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Endocrine system > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the biosynthetic pathway of aldosterone?

A
  1. cholesterol → pregnenolone; desmolase/CCE
  2. pregnenolone → progesterone; 3β-HSD/Δ5,4
  3. progesterone → 11-deoxycorticosterone; 21-hydroxylase
  4. 11-deoxycorticosterone → corticosterone; 11-hydroxylase
  5. corticosterone → aldosterone; aldosterone synthase/18-hydroxylase
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2
Q

What are the factors that increase activity of the renin–angiotensin–aldosterone system?

A
  • ECF volume depletion (by hemorrhage, low Na+, dehydration, etc.)
  • Upright posture
  • Hyperkalemia
  • ACTH (minor effect)
  • Vasodilators
  • Adrenergic antagonists
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3
Q

What are the factors that decrease activity of the renin–angiotensin–aldosterone system?

A
  • Increased ECF volume
  • Renin-release inhibitors (drugs ending in -kiren: aliskiren, remikiren, enalkiren; β1 blockers)
  • ACE inhibitors (drugs ending in -pril: captopril, enalapril, benzopril, fosinopril, lisinopril, ramipril)
  • Angiotensin II receptor blockers (drugs ending in -sartan: candesartan, losartan, irbesartan, telmesartan)
  • Aldosterone antagonists (spironolactone, eplerenone)
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4
Q

What are the renin inhibitors?

A

Drugs ending in -kiren:

  • Aliskiren
  • Remikiren
  • Enalkiren
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5
Q

What are the angiotensin II receptor blockers?

A

Drugs ending in -sartan:

  • Candesartan
  • Losartan
  • Irbesartan
  • Telmesartan
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6
Q

What are the aldosterone antagonists?

A
  • Spironolactone
  • Eplerenone
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7
Q

What are the uses of fludrocortisone?

A

The most widely used mineralocorticoid; used for adrenocortical insufficiency associated with mineralocorticoid deficiency

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8
Q

What is the biosynthetic pathway of cortisol?

(Using progesterone as a precursor)

A
  1. cholesterol → pregnenolone; desmolase/CCE
  2. pregnenolone → progesterone 3β-HSD/Δ5,4
  3. progesterone → 17-hydroxyprogesterone 17-hydroxylase
  4. 17-hydroxyprogesterone → 11-deoxycortisol 21-hydroxylase
  5. 11-deoxycortisol → cortisol 11-hydroxylase
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9
Q

What are the steroid synthesis inhibitors?

A
  • Mitotane
  • Aminoglutethimide
  • Ketoconazole
  • Trilostane
  • Etomidate
  • Metyrapone
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10
Q

What is mitotane?

A

A steroid synthesis inhibitor that exerts a cytotoxic effect on the adrenal cortex. It is used in cases of adrenal carcinoma when excision or radiotherapy are not feasible.

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11
Q

What is aminoglutethimide?

A

A steroid synthesis inhibitor that inhibits desmolase (cholesterol cleavage enzyme). It is used in cases of breast carcinoma and Cushing syndrome due to adrenocortical cancer (alongside metyrapone or ketoconazole)

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12
Q

What is ketoconazole?

(In the context of endocrinology)

A

A nonselective inhibitor of adrenal and gonadal steroid synthesis. It is used in treatment of Cushing syndrome and prostate cancer

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13
Q

What is trilostane?

A

A competitive inhibitor of 3β-HSD that interferes with adrenal and gonadal hormone synthesis.

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14
Q

What is etomidate?

A

The only parenteral medication available for treatment of Cushing syndrome. It inhibits 11-hydroxylase.

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15
Q

Which steroid synthesis inhibitor is cytotoxic?

A

Mitotane

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16
Q

Which steroid synthesis inhibitor is parenteral?

A

Etomidate

17
Q

What is metyrapone?

A

A selective inhibitor of 11-hydroxylase, interfering with cortisol and corticosterone synthesis. It is mostly used for diagnosis of Cushing disease

18
Q

Which steroid synthesis inhibitor is mostly used for diagnosis of ACTH-dependent Cushing syndrome (Cushing disease)

A

Metyrapone

19
Q

What are the short-acting glucocorticoids?

A
  • Cortisol (hydrocortisone)
  • Cortisone
  • Corticosterone
  • Fludrocortisone
20
Q

What is the half-life of the short-acting glucocorticoids?

A

10 hours

21
Q

What are the intermediate-acting glucocorticoids?

A
  • Prednisone
  • Prednisolone
  • Methylprednisolone
  • Triamcinolone
  • Beclomethasone
22
Q

What is the half-life of the intermediate-acting glucocorticoids?

A

20 hours

23
Q

What are the long-acting glucocorticoids?

A
  • Betamethasone
  • Dexamethasone
24
Q

What is the half-life of the long-acting glucocorticoids?

A

50 hours

25
Q

What are the clinical uses of the glucocorticoids?

A
  • Chronic adrenal insufficiency (Addison disease)
  • Acute adrenal insufficiency (Addisonian crisis, Waterhouse–Friderichsen syndrome, etc.)
  • Allergic reactions: angioedema, bee stings, asthma, contact dermatitis, drug reactions, allergic rhinitis, urticaria
  • Chronic inflammatory conditions: IBD, giant cell arteritis, SLE, subacute hepatic necrosis, celiac disease, rheumatoid arthritis
  • Prevention of organ rejection
  • Hematologic disorders: hemolytic anemia, lymphoma, leukemia, multiple myeloma
26
Q

What are the adverse effects of glucocorticoid treatment?

A
  • Adrenal suppression and acute adrenal insufficiency upon sudden termination of therapy (the major, most dangerous side effect; treatment must be tapered slowly)
  • Iatrogenic Cushing syndrome (moon facies, buffalo hump, truncal obesity; hypertension; purple striae, proximal muscle weakness; osteoporosis; diabetes)
  • Immunosuppression
  • Posterior subcapsular cataracts (mostly in long-term treatment)
  • Glucocorticoids with mineralocorticoid effects (e.g. cortisone, cortisol) may lead to hypernatremia, hypokalemia, and hypertension—typically an issue in patients with heart disease
27
Q

What is the dosage regimen of glucocorticoids?

A
  • Initial therapy should be with the lowest dose possible of a short-acting steroid
  • Two-thirds the dose are given in the morning, one-third in the evening
  • Administration on alternate days decreases the risk of growth suppression in children and hypothalamic–pituitary–adrenal axis suppression in general
28
Q

What is pegvisomant?

A

A growth hormone–receptor antagonist used to treat acromegaly

29
Q

What drugs are used to treat hypersecretion of growth hormone (gigantism/acromegaly)?

A
  • Somatostatin analogs (octreotide, lanreotide)
  • Pegvisomant (GH-receptor antagonist)
  • Dopamine agonists (bromocriptine, cabergoline)
30
Q

What drugs are used to treat hyposecretion of growth hormone?

A
  • Growth hormone–releasing hormone (in cases of hypothalamic insufficiency)
  • Recombinant human growth hormone (rhGH)
  • Mecasermin (recombinant human IGF-1, in cases of IGF deficiency)

Endocrine system (2 decks)

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