Pharmacology of Adrenocorticosteroids

1
Pharmacology of Adrenocorticosteroids

• 2009 DCOM Pharmacology Lecture Series
• J. Richard Brown, Pharm.D., BCPS, FASHP
• Professor
• Colleges of Pharmacy and Medicine
• University of Tennessee
• Memphis, TN

2
Learning Objectives

• Discuss the physiology of adrenal gland function
  as it relates to corticosteroid synthesis
• Provide insight into use of select diagnostic
  drugs in adrenal pathological disorders
• Review feedback mechanisms in the HPA axis as it
  relates to drug induced adrenal suppression
• Offer an overview of pharmacology and review
  therapeutic application of available steroid
  preparations
• Provide potency comparisons of systemic steroids
  available for use
• Offer insight into regimens for steroid
  withdrawal and the complications associated with
  withdrawal
• Discuss Addisonian symptoms and provide insight
  into stress dosing of steroids to avoid this
  complication
• Review side effects associated with steroid use
• Provide usage pearls of wisdom for safe and
  effective prescribing of steroids

3
Adrenal glands

• Adrenal medulla
• Epinepherine
• Norepinephrine
• Adrenal cortex
• Salt
• Sugar (stress hormones)
• Sex

4
Adrenal Cortex

• SALT (mineralcorticoids)
• SUGAR (glucocorticoids)..aka Steroids
• SEX (gonadocorticoids)

5
Adrenal Cortex Anatomy

• The adrenal cortex is composed of three zones
  histologically.
• Outer zona glomerulosa, site for aldosterone
  synthesis.
• Central zona fasciculata and inner zona
  reticularis produce both cortisol and androgens.

6
(No Transcript)
7
Zona Glomerulosa

• Outermost zone just below the adrenal surface
  capsule
• Secretes mineralocorticoids.
• Mineralocorticoids are aptly termed as they are
  involved in regulation of electrolytes in ECF.
• The naturally synthesized mineralocorticoid of
  most importance is aldosterone.

8
Zona Fasciculata

• Middle zone between the glomerulosa and
  reticularis
• Primary secretion is glucocorticoids.
• Glucocorticoids, as the term implies, are
  involved the increasing of blood glucose levels.
  However they have additional effects in protein
  and fat metabolism.
• The naturally synthesized glucocorticoid of most
  importance is cortisol.

9
Zona Reticularis

• Innermost zone between the fasciculata and
  medulla
• Primarily responsible for secretion is androgens.
• Androgenic hormones exhibit approximately the
  same effects as the male sex hormone
  testosterone.
• Overlap in the secretions of androgens and
  glucocorticoids exist between the fasciculata and
  reticularis.

10
(No Transcript)
11
POMCThe Origin of ACTH

• Pro-OpioMelanoCortin Precursor Protein
• Produces biologicals that act on 5 melanocortin
  receptor subtypes (MCR1-5)
• Large precursor protein to ACTH
• ACTH is MCR2 specific at adrenal level but may
  overide to MCR1 in excess
• Source of other biological peptides
• Endorphins
• Liptropins
• Melanocyte stimulating hormones (MCR1 specific)
• Mutationally impaired process in synthesis may
  lead to adrenal insufficiency

12
Adrenocorticotrophic Hormone (ACTH or
Corticotrophin)

• Synthesized as part of a larger precursor
  protein, pro-opiomelanocortin (POMC)
• Acting via MCR2, ACTH stimulates the adrenal
  cortex to secrete glucocorticoids,
  mineralocorticoids, and the androgen precursor
  dehydroepiandrosterone (DHEA)
• ACTH is a melanocortin similar to MSH
• In excess, ACTH can signal through the MCR1 and
  cause hyperpigmentation
• Synthesis follows 24 hour diurnal pattern..high
  in the AM and low in late PM with some production
  following food ingestion

13
ACTH as a Drug

• Used mainly for diagnostic purposes
• Limited therapeutic value in conditions
  responsive to corticosteroids
• Current and past products
• Cosyntropin (Cortrosyn), a synthetic ACTH
• Corticotropin Injection (Acthar Gel)
• Repository corticotropin injection (H.P. Acthar
  Gel)

14
A synthetic ACTH pharmaceutical
15
Site specific enzymatic inhibiton by metyrapone
to decrease cortisol level
16
Glucocorticoid Release Follows ACTH Release

• Cortisol, like ACTH, is secreted in a pulsitile
  manner and plasma levels closely parallel those
  of ACTH. Superimposed on this is a circadian
  rhythm that results in peak cortisol levels in
  the early morning and a nadir in the late
  evening.
• Physical and emotional stress (trauma, surgery,
  and hypoglycemia) can dramatically increase
  cortisol secretion by stimulating release of CRH
  and ACTH from hypothalamus and pituitary
  respectively.

17
(No Transcript)
18
(No Transcript)
19
Regulators of the HPA axis

• Hypothalamic Corticotrophin Releasing Factor or
  Hormone (CRH) acting on CRF1 receptor in
  pituitary increases ACTH synthesis
• Cytokines (leukemia-inhibitory factor (LIF),
  interleukin-6 (IL-6)
• Stimulatory on POMC gene expression and ACTH
  expression
• Arginine vasopressin (AVP)
• Secretagogue for pituitary corticotropes
• Potentates the effects of CRH on ACTH release
• In contrast to CRH, does not increase ACTH
  synthesis
• Negative feedback by cortisol can down regulate
  HPA
• Stress can up regulate HPA significantly

20
Corticotrophin Releasing Hormones (CRH) Use as a
Drug

• CRH Stimulation Test for diagnosis only
• In US, ovine CRH with flushing as a side effect
• Corticorelin (ACTHREL)
• Differentiates between pituitary source and
  ectopic source in ACTH dependent hypercorticism
• In Cushings..ACTH increases with a 5-10 failure
  rate, so test is not perfect
• In ectopic..ACTH does NOT increase in the
  majority of patients

21
HPA Axis and Stress Response

• Acute stress
• Systemic and neurogenic
• Injury, cold, pain, fear, infection, hemorrhage,
  surgery
• Short term, enhanced secretion of ACTH and
  glucocorticoids over riding negative feedback
• Maximum production of cortisol is 200mg/24hours
• Immunological stress
• Stimulation by inflammatory cytokines (IL-1,
  IL-6, TNF-?
• Repeated stress
• Chronic stress

Endocr. Rev 2155-88, 2000.
22
Negative Feed-Back

• Is achieved with endogenous and exogenous
  systemically active steroids at
  supraphysiological doses
• Mediated by glucocorticoids at the level of the
  pituitary and hypothalamus to reduce ACTH
• Occurs in two phases
• Rapid feedback occurs within seconds (inhibition
  of CRH and ACTH release)
• Delayed occurs within hours (down regulation of
  CRH and POMC gene expression)
• Occurs through both MR and GR but predominantly
  GR

23
Negative feedback sites in HPA axis
24
Receptors Response in Feedback

• Glucocorticoids act on two receptors
• Mineralocorticoid receptors (MR)
• MR has a higher affinity for glucocorticoids than
  GR
• At lower concentrations in hippocampus and
  sensory and motor nuclei outside the hypothalamus
• Regulation of basal expression of CRH and AVP
• Glucocorticoid receptors (GR)
• At higher concentrations MR capacity exceeded
  (wash over)
• Hypothamic pituitary action to decrease ACTH
• Termination of the HPA axis response to stress

25
Major Functions of Adrenal Steroids

• Glucocorticoids
• increases gluconeogenesis
• increases glycogenesis
• increases protein catabolism
• decreases antibody response
• antiinflammatory response
• antineoplastic response

• Mineralocorticoids
• increase sodium and water retention
• promote potassium loss

26
(No Transcript)
27
Site specific enzymatic inhibiton by metyrapone
to decrease cortisol level
28
Endogenous Cortisol

• Normal daily production of cortisol is 10mg to
  30mg in non stressed patients
• The liver is the main site of metabolism.
• Two major metabolites are 17-hydroxycorticosteroid
  s and 17-ketosteroids that are excreted in the
  urine.
• Metabolism may be induced by CYP inducing drugs
  (rifampin, phenobarb, etc)

29
Steroid Metabolism
30
Normal Daily Production Rates and Circulating Levels of the Predominant Corticosteroids Normal Daily Production Rates and Circulating Levels of the Predominant Corticosteroids Normal Daily Production Rates and Circulating Levels of the Predominant Corticosteroids
  CORTISOL ALDOSTERONE
Rate of secretion under optimal conditions 20 mg/day 0.125 mg/day
Concentration in peripheral plasma    
8 A.M. 16 ug/100 ml 0.01 ug/100 ml
4 P.M. 4 ug/100 ml 0.01 ug/100 ml
31
Anti-inflammatory Effects of Steroids with a
Broad Application in Medicine

• Reduces phagocytic action of WBCs
• Decrease extravasation of leukocytes into areas
  of injury and thus decrease fibrosis
• Reduce fever
• Suppress transplant rejection
• Suppresses allergic reactions
• Decrease COX-II and NOS
• Reduce cytokine production
• inhibit the release of IL-1, IL-2 and IL-6 and
  TNF-alpha
• Decrease proteolytic and lipolytic enzymes
• Impairment of delayed-type hypersensitivity

32
Major Corticosteroid Products in Use Today

• Prednisone (a pro drug that requires hepatic
  activation via cortisone reductase)
• Prednisolone (preferred in severe liver disease?)
• Dexamethasone (Decadron)
• Methylprednisolone (Medrol, SoluMedrol for IV)
• Hydrocortisone (SoluCortef)
• Triamcinolone (Aristocort)
• Fludrocortisone (Florinef for mineralocorticoid
  replacement)

33
COMMONLY USED GLUCOCORTICOIDS
Hydrocortisone is the most active natural
glucocorticoid Prednisolone is a delta-1
derivative with greater potency (made
synthetically). It is the active form of
prednisone.
34
Potency Comparisons
Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids
       
  Agent Anti-Inflammatory Topical Salt-Retaining Equivalent Oral Dose (mg) Forms Available
Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids      
  Hydrocortisone (closest to cortisol) 1 1 1 20 Oral, injectable, topical
  Cortisone 0.8 0 0.8 25 Oral
  Prednisone 4 0 0.3 5 Oral
  Prednisolone 5 4 0.3 5 Oral, injectable
  Methylprednisolone 5 5 0 4 Oral, injectable
 
Potency is relative to hydrocortisone Potency is relative to hydrocortisone Potency is relative to hydrocortisone Potency is relative to hydrocortisone      
     
     
35
Potency Comparisons Continued

       
  Agent Anti-Inflammatory Topical Salt-Retaining Equivalent Oral Dose (mg) Forms Available
Intermediate-acting glucocorticoids Intermediate-acting glucocorticoids Intermediate-acting glucocorticoids Intermediate-acting glucocorticoids      
  Triamcinolone 5 5 0 4 Oral, injectable, topical
 
 
Long-acting glucocorticoids Long-acting glucocorticoids Long-acting glucocorticoids Long-acting glucocorticoids      
  Betamethasone 25-40 10 0 0.6 Oral, injectable, topical
  Dexamethasone 30 10 0 0.75 Oral, injectable, topical
Mineralocorticoids Mineralocorticoids Mineralocorticoids Mineralocorticoids      
  Fludrocortisone 10 0 250 2 Oral
 
     
Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone      
     
36
Converting Steroids

• Establish the total daily of physiological
  equivalent doses of the corticosteroid drug being
  administered
• Multiply this by the physiologically equivalent
  dosage of the drug you are converting to
• Dose the converted drug at the appropriate
  interval for that drug

37
Potency Comparisons
Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids Comparisons of natural and synthetic corticosteroids
       
  Agent Anti-Inflammatory Topical Salt-Retaining Equivalent Oral Dose (mg) Forms Available
Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids Short- to medium-acting glucocorticoids      
  Hydrocortisone (cortisol) 1 1 1 20 Oral, injectable, topical
  Cortisone 0.8 0 0.8 25 Oral
  Prednisone 4 0 0.3 5 Oral
  Prednisolone 5 4 0.3 5 Oral, injectable
  Methylprednisolone 5 5 0 4 Oral, injectable
 
Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone Note Potency is relative to hydrocortisone      
     
     
38
ChallengeConvert 80mg of methylprednisolone q6h
to an equivalent daily oral prednisone dose??

• 80mg times 4 doses equals 320mg
• 320mg divided by 4mg (1 equiv methylprednisolone
  dose)
• for a total of 80 equiv doses times
• 5mg (1 equiv prednisone dose)
• equals a total of 400mg oral daily prednisone
• Which, as you can see, is an industrial sized
  dose of prednisone to take once daily!!

39
Glucocorticoids Place in Therapy

• Too many to count

40
Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders
Disorder Examples
Allergic reactions Angioneurotic edema, asthma, bee stings, contact dermatitis, drug reactions, allergic rhinitis, serum sickness, urticaria
Collagen-vascular disorders Giant cell arteritis, lupus erythematosus, mixed connective tissue syndromes, polymyositis, polymyalgia rheumatica, rheumatoid arthritis, temporal arteritis
Eye diseases Acute uveitis, allergic conjunctivitis, choroiditis, optic neuritis
Gastrointestinal diseases Inflammatory bowel disease, nontropical sprue, subacute hepatic necrosis
Hematologic disorders Acquired hemolytic anemia, acute allergic purpura, leukemia, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, multiple myeloma
Systemic inflammation Acute respiratory distress syndrome (sustained therapy with moderate dosage accelerates recovery and decreases mortality)
Infections Acute respiratory distress syndrome, sepsis, systemic inflammatory syndrome
Inflammatory conditions of bones and joints Arthritis, bursitis, tenosynovitis
Neurologic disorders Cerebral edema (large doses of dexamethasone are given to patients following brain surgery to minimize cerebral edema in the postoperative period), multiple sclerosis
Organ transplants Prevention and treatment of rejection (immunosuppression)
Pulmonary diseases Aspiration pneumonia, bronchial asthma, prevention of infant respiratory distress syndrome, sarcoidosis
Renal disorders Nephrotic syndrome
Skin diseases Atopic dermatitis, dermatoses, lichen simplex chronicus (localized neurodermatitis), mycosis fungoides, pemphigus, seborrheic dermatitis, xerosis
Thyroid diseases Malignant exophthalmos, subacute thyroiditis
Miscellaneous Hypercalcemia, mountain sickness
41
Indications for Systemic Glucocorticoids

• Endocrine disorders
• primary or secondary adrenocortical
  insufficiency
• congenital adrenal hyperplasia
• thyroiditis
• hypercalcemia associated with cancer
• shock unresponsive to conventional therapy
• pan-hypopituitarism

42
Ophthalmic Application both Topical and Systemic

• Ophthalmic diseases
• allergic conjunctivitis
• keratitis
• allergic corneal marginal ulcers
• ophthalmic herpes zoster
• iritis and iridocyclitis
• optic neuritis
• retrobulbar neuritis

43
(No Transcript)
44
Indications for Systemic or Intra-articular
Glucocorticoids

• Spinal Trauma
• Rheumatological disorders
• rheumatoid arthritis
• ankylosing spondylitis
• acute and subacute arthritis
• acute nonspecific tenosynovitis
• osteoarthritis and bursitis
• acute gout
• Collagen diseases
• systemic lupus erythematosus
• acute rheumatic carditis
• systemic dermatomyositis

45
Intra articular methylprednisolone (Depo Medrol)
offers a duration of 1-5 weeks
46
Indications for Systemic Glucocorticoids

• Respiratory diseases
• symptomatic sarcoidosis
• berylliosis
• disseminated pulmonary tuberculosis
• pulmonary emphysema
• aspiration pneumonitis
• diffuse interstitial pulmonary fibrosis
• pneumocystis carinii pneumonia with hypoxia
• H.flu type b meningitis in children
• septic shock
• acute Respiratory Distress Syndrome (ARDS)
• asthma and COPD exacerbations

47
Indications for Systemic or Topical
Glucocorticoids

• Dermatological diseases
• pemphigus
• bullous dermatitis herpetiformis
• severe erythema multiforme (Stevens-Johnson)
• exfoliative dermatitis
• mycosis fungoides
• severe psoriasis
• reduction of hypertrophic scar (keloid) formation
• contact dermatitis

48
Topical formulations for dermatological uses are
numerous (OTC and RX)
49
Indications for Systemic or Topical
Glucocorticoids

• Allergic states
• seasonal or perennial allergic rhinitis
• bronchial asthma
• contact dermatitis
• atopic dermatitis
• serum sickness
• drug hypersensitivity reactions

50
Effect of Glucocorticosteroids in Asthma
Structural Cells
Inflammatory Cells
Epithelial cell
Eosinophil
Numbers (apoptosis)
Cytokines mediators
T-lymphocyte
Endothelial cell
Cytokines
Leak
Glucocorticoids
Mast cell
Numbers
Airway Smooth Muscle
Macrophage
b2-receptors
Cytokines
Mucus Gland
Dendritic cell
Mucus secretion
Numbers
51
ICS in Dry Powder and MDI Formulations for Asthma
and COPD
52
The TORCH Trial

• 6112 pts in a 3 yr multi-institutional double
  blind, placebo controlled, randomized,
  parallel-group study to evaluated mortality
  impact of treatment in COPD patients
• Compared fluticasone (500 bid) vs salmeterol (50
  bid) vs both FS(500/50 bid) vs placebo
• All cause mortality reduction Primary endpoint
  (875 deaths)
• 15.2 with placebo
• Reduced to 13.5 with salmeterol (NS)
• Increased to 16.0 with fluticasone (NS)
• Reduced to 12.6 with combination (NS _at_ p0.052)
• FS Combination achieved a 2.6 percentage point
  mortality reduction vs placebo (15.2-12.6) for a
  17.5 reduction in risk of death (NS)

NEJM 356775-789, 2007.
53
TORCH Trial

• Cause of deaths Cardiac 27, Cancer 21,
  Respiratory 35
• Admission rates lowered in FSC and Salm groups vs
  placebo by 17 (NNT 32 to prevent 1 admission in
  1yr)
• AEs reduced by 25 with FSC (NNT 4 to prevent 1
  AE)
• Adverse events (pneumonia)
• Significant increase in pneumonias in F and FSC
  arms vs placebo
• F 77 increase FSC 81 increase (plt0.001)
• No increase in ocular or bone adverse events

NEJM 356775-789, 2007.
54
ICS Linked to Pneumonia in COPD

• Cohort of 175,906 COPD pts treated from 1988 thru
  2003 including 23,942 hospitalized for pneumonia
  and 95,768 serving as controls
• COPD pts who used inhaled steroids had a 70
  increase in risk of pneumonia hospitalization
  over those not given ICS. Odds ratio of 1.70
  (1.63-1.77), confidence interval of 95.
• 48.2 of those admitted used ICS in the previous
  year vs 30.1 of controls

Am J Respir Crit Care 2007176162-166.
55
Distribution of Inhaled Corticosteroids
Lung
Mouth andpharynx
Lung deposition(10 to 30)
Swallowedfraction(70 to 90)
Absorption from the lung (A)
Liver
Systemic circulation
Absorptionfrom the gut
Active drug from the gut (B)
GI tract
Inactivation inthe liver first pass
Systemic concentration A B
Expert Panel Report 2 Guidelines for the
Diagnosis and Management of Asthma. National
Institutes of Health, National Heart, Lung, and
Blood Institute. 1997. NIH Publication No.
97-4051.
56
The TORCH Trial

• 6112 pts in a 3 yr multi-institutional double
  blind, placebo controlled, randomized,
  parallel-group study to evaluated mortality
  impact of treatment in COPD patients
• Compared fluticasone (500 bid) vs salmeterol (50
  bid) vs both FS(500/50 bid) vs placebo
• All cause mortality reduction Primary endpoint
  (875 deaths)
• 15.2 with placebo
• Reduced to 13.5 with salmeterol (NS)
• Increased to 16.0 with fluticasone (NS)
• Reduced to 12.6 with combination (NS _at_ p0.052)
• FS Combination achieved a 2.6 percentage point
  mortality reduction vs placebo (15.2-12.6) for a
  17.5 reduction in risk of death (NS)

NEJM 356775-789, 2007.
57
Indications for Systemic Glucocorticoids

• Neoplastic diseases
• leukemias and lymphomas in adults
• acute leukemia of childhood
• cerebral edema with brain mets
• chemotherapy induced nausea
• Hematological disorders
• idiopathic and secondary thrombocytopenia in
  adults
• acquired (autoimmune) hemolytic anemia

58
Adrenocortical Insufficiency

• Drug induced from supraphysiological dosing
• Chronic adrenocortical insufficiency
• Addisons disease
• weakness and anorexia
• nausea, vomiting and diarrhea
• hypotension
• sparce axillary hair
• increased skin pigmentation of creases, nipples
  and pressure areas (due to ACTH production)
• eosinophilia and lymphocytosis

59
Addisonian Symptoms Associated with Steroid
Withdrawal

• Weight loss, anorexia 90
• Nausea, vomiting 66
• Weakness, tiredness, fatigue 94
• GI complaints 61
• abdominal pain 28
• Diarrhea 18
• Muscle pain 16
• Salt craving 14
• Hypotension, dizziness, syncope 14
• Lethargy, disorientation 12

60
Stress Dosing of Steroids to Avoid Addisonian
Crisis

• Critical for patients on steroids chronically who
  are presumed to be suppressed
• For Minor stress
• requires doubling of base dose
• For Major Stress
• Standard dose for major stress including surgery
  is 100mg hydrocortisone q8h
• This approximates or exceeds the maximal cortisol
  24 hour secretory rate of 200mg the HPA can
  achieve

Endo Metab Clin North Amer 32367-383,2004
61
Effects of Aldosterone

• Renal and circulatory effects
• Promotes reabsorption of sodium from the ducts of
  sweat and salivary glands during excessive
  sweat/saliva loss.
• Enhances absorption of sodium from the intestine
  esp. colon absence leads to diarrhea.
• Responsible for regulating Na reabsorption in
  the distal tubule and the cortical collecting
  duct
• Maintains extracellular fluid (ECF) volume and
  regulation of sodium and potassium.
• Excess seen in CHF causes myocardial fibrosis

62
(No Transcript)
63
Regulation of Aldosterone Release Involves the
RAAS

• Indirect stimulators of release
• decreased blood pressure
• decreased macula densa blood flow
• Direct stimulators of release
• increased extracellular K (primary)
• decreased osmolarity
• ACTH
• water deprivation

64
(No Transcript)
65
Aldosterone and Renin

• Renin is also stimulated by hyperkalemia and
  inhibited by potassium depletion.
• Angiotensin II, a potent vasoconstrictor, also
  stimulates zona glomerulosa to secrete
  aldosterone.
• Aldosterone then stimulates reabsorption of
  sodium in exchange for potassium and hydrogen ion
  secretion.
• End result is Na and water retention with
  intravascular volume expansion and potassium loss
  in urine

66
Indications for Systemic Mineralocorticoids

• As replacement therapy for primary and secondary
  Adrenal insufficiency
• For salt wasting nephropathy
• For orthostatic hypotension /- midodrine (an
  alpha agonist)
• In US, treatment is limited to one oral
  medication, fludrocortisone (Florinef), with
  125x MR activity relative to cortisol

67
FLUDROCORTISONE
A potent steroid with both glucocorticoid
and mineralocorticoid activity. Used mainly
for its mineralocorticoid activity in
Addisons disease along with hydrocorisone
replacement.
dose 0.1 mg 2- 7 X weekly
68
Physical signs seen in Cushings Syndrome
moon face
buffalo hump
striae
69
Steroid Side Effects are Frequent and Serious

• Alopecia
• Hirsutism
• Acne
• Oral Candidiasis
• Cataracts (esp in children)
• Glaucoma
• Pseudo-tumor cerebri
• Diabetes
• Hypertension
• Ulcerogenic
• Osteoporosis (30-40 incid)
• Proximal limb muscle weakness
• Memory impairment
• Atrial fibrillation
• Immunosuppressive
• Striae

• Femoral head necrosis
• Poor wound healing
• Thinning of skin
• Purpura
• Menstrual Irregularity
• Demargination of WBCs
• Psychosis
• Euphoria
• Depression
• Weight gain
• Increased appetite
• Cushings symptoms
• Hypokalemic alkalosis
• Myocardial fibrosis (aldosterone)
• HPA suppression
• Growth retardation

70
(No Transcript)
71
Steroid Use Pearls

• Dexamethasone uniquely does not cross react with
  cortisol assay
• Single large doses and short courses of steroids
  (up to 1 week) are unlikely harmful
• Prolonged exposure requires tapering dose
• Stress may induce Addisonian symptoms for up to
  one year after stopping chronic use
• Single daily dosing should be done in AM
• Dexamethasone is most commonly used for CNS
  penetration (ie brain mets)
• Tapered doses are to reduce Addisonian risk AND
  reflaring of disease (ie COPD)

72
Steroid Use Pearls

• Chronic adrenal insufficiency replacement is
  usually done with hydrocortisone (20mg AM and
  10mg PM) /- fludrocortisone.
• Licorice may increase cortisols washover
  action on MR and increase BP (inhibits 11
  beta-hydoxysteroid dehydrogenase)
• Some chewing tobacco brands are flavored with
  licorice and can cause hypokalemia (MR action)
• Dose of steroids may need upward adjustment when
  given with hepatic inducing drugs such as
  rifampin, phenobarbital and phenytoin

73
Steroid Use Pearls

• Most common oral steroid is prednisone and most
  common parenteral drug is methylprednisolone
  (SoluMedrol)
• Steroid dosing is largely empiric
• The 125mg dose of methylprednisolone often seen
  is based on an attempt to use largest size
  bottle
• Topical and inhalational routes may cause
  systemic effects
• Steroids have a delayed onset of action
• Suggest a Med Alert Bracelet for steroid users