Hydrocortisone Acetate

A single hydrocortisone acetate dose (1mg/kg body weight) resulted in a 40% to 50% reduction of peripheral blood lymphocytes from lympholysis of lizards that lasted for approximately 4 weeks in one study.

From: Current Therapy in Reptile Medicine and Surgery , 2014

H

In Drugs for the Geriatric Patient, 2007

hydrocortisone

(hye-droe-kor'-ti-sone)

▪ Brand Name(s): Acticort 100, Aeroseb-HC, A-Hydrocort, Ala-Cort, Ala-Scalp HP, Anucort-HC, Anumed-HC, Anusol-HC, Anutone-HC, Caldecort, Cetacort, Colocort, Cortane, Cortaid, Cort-Dome High Potency, Cortef, Cortenema, Cortifoam, Cortizone-5, Cortizone-10, Cotacort, Emcort, Gly-Cort, Hemorrhoidal HC, Hemril-30, Hemril-HC Uniserts, Hydrocortone, Hydrocortone Phosphate, Hytone, Instacort 10, Lacticare-HC, Locoid, Locoid Lipocream, Nupercainal Hydrocortisone Cream, Nutracort, Orabase HCA, Pandel, Penecort, Preparation H Hydrocortisone, Proctocort, Proctocream-HC, Procto-Kit 1%, Procto-Kit 2.5%, Proctosert HC, Proctosol-HC, Proctozone-HC, Rectasol-HC, Rederm, Scalp-Aid, Solu-Cortef, Texacort, WestCort

OTC: Cortaid, Cortizone, Dermolate, Gynecort Female Creme, Lanacort-5, Tegrin-HC

Combinations

Rx: with chloramphenicol (Chloromycetin/HC suspension—ophthalmic); with neomycin and polymyxin B (Cortisporin Otic, Drotic, Otocort—otic); with neomycin, polymyxin B, and bacitracin (Cortisporin Ointment, Neotricin HC—ophthalmic); with oxytetracycline (Terra-Cortril—ophthalmic); with urea (Carmol HC)

Chemical Class: Glucocorticoid

▪ Clinical Pharmacology:

Mechanism of Action: An adrenocortical steroid that inhibits accumulation of inflammatory cells at inflammation sites, phagocytosis, lysosomal enzyme release and synthesis, and release of mediators of inflammation. Therapeutic Effect: Prevents or suppresses cell-mediated immune reactions. Decreases or prevents tissue response to inflammatory process.

Pharmacokinetics:

Route Onset Peak Duration
IV N/A 4-6 hr 8-12 hr

Well absorbed after IM administration. Widely distributed. Metabolized in the liver. Half-life: Plasma, 1.5-2 hr; biologic, 8-12 hr.

▪ Available Forms:

•

Tablets (Cortef): 5 mg, 10 mg, 20 mg.

•

Oral Suspension, cypionate (Cortef): 10 mg/5 ml

•

Cream (Rectal): 1% (Nupercainal Hydrocortisone Cream, Cortizone-10, Preparation H Hydrocortisone, Proctocort, Procto-Kit 1%), 2.5% (Anusol-HC, Hemorrhoidal HC, Procto-Kit 2.5%, Proctosol-HC, Proctozone-HC).

•

Cream, butyrate (Topical [Locoid, Locoid Lipocream]): 0.1%.

•

Cream, probutate (Topical [Pandel]): 0.1%.

•

Cream, valerate (Topical [WestCort]): 0.2%.

•

Cream (Topical): 0.5% (Cortizone-5), 1% (Ala-Cort, Caldecort, Cortizone-10, Hycort, Hytone, Penecort), 2.5% (Hytone, Proctocream-HC).

•

Foam (Rectal [Cortifoam]): 10%.

•

Gel (Topical [Instacort 1%): 1%.

•

Lotion: 0.5% (Cetacort), 1% (Ala-Cort, Cetacort, Cortone, Lacticare-HC, Nutracort), 2.5% (Hytone, Lacticare-HC, Nutracort).

•

Ointment, butyrate (Topical [Locoid]): 0.1%.

•

Ointment, valerate (Topical [WestCort]): 0.2%.

•

Ointment (Topical): 0.5% (Cortizone-5), 1% (Anusol-HC, Cortaid, Cortizone-10, Hydrocortisone 1%, Hytone), 2.5% (Hytone).

•

Paste (Topical [Orabase HCA]): 0.5%.

•

Solution (Topical): 1% (Acticort 100, Gly-Cort, Penecort, Rederm, Scalp-Aid, Texacort), 2.5% (Texacort).

•

Solution, butyrate (Topical [Locoid]): 0.1%.

•

Spray (Topical [Aeroseb-HC]): 0.5%.

•

Suppositories: 25 mg (Anucort-HC, Anumed-HC, Anusol-HC, Anutone-HC, Cort-Dome High Potency, Hemorrhoidal HC, Hemril-HC, Proctosol-HC, Rectasol-HC), 30 mg (Emcort, Hemril-30, Proctocort, Proctosert HC).

•

Suppositories (Rectal [Colocort, Cortenema]): 100 mg/60 ml.

•

Injection (A-Hydrocort, Solu-Cortef): 100 mg, 250 mg, 500 mg, 1 g.

•

Injectable Solution, sodium phosphate (Hydrocortone Phosphate): 50 mg/ml.

•

Injectable Suspension, acetate: 25 mg/ml, 50 mg/ml.

▪ Indications and Dosages:

Acute adrenal insufficiency: IV 100 mg IV bolus; then 300 mg/day in divided doses q8h.

Anti-inflammation, immunosuppression: IV, IM 15-240 mg q12h. PO 15-240 mg q12h.

Status asthmaticus: IV 100-500 mg q6h.

Shock: IV 500 mg-2g q2-6h.

Adjunctive treatment of ulcerative colitis: Rectal 100 mg at bedtime for 21 nights or until clinical and proctologic remission occurs (may require 2-3 mo of therapy). Rectal (Cortifoam) 1 applicator 1-2 times a day for 2-3 wk, then every second day until therapy ends. Topical Apply sparingly 2-4 times a day.

▪ Contraindications: Fungal, tuberculosis, or viral skin lesions; serious infections

▪ Side Effects

Frequent

Insomnia, heartburn, nervousness, abdominal distention, diaphoresis, acne, mood swings, increased appetite, facial flushing, delayed wound healing, increased susceptibility to infection, diarrhea or constipation

Occasional

Headache, edema, change in skin color, frequent urination Topical: Itching, redness, irritation

Rare

Tachycardia, allergic reaction (such as rash and hives), psychological changes, hallucinations, depression

Topical: Allergic contact dermatitis, purpura

▪ Serious Reactions

•

Long-term therapy may cause hypocalcemia, hypokalemia, muscle wasting (especially in arms and legs), osteoporosis, spontaneous fractures, amenorrhea, cataracts, glaucoma, peptic ulcer disease, and CHF.

•

Abruptly withdrawing the drug after long-term therapy may cause anorexia, nausea, fever, headache, sudden severe joint pain, rebound inflammation, fatigue, weakness, lethargy, dizziness, and orthostatic hypotension.

▪ Patient/Family Education

•

May cause GI upset; take with meals or snacks

•

Take single daily doses in AM

•

Increased dose of rapidly acting corticosteroids may be necessary in patients subjected to unusual stress

•

Signs of adrenal insufficiency include fatigue, anorexia, nausea, vomiting, diarrhea, weight loss, weakness, dizziness, and low blood sugar

•

Avoid abrupt withdrawal of therapy following high-dose or long-term therapy

•

May mask infections

•

Do not give live virus vaccines to patients on prolonged therapy

•

Patients on chronic steroid therapy should wear medical alert bracelet

•

Avoid alcohol and limit caffeine intake during hydrocortisone therapy

•

Notify the dentist and other physicians that he or she is taking hydrocortisone or has taken it within the past 12 mo

•

Avoid contact with eyes

•

Apply topical hydrocortisone valerate after a bath or shower for best absorption. Do not cover the affected area with plastic pants, tight diapers, or other types of coverings unless the physician instructs otherwise

•

Steroids often cause mood swings, ranging from euphoria to depression

▪ Monitoring Parameters

•

Serum K and glucose

•

Edema, blood pressure, CHF, mental status, weight

•

Electrolytes

•

Pattern of daily bowel activity and stool consistency

•

Monitor the patient for signs and symptoms of hypocalcemia (such as cramps and muscle twitching), or hypokalemia (such as ECG changes, irritability, nausea and vomiting, numbness or tingling of lower extremities, and weakness)

▪ Geriatric side effects at a glance:

□

CNS

□

Bowel Dysfunction

□

Bladder Dysfunction

□

Falls

▪ U.S. Regulatory Considerations

□

FDA Black Box

□

OBRA regulated in U.S. Long Term Care

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Advances in Cellular Neurobiology

Jean M. Lauder , Helmut Krebs , in Advances in Cellular Neurobiology, 1984

2 Granule Cell Genesis in the Hippocampus

In rats treated with HCA on days 1–4 postnatal, cell proliferation in the hilus of the dentate gyrus (the main site of granule cell production; Bayer and Altman, 1974; Schlessinger et al., 1975) is suppressed during and immediately following treatment, particularly in the ventral hippocampus (Bohn, 1980). As in the cerebellum, a rebound of cell proliferation occurs following termination of the treatment (but only after a delay of 1–2 days) which is most pronounced in the ventral hippocampus.

It is possible that this more severe and less reversible inhibition of cell proliferation in the hippocampus, as compared to the cerebellum, can be explained on the basis of higher concentrations of steroid receptors in hippocampal granule cells (McEwen et al., 1975; Warembourg, 1975). In addition, these receptors may have a higher binding capacity in the ventral hippocampus at birth due to a spatiotemporal gradient in their development (Turner, 1978).

In the dorsal hippocampus, the time course of granule cell genesis is not altered by HCA treatment, whereas in the ventral hippocampus it is significantly depressed following termination of the treatment, and the peak of granule cell formation is delayed as a consequence (Bohn, 1980). However, in contrast to the effects of early HCA treatment on granule cell genesis in the cerebellum, no early last cell divisions of granule cells were observed. This could be due to the fact that at the time the treatment was given, only a small number of granule cells were being generated. This would mean that only these few cells would be nearing their last cell divisions and would thus be vulnerable to permanent inhibition of proliferation in response to the HCA treatment. Additionally, the delayed but strong rebound in cell proliferation after termination of the hormone treatment could explain the later cessation of cell proliferation in the majority of granule cells in these animals. It would be interesting to see if later HCA injections could "catch" a larger proportion of cells at the point where they might be induced to stop dividing prematurely, as observed in the cerebellum.

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Corticosteroids—glucocorticoids

In Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions (Fifteenth Edition), 2006

Class I immune reactions

Anaphylactic shock has been described after intranasal hydrocortisone acetate, intramuscular methylprednisolone (SEDA-21, 419) (251), intravenous methylprednisolone (SEDA-22, 448) (252), intramuscular dexamethasone (SEDA-22, 448) (253), and intra-articular methylprednisolone (SEDA-22, 449) (254). A life-threatening anaphylactic-like reaction to intravenous hydrocortisone has been described in patients with asthma (255). Acute laryngeal obstruction has been described for the first time after the intravenous administration of hydrocortisone (SEDA-22, 449) (256). There is some reason to believe that sodium succinate esters are more likely to cause hypersensitivity reactions (SEDA-17, 449), but unconjugated glucocorticoids can definitely produce allergy in some cases (SEDA-16, 452).

•

A 64-year-old woman with a history of bronchial asthma developed increasing shortness of breath after an upper respiratory tract infection (257). Her medication included inhaled salbutamol as necessary, theophylline 300   mg bd, and aspirin 325   mg/day. She was given nebulized salbutamol and ipratropium and hydrocortisone 200   mg intravenously. Within 30   minutes, she developed a generalized rash, fever (38.3   °C), and respiratory distress. She was promptly intubated and mechanical ventilation was started. No further doses of glucocorticoid were given. Skin testing with various parenteral formulations of glucocorticoids produced a 5   mm wheal at the site of hydrocortisone and methylprednisolone injections. She was subsequently given a challenge dose of triamcinolone using a metered-dose inhaler with no reaction, and was therefore continued on this medication.

•

An anaphylactoid reaction (angioedema, generalized urticaria, worsening bronchospasm, and marked hypotension) occurred in a 35-year-old man with multiple sclerosis who became allergic to methylprednisolone (dose not stated) after starting treatment with interferon beta-1b (258). He had previously been treated with different courses of methylprednisolone. Clinicians should be aware that the complexity of the effects of interferon beta-1b on the immune system can lead to unexpected outcomes. It is uncertain whether the sequence of events here was due to an effect of interferon beta-1b or to coincidence.

•

A 17-year-old boy, with an 11-year history of asthma, had anaphylaxis with respiratory distress shortly after he received intravenous methylprednisolone for an exacerbation of asthma while taking a tapering course of oral prednisone 15   mg/day (259). He had been glucocorticoid-dependent for at least 1 year. He reported having received intravenous glucocorticoids previously. He was treated with inhaled salbutamol and then intravenous methylprednisolone 125   mg over 15–30 seconds, and 3–4   minutes later became flushed and dyspneic, and developed diffuse urticarial lesions on his trunk and face and an undetectable blood pressure. He was treated with adrenaline, but required intubation. Sinus bradycardia developed and then asystole. He was successfully resuscitated and a 10–15 seconds period of generalized tonic-clonic activity was treated with diazepam. He remained unresponsive to stimulation for 30   minutes. However, he awoke 1   hour after his respiratory arrest and was extubated and discharged the following day taking a tapering dosage of prednisone.

•

An anaphylactoid reaction occurred in a 68-year-old woman after treatment with intravenous methylprednisolone for asthma. She had developed urticaria with methylprednisolone 1 year earlier, but the reaction had been thought to be related to the solvent in the formulation (260).

•

Forty minutes after a first dose of prednisone 25   mg, a 17-year-old girl with a history of aspirin intolerance had generalized flushing, hives, hypogastric pain, and abdominal cramps, followed by vomiting and diarrhea (261). She lost consciousness and developed arterial hypotension. She responded to intravenous diphenhydramine and hydrocortisone. Intradermal skin tests were positive for prednisone and negative for methylprednisolone and hydrocortisone. An oral challenge test with prednisone led to flushing, nausea, dizziness, tachycardia, and hypotension and responded to intravenous diphenhydramine and hydrocortisone. Challenge tests with intravenous methylprednisolone and hydrocortisone were negative.

•

A 30-year-old man with recurrent atopic eczema of the head and neck, generalized xerosis, keratosis pilaris of the arms, and a history of dyshidrosis was initially treated with prednisolone-21-acetate ointment (262). His skin eruption became worse. He was given oral prednisolone 25   mg, and 5   hours after the first dose developed intense generalized pruritus with erythema and swelling of the face. After 24   hours there was generalized erythema with disseminated partly follicular papules. There was an eosinophilia (1.1   ×   109/l). Total IgE was not raised. Patch tests showed delayed reactions to hydrocortisone 1%, prednisolone 1%, prednisolone-21-acetate ointment, and prednisolone 2.5%. Prick and intradermal tests with methylprednisolone succinate, hydrocortisone succinate, betamethasone, and triamcinolone acetonide in concentrations up to 1: 10 were negative at 15   minutes. However, 4   hours after intradermal testing, generalized pruritus developed and 24   hours later there was a disseminated partly follicular eczematous reaction with involvement of the flexural areas. Biopsy of the eruptions caused by prednisolone and of the positive skin reaction to methylprednisolone succinate showed superficial dermatitis with a perivascular infiltration consisting predominantly of CD4+ cells and some eosinophils. Immunofluorescence showed increased expression of HLA-DR molecules on the CD4+ and CD8+ cells. During the exanthema caused by prednisolone, interleukin-5 (14   pg/ml), interleukin-6 (38   pg/ml), and interleukin-10 (26   pg/ml) were detected in the blood; 2 months after recovery these cytokines were not detectable.

The authors of the last report commented that generalized delayed type hypersensitivity to systemic administration of a glucocorticoid is rare. Despite the potent immunosuppressive effect of glucocorticoids on immunocompetent cells, the clinical features, the skin biopsy specimen, and the positive delayed skin test reactions strongly suggested an immunological mechanism: T cells were clearly involved and the high concentrations of interleukins 5, 6, and 10 were consistent with a T helper type 2 reaction. The raised concentrations of interleukin-5 were probably responsible for the blood and tissue eosinophilia.

Budesonide has been marketed in oral form for intestinal inflammatory disease. An non-IgE-mediated anaphylactic reaction has been associated with oral budesonide (263).

•

A 32-year-old woman with Crohn's disease, who had taken prednisone 20   mg/day and azathioprine 150   mg/day, switched to budesonide 9   mg/day because of weight gain, and 5   minutes after the first capsule her tongue and throat swelled, accompanied by wheeziness and diarrhea. She was given clemastine and recovered after 4 ays. Intracutaneous tests with diluted budesonide suggested a non-IgE-mediated reaction. She had a previous history of a similar reaction to mesalazine. One year later her tongue and throat swelled after intravenous dexamethasone.

Urticaria with angioedema has been described in a patient taking deflazacort (264).

•

A 64-year-old woman with allergic alveolitis caused by parakeet feathers improved with intravenous methylprednisolone, and was given oral deflazacort 60   mg/day, to be reduced progressively. After 30 days she developed generalized itchy blotches and lip edema. At that time she was mistakenly taking deflazacort in a dose of 120   mg/day. She was given an antihistamine, without any improvement. Deflazacort was then replaced by prednisolone and her symptoms disappeared immediately. Skin tests (a prick test and an epicutaneous test) were positive with deflazacort. Oral provocation with deflazacort 30   mg was positive, with the immediate appearance of the same symptoms as in the initial episode.

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Hydrocortisone

Jennifer Minigh , in xPharm: The Comprehensive Pharmacology Reference, 2008

Basic Chemistry

Chemical Structure
Structure
Comments One-hundred twelve milligrams of hydrocortisone acetate is approximately equivalent to 100 mg of hydrocortisone. One-hundred nineteen milligrams of hydrocortisone butyrate is approximately equivalent to 100 mg of hydrocortisone. One-hundred twenty-eight milligrams of hydrocortisone hydrogen succinate is approximately equivalent to 100 mg of hydrocortisone. One-hundred thirty-four milligrams of hydrocortisone sodium phosphate is approximately equivalent to 100 mg of hydrocortisone. One-hundred thirty-four milligrams of hydrocortisone sodium succinate is approximately equivalent to 100 mg of hydrocortisone. One-hundred twenty-three milligrams of hydrocortisone valerate is approximately equivalent to 100 mg of hydrocortisone The Complete Drug Reference (2003).
Chemical Formula C21H30O5
Properties
Physical Properties Hydrocortisone, hydrocortisone acetate, and hydrocortisone butyrate are white, crystalline powders The Complete Drug Reference (2003).
Hydrocortisone hydrogen succinate and hydrocortisone sodium phosphate are white, or almost white, hygroscopic powders The Complete Drug Reference (2003).
Hydrocortisone sodium succinate is a white or nearly white, odorless, hygroscopic, amorphous solid The Complete Drug Reference (2003) The Merck Index (2001).
Molecular Weight 362.463
Solubility Hydrocortisone is practically insoluble in water, sparingly soluble in alcohol and in acetone, and slightly soluble in dichloromethane. Hydrocortisone acetate is practically insoluble in water, slightly soluble in dehydrated alcohol and in dichloromethane. Hydrocortisone butyrate is practically insoluble in water, soluble in alcohol, in acetone, and in methyl alcohol, freely soluble in chloroform, and slightly soluble in ether. Hydrocortisone hydrogen succinate is practically insoluble in water, freely soluble in dehydrated alcohol and in acetone. It dissolves in dilute solutions of alkali carbonates and alkali hydroxides. Hydrocortisone sodium phosphate is freely soluble in water, practically insoluble in dehydrated alcohol and in chloroform. A 0.5% aqueous solution has a pH of 7.5–9.0. Hydrocortisone sodium succinate is very soluble in water and in alcohol, very slightly soluble in acetone, and insoluble in chloroform.

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P

In Drugs for the Geriatric Patient, 2007

pramoxine hydrochloride

(pra-mox'-een hye-droe-klor'-ide)

▪ Brand Name(s): Analpram-HC, Anusol, Enzone, Epifoam, Itch-X, Pramosome, Prax, ProctoCream, ProctoFoam NS, Rectocort, Tronolane, Zone-A

Chemical Class: Morpholine derivative

▪ Clinical Pharmacology:

Mechanism of Action: A surface or local anesthetic which is not chemically related to the "caine" types of local anesthetics. Decreases the neuronal membrane permeability to sodium ions, blocking both initiation and conduction of nerve impulses, therefore inhibiting depolarization of the neuron. Therapeutic Effect: Temporarily relieves pain and itching associated with anogenital pruritus or irritation.

Pharmacokinetics: Onset of action occurs within a few minutes of application. Peak effect is reached in 3-5 minutes. Duration is several days.

▪ Available Forms:

•

Foam: 1% (ProctoFoam NS).

•

Cream: 1% (Tronolane).

•

Gel: 1% (Itch-X).

•

Lotion: 1% (Prax).

•

Ointment: 1% (Anusol).

•

Solution: 1% (Itch-X).

•

Suppository: 1% (Tronolane).

▪ Indications and Dosages:

Anogenital pruritus or irritation, dermatosis, minor burns, hemorrhoids: Topical Apply to affected area 3 or 4 times daily.

▪ Contraindications: Hypersensitivity to any component of the product.

▪ Side Effects

Occassional

Angioedema, contact dermatitis, burning, itching, irritation, stinging

Rare

Dryness, folliculitis, hypopigmentation, perioral dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.

▪ Serious Reactions

Special Considerations

•

Cross-sensitization with other local anesthetics unlikely

▪ Patient/Family Education

•

Do not use near eyes or nose

•

Contact clinician if condition fails to improve after 3-4 days, or worsens

•

Do not apply to large areas

•

Do not apply to unaffected areas

•

Notify the physician if bleeding at affected area, hoarseness, hives, rash, severe itching, difficulty breathing or swallowing, or swelling of the face, throat, lips, eyes, hands, feet, or ankles occurs

•

Wash hands before and after administration

▪ Monitoring Parameters

•

Therapeutic response

•

Skin for irritation

▪ Geriatric side effects at a glance:

□

CNS

□

Bowel Dysfunction

□

Bladder Dysfunction

□

Falls

▪ U.S. Regulatory Considerations

□

FDA Black Box

□

OBRA regulated in U.S. Long Term Care

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Dermatological Medications and Local Therapeutics

Maria-Magdalena Roth , Caius Solovan , in Clinical Pharmacology During Pregnancy, 2013

21.9.2 Local glucocorticosteroids

First-line topical treatment involves the daily/half-daily application of mild to moderate potent corticosteroids like hydrocortisone acetate 1% (category C) or betamethasone valerate 0.1% (category C) for no more than several weeks [57]. On the other hand, there is no academic consensus regarding the overall safety of what is proposed to be the second-line topical treatment for maternal inflammatory skin diseases, namely the therapy focused on potent/more potent corticosteroids like clobetasol propionate (category C), especially due to reports which associate it with infant lip/palate cleft after being used during the first trimester of pregnancy [58], and also with possible low birth weight.

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Designing Prodrugs and Bioprecursors

Yong Mi Choi-Sledeski , Camille G. Wermuth , in The Practice of Medicinal Chemistry (Fourth Edition), 2015

2 Derivatization of Aldehydes and Ketones

The ethylene ketal derivative of prostaglandin E2 (dinoprostone) possesses much improved solid-state stability. Functionalized spirothiazolidines of hydrocortisone and hydrocortisone 21-acetate (Figure 28.8), prepared with cysteine esters or related β-aminothiols, have shown improved topical anti-inflammatory activity. It is speculated that a Schiff base intermediate formed upon ring-opening results in the accumulation in the skin by binding (through its SH function) to thiol groups in the skin [46].

Figure 28.8. Prodrug possibilities starting from aldehyde or ketones.

Simple and substituted oximes are biostable unless intramolecular assistance is provided. This is the case for the oximes derived from oxyamino acetic acid that are possible water-soluble prodrugs of ketones and aldehydes.

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A worldwide yearly survey of new data in adverse drug reactions

J. Costa , M. Farré , in Side Effects of Drugs Annual, 2011

Pregnancy

The first large UK population-based study to assess the risk of maternal asthma and exposure to current asthma treatments during pregnancy on overall and system-specific major congenital malformations in their offspring has been reported [25 C]. It was a matched case-control study using The Health Improvement Network primary care database. Children with malformations were matched with control children by year of birth, general practice, and singleton or twin delivery. There were 5124 live-born children with major congenital malformations and 30   053 controls. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR   =   1.10, 95% CI   =   1.01, 1.20). However, there was no association in children born to mothers who had received asthma treatment in the year before or during pregnancy (OR   =   1.06; 95% CI   =   0.94, 1.20). In assessing the teratogenicity of the medications that had been used, there were no increases in the risks of malformation with gestational exposure to short- or long-acting β-adrenoceptor agonists, inhaled or oral glucocorticoids, other bronchodilators, or cromones. These findings were similar for each of 11 system-specific malformations, except for an increase in musculoskeletal system malformations associated with exposure to cromones. The findings suggest that gestational exposure to commonly used asthma medications is safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.

Methylprednisolone is used for the treatment of acute exacerbations of Crohn's disease in pregnancy, since its use is considered to be less harmful than the effect of the active disease on the fetus. However, adrenal suppression in a fetus has been associated with administration of methylprednisolone [26 A].

•

A 29-year-old pregnant woman with active Crohn's disease received high doses of methylprednisolone (32 mg/day) and a daily enema containing hydrocortisone acetate 100  mg for at least 1   month before labor. She delivered a boy at 37   weeks of gestation by elective cesarean section. At delivery the infant's weight was 3380   g, length 53   cm, head circumference 36   cm, and the Apgar score was 10 at 1 and 5   minutes. He cried normally and his breathing was effortless. However, 3   hours after birth he developed respiratory distress syndrome and a mild metabolic acidosis, and became hemodynamically unstable, with falls in blood pressure and anuria. An ACTH stimulation test confirmed profound adrenal suppression.

An adverse effect of the hydrocortisone acetate enemas in this case cannot be either confirmed or excluded. Since the concentration of methylprednisolone or its metabolites in the blood was not measured, the relation between adrenal insufficiency in the child and maternal exposure to methylprednisolone was not unequivocal.

Twin pregnancies have a much higher rate of glucose intolerance and/or gestational diabetes than singleton pregnancies. In a study of maternal glucose concentrations after the administration of dexamethasone in singleton versus twin pregnancies, 10 patients with singleton pregnancies and nine patients with twin pregnancies who needed glucocorticoids were enrolled at 24–34   weeks of gestation and received four doses of intramuscular dexamethasone 6   mg 12   hours apart [27 c]. Mean glucose concentrations were significantly higher in the twin group at 4   hours (6.33 versus 5.31   mmol/l), 8   hours (6.34 versus 5.00   mmol/l), and 24   hours (6.44 versus 4.50   mmol/l).

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Ulcerative Colitis

Ramona O. Rajapakse MD , Burton I. Korelitz MD , in GI/Liver Secrets (Fourth Edition), 2010

17 How do I treat proctitis and proctosigmoiditis?

For mild-to-moderate ulcerative proctitis, topical therapy may suffice. If disease is limited to the anorectal region, a Canasa suppository can be used once or twice daily. Hydrocortisone foam (Cortifoam) or hydrocortisone enemas (Cortenema) also may be used either alone or in alternation with the 5-ASA product. For proctosigmoiditis, the mesalamine enema, used alone or in alternation with a hydrocortisone enema, is effective. Only the mesalamine enema, not the Cortenema, has maintenance value. The patient must lie on the left side for at least 20 minutes after introducing the enema to ensure adequate delivery to the affected area. In some instances when tenesmus is severe, the enema is better introduced in the knee-chest position, taking advantage of the downhill gravity. Occasionally oral therapy may work better than enemas or suppositories; in other cases, a combination is required.

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Atopic Dermatitis

Amanda J. Kaufman MD, ABIHM , in Integrative Medicine (Fourth Edition), 2018

Topical Immunomodulators

Tacrolimus ointment and pimecrolimus cream, inhibitors of calcineurin, are additional nonsteroidal options for treatment of atopic dermatitis. These agents decrease T-cell activation and cytokine release while inhibiting mast cell and basophil degranulation. They have been studied largely as steroid-sparing agents for use after control of an acute flare to maintain remission. Investigators and clinicians were hopeful to find an agent to provide control without the risks of skin thinning and effects on the HPA axis.

After case reports of skin cancer and lymphoma with use of these agents appeared, the U.S. Food and Drug Administration issued a black box warning noting that although a causal relationship had not been established, these agents should be used with caution. Continued study has not demonstrated an increased risk of malignancy. 65 Patients with atopic dermatitis have an increased risk of lymphoma, and this risk increases with severity of disease. Experts comment mistaking cutaneous T-cell lymphoma for severe AD might account for the increased risk in these patients. Avoid the use of topical immunomodulators in immunocompromised patients or in those with a known neoplasm. If AD does not respond to usual treatments, perform a biopsy to rule out (CTCL) or other causes. Encourage sun protection to reduce photocarcinogenesis.

A meta-analysis of tacrolimus use in children found it safe and effective, with no statistical difference between tacrolimus 0.03% and 0.1% preparations and a good response compared with vehicle, 1% hydrocortisone acetate, and 1% pimecrolimus (odds ratio: 4.56, 3.92, and 1.58, respectively). 66 Use creams as infrequently as possible to maintain remission. Use only on lesional skin and without occlusive dressings. Use only in children who are older than 2 years old. Adverse effects include burning on application and photosensitivity.

Dosage

Tacrolimus 0.03% ointment is applied twice daily in patients older than 2 years, including adults with mild disease. For adults, tacrolimus 0.1% ointment is applied twice daily, or pimecrolimus 1% cream is applied twice daily. Typical use is twice daily for no longer than 6 weeks and then reduce to daily or every other day use. Tacrolimus used three times weekly has been proven effective in children to maintain remission. 67

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