Exam 4 - Antiinflammatory Steroids

Question 1

DRUG LIST

Answer 1

Gluc: Cortisol/Cortisone, Prednisolone, Dexamethasone
Mineralcorticoids: Aldosterone, Fludracortisone

Question 2

Glucocorticoids

Synthesis/Reg

Answer 2

-Hypothal/CRH->AntPit/ACTH->AdrCortex:
Zona fasciculata cells release glucocorticoids
-Cortisol provides neg feedback (and inhibs IL/TNF)
-highest cortisol secretion in morning

Question 3

Glucocorticoids

Effects

Answer 3

• liver incr glyogenesis, GNG
• incr bloog glc
• incr protein breakfown (musc wasting)
• incr FFA
• permissive effects on hormones (Epi, GH)
• HTN
• mood elevation, insomnia, anxiety, psychosis
• antiinflammatory at high dose (decr. PG, leukotrienes)

Question 4

Glucocorticoid

Receptor Mediation

Answer 4

-Class I nuclear receptors (Zn finger, cytoplasm)
-dimerization for transcription factor
-increased protein synthesis
-also has effect on minerlocorticoid receptors in
presence of black licorice… (11B-HSD1 inhibition)
-licorice-induced HTN

Question 5

Steroid types

Answer 5

all derived from cholesterol

• mineralcorticoids (aldosterone)
• glucocorticoids (cortisol)
• androgens (testosterone-related)

Question 6

Glucocorticoids

types

Answer 6

Cortisol - endogenous
Cortisone - cortisol replacement tx
Prednisolone - 4x antiinflamm, .8x Na+ retention
Dexmethasone - 25x antiinflamm, 0x Na+ retention

Question 7

Mineralcorticoids

types

Answer 7

Fludrocortisone (aldosterone replacement tx)

Question 8

Mineralcorticoids

Syntheis/Regulation

Answer 8

• kindey/angiotensinII+K->AdrCort (zona glomerulosa)/aldosterone
• aldosterone does not vary over the course of the day

Question 9

Cortisol Release

Answer 9

• Stress/Inflamm hormones (ILs, TNF) cause CRH release
• Cortisol release mitigates inflammatory response
• NOTE: also comes with immunosuppressive effects

Question 10

Cortisol Antiinflamm

4 mechanisms

Answer 10

1) increase annexin production
2) decrease PG/Leukotriene production
3) decrease COX2 up-regulation
3) decrease TNF production

Question 11

Cortisol Mechanisms

annexin increase

Answer 11

• annexin inhibits phospholipase A2 (PLA2)
• PLA2 inhibits arachadonic acid synthesis
• no arachadonic means no PG (via COX2)
• no leukotriene synth

Question 12

Cortisol Mechanisms

PG/Leuotriene decrease

Answer 12

• no arachadonic means no PG (via COX2)

- no leukotriene synth (via 5 lipoxygenase)

Question 13

Cortisol Mechanisms

TNF decrease

Answer 13

• glucocorticoid recepter-ligand complex increased ikB expression
• decrease NFKB production, TNF expression

Question 14

Glucocorticoid

ADME

Answer 14

• well absorbed (oral, iv, im)
• topical preparations
• liver metabolization, inactive metabolites in urine
• cortisol has 60-90 min half-life

Question 15

Glucocorticoid

Adverse

Answer 15

-adrenal involution
-adrenal cells become desensitized to ACTH
-adrenal insufficiency after 1 week
-mimics Cushing’s syndrome (fat redistribution, striae, acne)
-HTN, hyperglycemia, ^infxn’s, osteonecrosis, growth
suppression, osteoporosis, bx change

Question 16

Glucocorticoid

Withdrawal

Answer 16

• abrupt withdrawal causes fever/myalgia/malaise/arthralgia
• recovery can take weeks/months/years
• use tapering schedule to d/c cortisol therapy

Question 17

Glucocorticoid

Tx usages

Answer 17

• immunosuppressive actions (autoimmune dz)
• dexmethasome used to dx causes of hypercortism
• can benefit from a single large dose without harm
• use lowest possible therapeutic dose