Steroids and Immunotherapy Flashcards
1
Q
The actions of corticosteroids are classified according to the potencies of these drugs to what two effects?
A
- Mineralcorticoid effect
- Glucocorticoid effect
2
Q
What does the Mineralocorticoid effect do?
A
Evoke the distal renal tubule to reabsorb Na+ in exchange for K+
3
Q
What does the glucocorticoid effect do?
A
Produce an anti-inflammatory response
4
Q
What are the naturally occuring corticosteroids?
(5)
A
- Cortisol (hydrocortisone)
- Cortisone
- Corticosterone
- Desoxycorticosterone
- Aldosterone
5
Q
What effects does modification of natural corticosteroids produce? Example of a modification?
A
- More potent glucocorticoid effects than cortisol & cortisone
- Reduction of mineralocorticoid effects
- Reduced rate of hepatic metabolism
Introduction of the double bond in prednisone/prednisolone
6
Q
MoA of Glucocorticoids?
A
Enhance/Suppress changes in DNA transcription -> change in protein synthesis -> change secretion of cytokines
7
Q
Where are mineralocorticoid receptors located within the body?
A
- Distal renal tubules
- Colon
- Salivary glands
- Hippocampus
8
Q
Differences in mineralocorticoid & glucocorticoid receptors?
A
- Glucocorticoid receptors are more widely distributed
- Do not bind to aldosterone
Thus, glucocorticoid selective
9
Q
Purpose of permissive & protective effects of glucocorticoids?
A
Maitenance of homeostasis during severe stress
10
Q
When do permissive actions of glucocorticoids occur? what do they do?
A
- At low physiologic steroid concentrations
- Prepare the individual to respond to stress
11
Q
When do protective actions of glucocorticoids occur? what do they do?
A
- High plasma concentrations of steroids exerting anti-inflammatory/immunosuppressive effects
- prevents the host-defence mechanisms from overshooting & damaging the organism
12
Q
What routes may cortisol succinate & cortisone acetate be given?
A
- Cortisol succinate (water-soluble) - IV & IM
- Cortisone acetate - Oral & IM
13
Q
Is crotisol succinate or cortisone acetate the slow-releasing preparation? How long does it last?
A
cortisone acetate: slow-releasing preparation lasting 8-12 hours
14
Q
Description of Prednisolone? How supplied?
A
Synthetic analogue of cortisol
* oral or parenterally
15
Q
Prednisolone’s equivalent dose?
A
5mg = 20mg cortisol
16
Q
Anti-inflammatory & Sodium-retaining potency of Prednisolone?
A
Anti-inflammatory - 4
Na+ retaining - 0.8
17
Q
Which drugs are suitable for sole replacement w/ adrenocortical insufficiency? Why?
A
Prednisolone & Cortisol
* They have both gluco/mineralocorticoid effects
Technically, prednisone & cortisone but they’re converted to the drugs above
18
Q
Prednisone’s MoA
A
Converted to prednisolone after GI absorption
- anti-inflammatory/clinical effects similar to prednisolone
19
Q
Prednisone’s anti-inflammatory & Na+ retaining potencies?
A
Anti-inflammatory - 4
Na+ - 0.8
20
Q
Prednisone’s equivalent dose?
A
5mg = 20mg cortisol
21
Q
What is methylprednisolone?
A
The methyl derivative of prednisolone
22
Q
Methylprednisolone’s equivalent dosing?
A
4 mg = 20mg cortisol
23
Q
Unique feature of Methylprednisolone?
A
Intra-articular injection has prolonged effect
24
Q
Methylprednisolone’s anti-inflammatory/Na+ potency?
A
Anti-inflammatory - 5
Na+ - 0.5
25
Betamethasone description?
Fluorinated prednisolone derivative
26
Betamethasone equivalent dosing?
0.75 mg = 20mg of Cortisol
27
Betamethasone anti-inflammatory/Na+ retaining potency?
Anti-inflammatory - 25
Na+ - Zero
28
What property does Betamethasone have that makes it inappropriate to use?
Lacks mineralocorticoid properties
* **not acceptable for replacement in adrenocortical insufficiency**
29
Dexamethasone description?
Flourinated derivative of prednisolone
* isomer of betamethasone
30
Dexamethasone equivalent dosing?
0.75 mg = 20mg cortisol
Same as betamethasone
31
Which corticosteroid is commonly used in the treatment of cerebral edema?
Dexamethasone
32
Dexamethasone anti-inflammatory/Na+ retaining potencies?
Anti-inflammatory - 25
Na+ - 0 (zero)
| same a betamethasone
33
Triamcinolone description
Fluorinated derivative of prednisolone
34
Triamcinolone equivalent dosing?
4mg = 20mg cortisol
35
Specific use for triamcinolone hexacetonide?
Intra-articular injection may provide effects 3 months or longer
36
Adverse/Side effects of Triamcinolone?
* **Anorexia rather than appetite stimulation**
* **Sedation rather than euphoria**
* Increased skeletal muscle weakness
37
Which corticosteroid is often used for epidural injections in the treatment of lumbar disk disease?
Triamcinolone
38
Triamcinolone anti-inflammatory/Na+ retaining potency?
Anti-inflammatory - 5
Na+ potency - 0 (zero)
39
Aldosterone anti-inflammatory/Na+ retaining potency?
Anti-inflammatory - 0 (zero)
Na+ retaining potency - 3,000
40
Fludrocortisone anti-inflammatory/Na+ retaining potency?
Anti-inflammatory - 10
Na+ retaining potency - 250
41
Cortisol anti-inflammatory/Na+ retaining potency?
Anti-inflammatory - 1
Na+ retaining potency - 1
42
Fludrocortisone equivalent dosing?
2mg = 20mg cortisol
43
What is the only universally accepted use for corticosteroids?
Replacement therapy for deficiency states
44
Your patient is unresponsive to vasopressors/inotropes in a HoTN crisis, what would be safe to give?
A single large dose of a corticosteroid in unrecognized adrenal/pituitary insufficiency
45
Which corticosteroids are recommended for inflammatory states?
Prednisolone (Prednisone)
46
Masking inflammation via corticosteroids is at risk for what? Example?
Masking of symptoms may delay diagnosis of life threatening illness
* Peritonitis 2/2 peptic ulcer perforation
47
Dosing for treatment of Acute adrenal insufficiency?
Cortisol 100mg x1 -> 100 mg Q8hrs
48
Dosing for chronic adrenal insufficiency?
PO Cortisone 25 - 37.5 mg daily
(25mg in AM & 12.5 mg in afternoon to mimic diurnal cucle of adrenal secretion)
49
Treatment for Acute Adrenal insufficiency?
* Electrolyte/Fluid replacement
* Corticosteroids (supplemental)
50
Benefits/downsides of corticosteroids in allergy therapy?
* Benefit - Potent anti-inflammatory effects (Mainstay of Tx)
* Downside - Topical corticosteroids take 3-5 days of treatment to produce effect (compared to antihistamines taking 1-2 hours)
51
What drugs are often recommended as first-line therapy for Asthma?
Inhaled glucocorticoids
52
Inhaled glucocorticoids can be used preoperatively for what purpose?
In pts w/ active airway disease to prevent bronchospasm
53
Inhaled glucocorticoid dosing for intraoperative bronchospasm?
Dosing equivalent to 1-2mg/kg of Cortisol
54
Time of inhaled glucocorticoids preoperatively to prevent bronchospasm?
1-2 hrs before induction
55
How does dexamethasone prevent N/V?
If given near beginning of surgery, reduces surgery induced inflammation by inhibiting prostaglandin synthesis
56
What effect does a higher dose of dexamethasone provide better than a lower dose?
Similar antiemetic effect
8-10mg = 4-5mg
57
MoA of glucocorticoids on post-op analgesia?
Peripherally inhibit COX & lipoxygenase inflammatory chain reactions
58
What drug/dosing decreases post-op pain & opioid use?
Periop dexamethasone - 0.1mg/kg
59
Corticosteroids are useful in what situations in the neuro/trauma populations?
Large doses reduce/prevent cerebral edema -> & inc. in ICP
* Intrcranial tumors
* Metastatic lesions
* Bacterial meningitis
60
In which neuro/trauma pts are glucocorticoids not particularly useful?
* Severe head injury
* Cerebral infarction
* Intracranial hemorrhage
61
Despite no strong evidence, glucocorticoids are commonly given for what condition?
Aspiration pneumonitis
62
Alternative to surgical tx for lumbar disk disease? regimen?
Epidural corticosteroids w/ lidocaine
* 25-50mg of triamcinolone
* 40-80mg methylprednisolone
63
Benefits of epidural corticosteroids
Dec. inflammation/edema on nerve roots from compression
64
High doses of corticosteroids are given @ time of surgery to produce immunosuppression and decrease the risk of what? for what kind of surgery?
1. Rejection
2. Organ transplantation
65
Criteron for initiating corticosteroids in patients with RA
control of symptomatic flares and progressive disability despite maximal medical therapy
66
What important features of corticosteroid therapy is important to know in the tx of Arthritis?
* Administered in the smallest dose to provide significant but **not** complete symptom relief
* Risk of painless destruction of the joint w/ corticosteroids
67
Which collagen diseases (and which not) are treated by corticosteroids?
* Fulminating systemic lupus erythematosus
* Polymyositis
* polyarteritis nodosa
* Wegener granulomatosis
Not Scleroderma
68
Benefits of corticosteroids in the tx of collagen diseases?
Manifestations are decreased and longevity improved
69
Corticosteroid use in the eyes?
Reduce ocular inflammation, uveitis & iritis, to preserve sight
70
When should corticosteroids not be used in the eye?
* Tx for ocular abrasions (delayed healing/infection)
* Inc. IOP -> cataractogenesis
71
Concern with glucocorticoids in the tx of cutaneous disorders?
Systemic absorption
* may suppress the HPA axis -> cushing's syndrome
72
Dosing/drug for Post-intubation laryngeal edema? issue?
Dexamethasone 0.1-0.2mg/kg IV
Efficacy not confirmed
73
Drug/Dosing for tx of mild croup in children?
Dexamethasone - 0.6mg/kg orally
74
Corticosteroids may be given to what patients when their condition is unresponsive to medical/surgical therapy? When are corticosteroids most effective?
* Myesthenia Gravis
After thymectomy
75
Corticosteroids administered 24 hrs before delivery reduces what condition & in what population?
Respiratory distress syndrome in neonates (24-36 weeks gestation)
76
Side effects of chronic corticosteroid therapy?
| 8
1. Suppress HPA axis
2. Electrolyte/metabolic changes
3. Osteoporosis
4. Peptic ulcer disease
5. Skeletal muscle myopathy
6. CNS dysfunction
7. Peripheral blood changes
8. Inhibits normal growth
77
What time frame of corticosteroid adminstration is unlikely to cause side effects?
< 7 days even w/ high doses
78
What concern do you have in pts w/ chronic hypoadrenocorticism undergoing surgery?
Susceptible to CV collapse due to not releasing endogenous cortisol in response to surgical stimulation (they will need additional corticosteriod summplementation)
79
In patients with adrenal insufficiency, do they need unstressed cortisol levels, or supraphysiologic levels to maintain CV homeostasis during surgery?
Cortisol equivalents to unstressed production are sufficient
80
Definitive suppression of the HPA axis occurs with what duration/dose?
>20mg/day for >3 weeks of prednisone or equivalent
81
What dosing is there no concern of HPA axis suppression?
<5mg/day of prednisone = considered no suppression
82
Possible suppression of HPA axis may or may not exist with what duration/dose?
5-20mg/day of prednisone (or equivalent) for >3weeks
| Schrodinger's suppression
83
What may present via the corticosteroid effects on the distal renal tubules? Why?
Hypokalemic metabolic alkalosis
* Enhanced Na+ reabsorption/K+ excretion (via mineralcorticoid action)
84
What signs may present with the mineralocorticoid effect of corticosteroids?
1. **Edema**
2. **Weight gain**
85
Corticosteroids effects on metabolism?
Hyperglycemia
* Inhibit peripheral use of glucose
* Promotes hepatic gluconeogenesis
86
How can hyperglycemia 2/2 corticosteroid use be managed?
Diet & Insulin
87
Dosing for minor surgical stress (inguinal hernia repair)
Replacement of:
* 25mg of Hydrocortisone
Or
* 5mg of Methyprednisolone
88
Dosing for moderate surgical stress (non-lap cholecystectomy, colon resection, THR)
Replacement of:
Equivalent of 50-75 mg of hydrocortisone for 1-2 days
89
Dosing for major surgical stress (pancreatoduodenectomy, esophagectomy, CPBP)
Replacement of:
Equivalent of 100-150 mg of hydrocortisone for 2-3 days
90
What MSK s/e may warrant corticosteroid discontinuation? Why?
Osteoporosis
* Vertebral compression fx
* Rib Fx
* Fx in OR 2/2 positioning
91
What is skeletal muscle myopathy? When must corticosteroids be stopped?
Weakness of the proximal musculature 2/2 corticosteroids
* Weakness so severe, ambulation is impossible
92
What CNS s/e occur with corticosteroid therapy?
* Increased Neuroses/Psychoses
* Cataracts
93
Almost all patients taking corticosteroids will develop what disease? With what dose/duration?
Cataracts
20mg prednisone equivalents for 4 years
94
What immunological (peripheral blood changes) occur with a single dose of cortisol?
Reduction of:
* Lymphocytes by 70%
* Monocytes by 90%
in 4-6 hrs
95
Acute lymphocytopenia after cortisol administration reflects what?
Sequestration of lympho/monocytes from the blood rather than destruction
96
What does Parathyroid hormone regulate? where?
Extracellular Ca2+ concentration
* Bone
* Kidney
* Intestine
97
How is Parathyroid hormone stimulated? Net effect?
Hypocalcemia & hyperphosphatemia
* Increase in extracellular Ca2+
98
What two way may hypercalcemia be classified?
Parathyroid & non-Parathyroid dependent
99
Parathyroid dependent hypercalcemia is associated with what?
Bone loss & Osteoporosis
100
Management of hypercalcemia?
| 4
* IV fluids
* Bisphosphonates
* Calcitonin
* Glucocorticoids
101
Most common setting for hypocalcemia?
Within 12-24 hrs of surgery
* Particularly s/p total/sub-total thyroidectomy
or
* Four-gland parathyroid exploration/removal
102
Signs of hypocalcemia?
| 4
* Neuromuscular irritability
* Arrhythmias
* Dec. myocardial contractility
* HoTN
103
What value is severe hypocalcemia and what does it constitute?
Serum Ca2+ <7.5 mg/dL w/ normal albumin
* Medical emergency due to death from laryngeal spasm/grand-mal seizures
104
What hormones need to be replaced in patients undergoing surgery with a previous hypophysectomy?
Thyroid & Cortisol hormones
105
Which hormone may be omitted for several days and which must be provided continuously in pts with prior hypophysectomy?
Continuous - Cortisol
Thyroid hormones have long half-lives
106
What is octreotide? What does it treat?
Somatostatin analogue that inhibits Growth hormone
* effective for acromegaly
107
Octreotide may be life saving during what? What may occur during a bolus?
Acute carcinoid crisis
* Bradycardia and 2nd/3rd degree HB
108
Normal role of Adrenocorticotrophic hormone?
Stimulate secretion of corticosteroids from adrenal cortex
* mostly cortisol
109
Treatment of disease states with ACTH isn't physiologically equivalent to specific hormones, why?
ACTH exposes tissues to a mixture of gluco/mineralocorticoids & androgens
110
Administration of ACTH is associated with what side effects?
* Na+ retention
* Hypokalemic metabolic alkalosis
* Acne
111
What substance does the pineal gland prinicipally excrete?
Melatonin
112
What are the two principle hormones secreted by the posterior pituitary gland?
* Arginine vasopressin (ADH)
* Oxytocin
113
What hormones are excreted by the Anterior pituitary?
| 6
* Prolactin
* Growth Hormone
* Follicle-stimulating hormone
* Lutenizing hormone
* ACTH
* Thyroid stimulating hormone
114
Diabetes insipidus is due to what?
Inadequte secretion of ADH (vasopressin) by posterior pituitary
115
Diabetes insipidus leads to:
* Excessive water loss
* hypernatremia
via polyuria
116
What can cause DI?
| 4
* Trauma/Surgery of hypothalamus/pituitary
* Cerebral ischemia
* Cerebral maliginancy
* Nephrogenic by renal tubules not responding to ADH
117
Vasopressin is effective in treating:
Severe HoTN caused by:
* Perioperative ACEi/ARB adminstration
* Anaphylaxis
* Severe catecholamine deficiency s/p pheochromocytoma resection
118
What contributes to loss of vascular tone during sepsis?
* Excessive Nitric oxide
* Low plasma vasopressin (ADH)
* RAAS activation
119
What drug/dose can reverse severe HoTN & lower Norepi dosages in catecholamine resistant septic shock?
Vasopressin
* 0.01-0.04 unit/min
120
Vasopressin may be used as an adjunct in controlling what?
Esophageal varicies during:
* Abdominal surgery
* Cirrhosis
* Portal HTN
121
How does vasopressin control esophageal bleeding? Dose?
Decreases hepatic blood flow for 30 min
* 20 units over 5 min
122
Side effects of Vasopressin?
Small doses produce selective vasconstriction of coronary arteries
* angina pectoris
* EKG evidence of ischemia
* MI
123
Oxytocin effects and use?
Stimulates uterine muscle tone
* Induce labor
* prevents uterine atony
* Decreased hemorrhage in post-partum/abortion period
124
Side effect of high dose/bolus of oxytocin?
Decreased SBP & DBP via relaxation effect on vascular muscle tone
125
Use of estrogens clinically?
* Tx of side effects from menopause
* Prevent bone loss (vertebral/femoral fx)
* Combined with progestins for oral contraceptives
126
Androgen use clinically?
* Males -> stimulate primary/secondary sexual characteristics
* Females -> palliative management of metastatic breast cancer
* stimulate erythropoietin
* Tx of heredity angioedema
