Glucocorticoids

Glucocorticoid [Ref Harrison 17^th/e p. 2307; 15^th/e p.

Drugs causing Hyperglycemia

• Asparginase
• Chlorthalidone
• Diazoxide
• Encainide
• Ethacrynic acid
• Furosemide
• Glucocorticoids
• Growth hormones
• HIV protease inhibitors
• Niacin
• Oral contraceptives
• Phenytoin
• Pentamidine
• Thiazides

fiblocker usually cause hypoglycemia.

B and C

Functions of maternal / fetal corticosteroids in the fetus include Synthesis of surfactant in the lungs, induction of thymic involution, proper development of hypo-thalamo-pituitary axis. Development of functional thyroid is not found to be dependant on the maternal or fetal glucocorticoids.

Bronchopulmonary dysplasia

A i.e. Glucocorticoids; B i.e. GH; C i.e. Epinephrine

A i.e. Epinephrine; B i.e. GH; C i.e. Glucocorticoid

Glucagon, catecholamines (epinephrine & norepinephrine), cortisol, ACTH, GH (growth hormone) are increased in stress (infection, surgery, hypoglycemia) whereas, insulin is suppressed (decreased)Q.

• In maintenance of internal homeostasis (ie avoiding stress) and reproduction processes, multiple hormones cooperate to bring about organized biochemical & physiological responses.

Stress Syndrome: CRH – ACTH – Cortisol Axis

• The primitive signal of glucose (substrate) lack is expanded to a broder signal of fright or stress and evokes a coordinated neural and endocrine response. Any stressful event eg. surgery, infection, burn triggers a hypermetabolic state in which a resting energy expenditure is increased alongwith body temperature.
• CRH-ACTH – cortisol axis is central to this integrated response to stress.

• Features of Stress Syndrome

  – Corticotropin releasing hormone (CRH) is increased in response to noxious environmental stimuli like pain, trauma,

  hypoglycemia, infection, surgery, hypovolemia. Various nervous impulses using several neuro transmitters (NTs) like norepinephrine, serotonin, acetylcholine, dopamine, and GABA reach CRH neurosecretory cells and cause release of CRH

  –                In response to CRH, both ACTH and p endorphins (secreted 13-LPH & mature p-endorphin) are released in equimolar quantities 13-endorphin produce central analgesic response.

  – Glucagon & catecholamines (epinephrine & norepinephrine) are increased, stimulating glycogenolysis (glucose

  production in liver) for immediate use by critical organs such as the brain.

  –                Cortisol production is increased in adrenal cortex which induces gluconeogenesis (glucose production from noncarbohydrate source like muscles & other body proteins)

  –                Glucogon, epinephrine, ACTH and growth hormone (GH) stimulate lipolysis and free fatty acids (FFA) & ketones are

  released into the circulation to be used as an alternative metabolic fuel.

  –                Insulin is suppressedQ that results in decrease in glucose utilization.

  –                One form of stress that is cold, specially in neonate causes increased TRH secretion due to depressed metabolism of neurons in pre- optic area by cooling which release inhibitory discharge, permitting TRH secretion.

  –                ADH (vasopressin), angiotensin & aldosterone synthesis is increased enhancing salt water retention

  –                So increased glucose production (by glycogenolysis & gluconeogenesis) and decreased utilization of glucose results in hyperglycemia. There is marked increase in release of aminoacids from tissue protein, particularly from skeletal muscle for gluconeogenesis. However, synthesis of specific proteins may increase

  –                These metabolic changes are coordinated with increased sympathetic nervous system activity causing peripheral vasoconstriction and increased blood pressure.

Bronchopulmonary dysplasia

Ans. is ‘d’ i.e., Oral candidiasis can occur as a side effect

Ans. is ‘c’ i.e., ↑ Lipocortin

o Corticosteroids induce the production of lipocortins that are responsible for the inhibition of phosholipase A₂, an enzyme which is involved in the production of inflammatory mediators (PGs, LTs, PAF).

Ans. is ‘b’ i.e., Cortisone

Least potent glucocorticoid —> Cortisone

Ans. is ‘c’ i.e., Dexamethasone

Ans. is ‘c’ i.e., Hydrocortisone

o Short acting glucocorticoids (t1/2 : 8-12 hrs.) : Cortisol, hydrocortisone.

o Intermediate acting glucocorticoids (t1/2 : 12-36 hrs.) : Prednisolone, methylprednisolone, triamcinolone. o Long acting glucocorticoids (t1/2 : 36-54 hrs.) : Dexamethasone betamethasone.

Ans. is ‘d’ i.e., Dexamethasone

Ans. is ‘b’ i.e., Hypoglycemia

o Glucocorticoids cause hyperglycemia.

o All other are side effects of glucocorticoids

o Side effects of glucocorticoids are cuhing’s habits, fragile skin, purple striae, muscular weakness, hyperglycemia, delayed wound healing hypokalemia, Na⁺ and water retention, hypertension, peptic ulcer, cataract, glaucoma, osteoporosis, mild euphoria, growth retardation and AVN of femoral head. Among cutaneous side effects are folliculitis (most common), atrophic changes, hypertrichosis, and purple stria are common.

Ans. is ‘b’ i.e., Hyperkalemia

o Glucocorticoids have some mineralocorticoid activity, thus they cause hypokalemia (not hyperkalemia).

Ans. is ‘d’ i.e., Reduced appetite

Ans. is ‘a’ i.e., Suppression of inflammation and improvement in functional capacity

Ans. is ‘b’ i.e., Glucocorticoid

Drugs causing hyperglycemia

o Asparaginase                     o Ethacrinic acid

o Chlorthalidone                    o Frusemide

o Diazoxide                          o Glucocorticoids

o Encainide                          o Growth-hormone

o Thyroid hormones              o Vacor

o HIV protease inhibitors       o Niacin

o OCP                                o Pentamidine

o Phenytoin                        o Thiazides

o Clozapine                        o beta-adrenergic agonists (propranolol)

Ans. is ‘b’ i.e., Glucocorticoids

Drugs Causing neutrophilia

Acute: Smoking, glucocorticoids, epinephrine, venoms, Colony-Stimulating factors Chronic: All drugs which cause acute neutrophilia, Lithium.

Ans. C: Betamethasone

Betamethasone and dexamethasone are very potent and highly selective glucocorticoids.

Long acting, causes marked pituitary-adrenal suppression, but fluid retention and hypertension is not a problem. Hence they are preferred in situations in which fluid retention must be avoided like cerebral edema.

Ans. A: Hypoglycemia

• Immunosuppression
• Hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance (“steroid diabetes”); caution in those with diabetes mellitus
• Increased skin fragility, easy bruising
• Negative calcium balance due to reduced intestinal calcium absorption
• Steroid-induced osteoporosis: reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)
• Weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation
• Adrenal insufficiency (if used for long time and stopped suddenly without a taper)
• Muscle breakdown (proteolysis), weakness; reduced muscle mass and repair
• Expansion of malar fat pads and dilation of small blood vessels in skin
• Anovulation, irregularity of menstrual periods
• Growth failure, pubertal delay
• Increased plasma amino acids, increased urea formation; negative nitrogen balance
• Excitatory effect on central nervous system (euphoria, psychosis)
• Glaucoma due to increased cranial pressure
• Cataracts

Ans. D: Helps fetal lung maturity

This helps in fetal lung maturation so that the incidence of respiratory distress syndrome, intraventricular hemorrhage and NEC are minimised

Glucocorticoids induce apoptosis in a cell.

Inducers of apoptosis are growth factor withdrawal, detachment from matrix, glucocorticoids, cytotoxic drugs and immune cytolysis.

Ans. is ‘b’ i.e., Decreased Serum Calcium, phosphorus and alkaline phosphatase is seen

Osteoporosis is a state of decreased mass per unit volume of a normally mineralized bone. Osteoporosis is the commonest metabolic bone disease. Osteoporosis is characterized by an abnormally low bone mass (low bone density) and defects in bone structure, a combination of which renders the bone unusually fragile and at greater than normal risk of fracture. Bone depletion may be brought about by predominant bone resorption, decreased bone formation or a combination of the two.

Ans. is ‘a’ i.e., Pregnenolone

Ans. is ‘c^‘ i.e., Glucocorticoids

Ans. is ‘a’ i.e., Dexamethasone

Ans. a. Glucocorticoids

Ans. is `b’ i.e., Hydroxylation 

Ans. is ‘c’ i.e., Hydrocortisone 

Steroids compared

Ans. is ‘d’ i.e., Dexamethasone