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pharm 2 > Glucocorticoids > Flashcards

Glucocorticoids Flashcards

1
Q

Adrenal cortex

A
  • The adrenal cortex is divided into 3 zones that synthesize various steroids from cholesterol.
  • From outermost layer to the innermost layer, the adrenal cortex is divided into:
  • Zona glomerulosa - Mineralocorticoids
  • Zona fasiculata – Glucocorticoids
  • Zona reticularis – Sex steroids

Aldosterone – Mineralocorticoid
Cortisol - Glucocorticoid
DHEA, Testosterone, Estrogen and Progesterone – Sex steroids

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2
Q

Glucocorticoids

A
  • The principal glucocorticoid hormone in humans is cortisol. The physiologic effects of glucocorticoids are diverse. Cortisol is synthesized from progesterone
  • These agents regulate the metabolism of proteins, carbohydrates, and lipids.
  • Glucocorticoids promote gluconeogenesis in the liver, which leads to increased blood glucose levels.
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3
Q

Glucocorticoids and BP

A

Glucocorticoids can cause a mild increase in blood pressure believed to be due to enhancing the vasoconstrictive effect of adrenergic stimuli on small blood vessels.

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4
Q

Glucocorticoids and immune cells

A

Glucocorticoids cause an increase in the numbers of circulating neutrophils, hemoglobin, and erythrocytes.
• Glucocorticoids cause a decrease in circulating lymphocytes (including T cells), eosinophils, basophils, monocytes, and macrophages.
• The anti-inflammatory effects of glucocorticoids are related to decreased production of prostaglandins and leukotrienes.

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5
Q

Glucocorticoids at cellular level

A

glucocorticoids inhibit the access of leukocytes to inflammatory sites, interfere with the functions of leukocytes, endothelial cells, and fibroblasts, and suppress the production and the effects of multiple factors involved in the body’s inflammatory response.

Inhibition of phospholipase A2 blocks the release of arachadonic acid, the precursor of the prostaglandins and leukotrienes from membrane bound phospholipids.
• Histamine release and kinin activity is also suppressed by glucocorticoids.

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6
Q

Glucocorticoids are often indicated for

A 
• Inflammatory and allergic conditions
(oral, inhaled and topical preparations)
• Reactive airways disease
• Allergies (rhinitis, hay fever, drug allergy) • Arthritis
• Auto-immune conditions
• Replacement therapy for Addison’s
disease (needed for patient survival)
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7
Q

tachyphylaxis

A

Tachyphylaxis is a rapid decrease in the response to a drug over a short time period.
• Some physicians may recommend using a topical steroid for 3 consecutive days on, followed by 4 consecutive days off.

cause of tachyphylaxis is felt to be depletion of a neurotransmitter that is involved in the action of the drug. The drug causing tachyphylaxis acts indirectly by causing release of the stored neurotransmitter from the nerve terminal. After a few doses the neurotransmitter stores are depleted and no more response is obtained.

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8
Q

Glucocorticoids SE

A

Adverse effects of glucocorticoids include reduced resistance to infections, hyperglycemia and possible diabetes mellitus, severe bone loss, avascular necrosis, cataracts, myopathy, thinning of skin, diminished wound healing, easy bruising, insomnia and mental status changes.
• Increased appetite is a commonly reported side effect as is weight gain from salt and water retention

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9
Q

Glucocorticoids metabolism

A

Corticosteroids are metabolized by the liver microsomal oxidizing enzymes.

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10
Q

Duration of action

A

Duration of action
Short acting (8 - 12 hours)
• Hydrocortisone, Cortisone

Intermediate acting (18 - 36 hours)
• Prednisone, Prednisolone,
Methylprednisolone, Triamcinolone

Long acting (24 - 72+ hours)
• Paramethasone, Dexamethasone,
Betamethasone

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11
Q

Anti-inflammatory effect scale

A
  • Hydrocortisone – if considered a “1” then:
  • Cortisone – 0.8
  • Prednisone - 4
  • Prednisolone - 5
  • Methylprednisolone - 5
  • Triamcinalone - 5
  • Paramethasone - 10
  • Dexamethasone - 30
  • Betamethasone - 35
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12
Q

Mineralocorticoid effect

A
  • An important rule is that the stronger the corticosteroid effect, the weaker the mineralocorticoid effect.
  • The reverse is also true, the weaker the corticosteroid effect, then the stronger the mineralocorticoid effect.
  • For example, prednisone has a greater mineralocorticoid effect relative to Beclomethasone which has relatively minor mineralocorticoid effects.
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13
Q

abrupt weaning

A

Abrupt discontinuation can result in acute adrenal insufficiency syndrome (Addisonian crisis) which can be lethal.

CRH and ACTH arent around in the right amountds

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14
Q

Addisonian crisis

A
  • Severe lethargy
  • Severe vomiting and diarrhea, often resulting in dehydration
  • Low blood pressure
  • Confusion
  • Hyponatremia and hypoglycemia
  • Loss of consciousness
  • Convulsions
  • If untreated – Addisonian crisis is usually fatal
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15
Q

Hydrocortisone/ Cortef

A
  • Class: Glucocorticoid/ corticosteroid
  • Indications: See prior slides. Preferred drug for cortisol replacement therapy.
  • MOA: Affects gene transcription to either stimulate or repress protein production.
  • Char: PO/IV/IM/topical. Chemically identical to naturally occurring cortisol. Short duration of action.
  • Side effects: See prior slides.
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16
Q

Prednisone/ Deltasone

A

• Class: Glucocorticoid/ corticosteroid • Indications: See prior slides. Preferred
drug for reactive airways disease or moderate to severe allergic reaction. Important drug for leukemia reaction.
• MOA: Affects gene transcription to either stimulate or repress protein production.
• Char: PO. Intermediate duration of action.
• Side effects: See prior slides.

17
Q

Dexamethasone/ Decadron

A

• Class: Fluorinated corticosteroid
• Indications: See prior slides. Extremely
potent anti-inflammatory. Also useful in IV
form for reducing intracranial pressure. • MOA: Affects gene transcription to either stimulate or repress protein production.
• Char: PO/IV/topical/inhaled. Long acting duration of action. Minimal mineralocorticoid effects.
• Side effects: See prior slides.

18
Q

Triamcinolone inhaler/Azmacort

A 
Class: Corticosteroid
• Indications: Asthma, COPD. Not
indicated for treating an acute asthma
attack once it has already begun.
• MOA: Diminishes inflammation of
bronchial wall . Affects gene transcription and alters protein production.
• Char: Oral inhaler
19
Q

Triamcinolone inhaler/Azmacort dosing and SE

A
  • Usually dosed as 1 to 2 inhalations (75 mcg to 150 mcg) given 3 to 4 times a day. Alternatively, 2 to 4 inhalations (150 mcg to 300 mcg) may be given twice daily.
  • Patients should contact you if they feel the need to use their inhaler more than 4 times per day to achieve asthma control.
  • Side effects: Thrush, sore throat, nosebleeds, increased coughing, headache, runny nose and other side effects as noted in prior slides.
20
Q

Beclomethasone/Qvar or Vancenase

A
  • Beclomethasone dipropionate is a pro-drug of the corticosteroid, Beclometasone.
  • In the form of an inhaler (i.e. Qvar, Clenil), it is used for the prophylaxis of asthma.
  • As a nasal spray (i.e. Vancenase, Beconase), it is used for the treatment of rhinitis, hay fever and sinusitis. In some instances, it is used in the treatment of unusually severe aphthous ulcers.
21
Q

Mineralocorticoids

A
  • The outermost section (the zona glomerulosa) of the adrenal cortex produces and releases mineralocorticoids (such as aldosterone) which are responsible for regulating intravascular volume and blood pressure.
  • Aldosterone acts primarily on the renal tubule cells, causing retention of sodium, bicarbonate and water and decreasing resorption of potassium.

SALT–>Sugar–> Sex

22
Q

Addisons vs Conn’s and aldosterone levels

A

Aldosterone levels are reduced in patients with Addison’s disease and treatment is generally with a glucocorticoid that has potent mineralocorticoid properties.

Aldosterone levels are increased in patients with Conn’s syndrome and treatment is an aldosterone antagonist such as Spironolactone. Renin and aldosterone are measured, and the ratio (very low) is diagnostic

23
Q

Fludrocortisone/ Florinef

A

• Class: Halogenated glucocorticoid/ Mineralocorticoid agonist
• Indications: Mineralocorticoid replacement for patients with Addison’s disease and in other cases of hyponatremia.
• MOA: Sodium retention. Main effect is via reduction of sodium loss to the urine at the renal tubular cells.
Char: PO. Potent mineralocorticoid effects. Long acting duration of action. Minimal glucocorticoid effects. Not indicated as an anti-inflammatory agent.

24
Q

Fludrocortisone/ Florinef SE

A

Side effects: Salt retention, edema, hypertension, rash, nausea and vomiting, as well as the potential side effects that are attributable to glucocorticoids.

25
Q

Dehydroepiandrosterone (DHEA)

A

• The innermost region of the adrenal cortex, the Zona reticularis, produces the adrenal androgen, dehydroepiandrosterone (DHEA), which is converted to testosterone and estrogen.

DHEA supplementation to be helpful in the treatment of osteoporosis, depression, SLE, and patients undergoing skin grafting.

DHEA use should be decreased or discontinued when patients experience acne or hirsutism. patients with a personal history of sex hormone responsive cancers, such as breast, uterine, ovarian or prostate cancer.

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