Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. These medications are also used for conditions requiring physiologic glucocorticoid replacement. Despite their extensive use, glucocorticoids can produce many and varied adverse effects and should be used judiciously. Because of their immunosuppressive effect, these medications may predispose individuals to infection and should be avoided in those with uncontrolled infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease. In addition, long-term therapy can lead to suppressionSuppressionDefense Mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis, so discontinuation of therapy should be done carefully to avoid adrenal insufficiencyAdrenal InsufficiencyConditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus.Adrenal Insufficiency and Addison Disease.
The chemical structure of prednisone:
The molecule appears similar to cortisol; however, it differs in the ketone group at carbon 11 and the double bond between carbon 1 and carbon 2.
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The chemical structure of methylprednisolone:
This molecule differs from cortisol’s structure due to the methyl group at carbon 6 and the double bond between carbons 1 and 2.
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The chemical structure of dexamethasone:
This structure differs from cortisol due to the presence of a fluorine at carbon 9, a methyl group at carbon 16, and a double bond between carbons 1 and 2.
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Physiology
Endogenous glucocorticoids are:
Derived from cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism (which is synthesized from acetyl-CoAAcetyl-CoAAcetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent.Citric Acid Cycle)
Secreted from the zona fasciculataZona FasciculataThe wide middle zone of the adrenal cortex. This zone produces a series of enzymes that convert pregnenolone to cortisol (hydrocortisone) via 17-alpha-hydroxyprogesterone.Adrenal Glands: Anatomy
Effects: respond to immediate stressors
↑ Immediate available energy through:
Fat and protein catabolism → ↑ blood amino acidAmino acidAmino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids and lipid levels
GluconeogenesisGluconeogenesisGluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
Appetite stimulation
↑ RBCsRBCsErythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production.Erythrocytes: Histology
↑ Serum calciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes from bone resorptionBone resorptionBone loss due to osteoclastic activity.Bones: Remodeling and Healing (leads to ↓ boneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types mineral density over time)
Antiinflammatory effects:
↓ InflammationInflammationInflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
↓ Blood vessel permeability
Long-term exposure suppresses the immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs
Regulated by the hypothalamic-pituitary-adrenal (HPA) axis
Flowchart showing the hypothalamic-pituitary-adrenal cortex axis: Stresses may be physical (e.g., exercise), mental (e.g., fear), or biochemical (e.g., low blood glucose). Biologic rhythms include circadian rhythms as well as longer rhythms associated with growth and development. ACTH: adrenocorticotropic hormone CRH: corticotropin-releasing hormone
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Overview of the steroidogenesis pathways:
Cholesterol is initially converted to pregnenolone and then to progesterone. From there, the pathway diverges, with many potential end products, including glucocorticoids, mineralocorticoids, androgens, and estrogens.
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Mechanism of action
Glucocorticoids enter cell → bindBINDHyperbilirubinemia of the Newborn to glucocorticoid receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors
Translocation to the nucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles → bindBINDHyperbilirubinemia of the Newborn to specific DNADNAA deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).DNA Types and Structure sequences (glucocorticoid response elements) → result in either:
Activation of transcriptionTranscriptionTranscription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
RepressionRepressionDefense mechanisms involving approach and avoidance responses to threatening stimuli. The sensitizing process involves intellectualization in approaching or controlling the stimulus whereas repression involves unconscious denial in avoiding the stimulus.Defense Mechanisms of transcriptionTranscriptionTranscription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription
Results in metabolic effects (similar to normal physiology)
Specific genomic immune systemImmune systemThe body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.Primary Lymphatic Organs effects include:
Blocking promotor sites for proinflammatory genesGenesA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.DNA Types and Structure
Promoting transcriptionTranscriptionTranscription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of antiinflammatory geneGeneA category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Basic Terms of Genetics products
Diminish synthesisSynthesisPolymerase Chain Reaction (PCR) of inflammatory cytokinesCytokinesNon-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Adaptive Immune Response
↑ ACE synthesisSynthesisPolymerase Chain Reaction (PCR) → bradykininBradykininA nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) degradation
HydrocortisoneHydrocortisoneThe main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Immunosuppressants
BeclomethasoneBeclomethasoneAn anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma.Asthma Drugs
BudesonideBudesonideA glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis.Asthma Drugs
HydrocortisoneHydrocortisoneThe main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Immunosuppressants
PrednisolonePrednisoloneA glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.Immunosuppressants
PrednisonePrednisoneA synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver.Immunosuppressants
Topical steroidsSteroidsA group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus.Benign Liver Tumors are classified as classes I–VII based on their potency.
Class I: most potent; includes:
Clobetasol propionateClobetasol propionateA derivative of prednisolone with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than fluocinonide, it is used topically in treatment of psoriasis but may cause marked adrenocortical suppression.Bullous Pemphigoid and Pemphigus Vulgaris
Betamethasone dipropionate
Diflorasone diacetate
Fluocinonide
Class VII: least potent; includes hydrocortisoneHydrocortisoneThe main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Immunosuppressants
Pharmacokinetics
The following summarizes the pharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics for systemic glucocorticoids:
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption
Oral absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption is:
Rapid
Complete
Formulations/routes of administration:
Oral
IV
IM
Intraarticular
Distribution
Protein binding:
Natural glucocorticoids are highly protein-bound:
Corticosteroid-binding globulin (CBG)
AlbuminAlbuminSerum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood.Liver Function Tests
Synthetic steroidsSteroidsA group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus.Benign Liver Tumors are generally less protein-bound.
Systemic glucocorticoids are commonly used for the short- and/or long-term management of a variety of conditions, including:
Physiologic glucocorticoid replacement
Inflammatory diseases
Allergic conditions
Autoimmune diseasesAutoimmune diseasesDisorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Selective IgA Deficiency
Table: Common indications for glucocorticoids (list is not exhaustive)
System
Indications
Allergic conditions
AnaphylaxisAnaphylaxisAn acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death.Type I Hypersensitivity Reaction
Seasonal allergic rhinitisAllergic rhinitisAn inflammation of the nasal mucosa triggered by allergens.Rhinitis
Serum sicknessSerum sicknessImmune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses.Type III Hypersensitivity Reaction
Transfusion reactionsTransfusion reactionsTransfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions
Contact dermatitisContact dermatitisA type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms.Male Genitourinary Examination
Pemphigus vulgarisPemphigus vulgarisBullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Bullous Pemphigoid and Pemphigus Vulgaris
Stevens-Johnson syndromeStevens-Johnson syndromeStevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome
Severe psoriasisPsoriasisPsoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
Endocrine
Congenital adrenal hyperplasiaHyperplasiaAn increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells.Cellular Adaptation
HypercalcemiaHypercalcemiaHypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia associated with malignancyMalignancyHemothorax
Nonsuppurative thyroiditisThyroiditisThyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis
Primary/secondary adrenocortical insufficiency
Septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock unresponsive to IV fluid resuscitationResuscitationThe restoration to life or consciousness of one apparently dead. .Neonatal Respiratory Distress Syndrome
GI
Inflammatory bowel disease
Symptomatic therapy for nauseaNauseaAn unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Antiemetics/vomitingVomitingThe forcible expulsion of the contents of the stomach through the mouth.Hypokalemia
Hematologic
Autoimmune hemolytic anemiaAutoimmune Hemolytic AnemiaAutoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self RBCs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia
Congenital (erythroid) hypoplastic anemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
Immune thrombocytopeniaThrombocytopeniaThrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
Lymphomas and leukemias
Neurologic
Cerebral edemaCerebral edemaIncreased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus).Increased Intracranial Pressure (ICP)
Multiple sclerosisSclerosisA pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve.Wilms Tumor
ChorioretinitisChorioretinitisChorioretinitis is the inflammation of the posterior segment of the eye, including the choroid and the retina. The condition is usually caused by infections, the most common of which is toxoplasmosis. Some of these infections can affect the fetus in utero and present as congenital abnormalities. Chorioretinitis
Herpes zoster ophthalmicusHerpes zoster ophthalmicusVirus infection of the gasserian ganglion and its nerve branches characterized by pain and vesicular eruptions with much swelling. Ocular involvement is usually heralded by a vesicle on the tip of the nose. This area is innervated by the nasociliary nerve.Herpes Zoster (Shingles)
IritisIritisInflammation of the iris characterized by circumcorneal injection, aqueous flare, keratotic precipitates, and constricted and sluggish pupil along with discoloration of the iris.Leprosy and iridocyclitisIridocyclitisAcute or chronic inflammation of the iris and ciliary body characterized by exudates into the anterior chamber, discoloration of the iris, and constricted, sluggish pupil. Symptoms include radiating pain, photophobia, lacrimation, and interference with vision.Relapsing Fever
Optic neuritisOptic neuritisInflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis).Cranial Nerve Palsies
AsthmaAsthmaAsthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
Symptomatic sarcoidosisSarcoidosisSarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
Ankylosing spondylitisAnkylosing spondylitisAnkylosing spondylitis (also known as Bechterew’s disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis
Psoriatic arthritisPsoriatic ArthritisA type of inflammatory arthritis associated with psoriasis, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of hla-b27-associated spondyloarthropathy, and the absence of rheumatoid factor.Psoriasis
SynovitisSynovitisInflammation of the synovial membrane.Rheumatoid Arthritis of osteoarthritisOsteoarthritisOsteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis
DermatomyositisDermatomyositisA subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms.Paraneoplastic Syndromes
Systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected.Systemic Lupus Erythematosus
VasculitisVasculitisInflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body.Systemic Lupus Erythematosus
Topical
Topical glucocorticoids can be used for a number of dermatologic conditions, including (list is not exhaustive):
PsoriasisPsoriasisPsoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
Acute radiationRadiationEmission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles).OsteosarcomadermatitisDermatitisAny inflammation of the skin.Atopic Dermatitis (Eczema)
Lichen planusLichen planusLichen planus (LP) is an idiopathic, cell-mediated inflammatory skin disease. It is characterized by pruritic, flat-topped, papular, purple skin lesions commonly found on the flexural surfaces of the extremities. Other areas affected include genitalia, nails, scalp, and mucous membranes. Lichen Planus
VitiligoVitiligoVitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. Vitiligo
Eosinophilic esophagitisEosinophilic esophagitisChronic esophagitis characterized by esophageal mucosal eosinophilia. It is diagnosed when an increase in eosinophils are present over the entire esophagus. The reflux symptoms fail to respond to proton pump inhibitors treatment, unlike in gastroesophageal reflux disease. The symptoms are associated with ige-mediated hypersensitivity to food or inhalant allergens.Esophagitis (not inhaled, but swallowed)
Cushing syndromeCushing syndromeA condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent.Paraneoplastic Syndromes
HyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus and diabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus mellitus
Immunosuppression → invasive infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Hematologic: neutrophilia from demargination
GI:
Ulcers
GastritisGastritisGastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
Neurologic:
Psychosis
InsomniaInsomniaInsomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking.Insomnia
Irritability
AnxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder
Mood lability
↑ Appetite
Ophthalmologic:
GlaucomaGlaucomaGlaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
OsteoporosisOsteoporosisOsteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
Osteonecrosis
Dermatologic:
SkinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and FunctionsatrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation
Striae
Purpura
Impaired wound healingWound healingWound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing
Abrupt discontinuation may cause adrenal insufficiencyAdrenal InsufficiencyConditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus.Adrenal Insufficiency and Addison Disease
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation and precautions
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation:
Recent administration of live or live attenuated vaccines
Systemic fungal infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Other uncontrolled active infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
OsteoporosisOsteoporosisOsteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
DiverticulitisDiverticulitisInflammation of a diverticulum or diverticula.Diverticular Disease or recent intestinal anastomoses → risk of perforationPerforationA pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force.Esophagitis
Severe hepatic or renal impairment
Recent acute MIMIMI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms.Myocardial Infarction → risk of wall rupture
↓ AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of glucocorticoids:
PhenobarbitalPhenobarbitalA barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates gamma-aminobutyric acid action on gaba-a receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.First-Generation Anticonvulsant Drugs
PhenytoinPhenytoinAn anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.First-Generation Anticonvulsant Drugs
RifampinRifampinA semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms.Epiglottitis
RitonavirRitonavirAn HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits cytochrome p-450 cyp3a.Anti-HIV Drugs
ClarithromycinClarithromycinA semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50s ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation.Macrolides and Ketolides
VoriconazoleVoriconazoleA triazole antifungal agent that specifically inhibits sterol 14-alpha-demethylase and cytochrome p-450 cyp3a.Azoles
Dosing adjustment may be necessary for antidiabetic agents.
