Pharm 1 - Corticosteroids Q&As

drraythe's version from 2015-06-13 20:27


Question Answer
What are the 3 layers of the adrenal cortex & what do they synthesize?OUTER: Zona Glomerulosa (mineralocorticoid synthesis)
MIDDLE: Zona Fascicilata (glucocorticoid synthesis)
INNER: Zona Reticularis (androgen synthesis) (the deeper you go the sweeter it gets! & GFR)
What is synthesized in the adrenal medulla? (What are they made from?)Secretes catecholamines synthesized by the oxidation of tyrosine (amino acid)
3 examples of catecholamines?Norepi, Epi, Dopamine
What is the precursor of the 5 classes of steroid hormones? The classes?Precursor is CHOLESTEROL!
In the hypothalamic-pituitary-adrenal axis, what is released from each?Stress makes hypothalamus release corticotrophin releasing hormone (CRH). CRH then stimulates the release of corticotrophin (ACTH) from anterior pituitary. Then ACTH stims release of cortisol (& androgens) from the adrenal cortex
What is the negative feedback mechanism in the hypothalamic-pituitary-adrenal axis?Cortisol exerts a neg feedback on CRH & ACTH release (corticotrophin releasing hormone, corticotrophin)
Glucocorticoids have what effect on plasma glucose levels & why?Glucose dependent organs (heart, brain) during times of starvation are protected by glucocorticoids (bc ↑ in glucocorticoids result in ↑ of gluconeogenesis which leads to ↑ in plasma glucose levels)
Glucocorticoids have what effect on protein metabolism & why?↑ proteolysis leads to ↑ of amino acids, enzyme synth & liver protein & ↑ gluconeogenesis for more sugar for fight or flight
(Corticosteroid effect on lipid metabolism?)↑ redistribution of fat (possibly due to diff response to insulin & glucocorticoids by truncal & peripheral fat) & ↑ action of lypolytic hormones such as growth hormones & beta-adrenergic receptor agonists
Glucocorticoids cause PU/PD, why?↑ glucocorticoids leads to ↓ vasopressin (ADH) secretion, & they ↑ CV fxn which leads to ↑ GFR & ↑ Na+ & H2O secretion
Mineralocorticoids cause ↑ Na+ reabsorption in the kidneys & absorption in the LI. What effect does this have on water balance?Causes water conservation (more water stays in body than is excreted)
How is parathyroid hormone influenced by glucocorticoids?↑ glucocorticoids → ↓ GIT absorption & renal absorption of Ca++. Leads to ↓ of plasma Ca++ which leads to an ↑ in PTH (parathyroid hormone)
What is the effect of glucocorticoids on the feeling of well-being?↑ of euphoria & excitation, appetite improves, a ↓ will lead to depression
Mineralocorticoids effects on the CV system have what influence on the Ca++ levels in the myocardium?MCs ↑ Na in the ECF (↑ BP), which leads to ↓ K in ECF (which leads to ↑ Ca++ in myocardium)
Glucocorticoid effects on the CV system include BV constriction & ↑ in heart rate, contractibility & CO. Why is this?This is due to an ↑ in Epi formation which will lead to an ↑ in alpha-adrenergic receptors (BV constriction) & an ↑ in beta-1-adrenergic receptors (↑ HR, contractility, & CO). ALSO ↑ in angiotensinogen productions (↑ ACE & angiotensin II = ↑ BP)
Why do glucocorticoids lead to bronchodilation?Bc ↑ in Beta-2 adrenergic receptor expressions (know beta dilates things, & there are 2 lungs)
Give a reason why glucocorticoids are anti-inflammatory in the resp system?Bc of a ↓ in mast cell retention, leading to a ↓ in histamine release
What are the effects of mineralocorticoids in skeletal mm?↑ mineralocorticoid levels lead to hypokalemia & mm weakness
What are the effects of glucocorticoids in skeletal mm?↑ levels over a long time lead to mm weakness due to wasting of mm (from proteolysis)
What are the 3 blood cells that ↑ in number in the circulation as a result of glucocorticoid use?RBC, Neutrophils & Platelets ( play MORE bloody new rock)
What are 4 blood cells that ↓ in number in the circulation as a result of glucocorticoid use?Lymphocytes
What are 4 ways glucocorticoids have anti-inflammatory actions?(1) ↓ IL-8, the chemo-attractive factor/adhesion factor(results in ↓ migration of WBC to area of inflammation)
(2) ↓ PLA2 or ↓ arachidonate formation from cell membrane breakdown
(3) ↓ Autocoids-like histamine, from mast cells
(4) ↓ Proteolytic enzymes
How is skin/hair growth effected by glucocorticoids?↓ skin & hair growth (alopecia)
The structure of corticosteroids imparts what two characteristics?The action & the duration of action
Which bonds impart corticosteroid activity? Glucocorticoid activity?Corticosteroids = 3-keto & 4,5-delta. (Cortico is a broader category, so most basic numbers - 3,4,5) Glucocorticoids = 11Beta- & 17alpha-OH (glucose has a lot of sugar- & 1 & 7 can benefit from that...also much more complicated than cortico so, 11 & 17)
Long acting corticosteroids have what structural characteristics? (Which bonds strengthen & protect other bonds?) (3)(1) 4,5 delta (cortico) is protected by 1,2 delta
(2) 11-OH (gluco?) is protected by 6,9 floro & 6-CH3
(3) 17-OH (gluco) is protected by 16-CH3-OH
What are the 4 variables which influence the duration of action of glucocorticoids?(1) % of drug bound to plasma proteins (↑ pp is ↑ duration)
(2) Affinity the drug has for the enzymes involved in their metabolism (↓ affinity is longer duration)
(3) Lipofilicity of the drug (↑ lipophilic is ↑ duration)
(4) Affinity the drug has for the glucocorticoid receptor (↑ affinity ↑ duration)
List one short acting corticosteroidHydrocortisone
List 4 intermediate corticosteroidsPrednisolone & prednisone, methyl-prednisolone, triamcinolone acetonide
List 3 long acting corticosteroids? (3 others listed somehow)Flumethasone, betamethasone, dexamethasone (fludrocortisone acetate, deoxycorticosterone pivalate, isoflupredone acetate) (long acting are a FBD- fucking big deal)
Why is prednisolone preferentially given to horses & cats?Cats & horses are not efficient at absorbing/converting prednisone → prednisolone. So give them prednisolone.
List 2 glucocorticoids which can be used to treat Addison's dz in small animals?Fludrocortisone acetate & deoxycortisterone pivalate (DOCP)
If you look at a bottle of injectable drug, what are the 3 moieties which would indicate that it should be given IV?Succinate, phosphate, polyethylene glycol (water soluble)
If you look at a bottle of injectable drug, what are the 2 moieties which would indicate that it should be given IM or SC?Acetate, pivolate (water insoluble)
**If ongoing glucocorticoid therapy admin is abruptly stopped & the neg feedback mechanism of ACTH release from the anterior pituitary is still in effect what may occur?Iatrogenic Addison's disease may occur (ACTH initiates natural glucocorticoid secretion by the adrenal glands)
What are some of the side effects of corticosteroid administration? (9)↑ susceptibility to infection, ↓ wound healing, GIT ulceration, myopathy, edema resulting from fluid & electrolyte imbalance, diabetes mellitus, abortion, laminitis in horses, hepatotoxicity
In what conditions should glucocorticoids not be used? (7)Corneal ulcers, burns, diabetes mellitus, uncontrolled infection, cardiac disorders, late pregnancy, **using oral corticosteroids & NSAIDs is not currently recommended
What is another name for hyperadrenocorticism?Cushing’s disease
What are the two types of hyperadrenocortisism? What percentages are associated with dogs?(1) Pituitary dependent hyperadrenocortisism (PTH) for 85% of dogs
(2) Adrenal-dependent hyperadrenocorticosism. 15% of dogs have adrenal tumors
What are 4 adrenal steroid inhibitors & how do they work?(1) Mitotane (irreversibly destroys the cells of the Zona fasciculata & Zona reticularis.)
(2) Ketoconazole (used to treat hyperadrenocortisism when mitotane isnt working, inhibits steroid synthesis reversibly by blocking cytochrome p450 enzyme system)
(3) Selegiline (inhibits ACTH secretion)
(4) Trilostane (reduces or inhibits synth of cortisol, aldosterone & androgens)
Ketoconazole is an anti-____ drug?Antifungal drug
Why does ketoconazole have drug interactions?Due to the fact that it causes enzyme inhibition of cytochrome p450, it has several drug interactions
Which drug used as an adrenal steroid inhibitor is also used to treat old age dementia?Selegilene can also be used for canine cognitive dysfunction (Gil is senile)
Why does trilostane reduce the synthesis of cortisol, aldosterone, & androgens?It is a competitive inhibitor of 3-beta hydroxysteroid dehydrogenase (which is needed to make this crap)
What is another name for hypoadrenocortisism?Addison's disease
In vet med, which animal species at what age is hypoadrenocortisism most seen?Dogs, young to middle age (ESP. young adult female dogs). Occasionally seen in horses.
Which layers of the adrenal cortex are affected in Addison’s disease?(Hypo) all three zones reduced in thickness
What electrolyte imbalances are seen in pts with Addison’s?Hyponatremia (↓ Na+) & hyperkalemia (↑ K+)
**Will a drug with primarily glucocorticoid activity be a good drug to use as a maintenance treatment in a dog with Addison’s disease?Maintenance therapy requires a mineralocorticoid replacement also