8th lecture - glucocorticoids

Question 1

Adrenocorticotropic hormone is released from the

Answer 1

adenohypophysis

Question 2

Adrenocorticotropic hormone stimulates

Answer 2

ACTH stimulates secretion of glucocorticoid steroid hormones from adrenal cortex cells, especially in the zona fasciculata of the adrenal glands.

Question 3

the adrenal cortex of the adrenal glands synthesizes what

Answer 3

The cortex produces steroid hormones: glucocorticoids, mineralocorticoids, and adrenal androgens

(and the medulla produces the catecholamines, epinephrine, and norepinephrine)

Question 4

Broad function of Glucocorticosteroids

Answer 4

they impact the metabolism of proteins, lipids, carbohydrates and they have an anti-inflammatory effect.

They maintain homeostasis of liquids in an organism.

They maintain microcirculation, normal vascular permeability, stability of lysosomal membranes, they suppress inflammatory reactions.

Question 5

Broad function of Mineralocorticosteroids

Answer 5

they impact the metabolism of water and electrolytes.

Aldosterone is the most impostant mineralocortocoid.

Question 6

the most impostant mineralocorticoid

Answer 6

aldosterone

Question 7

aldosterone main role

Answer 7

main role is to regulate salt and water in the body, thus having an effect on blood pressure.

Question 8

Natural Representatives of glucocorticosteroids (2)

Answer 8

cortisone, hydrocortisone

Question 9

Synthetic Representatives of glucocorticosteroids (4)

Answer 9

prednisolone,
dexamethasone,
triamcinolone,
flumethasone and many others

Question 10

Effects of glucocorticosteroids In the metabolism of proteins, lipids and carbohydrates (4)

Answer 10

Increased gluconeogenesis

Antagonism of insulin

Increased catabolism of proteins

Fatty degeneration (the relocation of lipids, increase in appetite)

Question 11

Glucocorticoids inhibit bone formation by inhibiting osteoblast proliferation and the synthesis of bone matrix.

In people, chronic administration of glucocorticoids can result in?

Answer 11

osteoporosis

Question 12

Glucocorticoids potentiate the action of what hormone?

Answer 12

parathyroid hormone and decrease the gut absorption of Ca.

Question 13

How might excessive glucocorticoids affect young animals?

Answer 13

may reduce growth

Question 14

General effects of glucocorticosteroids (2-3)

Answer 14

Anti-inflammatory effect
Immunosuppressive, antiallergic effect

Question 15

duration of effect of Natural steroids

Answer 15

are short acting.

Question 16

Glucocorticoids are metabolised in the

Answer 16

liver.

They are excreted to the extent of 75% in urine and to the extent of 25% in faeces.

Question 17

The effect of glucocorticosteroids is to a large extent based on

Answer 17

the inhibition of protein, including enzyme protein synthesis and the deceleration of the proliferation of cells.

Question 18

Glucocorticoids effect on protein metabolism.

Answer 18

They cause catabolism, which leads to a negative nitrogen balance. A large amount of nitrogen and uric acid is secreted into urine.

Anabolism is impeded, growth disturbance occurs, wounds heal badly.

Animals become weakened and passive (this happens in case of a long-term administration of glucocorticoids), the synthesis of antibodies is decelerated.

Question 19

Glucocorticoids effect on carbohydrate metabolism.

Answer 19

Gluconeogenetic effect - they improve the formation of glucose from lactate, glycerol and glucogenic amino acids.

They inhibit the break down of glucose.

Hyperglycaemia and glycosuria are experienced in case of an overdose.

Question 20

Glucocorticoids effect on lipid metabolism.

Answer 20

Fatty degeneration occurs – deposition of fat on the stomach, back and face (Cushing’s syndrome, moon face in people).

The mechanism of how the metabolism of lipids occurs is not exactly known.

Question 21

How do large doses of glucocorticoids effect water and electrolyte metabolism?

Answer 21

Large doses cause oedemas, hypokalaemia and metabolic alkalosis.

Question 22

Anti-inflammatory effects of glucocorticoids.

Answer 22

They suppress the reaction of tissue tochemical, thermal, traumatic, allergic and infectious factors.

The classic features of inflammation resolve (oedema, redness, fever, pain).

This is related to the capability of steroids to stabilise cell membranes, reduce the migration of leukocytes to the site of the inflammation, to weaken the phagocytosis capacity of granulocytes and monocytes.

Due to the decreased permeability of blood vessels, the edemas will resolve.

Gucocorticoids inhibit al types of inflammatory response.

Question 23

musculoskeletal effects of glucocorticoids

Answer 23

Muscles will be weakened after long-term administration as a result of decreased potassium quantities.

The excretion of Ca2+, phosphorus and nitrogen will also be increased, resulting in loss of calcium from the bones.

Muscle mass is reduced.

Question 24

Effects of glucocorticoids on the endocrine system

Answer 24

Chronic use of corticosteroids inhibits the function of the hypothalamic-pituitary-adrenal axis by negative feedback, which may cause adrenal insufficiency after the cessation of corticosteroid treatment.

Adrenal insufficiency is a serious, potentially life-threatening side effect of corticosteroid use.

Thus, long-term treatment must be concluded by reducing the doses slowly.

Question 25

Effects of glucocorticoids on the immune system

Answer 25

They inhibit the immune system. Their use is not recommended in case of an infection. Are used to suppress the rejection reaction after an organ transplant.

Question 26

Explain more specifically how glucocorticoids suppress the immune system.

Answer 26

Glucocorticoids induce lipocortin synthesis, that inhibits arachidonic acid release, and Glucocorticoids also block cytokine synthesis and T-cell activation. Antibody production is generally not affected, but can be affected at high Glucocorticoid dosages and long-term therapy. They decrease formation of induced histamine and antagonize toxins and kinins – reducing inflammation.

Question 27

Glucocorticoid Cardiorespiratory effect

Answer 27

Direct positive inotropic and chronotropic effect on the heart. They cause vasoconstriction if injected in the blood vessels. They may cause hypertension. They increase the number and affinity of beta-adrenergic receptors. They increase the potency of the effect of beta-adrenergic substances on the smooth muscle of the bronchi - this is important for asthmatics.

Question 28

Glucocorticoid Dermatologic effects

Answer 28

They reduce collagen synthesis – cause reduced wound healing. The skin becomes thin. Dogs may develop bilateral symmetrical alopecia.

Question 29

Glucocorticoid Reproductive effects

Answer 29

High doses can induce parturition during the latter part of pregnancy in ruminants and horses. Glucocorticoids generally have teratogenic effects during early pregnancy.

Question 30

Glucocorticosteroids in treatment of shock

Answer 30

Effect improves gluconeogenesis and suppresses inflammation. In treatment of shock, it is administered for a short period of time in large doses.

Question 31

Main indications for glucocorticoid use (4)

Answer 31

Chronic non-infectious inflammatory diseases (arthritis, bursitis, rheumatism) Other chronic processes (asthma, muscle aches and pains) Strong allergic reactions, anaphylactic shock. Autoimmune diseases

Question 32

A general rule for glucocorticoid use is to not commbine them with...?

Answer 32

do not administer with antibiotics! A steroid suppresses the inflammation, an antibiotic typically exerts its effect against replicating microbes, i.e. in the setting of the steroid the effect of the antibiotic will be reduced. While the signs of inflammation may disappear, the bacterium will remain and it will lead to the exacerbation of the infectious inflammation once again.

Question 33

Contraindications for glucocorticoid use. (5)

Answer 33

Pregnant animals (abortion) Infectious disease Diabetes Osteoporosis Renal impairment

Question 34

Toxicity/Side effects of glucocorticoids on the endocrine system

Answer 34

Cushing's syndrome (relocation of fat depots), adrenal insufficiency in case of long-term use

Question 35

Toxicity/Side effects of glucocorticoids on the CNS

Answer 35

behavioural changes (depression)

Question 36

Toxicity/Side effects of glucocorticoids on the Musculoskeletal system

Answer 36

Osteoporosis, muscle atrophy

Question 37

Toxicity/Side effects of glucocorticoids on the Gastrointestinal tract

Answer 37

pancreatitis, liver function disorders, ulceration

Question 38

Toxicity/Side effects of glucocorticoids on the skin

Answer 38

impaired wound healing (reduced synthesis of collagen) Administration of large doses causes bilaterally symmetrical alopecia in dogs.

Question 39

Toxicity/Side effects of glucocorticoids on the repro. system

Answer 39

Induction of abortion/parturition in ruminants and horses. Teratogenic effect at the beginning phase of gestation.

Question 40

Mineralocorticoids target organ

Answer 40

the kidneys M-s bind to specific receptor.

Question 41

the most potent regulator of electrolyte excretion

Answer 41

aldosterone

Question 42

WHat is Desoxycorticosterone

Answer 42

is a mineralocorticoid medication for treatment of hypoadrenocorticism in dogs

Question 43

effects of desoxycorticosterone

Answer 43

Na+ retention, K+ excretion

Question 44

Adrenolytic drugs are typically used for what indication? (2)

Answer 44

Therapy for hyperadrenocorticism (excess secretion of cortisol, mainly caused by excess ACTH production by the pituitary). Cushing's disease – adrenal glands are bilaterally hypertrophied, producing excess cortisol. Mainly diagnosed in dogs, but also in cats and horses.

Question 45

describe Mitotane

Answer 45

is a steroidogenesis inhibitor Cytotoxic effect toward canine dog adrenal cortex, cortisol secretion becomes minimal. Can also be used in case of adrenal tumors. Side effects (mild): vomiting, anorexia, hypoglycemia (diabetic animals must be monitored!), CNS depression.

Question 46

describe trilostane

Answer 46

= Vetoryl, used in the treatment of Cushing's syndrome. Supresses the adrenal cortex, blocks synthesis of adrenal steroids. For dog, cat and horse. Side effects: diarrhea, vomiting, lethargy.

Question 47

describe ketoconazole for adrenal related use

Answer 47

Imidazole derivative, typically an antifungal but ketoconazole also reduces cortisol synthesis by inhibiting several CYP enzymes in the adrenal glands resulting in a rapid and marked reduction in adrenal steroid production. Inhibits the synthesis of hormones from cholesterol: cortisol, estradiol, testosterone. Is used to decrease cortisol concentrations in dogs with pituitary- dependent hyperadrenocorticism. About 25% of dogs will not respond to that therapy. Side effects: vomiting, anorexia.

Question 48

describe L-deprenyl (selegiline)

Answer 48

Irreversible inhibitor of MAO. Decreases the metabolism of dopamine and other catecholamines. The increase in dopamine concentration decreases ACTH secretion and in turn cortisol secretion? Is used for the treatment of uncomplicated Cushing disease in dogs. Quite safe, mainly GI signs on long-term treatment.