3-4. adrenal cortex & thyroid pharmacology

how is hypoadrenocorticism treated?

lifelong replacement of glucocorticoids & mineralocorticoids

what type of drug is prednisolone/prednisone? which receptors does it interact with?

synthetic glucocorticoid

• binds glucocorticoid receptors

• minimal to no mineralocorticoid activity

in which species is prednisolone vs. prednisone used? why?

prednisone is a pro-drug → converted to active prednisolone in the liver

• cats & horses lack enzyme → prednisolone must be used in cats & horses

• prednisone great for dogs

what type of drug is desoxycorticosterone pivalate (DOCP)? which receptors does it interact with?

synthetic mineralocorticoid

• binds mineralocorticoid receptors only

• no glucocorticoid activity

how is DOCP administered?

• injection only

• administer ~q28d

what type of drug is fludrocortisone acetate? what receptors does it interact with?

synthetic corticosteroid with dual activity

• binds both glucocorticoid and mineralocorticoid receptors

why is fludrocortisone acetate not always a good sole therapy for Addison’s disease (hypoadrenocorticism)?

glucocorticoid effects often too strong at the dose required to normalize electrolytes → iatrogenic hyperadrenocorticism

trilostane effects

reduces production of all adrenal cortex hormones

• both cortisol & aldosterone affected

• impacts cortisol > aldosterone

how is trilostane used in primary vs. secondary hyperadrenocorticism?

• efficacious for secondary hyperadrenocorticism

• can be used in primary hyperadrenocorticism to limit tumor production of cortisol if surgery is not an option — success variable

  • impacts on aldosterone may be more severe

what is an important adverse effect of trilostane?

hypoadrenocorticism

contraindications of trilostane

• pregnancy

• patients with primary liver or kidney disease

• patients with hyperkalemia — fix that first

trilostane drug interactions

• ACE inhibitors

• K-sparing diuretics

how is trilostane administered?

• BID dosing ideal

• give with food

  • improved bioavailability

  • reduce risk of GI side effects

spirolactone mechanism of action

aldosterone receptor antagonist (treat hyperaldosteronism — Conn’s disease)

what type of drug is pergolide mesylate? (what does it treat?) adverse effects?

• dopamine agonist

  • treat pars pituitary intermedia dysfunction (PPID)

• minimal adverse effects — usually well tolerated

what type of drug is levothyroxine? (what does it treat?)

• synthetic thyroxine / T4

  • treat hypothyroidism

• measure total T4 (serum) to ensure adequate dose

methimazole mechanism of action

inhibits thyroid peroxidase → interferes with oxidation of iodine and iodination of tyrosine residues → decreased formation of pre-T3, pre-T4 → decreased formation of active T3, T4

why should oral methimazole be given with food?

decreases side effects

methimazole adverse effects

• GI: vomiting, anorexia — oral tablets only

• pruritis, especially facial

• hepatic changes

• decreased glomerular filtration rate

  • due to correction of hyperthyroid state (not an effect of the drug)

    • correcting hyperthyroidism may make renal sufficiency apparent

  • caution in patients with renal disease

how does radioactive iodine treatment work? what should be done prior to treatment?

• tumorous follicular cells take up radioactive iodine and are destroyed

• normal thyroid tissue is spared

• pre-workup for concurrent disease

  • ensure patient can handle euthyroid state

  • bloodwork (liver & kidney values), imaging (echo, thoracic rads, abdominal US)

  • pre-treatment with methimazole for 2-3 months common

why is normal thyroid tissue spared during radioactive iodine treatment?

TSH is low in primary hyperthyroidism → normal follicular cells are quiescent and do not uptake radioactive iodine