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Therapeutic Pharmacology 2 > Endocrine System > Flashcards

Endocrine System Flashcards

1
Q

Where are mineralocorticoids produced?

A

Zona glomerulosa of the adrenal cortex

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2
Q

Where are glutocorticoids produced?

A

Zona fasciculata of the adrenal cortex

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3
Q

Give an example of a minerocorticoid

A

Aldosterone

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4
Q

What is the function of aldosterone?

A

Tubular reabsorption of Na+, Cl-

Tubular K+ excretion

Osmotic retention of H2O ; increase in blood pressure

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5
Q

Give an example of a glucocorticoid

A

Hydrocortisone

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6
Q

How is the synthesis and secretion of adrenal corticosteroids regulated?

A

Adrenocorticotrophic hormone (ACTH) stimulates synthesis and release of glucocorticoids (eg. hydrocortisone) from the adrenal cortex

Corticotrophin-releasing factor (CRF) from the hypothalamus regulates ACTH release and is regulated in turn by neural factors and negative feedback from plasma glucocorticoids.

Mineralocorticoid (aldosterone) release from the adrenal cortex is predominantly controlled by the renin angiotensin system

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7
Q

What is the mechanism of action of glucocorticoids?

A

Bind intracellular receptors which dimerise, migrate to the nucleus and interact with DNA to modify gene transcription and protein synthesis

Induce synthesis of some proteins and inhibit synthesis of others.

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8
Q

What is the mechanism of the anti-inflammatory/immunosupressive actions of glucocorticoids?

A

Inhibit the transcription of genes whose protein products are involved in the inflammatory response (COX-2)

Increase the expression of genes whose protein products are anti-inflammatory (annexin-1)

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9
Q

Describe the structure of the glucocorticoid receptor

A

The glucocorticoid receptor protein has 3 domains

Two zinc fingers are located in the central region and believed to wrap around the DNA helices.

There are also phosphorylation sites and regions of hormone-independent activation function (AF1) and hormone-dependent activation function (AF2) related to transcription.

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10
Q

What is the function of parathyroid hormones?

A

Controls blood calcium and phosphate levels

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11
Q

How does parathyroid hormone control blood calcium levels?

A

Stimulates release of Ca2+ from bone

Reabsorption of Ca2+ from urine

Absorption of Ca2+ from the gut

High plasma levels lead to decreased secretion via binding of Ca2+ to Ca2+ sensing GPCRs on parathyroid gland

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12
Q

Name two hormones secreted by the adrenal medulla

A

Adrenaline

Noradrenaline

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13
Q

What are the functions of adrenaline and noradrenaline?

A
  • Control metabolism
  • Cardiovascular function
  • Response to stress
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14
Q

What are the effects of adrenaline?

A
  • Increase in cardiac output
  • Dilates bronchi
  • Dilates pupils
  • Relaxes gut smooth muscle
  • Stimulates cortisol production/secretion
  • Stimulates glucose release from liver
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15
Q

What types of hormones are released from the adrenal cortex?

A

Mineralocorticoids

Glucocorticoids

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16
Q

What are the functions of hydrocortisone?

A

Controls metabolism

Stress response

Suppression of immune response

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17
Q

What are the domains of the glucocorticoid receptor protein?

A
  • Amino terminus (regulatory domain)
  • Carboxyl terminus for hormone binding
  • DNA binding domain (DBD)
18
Q

What causes Addison’s disease?

A

Autoimmune disease or chronic inflammatory condition (e.g. TB)

19
Q

What are the symptoms of Addison’s disease?

A

Low blood pressure
Weight loss
Depression
Malaise

20
Q

What is the treatment for Addison’s disease?

A

Glucocorticoids used in replacement therapy

21
Q

Glucocorticoids are used as antiinflammatory/immunosuppressive agents in what diseases?

A

Asthma
Eczema
Rheumatoid arthritis

22
Q

How are glucocorticoids administered in asthma treatment?

A

Inhaler

Orally if inhaled treatment insufficient

23
Q

How are glucocorticoids administered in eczema treatment?

24
Q

What glucocorticoid is used in cancer treatment?

A

Dexamethasone

25
Why is dexamethasone used in cancer treatment?
Cancer patients undergoing chemotherapy are given dexamethasone to counteract certain side effects of their antitumor treatment
26
Why are glucocorticoids administered to patients with brain tumours?
To reduce cerebral oedema in patients with metastatic or primary brain tumours
27
What are the side effects of glucocorticoids?
Suppression of responses to infection Osteoporosis (↓ activity of osteoblasts but ↑ activity of osteoclasts) Cushing’s disease (iatrogenic) Suppression of endogenous glucocorticoid synthesis ↓ fibroblast function, ↓ production of collagen and glycoseaminoglycans, reduced angiogenesis, fibrosis, therefore reduced wound healing and repair
28
When do side effects from glucocorticoids appear?
Often after prolonged use
29
What are the symptoms of Cushing's disease?
``` Euphoria Buffalo hump Hypertension Cataracts Moon face, with red cheeks Increased abdominal fat Easy bruising Poor wound healing Thinning of skin Thin arms and legs (wasting) ```
30
What causes Cushing's disease?
Caused by excessive exposure to glucocorticoids, but also Increased free circulating levels Glucocorticoids owing to Increased ACTH (pituitary tumour) Increased cortisol secretion caused by adrenal tumour There is an alcohol induced pseudo form of the syndrome
31
By what mechanism do mineralocorticoids act?
Binds to intracellular receptors Receptor binding initiates transcription and translation of proteins resulting in : ↑ no. of Na+ channels in the apical membrane ↑ No. of Na+-K+-ATPase molecules in the basolateral membrane
32
What are the clinical uses for mineralocorticoids?
Main use in replacement therapy in Addison’s disease Main agent fludrocortisone Administered orally to produce a mineralocorticoid effect Acts on intracellular receptors to modulate synthesis of various protein regulators ↑ Na+ reabsorption in distal tubes ↑ K+ and H+ efflux into the tubules Used in combination with glucocorticoids in replacement therapy
33
What are the central tenets of the control of blood glucose?
Glucose is the obligatory source of energy for the adult brain Physiological control of blood glucose reflects the need to maintain adequate fuel supplies in the face of intermittent food intake and variable metabolic demands More fuel is made available by feeding that is required immediately and excess calories are stored as glycogen or fat. During fasting, these energy stores are mobilised in a regulated manner The most important regulatory hormone is insulin Increased blood glucose stimulates insulin secretion Reduced blood glucose reduces insulin secretion
34
What are the 4 main cell types in the islets of Langerhans?
Alpha cells Beta cells Delta cells F cells
35
What is the function of the alpha cells in the islets of Langerhans?
Alpha cells secrete glucagon (increases blood glucose, breaks down glycogen into glucose)
36
What is the function of the beta cells in the islets of Langerhans?
Beta cells secrete insulin (decreases blood glucose, by facilitating glucose uptake into tissues and promotes the synthesis of glycogen from glucose)
37
What is the function of the delta cells in the islets of Langerhans?
Delta cells secrete somatostatin which inhibits the secretion of glucagon and insulin from a and b cells, respectively.
38
What is the function of the F cells in the islets of Langerhans?
F cells produce pancreatic polypeptide which regulates the secretion of digestive juices
39
What stimulates the secretion of insulin?
Presence, in the blood, of: Glucose Amino acids and fatty acids Gastro-intestinal (GIT) hormones; incretins
40
What are the main incretins?
GLP-1 (glucagon-like peptide 1) GIP (glucagon-like insulinotropic peptide)
41
What are incretins and what are their function?
Incretins are GI peptides which stimulate insulin secretion Inhibit pancreatic glucagon secretion from a cells Slow the rate of absorption of digested foods by decreasing gastric emptying
42
What tissues does insulin target?
Skeletal muscle Adipose tissue Liver

Therapeutic Pharmacology 2 (7 decks)

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