Pharmacology Flashcards by Yousof Tuffaha

What is the biosynthetic pathway of aldosterone?

cholesterol → pregnenolone; desmolase/CCE
pregnenolone → progesterone; 3β-HSD/Δ^5,4
progesterone → 11-deoxycorticosterone; 21-hydroxylase
11-deoxycorticosterone → corticosterone; 11-hydroxylase
corticosterone → aldosterone; aldosterone synthase/18-hydroxylase

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

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

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

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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What are the renin inhibitors?

Drugs ending in -kiren:

Aliskiren
Remikiren
Enalkiren

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What are the angiotensin II receptor blockers?

Drugs ending in -sartan:

Candesartan
Losartan
Irbesartan
Telmesartan

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What are the aldosterone antagonists?

Spironolactone
Eplerenone

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What are the uses of fludrocortisone?

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

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What is the biosynthetic pathway of cortisol?

(Using progesterone as a precursor)

cholesterol → pregnenolone; desmolase/CCE
pregnenolone → progesterone 3β-HSD/Δ^5,4
progesterone → 17-hydroxyprogesterone 17-hydroxylase
17-hydroxyprogesterone → 11-deoxycortisol 21-hydroxylase
11-deoxycortisol → cortisol 11-hydroxylase

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What are the steroid synthesis inhibitors?

Mitotane
Aminoglutethimide
Ketoconazole
Trilostane
Etomidate
Metyrapone

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What is mitotane?

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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What is aminoglutethimide?

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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What is ketoconazole?

(In the context of endocrinology)

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

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What is trilostane?

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

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What is etomidate?

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

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Which steroid synthesis inhibitor is cytotoxic?

Mitotane

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Which steroid synthesis inhibitor is parenteral?

Etomidate

What is metyrapone?

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

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

Metyrapone

What are the short-acting glucocorticoids?

Cortisol (hydrocortisone)
Cortisone
Corticosterone
Fludrocortisone

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

10 hours

What are the intermediate-acting glucocorticoids?

Prednisone
Prednisolone
Methylprednisolone
Triamcinolone
Beclomethasone

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

20 hours

What are the long-acting glucocorticoids?

Betamethasone
Dexamethasone

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

50 hours

What are the clinical uses of the glucocorticoids?

* 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

What are the adverse effects of glucocorticoid treatment?

* 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

What is the dosage regimen of glucocorticoids?

* 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

What is pegvisomant?

A growth hormone–receptor antagonist used to treat acromegaly

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

* Somatostatin analogs (octreotide, lanreotide) * Pegvisomant (GH-receptor antagonist) * Dopamine agonists (bromocriptine, cabergoline)

What drugs are used to treat hyposecretion of growth hormone?

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