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Pharmacology > 8th lecture - glucocorticoids > Flashcards

8th lecture - glucocorticoids Flashcards

1
Q

Adrenocorticotropic hormone is released from the

A

adenohypophysis

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2
Q

Adrenocorticotropic hormone stimulates

A

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

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3
Q

the adrenal cortex of the adrenal glands synthesizes what

A

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

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

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4
Q

Broad function of Glucocorticosteroids

A

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.

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5
Q

Broad function of Mineralocorticosteroids

A

they impact the metabolism of water and electrolytes.

Aldosterone is the most impostant mineralocortocoid.

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6
Q

the most impostant mineralocorticoid

A

aldosterone

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7
Q

aldosterone main role

A

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

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8
Q

Natural Representatives of glucocorticosteroids (2)

A

cortisone, hydrocortisone

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9
Q

Synthetic Representatives of glucocorticosteroids (4)

A

prednisolone,
dexamethasone,
triamcinolone,
flumethasone and many others

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10
Q

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

A

Increased gluconeogenesis

Antagonism of insulin

Increased catabolism of proteins

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

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11
Q

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

In people, chronic administration of glucocorticoids can result in?

A

osteoporosis

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12
Q

Glucocorticoids potentiate the action of what hormone?

A

parathyroid hormone and decrease the gut absorption of Ca.

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13
Q

How might excessive glucocorticoids affect young animals?

A

may reduce growth

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14
Q

General effects of glucocorticosteroids (2-3)

A

Anti-inflammatory effect
Immunosuppressive, antiallergic effect

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15
Q

duration of effect of Natural steroids

A

are short acting.

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16
Q

Glucocorticoids are metabolised in the

A

liver.

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

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17
Q

The effect of glucocorticosteroids is to a large extent based on

A

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

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18
Q

Glucocorticoids effect on protein metabolism.

A

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.

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19
Q

Glucocorticoids effect on carbohydrate metabolism.

A

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.

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20
Q

Glucocorticoids effect on lipid metabolism.

A

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.

21
Q

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

A

Large doses cause oedemas, hypokalaemia and metabolic alkalosis.

22
Q

Anti-inflammatory effects of glucocorticoids.

A

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.

23
Q

musculoskeletal effects of glucocorticoids

A

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.

24
Q

Effects of glucocorticoids on the endocrine system

A

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.

25
Q

Effects of glucocorticoids on the immune system

A

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.

26
Q

Explain more specifically how glucocorticoids suppress the immune system.

A

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.

27
Q

Glucocorticoid Cardiorespiratory effect

A

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.

28
Q

Glucocorticoid Dermatologic effects

A

They reduce collagen synthesis – cause reduced wound healing. The skin becomes thin.

Dogs may develop bilateral symmetrical alopecia.

29
Q

Glucocorticoid Reproductive effects

A

High doses can induce parturition during the latter part of pregnancy in ruminants and horses.

Glucocorticoids generally have teratogenic effects during early pregnancy.

30
Q

Glucocorticosteroids in treatment of shock

A

Effect improves gluconeogenesis and suppresses inflammation.

In treatment of shock, it is administered for a short period of time in large doses.

31
Q

Main indications for glucocorticoid use (4)

A

Chronic non-infectious inflammatory diseases (arthritis, bursitis, rheumatism)

Other chronic processes (asthma, muscle aches and pains)

Strong allergic reactions, anaphylactic shock.

Autoimmune diseases

32
Q

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

A

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.

33
Q

Contraindications for glucocorticoid use. (5)

A

Pregnant animals (abortion)
Infectious disease
Diabetes
Osteoporosis
Renal impairment

34
Q

Toxicity/Side effects of glucocorticoids on the endocrine system

A

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

35
Q

Toxicity/Side effects of glucocorticoids on the CNS

A

behavioural changes (depression)

36
Q

Toxicity/Side effects of glucocorticoids on the Musculoskeletal system

A

Osteoporosis, muscle atrophy

37
Q

Toxicity/Side effects of glucocorticoids on the Gastrointestinal tract

A

pancreatitis, liver function disorders, ulceration

38
Q

Toxicity/Side effects of glucocorticoids on the skin

A

impaired wound healing (reduced synthesis of collagen)

Administration of large doses causes bilaterally symmetrical alopecia in dogs.

39
Q

Toxicity/Side effects of glucocorticoids on the repro. system

A

Induction of abortion/parturition in ruminants and horses.

Teratogenic effect at the beginning phase of gestation.

40
Q

Mineralocorticoids target organ

A

the kidneys

M-s bind to specific receptor.

41
Q

the most potent regulator of electrolyte excretion

A

aldosterone

42
Q

WHat is Desoxycorticosterone

A

is a mineralocorticoid medication for treatment of hypoadrenocorticism in dogs

43
Q

effects of desoxycorticosterone

A

Na+ retention, K+ excretion

44
Q

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

A

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.

45
Q

describe Mitotane

A

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.

46
Q

describe trilostane

A

= 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.

47
Q

describe ketoconazole for adrenal related use

A

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.

48
Q

describe L-deprenyl (selegiline)

A

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.

Pharmacology (19 decks)

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