Steroidal Anti-Inflammatory Drugs (complete) Flashcards Preview

D&D Unit 2 > Steroidal Anti-Inflammatory Drugs (complete) > Flashcards

Flashcards in Steroidal Anti-Inflammatory Drugs (complete) Deck (22)
Loading flashcards...
1
Q

Describe the regulation of glucocorticoid secretion by the hypothalamic-pituitary-adrenal gland axis

A

hypothalamus —» secretes CRF —» anterior pituatary + ADH —» secretes ACTH —» adrenal cortex—» secretes glucocorticoids and mineralocorticoids

ACTH: (-)ve fdbk to hypothalamus

Glucocorticoids: (-)ve fdbk to ant. pituatary, hypothalamus (also exogenous glucocorticoids)

2
Q

Describe how the mechanism of glucocorticoid drug-induced suppression of adrenal gland function regulates the hypothalamic-pituitary-adrenal gland axis

A

When exogenous glucocorticoids are ingested, there’s a (-)ve feedback to the ant. pituitary

Leads to adrenal gland suppression (then it’ll stop doing it’s job!)

3
Q

What are the metabolic effects associated with glucocorticoids?

A
  • Carbohydrate
  • Protein
  • Fat
4
Q

Describe the carbohydrate metabolic effect associated with glucocorticoids

A

^ gluconeogenesis —» ^ blood glucose (^ insulin)

Causes diabetes-like state

5
Q

Describe the protein metabolic effect associated with glucocorticoids

A

Decrease protein synthesis —» ^ AA conversion to glucose

Causes: muscle wasting, skin-CT atrophy

6
Q

Describe the fat metabolic effect associated with glucocorticoids

A

^ lipolysis (peripherally) —» ^ free fatty acids

Causes:

  • net effect is lipogenesis due to ^ insulin release
  • centripetal obesity (buffalo hump, ab fat)
7
Q

Describe the mineralocorticoid effects (aldosterone) associated with glucocorticoids

A
  • ^ Na+ reabsorption at kidney —»> ^ blood volume and BP
  • Also ^ K+ and H+ secretion

Causes: fluid retention, hypertension, hypokalemia, metabolic alkalosis

8
Q

Describe the mechanism of anti-inflammatory and immunosuppressive actions

A

Vascular effects: reduced vasodilation, decreased fluid exudation

Cellular effects:

  • overall decrease in accumulation/activation of inflammatory and immune cells
  • Decreased synthesis of inflammatory and immune mediators

PROS: suppress chronic inflammation and autoimmune rxns

CONS: decrease healing and diminish immunoprotection

9
Q

Describe the metabolic pathways (activating/inactivating)

A

Liver inactivation:
- reduce double bonds —» conjugation from cortisol to glucoronide

Kidney inactivation: 11B-HSD II converts cortisol to cortisone

Liver activation: 11B-HSD I converts cortisone back to coritsol

10
Q

Describe glucocorticoid metabolism in pregnant women

A
  • Placental 11B-HSD II is active, but not 11B-HSD I
  • Can treat mom w/ GCs w/o effect on fetus
  • Placental enzyme converts active drug back to prodrug

To treat fetus:
- use agent that is poor substrate for 11B-HSDII

11
Q

The activity of a glucocorticoid is determined by the 11-carbon on the general structure. Which group is the active form? Which group is the inactive form?

A

Active: -OH (hydroxyl group)

Inactive: =O (keto group)

The inactive form is used as a prodrug. Must bypass the liver to be activated

12
Q

What are the clinical considerations for the use of cortisol?

A

AKA: hydrocortisone

  • Physiologic doses for replacement therapy and emergencies
  • GC and MC actions! [1:1]
  • Administered orally and parenterally
13
Q

What are the clinical considerations for the use of prednisone?

A
  • in the keto form (a prodrug) — activated to prednisolone in liver
  • Most commonly used oral agent when burst therapy is desired
  • GC and MC actions! [13:1]
  • NO TOPICAL ACTIVITY — not activated until first pass hepatic metabolism
14
Q

What are the clinical considerations for the use of methylprednisolone?

A
  • Used if parenteral administration desired for steroid burst
  • Not better than oral prednisolone in acute asthma exacerbations
  • MINIMAL MC action
  • Oral and parenteral forms
15
Q

What are the clinical considerations for the use of dexamethasone?

A
  • Most potent anti-inflammatory agent
  • Used in cerebral edema or chemo induced vomiting
  • NO MC action
  • Greatest suppression of ACTH secretion in pituitary
16
Q

What are the clinical considerations for the use of Triamcinolone?

A
  • Potent systemic agent
  • Excellent topical activity
  • NO MC action
17
Q

Explain the rationale for alternate day therapy for chronic GC use

A
  • Minimalize adrenal suppression

- Overall — you want anti-inflammatory actions to outlast HPA suppression

18
Q

Explain the rationale for the necessity for taper withdrawal following chronic GC use

A
  • Minimizes disease rebound
  • Gives adrenal gland opportunity to get going again!
  • Minimizes symptoms for adrenal insufficiency (adrenal crisis)
19
Q

What are the routes of administration

A

1) Oral
2) Topical
3) Ophthalmic
4) Intra-articular
5) Enemas
6) Inhalants
7) Nasal spray

20
Q

Describe oral administration

A
  • Most common

- Systemic actions (also given IV and IM)

21
Q

Describe topical administration

A
  • Relatively insoluble
  • HOWEVER Systemic effects possible if potent steroids are applied for long periods
  • or occlusive dressings used
  • or applied over large areas
22
Q

What are some considerations you should take into account when dosing?

A
  • MC side effects vary w/ agent
  • Dosage = trial and error
  • Reduce dosage once therapy objectives are achieved
  • Alternate days
  • Taper once therapy is complete

OVERALL: Use large doses for a short amount of a time!!