Chapter 28: Adrenocorticosteroid Pharmacology — Module 3: Adverse Effects, GIO Management, and Drug Interactions
1. A 61-year-old man with type 2 diabetes is started on once-daily morning prednisone 40 mg for giant cell arteritis. His fasting glucose remains near 120 mg per dL, but he reports feeling unwell in the late afternoon. His clinician suspects glucocorticoid-induced dysglycemia that routine fasting checks are missing. Which step will most sensitively detect and best guide management of his glucocorticoid-induced hyperglycemia?
A) Increase basal long-acting insulin and continue checking only fasting morning glucose
B) Repeat HbA1c (hemoglobin A1c) in 2 weeks and adjust therapy based on that value alone
C) Check point-of-care glucose about 2 hours after the largest meal of the day and target therapy to the afternoon and early-evening peak
D) Move the prednisone to bedtime to shift the glucose peak overnight
E) Stop home glucose monitoring because the fasting values are acceptable
ANSWER: C
Rationale:
Once-daily morning prednisone produces a postprandial-dominant pattern with an afternoon and early-evening glucose peak that fasting checks and HbA1c (hemoglobin A1c) underestimate, so point-of-care glucose roughly 2 hours after the largest meal is the most sensitive detection method and best directs therapy timed to that peak.
Option A: Option A is incorrect because basal insulin and fasting-only monitoring miss the postprandial peak that is the predominant abnormality.
Option B: Option B is incorrect because HbA1c underestimates postprandial excursions, especially in the first 8 to 12 weeks, so it should not guide therapy alone.
Option D: Option D is incorrect because bedtime dosing would tend to shift hyperglycemia into the overnight and fasting window rather than resolve it.
Option E: Option E is incorrect because acceptable fasting glucose does not exclude significant postprandial dysglycemia, which still requires monitoring.
2. A 68-year-old woman with polymyalgia rheumatica has been on dexamethasone (a fluorinated glucocorticoid) for 4 months. She now reports difficulty rising from a chair and lifting objects overhead. Examination shows symmetrical proximal weakness with preserved reflexes; creatine kinase (CK) is normal and inflammatory markers are at her baseline. Which interpretation and management is most appropriate?
A) This is steroid myopathy; reduce the glucocorticoid dose and consider switching from the fluorinated agent to a non-fluorinated glucocorticoid
B) This is an inflammatory disease flare; increase the dexamethasone dose
C) This is statin-associated myopathy and requires no change to the glucocorticoid
D) The normal CK excludes any myopathy, so reassurance alone is appropriate
E) Begin high-dose intravenous immunoglobulin for presumed inflammatory myositis
ANSWER: A
Rationale:
Gradual proximal weakness with preserved reflexes, a normal CK, and inflammatory markers at baseline in a patient on a fluorinated glucocorticoid is the classic picture of steroid myopathy; management is dose reduction, and because fluorinated agents carry higher myopathy risk, switching toward a non-fluorinated glucocorticoid is reasonable.
Option B: Option B is incorrect because a normal CK and baseline inflammatory markers argue against a flare, and increasing the dose would worsen steroid myopathy.
Option C: Option C is incorrect because there is no statin in this vignette and the picture fits steroid myopathy.
Option D: Option D is incorrect because a normal CK does not exclude steroid myopathy, in which CK is characteristically normal or only mildly elevated.
Option E: Option E is incorrect because the findings point to steroid myopathy rather than inflammatory myositis, so escalating immunosuppression is not indicated.
3. A 44-year-old man with no psychiatric history is started on prednisone 80 mg per day for a severe autoimmune flare. Within 6 days he develops paranoid delusions, agitation, and disorganized thinking. He is medically stable and the underlying disease is responding. Which management approach is most appropriate?
A) Continue the current high dose unchanged and provide only reassurance, since the symptoms will not respond to dose changes
B) Permanently discontinue all glucocorticoids abruptly regardless of disease control
C) Conclude that he has a primary psychotic disorder unrelated to the medication and defer to long-term antipsychotic therapy alone
D) Escalate the prednisone dose to treat presumed central nervous system involvement of his disease
E) Recognize steroid psychosis, reduce the glucocorticoid dose as the disease allows, and use a temporary antipsychotic during the acute phase
ANSWER: E
Rationale:
New psychosis emerging within days of high-dose glucocorticoid initiation in a patient with no psychiatric history is characteristic of steroid psychosis, which is dose-related and typically resolves within days to weeks of dose reduction; temporary antipsychotic treatment is appropriate during the acute phase.
Option A: Option A is incorrect because steroid psychosis is generally responsive to dose reduction rather than fixed at the current dose.
Option B: Option B is incorrect because abrupt complete discontinuation risks adrenal insufficiency and loss of disease control; the dose is reduced as the disease allows.
Option C: Option C is incorrect because the temporal link to high-dose initiation points to steroid psychosis rather than a primary psychotic disorder.
Option D: Option D is incorrect because escalating the dose would worsen the steroid-induced psychosis.
4. A 57-year-old woman on systemic glucocorticoids for 14 months reports glare and trouble driving at night, with preserved central vision. On screening, her intraocular pressure (IOP) is 27 mmHg; her father has primary open-angle glaucoma. Which assessment and next step is most appropriate?
A) The symptoms and IOP are unrelated to glucocorticoids, so no ophthalmologic referral is needed
B) She likely has both a posterior subcapsular cataract (causing the glare) and a glucocorticoid IOP response (a steroid responder); refer to ophthalmology for the elevated IOP and arrange slit-lamp evaluation, while reducing glucocorticoid exposure where possible
C) The elevated IOP is harmless because steroid-induced IOP elevation never causes optic nerve damage
D) Antioxidant supplementation will reverse both the lens changes and the IOP elevation
E) The glare indicates acute angle-closure glaucoma requiring no change to the glucocorticoid
ANSWER: B
Rationale:
Glare with preserved central vision after prolonged glucocorticoid use suggests posterior subcapsular cataract, while an IOP of 27 mmHg in a patient with a family history of open-angle glaucoma indicates a glucocorticoid IOP response (steroid responder); appropriate steps are ophthalmology referral for the elevated IOP (referral threshold IOP greater than 21 mmHg), slit-lamp evaluation, and reducing glucocorticoid exposure where the disease allows.
Option A: Option A is incorrect because both findings are recognized glucocorticoid ocular effects warranting referral.
Option C: Option C is incorrect because a subset of steroid responders develop IOP elevation sufficient to cause glaucomatous optic nerve damage.
Option D: Option D is incorrect because posterior subcapsular cataract is not oxidative-stress driven and does not respond to antioxidants, and antioxidants do not lower IOP.
Option E: Option E is incorrect because the picture is chronic posterior subcapsular cataract and steroid-induced IOP elevation, not acute angle closure, and glucocorticoid exposure should be reduced where possible.
5. A 64-year-old postmenopausal woman is beginning prednisone 20 mg per day for an inflammatory condition expected to require at least 9 months of therapy. Her FRAX (Fracture Risk Assessment Tool) score, after the glucocorticoid adjustment, places her at high fracture risk. Which bone-protection plan is most appropriate at initiation?
A) Begin teriparatide as first-line because she is postmenopausal
B) Defer all bone protection until a fragility fracture occurs
C) Start calcium and vitamin D and add an oral bisphosphonate (such as alendronate or risedronate), because her high FRAX-adjusted risk and a course of 3 months or longer meet the threshold for pharmacological protection
D) Provide calcium and vitamin D only and avoid antiresorptive therapy despite the high risk
E) Withhold therapy because glucocorticoid courses shorter than 1 year do not affect bone
ANSWER: C
Rationale:
For an anticipated course of 3 months or longer, calcium and vitamin D are recommended universally, and for medium-to-high fracture risk an oral bisphosphonate (alendronate or risedronate) is added; her high FRAX (Fracture Risk Assessment Tool)-adjusted risk meets that threshold, so calcium, vitamin D, and a bisphosphonate are appropriate at initiation.
Option A: Option A is incorrect because teriparatide is reserved for very high fracture risk, not used first-line on the basis of menopausal status.
Option B: Option B is incorrect because high risk warrants proactive protection rather than waiting for a fracture.
Option D: Option D is incorrect because calcium and vitamin D alone are insufficient for a high-risk patient, who should also receive an antiresorptive.
Option E: Option E is incorrect because a course of 3 months or longer at this dose causes clinically meaningful bone loss, so protection is warranted.
6. A 72-year-old man with chronic kidney disease (estimated GFR [glomerular filtration rate] 28 mL per minute per 1.73 m2) on chronic glucocorticoids has been receiving denosumab for bone protection because bisphosphonates were contraindicated by his renal function. He now wishes to stop the denosumab. Which plan best addresses the risk of discontinuation?
A) Stop denosumab abruptly with no further therapy, since its protective effect persists for years
B) Reassure him that rebound bone loss does not occur in patients with kidney disease
C) Simply extend the dosing interval indefinitely, which prevents any rebound effect
D) Avoid abrupt cessation and plan a carefully considered transition to an antiresorptive (recognizing his renal impairment limits bisphosphonate options), because denosumab withdrawal can cause rapid rebound bone loss with increased fracture risk
E) Replace denosumab with teriparatide indefinitely, since anabolic therapy carries no time limit
ANSWER: D
Rationale:
Denosumab's antiresorptive effect wanes rapidly after the dosing interval lapses, and discontinuation can cause rebound bone loss with increased, including vertebral, fracture risk; the standard mitigation is transition to a bisphosphonate, but his renal impairment limits that option, so an abrupt stop should be avoided and the transition planned carefully.
Option A: Option A is incorrect because the effect does not persist for years and abrupt cessation risks rebound.
Option B: Option B is incorrect because rebound bone loss is not confined to patients with normal renal function.
Option C: Option C is incorrect because extending the interval does not prevent rebound.
Option E: Option E is incorrect because teriparatide carries a 24-month treatment limit and cannot be continued indefinitely.
7. A 70-year-old woman on long-term prednisone has sustained two vertebral compression fractures despite calcium, vitamin D, and an oral bisphosphonate, and her FRAX-adjusted risk is very high. Her renal function is normal. Which therapeutic choice and follow-up plan is most appropriate?
A) Switch to teriparatide, the anabolic PTH (parathyroid hormone) 1-34 fragment preferred for very high fracture risk, and plan transition to an antiresorptive after the 24-month treatment limit to preserve the gains
B) Continue the same oral bisphosphonate at the same dose, since it remains optimal despite the new fractures
C) Stop all bone-directed therapy and rely on calcium and vitamin D alone
D) Begin teriparatide and plan to continue it indefinitely without any time limit or follow-on therapy
E) Add a second oral bisphosphonate to the current one for a dual antiresorptive effect
ANSWER: A
Rationale:
With very high fracture risk and incident vertebral fractures despite antiresorptive therapy, teriparatide, the anabolic PTH (parathyroid hormone) 1-34 fragment that stimulates osteoblast activity and has shown superiority over alendronate for vertebral fracture prevention in glucocorticoid-induced osteoporosis, is preferred; because of the 24-month treatment limit, transition to an antiresorptive afterward is planned to preserve the gains.
Option B: Option B is incorrect because continuing the same regimen that failed does not address the very high risk.
Option C: Option C is incorrect because stopping therapy in a very-high-risk patient is inappropriate.
Option D: Option D is incorrect because teriparatide has a 24-month limit and requires follow-on antiresorptive therapy.
Option E: Option E is incorrect because combining two bisphosphonates is not a standard or evidence-based strategy.
8. A 52-year-old kidney transplant recipient maintained on prednisolone is started on rifampin (rifampicin) for a serious infection. Rifampin strongly increases the activity of the liver enzyme (CYP3A4, cytochrome P450 3A4) that metabolizes glucocorticoids. Which management plan best protects this patient?
A) Reduce the prednisolone dose, since rifampin will raise glucocorticoid levels
B) Make no dose change, since rifampin does not affect glucocorticoid metabolism
C) Increase the glucocorticoid dose to maintain therapeutic effect during co-administration to avoid under-immunosuppression and rejection, and plan a careful dose reduction with monitoring when rifampin is later stopped
D) Stop the prednisolone entirely while on rifampin and resume it only after the antibiotic course
E) Add a CYP3A4 (cytochrome P450 3A4) inhibitor to cancel out the rifampin, then keep all doses unchanged thereafter
ANSWER: C
Rationale:
Rifampin (rifampicin) is a potent CYP3A4 (cytochrome P450 3A4) inducer that can reduce prednisolone exposure substantially, risking loss of immunosuppressive effect and transplant rejection, so the glucocorticoid dose is increased during co-administration; when rifampin is stopped, enzyme activity returns toward baseline over about 2 to 4 weeks, so the dose must then be carefully reduced with monitoring to avoid toxicity.
Option A: Option A is incorrect because induction lowers, not raises, glucocorticoid levels, so a dose increase is needed.
Option B: Option B is incorrect because rifampin has a clinically significant inducing effect on glucocorticoid metabolism.
Option D: Option D is incorrect because stopping immunosuppression in a transplant recipient risks rejection.
Option E: Option E is incorrect because adding an inhibitor to offset an inducer produces unpredictable, hard-to-manage exposure rather than safe steady dosing.
9. A 59-year-old man is started on prednisone 30 mg per day as monotherapy (no other immunosuppressants) for an inflammatory condition expected to continue for at least 8 weeks. He has no sulfonamide allergy. Which preventive measure is most appropriate for opportunistic infection risk?
A) No prophylaxis is indicated at any glucocorticoid dose in non-HIV patients
B) Begin isoniazid for PCP (Pneumocystis jirovecii pneumonia) prophylaxis
C) Begin prophylaxis only if he develops respiratory symptoms
D) Begin TMP-SMX (trimethoprim-sulfamethoxazole) for PCP (Pneumocystis jirovecii pneumonia) prophylaxis, since his prednisone exceeds 20 mg per day for more than 4 weeks; for sulfonamide intolerance, dapsone or atovaquone is an alternative
E) Begin acyclovir as PCP (Pneumocystis jirovecii pneumonia) prophylaxis
ANSWER: D
Rationale:
In glucocorticoid monotherapy, PCP (Pneumocystis jirovecii pneumonia) prophylaxis is generally indicated when prednisone exceeds 20 mg per day for more than 4 weeks; first-line is TMP-SMX (trimethoprim-sulfamethoxazole), with dapsone or atovaquone as alternatives for sulfonamide intolerance.
Option A: Option A is incorrect because prophylaxis is indicated above this monotherapy threshold even in non-HIV patients.
Option B: Option B is incorrect because isoniazid is used for latent tuberculosis, not PCP prophylaxis.
Option C: Option C is incorrect because prophylaxis is given to prevent a first episode in at-risk patients, not started only after symptoms appear.
Option E: Option E is incorrect because acyclovir targets herpesviruses, not Pneumocystis.
10. A 66-year-old woman on chronic prednisone for rheumatoid arthritis takes a daily NSAID (non-steroidal anti-inflammatory drug) for pain and is also anticoagulated with warfarin. She presents for a routine review. Which management plan best addresses her combined medication risks?
A) No additional measures are needed, since these drugs do not interact
B) Start a proton pump inhibitor for gastrointestinal protection given the markedly increased peptic ulcer complication risk from the glucocorticoid-NSAID combination, and monitor the INR (international normalized ratio) around any glucocorticoid dose change because glucocorticoids can shift it
C) Stop the warfarin permanently because glucocorticoids reliably normalize the INR (international normalized ratio)
D) Increase the prednisone dose to counteract NSAID-induced enzyme induction
E) Reassure her that the NSAID protects the stomach when combined with a glucocorticoid
ANSWER: B
Rationale:
Glucocorticoids and NSAIDs (non-steroidal anti-inflammatory drugs) each impair prostaglandin-mediated gastric mucosal defense and together greatly increase peptic ulcer complication risk, so proton pump inhibitor prophylaxis is indicated; separately, glucocorticoids can produce variable INR (international normalized ratio) changes, so warfarin should be monitored around glucocorticoid initiation or dose changes.
Option A: Option A is incorrect because both the gastrointestinal and anticoagulation interactions are clinically significant.
Option C: Option C is incorrect because the INR effect is variable and unpredictable, not a reliable normalization that justifies stopping warfarin.
Option D: Option D is incorrect because the glucocorticoid-NSAID interaction is pharmacodynamic, not an NSAID induction of glucocorticoid metabolism.
Option E: Option E is incorrect because the combination increases rather than reduces gastric mucosal injury.
11. A 34-year-old woman with lupus nephritis has required prednisone above 7.5 mg per day for more than 3 months to control her disease, and her clinician is concerned about cumulative glucocorticoid toxicity. She is counseled on reliable contraception. Which steroid-sparing strategy is most appropriate for her condition?
A) Avoid any steroid-sparing agent, since the glucocorticoid alone is always the safest option
B) Add methotrexate, which is the preferred steroid-sparing agent specifically for lupus nephritis
C) Add tocilizumab, an interleukin-6 (IL-6) receptor antagonist, as established first-line steroid-sparing therapy for lupus nephritis
D) Continue glucocorticoid monotherapy and simply accept the long-term adverse-effect burden
E) Add mycophenolate, which selectively inhibits IMPDH (inosine monophosphate dehydrogenase) type II in lymphocytes and is a preferred steroid-sparing agent in lupus nephritis, while ensuring effective contraception because it is teratogenic
ANSWER: E
Rationale:
With glucocorticoid requirements above roughly 7.5 mg per day for more than 3 months, a steroid-sparing agent is justified to limit cumulative toxicity; in lupus nephritis, mycophenolate, which selectively inhibits IMPDH (inosine monophosphate dehydrogenase) type II in activated lymphocytes, is a preferred agent, and because it is teratogenic, effective contraception is required in women of childbearing potential.
Option A: Option A is incorrect because at this exposure the chronic glucocorticoid toxicity burden makes adding a sparing agent advantageous.
Option B: Option B is incorrect because methotrexate inhibits dihydrofolate reductase and is not the preferred agent for lupus nephritis (and is also teratogenic).
Option C: Option C is incorrect because tocilizumab's established steroid-sparing role is in giant cell arteritis, not as first-line for lupus nephritis.
Option D: Option D is incorrect because accepting ongoing high-dose glucocorticoid toxicity when an effective steroid-sparing option exists is not appropriate.
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