Steroids & Immunotherapy Flashcards
1
Q
The actions of corticosteroids are
classified according to the potencies in their ability to?
A
–Evoke distal renal tubular reabsorption
of sodium in exchange for potassium
ions
[* Mineralocorticoid effect]
– Produce an anti-inflammatory response
[* Glucocorticoid effect]
2
Q
Naturally occurring corticosteroids are?
A
– Cortisol (hydrocortisone)
– Cortisone
– Corticosterone
– Desoxycorticosterone
– Aldosterone
3
Q
Modifications of structure have
resulted in synthetic
corticosteroids with ______
glucocorticoid effects than the
two closely related natural
hormones, ______ and _____.
A
more potent
cortisol and cortisone
4
Q
What is the chemical change in prednisolone and prednisone that alter their potency compared to endogenous corticosteroids?
A
Introduction of a double bond
5
Q
How does the rate of hepatic metabolism and mineralcorticoid effects differ in the synthetic corticosteroids compared to the natural hormones?
A
Less mineralcorticoid effects and less hepatic metabolism
6
Q
MOA of Glucocorticoids
A
– Enhance or suppress changes in the transcription of
DNA and therefore the synthesis of proteins
– Inhibit the secretion of cytokines via
posttranslational effects
7
Q
Mineralcorticoid receptors are present in?
A
- Distal renal tubules
- colon
- salivary glands
- hippocampus
8
Q
How does glucocorticoid receptor distribution differ from mineralcorticoid receptor distribution? What do they NOT bind?
A
Glucocorticoids receptors are more widely
distributed and do not bind aldosterone making these receptors glucocorticoid-selective
9
Q
Permissive and protective effects of
glucocorticoids are critical for the maintenance
of homeostasis during severe stress. What are the two phases/actions of glucocorticoids?
A
- Permissive actions: of glucocorticoids occur at low
physiologic steroid concentrations and serve to
prepare the individual for responding to stress - Protective actions: of glucocorticoids occur when
high plasma concentrations of steroids exert anti-
inflammatory and immunosuppressive effects
(This protective response prevents the host-defense
mechanisms that are activated during stress from
overshooting and damaging the organism)
9
Q
Water-soluble cortisol succinate can be administered?
A
intravenously to achieve prompt increases in plasma
concentrations
– More prolonged effects are possible with intramuscular
injection
10
Q
Cortisone acetate may be given? The acetate preparation is a __________ and after release, cortisone is converted to?
A
orally or IM but cannot be administered IV
- is a slow-release preparation lasting 8 to 12 hours
– After release, cortisone is converted to cortisol in the liver
11
Q
Are corticosteroids well absorbed after topical or aerosol administration?
A
Yes, promptly absorbed.
12
Q
Name 6 Synthetic Corticosteroids
A
Prednisone
Prednisolone
Methylprednisolone
Betamethasone
Triamcinolone
Fludrocortisone
13
Q
Prednisolone is an analogue of? And can be administered?
A
Cortisol that is available as an oral or parenteral preparation
14
Q
The anti-inflammatory effect of 5mg of Prednisolone is equivalent to ________ or cortisol.
A
20mg! (so 4x more potent)
15
Q
What to drugs are suitable for the sole replacement therapy in Adrenocortical Insufficiency because of the presence of glucocorticoid and mineralcorticoid effects?
A
Cortisol and Prednisone
16
Q
Prednisone is a prodrug, because after its absorption from the GI Tract it is rapidly converted to?
A
Prednisolone
– Anti-inflammatory effect and clinical uses are similar to those of prednisolone
17
Q
How does Methylprednisolone differ from Prednisolone? How does its potency compare to cortisol?
A
Is a methyl derivative of prednisolone.
4mg of Methylpred is equivalent to 20mg of Cortisol.
18
Q
The acetate preparation of methylprednisolone has a prolonged effect when administered?
A
Intraarticularly
19
Q
How is betamethasone chemically different than prednisolone?
A
Is a fluorinated derivative of prednisolone
20
Q
What is the anti-inflammatory effect of betamethasone compared to cortisol?
A
The anti-inflammatory effect of 0.75 mg of betamethasone is equivalent to 20 mg of cortisol
21
Q
What property does betamethasone lack compared to cortisol?
A
Lacks mineralcorticoid properties. Making it not acceptable for sole replacement therapy in adrenocortical insufficiency.
22
Q
How is dexamethasone chemically different than prednisolone and betamethasone?
A
Is a fluorinated derivative of prednisolone and an isomer of betamethasone
23
Q
Which corticosteroid is commonly chosen to treat certain types of cerebral edema?
A
Dexamethasone
24
What is the potency equivalent of dexamethasone compared to cortisol?
The anti-inflammatory effect of 0.75 mg of dexamethasone is equivalent to 20 mg of cortisol
25
How is Triamcinolone chemically different than prednisolone?
A fluorinated derivative of prednisolone
26
What is the potency equivalent of Triamcinolone compared to cortisol?
The anti-inflammatory effect of 4mg Triamcinolone is equivalent to 20mg Cortisol
27
The hexacetonide preparation of Triamcinolone injected intraarticularly may provide theraprutic effects for?
3 months or longer
28
Triamcinolone is often used for?
Injections in the treatment of Lumbar Disk Disease
29
What is an unusual adverse side effect of Triamcinolone?
An increased incidence of skeletal muscle weakness
30
What GI and CNS effects may accompany Triamcinolone administration?
Anorexia rather than appetite stimulation, and
sedation rather than euphoria
31
After aldosterone, what corticosteroid has the most sodium retaining potency?
Fludrocortisone
32
Which three corticosteroids have zero sodium retaining potency/effects?
Betamethasone
Dexamethasone
Triamcinolone
33
Which corticosteroid can only be administered orally?
Prednisone
34
Which two corticosteroids have the most anti-inflammatory potency compared to cortisol?
Betamethasone and dexamethasone.
Both are 25x more anti-inflammatory than cortisol
35
Which corticosteroid has the shortest elimination halftime?
Cortisone - elimination halftime 0.5hours (30min)
36
Which corticosteroid has zero anti-inflammatory potency/effect?
Aldosterone
37
Which two corticosteroids have the longest potential duration of action?
Betamethasone and dexamethasone
Duration of action: 36-54hrs
38
What is the only universally accepted clinical use of corticosteroids and their synthetic derivatives?
As replacement therapy for deficiency states
39
Corticosteroids can mask symptoms of inflammation, which could delay diagnosis of life-threatening illnesses, such as?
Peritonitis due to perforation of a peptic ulcer
40
What two corticosteroids are recommended when an anti-inflammatory effect is desired? (presumably outpatient scenario?)
Prednisone and prednisone
41
In deficiency states, such as acute adrenal insufficiency, what are some steps to treatment and dosing of corticosteroids?
Requires electrolyte and fluid replacement as well as supplemental corticosteroids
-cortisol administered 100 mg IV every eight hours after an initial injection of 100 mg
42
What is the dosing of corticosteroids when using them for the management of chronic adrenal insufficiency in adults? How does it supplement adrenal secretion?
Daily oral administration of Cortisone, 25-37.5mg
Typical regiment is 25 mg in the morning and 12.5 mg in the late afternoon
Mimics the normal diurnal cycle of adrenal secretion
43
Describe the use of corticosteroids for allergy therapy compared to antihistamines.
Topical corticosteroids are capable of
potent anti-inflammatory effects and are the mainstay of allergic therapy.
Unlike antihistamines that provide
pharmacologic effects within 1 to 2 hours, topical corticosteroids may require 3 to 5 days of treatment to produce a therapeutic effect
44
How are glucocorticoids used in asthma management?
Since asthma is an inflammatory disease of the lungs, inhaled glucocorticoids are often recommended as first line therapy for controlling symptoms.
-inhaled glucocorticoids are commonly used
45
In a patient with active reactive airway disease when should you administer corticosteroids before induction of anesthesia?
One to two hours before induction since beneficial effects of corticosteroids may not fully manifest for several hours
46
For the treatment of intraoperative bronchospasm, what dose of corticosteroid is commonly used?
1-2mg/kg of cortisol (or equivalent dose of prednisolone)
47
What is the equivalent dose of prednisolone to 20 mg cortisol?
5 mg.
48
If you have a 70 kg patient and you wanted to give 1-2mg/kg cortisol but given as prenisolone, how much would you give the patient?
5 mg prednisolone = 20 mg cortisol
(1 mg prednisolone = 4 mg cortisol)
1. Cortisol dose range for 70 kg patient:
Low end: 1 mg/kg × 70 kg = 70 mg cortisol
High end: 2 mg/kg × 70 kg = 140 mg cortisol
2. Convert cortisol to prednisolone:
Since 1 mg prednisolone = 4 mg cortisol, divide by 4:
For a 70 kg patient, the equivalent prednisolone dose would be between 17.5 mg and 35 mg, depending on clinical severity and judgment.
49
When does dexamethasone need to be administered during surgery to provide postoperative anti-emetic effects?
When administered near the beginning of surgery, probably by reducing surgery induced inflammation due to inhibition of prostaglandin synthesis. Additionally has a delayed onset of action.
50
True or false: administration of higher doses (8-10mg) of dexamethasone has a similar antimetic effect to lower doses (4-5mg)
TRUE
51
True or false: dexamethasone is also effective and suppressing chemotherapy induced nausea and vomiting
TRUE
52
What is the MOA of glucocorticoids for postoperative analgesia?
Peripherally inhibit the inflammatory chain reaction along both the cyclooxygenase and lipooxygenase pathways. Effective in decreasing postoperative pain without the side effect profile of NSAIDS.
53
What is the perioperative IV dexamethasone dose for postoperative analgesia?
IV doses more than 0.1mg/kg decreases acute postoperative pain and reduces opioid use.
54
Which corticosteroid is frequently selected for cerebral edema?
Dexamethasone, which has a minimal mineralocorticoid activity is frequently selected
55
Which conditions that increase cerebral edema and ICP are corticosteroids useful? What conditions are they not useful?
Enlarged doses are useful in the reduction or prevention of cerebral edema and resulting increase ICP seen with intracranial, tumors, metastatic lesions, and bacterial meningitis.
Administration of glucocorticoids to patients with severe head injury, cerebral infarction, and intracranial hemorrhage is NOT useful.
56
True or false: despite the strong confirming evidence, it is not uncommon to include steroids in the treatment of aspiration pneumonitis.
True,
57
What is the common dosing for epidural injection for lumbar disk disease using Triamcinolone or Methylprednisolone?
Triamcinolone: 25-50mg
Methylprednisolone: 40-40mg
Injected in a solution containing lidocaine at or near the interspace corresponding to the distribution of pain.
58
What is the proposed MOA of corticosteroids as an alternative to surgical treatment for lumbar disk disease?
Corticosteroids administered via epidural, may decrease, inflammation and edema of the nerve root that has resulted from compression
59
How are corticosteroids utilized during organ transplantation?
High doses of corticosteroids are often administered at the time of surgery to produce immunosuppression and decrease the risk of rejection of the newly transplanted organ
60
How are corticosteroids used in arthritis?
In patients with rheumatoid arthritis, corticosteroid therapy may be initiated for rapid control of symptomatic, flares and progressive disability, despite maximum medical therapy.
Administered in the smallest dose possible that provides significant but not complete symptom relief.
61
What is a risk of using corticosteroid therapy for arthritis?
Painless destruction of the joint is a risk of this treatment
62
How are corticosteroids used in collagen diseases?
Manifestations of collagen disease diseases, except for scleroderma, are decreased and longevity is improved by corticosteroid therapy
63
How are corticosteroids used for ocular inflammation?
Are used to suppress ocular inflammation, uveitis and iritis, to preserve site.
64
Topical and intraocular corticosteroid therapy often increases?
Intraocular pressure and is associated with cataractogenesis
65
Why should topical corticosteroids not be used for treatment of ocular abrasions?
Delayed healing and infections may occur
66
How are corticosteroids used for cutaneous disorders?
Tropical admin of corticosteroids is frequently effective in the treatment of skin diseases
67
What is a possible side effect or adverse effect that can occur using the topical administration of corticosteroids for the treatment of skin disease diseases?
Systemic absorption is also occasionally enhanced to the degree that suppression of the hypothalamic- pituitary-adrenal (HPA) axis occurs
or manifestations of Cushing syndrome appear
68
What is the dose of dexamethasone that should be used for the treatment of post intubation laryngeal edema?
0.1-0.2mg/kg IV
(* Efficacy of corticosteroids for treatment of
this condition has not been confirmed)
69
What dose of dexamethasone is an effective treatment for children with mild croup?
0.6mg/kg Oral Dexamethasone
70
When are corticosteroids usually used for patients with myasthenia gravis? When are they usually most effective?
usually reserved for patients with MG who are unresponsive to medical or surgical therapy
– These drugs seem to be most effective
after thymectomy(removal of thymus gland).
71
72
When my administration of corticosteroids decrease the incidence and severity of respiratory distress syndrome in neonate born between 24 and 36 weeks?
Administration at least 24 hours before delivery decreases the incidence and severity.
73
List some side effects of chronic corticosteroid therapy:
-suppression of the HPA axis
-electrolyte and metabolic changes
-osteoporosis
-peptic ulcer disease
-skeletal muscle myopathy
-CNS dysfunction
-peripheral blood changes
-inhibition of normal growth
74
Are inhaled corticosteroids likely to evoke adverse systemic effects?
No, unlikely to evoke adverse systemic effects
75
True or false: systemic corticosteroids use for short periods of time (<7days) even at high doses are unlikely to cause adverse side effects.
True
76
Patients being treated for _______ ____________ who are undergoing a surgical procedure should be given increased corticosteroid supplementation. Why?
Chronic Hypoadrenocorticism
Based on the concern that these patients are susceptible to cardiovascular collapse because they cannot release additional indigenous cortisol in response to the stress of surgery.
77
What doses of glucocorticoid prophylaxis should be given for surgical stress in patients with chronic hyperadrenocorticism?
Doses of cortisol equivalent to the daily unstressed cortisol production rate are sufficient. No advantage to supraphysiologic glucocorticoid prophylaxis.
78
After how long of extended prednisone use do patients who are taking greater than 20mg per day start to have a suppressed HPA axis?
Patients taking greater than 20 mg per day of prednisone or it's equivalent for more than three weeks have a suppressed HPI axis
79
Do patients taking less than 5 mg per day of prednisone or it's equivalent have HPI Axis suppression?
No, not typically.
80
Patients taking ____mg to ____mg a day of prednisone or it's equivalent for more than three weeks may or may not have suppression of the HPI access
5mg-20mg
81
What electrolyte and metabolic changes reflect mineralocorticoid effects on distal renal tubules?
Hypokalemic metabolic alkalosis, leads to enhance absorption of sodium and loss of potassium. Leading to edema and weight gain that accompany this corticosteroid effect.
82
How do corticosteroids influence glucose?
Inhibit the use of glucose in peripheral tissues and promote hepatic gluconeogenesis. Hyperglycemia can usually be managed with diet, insulin, or both.
83
For minor surgical stress, such as an inguinal hernia repair, what should the glucocorticoid replacement dose be of hydrocortisone or methyl prednisone?
25mg Hydrocortisone
or
5mg Methyprednisolone
84
For moderate surgical stress, such as an non-laparoscopic cholecystectomy, colon resection, or total hip replacement, what should the glucocorticoid replacement dose be of hydrocortisone?
Glucocorticoid requirement is about 50 to 75 mg daily of
hydrocortisone for 1 to 2 days
85
For major surgical stress, such as a pancreatoduodenectomy, esophagectomy, or cardiopulmonary bypass, what should the glucocorticoid replacement dose be of hydrocortisone?
Glucocorticoid dose should be 100 to 150 mg of
hydrocortisone daily for 2 to 3 days
86
What are some serious bone complications of corticosteroid therapy that may indicate I need to withdraw the therapy?
Osteoporosis, vertebral compression fractures, and rib fractures are common in serious complications of corticosteroid therapy.
-The presence of osteoporosis could
predispose patients to fractures during
positioning in the operating room
87
What muscles like side effect can be seen impatience, taking large doses of corticosteroids?
Skeletal muscle myopathy, characterized by weakness of the proximal musculature is occasionally observed
88
What condition develops in almost all patients who receive prednisone 20 mg daily or it's equivalent to for 4 years?
Cataracts
89
What kind of CNS dysfunction is associated with corticosteroid therapy?
Associated with an increase of neuroses and psychoses
90
What peripheral blood changes are seen with a single dose of cortisol? Likely MOA?
Decreases by almost 70% the number of circulating lymphocytes and by more than 90% in the number of circulating monocytes in 4 to 6 hours.
This acute lymphocytopenia most likely
reflects sequestration from the blood
rather than destruction of cells
91
What is the function of parathyroid hormone (PTH)?
Regulate extracellular, calcium, concentration through action on the bone, kidney, and intestine.
92
What activates parathyroid hormone secretion?
Activated by hypocalcemia and elevated phosphorus levels
93
What is the net effect/goal of parathyroid hormone?
To increase extracellular calcium
94
Hypercalcemia can be categorized into what two categories?
1. Parathyroid dependent
or
2. Non-parathyroid dependent.
95
Hypercalcemia from parathyroid disease is associated with?
Bone loss and osteoporosis
96
Management of hypercalcemia includes?
-IV fluids
-Bisphosphonates
-Calcitonin
-Glucocorticoids
97
The most common setting for symptomatic hypocalcemia is?
Within 12-24 hours after surgery, particularly after total or subtotal thyroidectomy or 4-gland parathyroid exploration or removal
98
Hypocalcemia can cause:
Neuromuscular irritability, arrhythmias, decreased myocardial contractility, and hypotension
99
Acute, severe hypocalcemia is characterized by total serum level ________, with normal albumin.
Total serum levels <7.5mg/dL
100
Serum calcium levels less than 7.5mg/dL with normal albumin is a medical emergency associated with:
Death from laryngeal spasm or grandma seizures
101
What drug is indicated for acute symptomatic hypocalcemia?
IV Calcium
102
What percent of serum calcium is bound to Albumin?
a significant portion of calcium in the blood is bound to albumin (about 40–45%)
103
True or False: Perioperative replacement of anterior
pituitary hormones may be necessary for patients receiving exogenous hormones because of a prior
hypophysectomy.
True
104
What drug is an effective tx for patients with acromegaly? Why?
Octreotide
A somatostatin analogue that inhibits the release of growth hormone.
105
What are Octreotide's effects on glucose?
Inhibits the secretion of insulin, therefore
decreased glucose tolerance and hyperglycemia might be observed.
106
Octreotide can be lifesaving in patients experiencing an?
acute carcinoid crisis
107
Bolus of Octreotide may be accompanied by?
bradycardia and second- and third-degree heart block
108
Adrenocorticotrophic Hormone (ACTH) stimulates the secretion of?
corticosteroids from the adrenal cortex, principally cortisol
109
An important clinical use of ACTH is as a diagnostic aid in patients with?
Suspected Adrenal Insufficiency
110
Treatment of disease states with ACTH is not physiologically equivalent to administration of a specific hormone because?
ACTH exposes the tissues to a mixture of glucocorticoids, mineralocorticoids, and androgens.
111
What is the principle substance secreted by the Pineal Gland?
Melatonin
112
What are the two principal hormones secreted by the posterior pituitary?
Arginine vasopressin, also known as antidiuretic hormone, and oxytocin
113
Arginine vasopressin is the exogenous
preparation of vasopressin used to treat a variety of
clinical conditions such as:
Diabetes insipidus
Hypotension during anesthesia
Septic Shock
Esophageal Varices
114
Why is exogenous vasopressin used for Diabetes Insipidus?
Diabetes Insipidus is due to inadequate
secretion of vasopressin by the posterior
pituitary, excessive water loss and
hypernatremia via polyuria follow
115
Causes of Diabetes Insipidus
Neuro Causes: Neurotrauma and surgery of the pituitary and hypothalamus, cerebral ischemia, or cerebral
malignancy can cause diabetes insipidus.
Renal Causes: Nephrogenic diabetes insipidus resulting from an inability of the renal tubules to respond to adequate amounts of centrally produced AVP. Does NOT respond to exogenous administration of the hormone or its congeners(tf?)
116
What drug may be effective to treat hypotension from anaphylaxis and from severe catecholamine deficiency after resection of a pheochromocytoma?
Vasopressin
117
What dose of Vasopressin Infusion can be used to reverse systemic hypotension and decrease norepinephrine dosages in catecholamine-resistant septic shock?
0.01-0.04 unit per minutes
118
How can Vasopressin help in the management in Esophageal Varices?
may serve as an adjunct in the control of bleeding esophageal varices and during abdominal surgery in patients with cirrhosis and portal hypertension.
119
How should you dose Vasopressin for use in esophageal varices?
Infusion of 20 units over 5 minutes results in marked decreases in hepatic blood flow lasting about 30 minutes.
120
Vasopressin, even in small doses, may produce selective vasoconstriction of:
the coronary arteries, with decreases in coronary blood flow manifesting as angina pectoris,
electrocardiographic evidence of myocardial ischemia, and, in some instances, myocardial infarction.
121
Vasoconstriction and increased systemic blood pressure occur only with doses of vasopressin that are much larger than those administered for the treatment of?
Diabetes Insipidus
122
Oxytocin stimulates and is used for?
stimulates uterine muscle and is administered to induce labor at term, reduce and prevent uterine atony, and decrease hemorrhage in the postpartum or post abortion period.
123
All preparations of oxytocin used clinically are ______ and their potency is described in ____.
Synthetic
Units
124
Side effects of Oxytocin
High and bolus doses of oxytocin are more likely to decrease systolic and diastolic blood pressure via a direct relaxant effect on vascular smooth muscles.
125
There is evidence that administration of estrogen to postmenopausal women prevents:
bone loss, and vertebral and femoral bone fractures
126
Estrogens are effective in treating unpleasant side effects of?
Menopause
127
An important use of estrogens is in combination with?
progestins as oral contraceptives
128
Androgens are administered to males to stimulate the development and maintenance of?
secondary sexual characteristics
129
The most common indication of androgen therapy in females is?
palliative management of metastatic breast cancer
130
Androgens enhance erythropoiesis by stimulation of
renal production of erythropoietin
131
Certain androgens may be useful in the treatment of hereditary _________.
angioedema
