the hormones involved and their role

A
74
Q

Tell me the role of FSH, 17b oestradiol and LH role on ovulation?

A
  • FSH stimulates growth of ovarian follicles (each follicle contains one oocyte).
  • 17b oestradiol is produced by growing follicles. 17b oestradiol negative feedback prevent excessive FSH production.
  • In humans only one follicle fully matures (Graafian Follicle- GF)
  • 17b oestradiol triggers release of Luteinising Hormone
  • Ovulation triggered by a LH rise
75
Q

Tell me the role of progesterone in the female reproductive system?

A
  • GF forms corpus luteum (CL) after ovulation. CL produces hormone progesterone (and some 17b oestradiol)
  • Progesterone stimulates uterus for embryo implantation
  • Progesterone prevents formation of new CL by inhibiting FSH release.
  • Progesterone= hormone of pregnancy
  • Progesterone stimulate cervix to produce a mucous that prevents sperm entry
76
Q

Name the oestrogens?

A

17b-oestradiol

Oestrone

Oestriol

77
Q

Tell me the major functions of the oestrogens in pregnancy?

A

17b-oestradiol, oestrone, oestriol in pregnancy

  • Puberty
  • Pregnancy functions (breast development, childbirth)
  • Maintain menstrual cycle
  • Sexual desire (some species)
  • Prevent bone resorption
  • Increase blood coagulation (increase blood factors)
  • Decrease blood platelet aggregation
  • Increase Blood High-density Lipoprotein (HDL)
  • Decrease Blood Low-Density Lipoprotein (LDL)
  • Decrease plasma cholesterol
78
Q

What are the major uses of oestrogen drugs? Why may it be given to the patients in each case?

A
  1. Primary hypogonadism: stimulates development of secondary sexual characteristics and accelerates growth in children.
  2. Primary amenorrhea (no periods): induces an artificial menstrual cycle in adults.
  3. Contraception: as an oral contraception in women. Given with a progestogen.
  4. Hormone Replacement Therapy (HRT): Given to women at or after the menopause. HRT helps physical symptoms of menopause and bone loss (osteoporosis).
79
Q

Tell me the combination of oestrogen and progestins in oral contraceptives?

When are they administered?

A

Combination of oestrogens and progestins

  • oestrogen: ethinyl oestradiol
  • progestin: norethindrone

Administered orally, daily Day 5 - 21 of ovarian cycle

80
Q

What are the three types of formulation in oral contraceptives?

A

Three types of formulation: monophasic, biphasic and triphasic

81
Q

How do oral contraceptives act?

A

Act by providing negative feedback to the pituitary and shut down secretion of LH and FSH

82
Q

What are the adverse effects of oral contraceptives?

A
  • Abnormal menstrual bleeding
  • Hypertension (due to the CV effects of hormones)
  • Increased appetite, weight gain
  • Nausea, oedema, breast tenderness
83
Q

What are the uses of antiprogestogens?

A
  • Medical termination of pregnancy (arbortifacient): mifepristone (RU-486). Emergency ‘Contraception’.
  • Endometrial shedding and embryo loss from site of implantation; cervix softening.
84
Q

What do Oestrogens bind?

A

Nuclear receptors in target cells

85
Q

What are the Oestrogens receptors?

A

Oestrogen receptors are: Estrogen Receptor α (ERα) or Estrogen Receptor β (ERβ).

There are multiple forms of ERα and ERβ.

86
Q

Tell me the types of ER (estrogen receptors) tissues can have?

Give example locations

A

A tissue can have just one type of ER (e.g brain regions) or both (eg prostate).

87
Q

Tell me the actions of anti-oestrogens?

A

Due to variety of ER’s, actions of anti-oestrogens can be varied and tissue specific.

88
Q

Tell me about the drug Clomiphene?

What does it induce?

What type of drug is it?

What is it used for?

A
  • Clomiphene – induces ovulation by reducing negative feedback inhibition of oestrogen on hypothalamus and anterior pituitary gland.
  • Clomiphene - non-steroidal oestrogen antagonist
  • Used in fertility treatment for anovulation
89
Q

Explain the action of Clomiphene?

A
90
Q

What do Oestrogens bind?

A

Oestrogens bind nuclear receptors in target cells (ERα or ERβ) modification of gene transcription.

91
Q

Tell me about the antioestrogen SERMs?

What is the SERM Tamoxifen and Raloxifene used to treat?

A
  • SERMS (Selective oEstrogen Receptor Modulators) = competitive antagonists or partial agonists of oestrogen- ER binding
  • SERM- Tamoxifen is used in oestrogen-dependent breast cancer.
  • SERM- Raloxifene is used to treat postmenopausal bone loss.
92
Q

LO checklist

A
  • Be able to describe the hormonal control of sperm production in the testis.
  • Be able to describe the synthesis relationship between oestrogen and testosterone.
  • Be able to describe the hormonal control of ovulation and pregnancy.
  • Be able to describe what is meant by progestins, oestrogens, and antiestrogens (including SERMs)
93
Q

Name the two cells in the pancreas?

What is their role?

A

Alpha cell: Glucagon-secreting cell

Beta cell: Insulin-secreting cell

94
Q

What is the collection of alpha and beta cells called?

A

The Islet of Langerhans in the pancreas

95
Q

Tell me the chain of events when there is high blood glucose?

A
96
Q

Tell me the chain of events when there is low blood glucose?

A
97
Q

Tell me the factors that regulate insulin secretion?

A
98
Q

Tell me the disorders of glucose homeostasis and the treatments?

A

Disorders of glucose homeostasis

  • Diabetes- Type 1 and Type 2

Treatments:

  • Insulin replacement
  • Oral hypoglycaemics
99
Q

Tell me oral hypoglycaemic agents

A
  • Sulfonylureas
  • Biguanides
  • Alpha-glucosidase inhibitors
  • Thiazolidinediones
100
Q

Summary

A
  • You should have an overview of the disorders of the endocrine system and therapeutic drugs
  • Sample exam questions:
  • 1. Outline two endocrine disorders that result from abnormal function of the hypothalamic-pituitary axis. What are the symptoms and how can they be ameliorated?
  • 2. What clinical conditions can be treated with glucocorticoids? Include in your answer a description of the side-effects of drug treatment and how they arise.
  • 3. Write short notes on BOTH of the following

a) oral contraceptive drugs

b) oral hypoglycaemic drugs

BIOL2049 S2 (10 decks)

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