Adrenocorticoid Steroids

Question 1

Physio GCs

Answer 1

Immune and metabolism

Question 2

Physio MCs

Answer 2

Blood presseure (salt stuff)

Question 3

Pharmaco use of GCs

Answer 3

Inflam and autoimmune dzs

Question 4

Pharma use of MCs

Answer 4

Hypertension and heart failure

Question 5

Glucocorticoid metabolic effects

Answer 5

Increase gluconeogenesis
Decrease glucose uptake in muscles and fat
Increase fat breakdown

Net effect is increase in plasma glucose…can worsen glucose control in diabetic patients

PEPCK enzyme is important

Question 6

Glucocorticoids and stress

Answer 6

Provides body with increased energy via increased glucose levels…causes increased in blood pressure by activating vasoconstrictor stimuli

Question 7

GC and blood cell levels

Answer 7

Decrease eosinophils, basophils, monocytes, and lymphocytes
Increases Hemoglobin, erythrocytes, platelets, and PMNs

Decrease in Th17s

Both innate nad immune response decreased

Question 8

Most important therapeutic property of GCs

Answer 8

Anti-inflam

Decrease synthesis of pro inflam cytokines and increase synthesis of anti-inflam cytokines

Question 9

Bad effects of GCs

Answer 9

Exacerbation of ulcers via gastric acid and pepsin production
Altered mental status
Exaerbate bone loss

Question 10

GC mechanism of action at nuclear level

Answer 10

Interact with GR…moves to nucleus to increase anti-inflam genes, decrease expression of pro-inflam, interfere with NF-kB to decrease pro-inflam cytokines

Takes a while

Question 11

GC other mech of action

Answer 11

Decreases expression of COX 2 which decreases prostanoid expression

Also inccreases Annexin 1 when inhibits phospholipase A2 and is also agonist of lipoxin receptor than inhibits inflam response

Decreased AA and decreased prostanoids

Question 12

Cortisol affinity

Answer 12

Same for Anti-inflam effect and salt effect

Question 13

Prednisone as a prodrug

Answer 13

Converted to prednisolone…metabolized by CYP3A4…good for tapering

Question 14

Uses of GCs

Answer 14

Replacement therapy 
Acute inflammation 
Neoplastic dz 
Autoimmune dz 
Chornic inflammation

Question 15

Adverse effects of GCs

Answer 15

Decreased growth in children
Osteoporosis 
Glaucoma 
Increased infection risk 
Centripetal distr of body fat 
Hirsutism 
Increased appetite 
Hypertension
Emotional
Peripheral edema
Peptic ulcer
Hypokalemia

Question 16

When to withdraw GCs

Answer 16

When max benefit obtained
When indequate benefit obtained after adequate trial
Side effects

Question 17

Immediate cessation of GCs

Answer 17

Seroid induced acute psychosis unresponse to antipsychotics

Herpes viral corneal infections

Question 18

Typical withdrawl of GCs

Answer 18

If tx up to 10mg/day, then reduce by 2.5 mg until 5mg/day, after that, reduce by 1 mg/day

Question 19

Asthma pathology

Answer 19

Bronchial smooth muscle contracts
Bronchial walls inflamed
Mucus secretions are high

Question 20

GCs to treat asthma

Answer 20

Inhaled is first choice, but can more to oral if there if severe

No others are as effective as inhaled GCs to control long term asthma

Question 21

Benefits of GCs to tx asthma

Answer 21

Reduced bronchial hyper-responsiveness, prevention of late asthmatic response, and enhanced lung funciton

Question 22

Inhaled GCs to prevent asthma and advantage

Answer 22

Budesonide

Minimal side effects 
Low oral bioavailabiltiy 
Delivered directly to airways 
Fraction of dose used systemically
Small amount absorbed 

Undergoes first pass effect

Question 23

GC adverse effects in the asthmatic patient

Answer 23

Growth retardation…less severe side effects overall than oral

Dysphonia (hoarse voice)

Topical candidiasis (use larger spacer and rinse to prevent)

Question 24

GCs to treat autoimmunes

Answer 24

Achieve lowest possible disease activity is the goal…improve the quality of life, don’t cure

Question 25

SLE and how GCs used

Answer 25

Lupus
Basically body creates antibodies to itself due tp apoptotic and necrotic cells

Low dose GCs can be used to treat most…GCs should be used mostly just for acute or subacute control of symptoms

Question 26

Tx of cutaneous lupus

Answer 26

Topical glucocorticoids or intralesional injecion of triamcinalone

Question 27

Treatment of mild SLE

Answer 27

Induction therapy of prednisone for 4-6 weeks and then tapered to lower dose for maintenance therapy

Question 28

Treatment of severe acute flares of SLE

Answer 28

Pulse high dose for 3 days…few side effects

Question 29

Side effects associated with prednisone cutoff

Answer 29

7.5 mg/day

Question 30

Low doses of prednisone

Answer 30

Few adverse effects

Question 31

most rheumatologists avoid doses above

Answer 31

30 mg

Question 32

Glucocorticoid induced osteoporosis

Answer 32

Bone resorption increased, formation decreased, decreased calcium absorption from vit D interruptio

Also muscle atrophy leads to increased risk of fall

Question 33

Prevention of glucocorticoid induced osteoporosis

Answer 33

Lowest possible dose
Consider alternate route and schedule of administration (every other day, etc.)
Ensure sufficient intake of calcium, protein, and Vit D
Increase weight bearing exercise
Risk of falls

Question 34

Tx for glucocoritcoid induced osteoporosis

Answer 34

Ca intake
Vit D intake
Bisphosphonates

Question 35

MCs mechanism

Answer 35

Bind to MR receptor and upregulated the ENaC genes (sodium channel)

Question 36

Use of MCs

Answer 36

Use of agonist - fludrocortisone
Replacement therapy

Used instead of aldosterone bc aldosterone has very low bioavailability

Question 37

Metyrapone

Answer 37

Inhibits CYP11B1…treats patients with hypercortisolism from adrenal neoplasms or ACTH producing tumors

Question 38

Aminoglutethimide

Answer 38

Inhibits CYP11A and rate limiting biosynthetic step

Treats Cushings syndrome

Affects both Aldosterone and cortisol production

Question 39

Ketoconazole

Answer 39

inhibits CYP17

Most effective inhibitor for Cushing’s dz