Transcript Drug Therapy r/t Metabolism

Key concepts to know for Drug Therapy r/t Geriatrics
• Physiological differences in older adults that
impact pharmacokinetic & pharmacodynamic
processes, and the organs involved in PK
processes…
• Why are older adults at risk for adverse events?
• Polypharmacy
• decreased renal function, decreased elimination and
therefore drug accumulation in the blood
• multiple and more severe diseases
• multiple prescribers, limited oversight
• ADRS may be undetected in older adults because they
can mimic characteristics, problems, diseases, or
symptoms commonly present in the elderly
• Symptoms of ADR in older adults are often nonspecific
and therefore difficult to identify as a specific-drugrelated problem
Which pharmacokinetic change is responsible for
most ADRs in older adults? → Reduced renal
excretion
To monitor organ functioning:
Liver• PT/INR good indicators of hepatic function AST,
ALT are markers for hepatic inflammation
albumin levels.
Kidneys –
• creatinine clearance is used for elders!
• use the Cockgroft Gault Equation
Age-related Physiologic changes: gastrointestinal changes
affect pharmacokinetics r/t absorption
Age-related changes to GI tract
 Reduced GI blood flow
 Reduced motility
 Delayed gastric emptying
 Atrophy of mucosa and glands
 Reduced digestive secretions
 Decrease in number of absorptive cells; decreased
absorptive surface area
 Reduced gastric acid production, though in some
people this remains unchanged
Effect on pharmacokinetics
 Despite the many and significant above changes, overall
percentage (amount) absorbed of MOST oral meds does
not change with age (occasional exceptions)
Age-related Physiologic changes: body composition changes
affect pharmacokinetics r/t distribution
Body composition/other changes affect volume of distribution
 Decreased percentage of lean body mass (↓muscle mass,
strength and functionality)
 Resulting in a relatively increased percentage of body fat
*Storage depot for lipid-soluble drugs
*Increased half-life of fat-soluble drugs
 Decreased total body water
*Increases serum concentration of water soluble drugs;
effects more intense
 Reduced concentration of plasma proteins (especially
serum albumin)
*Reduced protein binding of drugs and increased levels
of free drug
In some people, albumin levels and “physiologic reserve”
may be significantly reduced and depleted
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Age-related Physiologic changes: hepatic changes
affect pharmacokinetics r/t hepatic metabolism
Age-related changes to liver
—reduced hepatic blood flow
—reduced liver mass
—decreased activity of some hepatic enzymes occurs
 Hepatic metabolism declines with age
 Age – related changes combine with effects of
concomitant disease or social impacts such as
decreased nutritional status
Half-lives of some drugs may increase, responses may be
prolonged
Reduce dose or administer less frequently
Responses to some oral drugs may be enhanced
(eg drugs that undergo extensive first-pass effect)
Age-related Physiologic changes: renal changes
affect pharmacokinetics r/t renal excretion
Age-related changes to kidney:
 Renal function undergoes progressive decline beginning in
early adulthood, (~age 30 yrs); age-related decline in drug
elimination varies considerably from person to person
Reduction in renal blood flow PLUS Reduction in number of
functional nephrons
Leads to a decreased glomerular filtration rate (GFR)!
In addition, active tubular secretion decreases (important
only for some drugs)
 Cumulatively, these changes result in a decreased renal
excretion of drugs!
(and a diminished ability to adapt to changes in electrolyte, acid levels.)
 Drug accumulation as a result of reduced renal excretion is
the most important cause of adverse drug reactions, drugdrug interactions, and may lead to toxicity in older adults
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Age-related Physiologic changes:
Assessment of Renal Function
 In older adults:
Use creatinine clearance to assess renal function
(rather than serum creatinine), because lean muscle
mass (source of creatinine) declines in parallel with
kidney function.
Sadly, there is an age-related decrease in muscle mass,
strength and functionality in everyone 
Creatinine levels may be normal even though kidney
function is greatly reduced! Therefore, relying on serum
creatinine can be a grossly misleading indicator of
renal function!
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Key Concepts – Parkinson’s Ch 21
• Pathophysiology; relationship of Dopamine to ACh & GABA
• Dyskinesias –
– observed in patients’ presenting symptoms,
– And those that result from drug therapy
– Extrapyramidal system and relationship to dyskinesias
• Goal of drug therapy from patient perspective (improve QOL, relieve
symptoms) & from a pharmacological perspective (replace dopamine)
• Think about: value and feasibility of giving Dopamine exogenously:
– Can’t administer dopamine orally because it would be digested in
the stomach
• Levodopa--- Implications of adding carbidopa to levodopa in terms of
dose, SEs, Mechanism of Action
• Drugs to know for PD Levodopa/Carbidopa (Sinemet)
Parkinson’s Disease (PD)
• Second most common neurodegenerative disease
– Affects 1% of population over 60 (men more than women)
• Slowly progressive neurodegenerative disorder
• Pathophysiology = dopaminergic neurons in substantia nigra
(brainstem) degenerate, therefore effects of other neurotransmitters
dominate
• Affected cells help control movement and coordination.
• Motor signs develop when >50% of dopaminergic neurons lose
function
• Dyskinesias – observed in patients’ presenting symptoms: mild and
asymmetric at first, (such as a mild tremor or a slight feeling that one
leg is stiff and dragging), but sx worsen over time.
• Dyskinesias that may result from drug therapy: increase over time
with ongoing levodopa use. Include: choreatic (writhing) movements
of the limbs and trunk – begin in 40-50% of cases after 5yrs,
80-100% by 10yrs
Parkinson’s Disease (PD)
CARDINAL FEATURES of PD:
• T tremor (70%)
• A akinesia/bradykinesia
• R cogwheel rigidity
• P postural instability (later in disease)
Patients often report that non-motor symptoms are more troubling than
motor problems, and may complain of:
−Autonomic: constipation, urinary incontinence, drooling, orthostatic
hypotension, cold intolerance, and erectile dysfuntion
−Sleep disturbances
−psychological disturbances, depression and impaired memory
TREATMENT:
• Several drug classes available
– Drug selection and dosages are determined by extent to which PD
interferes with work, dressing, eating, bathing, etc.
• Levodopa (or levodopa/carbidopa) is by far most commonly used and
most effective treatment for PD
• NO CURE – goal of drug therapy is to maintain QOL and provide
symptomatic relief
Mechanism
of Action of
Levodopa
Figure 21-2
Steps leading to
alteration of
CNS function by
levodopa.
Levodopa/Carbidopa
(Sinemet, Parcopa)
• Levodopa provides dopamine precursor to brain
• Addition of carbidopa greatly reduces breakdown of levodopa in
GI tract, therefore more levodopa is available to enter the brain
• Regular and continuous release (CR) forms.
– CR form is 30% less bioavailable & less predictable kinetics
• Half life 90-120 min. – but stays in brain longer in newer
onset/younger patients
• Later in disease progression, brain can’t store dopamine so
need more frequent dosing
• Side effects:
– Nausea/vomiting, orthostatic hypotension, drowsiness,
dyskinesias, hallucinations
Levodopa/Carbidopa (Sinemet, Parcopa)
• Levodopa provides dopamine precursor to brain
• Addition of carbidopa greatly reduces breakdown of levodopa in
GI tract, therefore more levodopa is available to enter the brain
• Regular and continuous release (CR) forms.
– CR form is 30% less bioavailable & less predictable kinetics
• Half life 90-120 min. – but stays in brain longer in newer
onset/younger patients
• Later in disease progression, brain can’t store dopamine so
need more frequent dosing
• Side effects:
– Nausea/vomiting, orthostatic hypotension, drowsiness,
dyskinesias, hallucinations
• Dyskinesias resulting from drug therapy occur at various times
End-of-dose wearing off.
Delayed “on” on “no-on” effect.
Unpredictable on/off symptoms.
Sudden “off” periods.
Peak dose dyskinesias.
• Therapeutic window decreases over time
Key Concepts: Alzheimer’s Disease
• In general, presenting symptoms; overall progression of disease
• Pathophysiology; as it relates to Acetylcholine
• Treatment goals from a patient perspective & from a pharmacological
perspective
• Drug therapy
– Cholinesterase inhibitors
Drugs to know for AD:
• Donepezil (Aricept)
Alzheimer’s Disease
• Alzheimer’s disease is most common neurodegenerative disease.
• AD is an irreversible, progressive brain disorder that slowly destroys
memory and thinking skills and, eventually, the ability to carry out
the simplest tasks.
Pathophysiology:
− Degeneration of neurons
− Reduced cholinergic transmission
− Beta-amyloid and neuritic plaques
 Damage/ degeneration to hippocampus (results in memory loss and
impaired emotion regulation)
 Damage/ degeneration to cerebral cortex (results in speech,
perception, reasoning, higher functioning problems)
Alzheimer’s Disease Symptoms
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Memory loss
Confusion
Disoriented
Impaired judgment
Personality changes
Difficulty with self-care
Behavior problems
– wandering, pacing, agitation, screaming
• Inability to recognize family members
• Inability to communicate
Alzheimer’s Disease Drug Therapy
• Cholinesterase Inhibitors
− Prevent breakdown of ACh by AChE with resulting
enhanced transmission
• Do not cure AD and do not stop progression but they may
slow progression
• For use in pts with mild to moderate symptoms
• May improve quality of life (QOL) & cognitive function for some
patients but no evidence of marked improvement or delay of
disease progression
• Donepezil (Aricept®)
– Daily dosing: Oral
– Metabolized P450 pathway
– can be used for severe Alzheimer's as well
– effective for some but not all people and may help only for a
limited time.
Key concepts – Epilepsy (Ch 24)
• Epilepsy – pathophysiology including initiation & propagation of
seizures
• Definition of seizure, convulsion, focus
• General effects & specific MOA of AEDs
• Therapeutic goals of AED therapy
• Guidelines for AED therapy (e.g. monitoring plasma drug levels,
matching drug to seizure, maximizing patient adherence,
withdrawing AEDs,)
• How newer AEDs differ from traditional AEDs in terms of efficacy,
side effects, cost, drug interactions
• Role of Phenobarbital as an antiepileptic drug; SEs of use
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Drugs to know for epilepsy
Phenytoin (Dilantin)
Carbamazepine (Tegretol)
Gabapentin (Neurontin)
Epilepsy- general
• ‘Umbrella term’ for a group of heterogeneous disorders characterized by
excessive excitability of neurons in the CNS
• Seizures range from tiny unnoticeable/or very subtle changes identifiable
only by the trained observer.... all the way to whole-body convulsive shaking.
Definitions• All seizures are caused by sudden, abnormal electrical disturbances in the
brain.
• Focal seizures (also called partial seizures) happen in just one part of the
brain.
• Generalized seizures are a result of abnormal activity on both sides of the
brain.
• A convulsion is a seizure in which a person's whole body shakes rapidly and
uncontrollably; it is very noticeable by others
• The seizure focus is the site in the brain from which the seizure originates.
• People who have recurring seizures due to a brain disorder have epilepsy.
• Seizures can have many causes, including medicines, high fevers, head
injuries and certain diseases.
• Different kinds of seizures are provoked by different stimuli
Epilepsy- drug considerations
• Drug therapy is tailored to individual needs.
• Most AEDs selective for specific seizure disorders
• Must accurately diagnose seizure
–try AED that treats patient’s type of seizure, evaluate effectiveness
–Frequent dosage adjustment may be needed
–May have to try several AEDs before effective regimen established
• Therapeutic monitoring of plasma drug levels may be required
–Helpful in major convulsive disorders
–Some AEDs have narrow therapeutic index
• Treatment goal: decrease seizures so patient can live a normal life
– Balance seizure control vs. acceptability of undesired side effects
• Adherence to drug therapy is essential for optimal seizure control
• Withdrawing antiepileptic drugs
–Spontaneous remission
–Withdraw slowly over a period of 6 weeks to several months
Phenytoin [Dilantin]
• Especially effective against specific types of seizures
(partial and tonic-clonic seizures)
• Mechanism of action: selective inhibition of sodium
channels
• Varied oral absorption
• High degree of plasma binding
• Therapeutic monitoring of plasma drug levels useful
• LOW therapeutic index (enough med to control
seizures, but not cause toxicity)
• Half-life: 8 to 60 hours
• Dosage is highly individualized
Phenytoin (cont’d)
• Adverse effects
– Nystagmus
– Sedation
– Ataxia
– Diplopia
– Cognitive impairment
– Gingival hyperplasia
– Skin rash
** Teratogenic in animals
& humans
Drug interactions need to be carefully considered (due to the
facts that phenytoin is a potent inducer of Cytochrome P450
enzymes, and this drug also exhibits a high degree of plasma
protein binding)
–Decreases the effects of oral contraceptives, warfarin, and
glucocorticoids
–Increases levels of diazepam, isoniazid, cimetidine, alcohol,
valproic acid
PHENYTOIN is an example of a drug
that has a LOW therapeutic index
Figure 24-1A Relationship between dose and plasma level for phenytoin compared with most
other drugs.
Elsevier Inc. items and derived items © 2007 by Saunders, an imprint of Elsevier Inc.
Most drugs have a wider range between
the minimum effective dose and a toxic
dose than phenytoin.
Figure 24-1B Relationship between dose and plasma level for phenytoin compared with most
other drugs.
Elsevier Inc. items and derived items © 2007 by Saunders, an imprint of Elsevier Inc.
Carbamazepine [Tegretol]
• Uses:
– Epilepsy
– Bipolar disorder
– Trigeminal and glossopharyngeal neuralgias
• Mechanism of action- Carbamazepine stabilizes the
inactivated state of voltage-gated sodium channels,
making fewer of these channels available to subsequently
open. This leaves the affected cells less excitable until the
drug dissociates.
• Adverse effects
– Neurologic effects: nystagmus, ataxia
– Hematologic effects: leukopenia, anemia,
thrombocytopenia
– Dermatologic effects: rash, photosensitivity reactions
Elsevier Inc. items and derived items © 2007 by Saunders, an imprint of Elsevier Inc.
GABAPENTIN (Neurontin) is a Newer AED
Newer AEDs are:
• First line treatment
• Are equally effective
• Are better tolerated
• Less drug interactions
– Oxcarbazepine (Trileptal)
– Gabapentin (Neurontin)
– Levetiracetam (Keppra)
– Pregabalin (Lyrica)
• Initially approved as adjunctive therapy but now some
agents approved for monotherapy
Key concepts – Drug Therapy r/t Metabolism: THYROID
• Hormones secreted by thyroid gland =
– T3 = tri-iodothyronine; most activre form; half-life 1 day
– T4 = tetra-iodothyronine; most abundant (least active, “prohormone”); half-life
6-7 days
– Both forms of thyroid hormone are highly (99.5%) plasma-protein bound;
thyroxin binding globulin is the main plasma protein to which thyroid hormone
binds
• Clinical importance of TSH
• Principal actions of thyroid hormones
• Hypothyroidism – 2 main causes, pathology (in general) and
treatments
• Hyperthyroidism (Graves’ disease) – pathology (in general) and
treatments
• Drugs to know for Metabolism: Thyroid
• Levothyroxine (Synthroid)
• Methimazole (Tapazole)
Thyroid Hormone (TH) Actions
• ALL cells are believed to be targets for thyroid hormone.
• Evidence of the clinical importance of thyroid hormone can be
gleaned from studying people with a deficiency or an excess of
TH production: such as hypothyroid (or if severe and advanced,
then myxedema; and during pregnancy, cretinism is seen in the
offspring) or hyperthyroid (if severe, then “thyroid storm.”)
• Thyroid hormones have three principal actions:
 Stimulation of energy use (metabolism)
 Stimulation of the heart (increase force and
rate of cardiac contraction)
 Promotion of growth & development
− normal levels of thyroid hormone are essential to the
development of the fetal and neonatal brain
• Thyroid Stimulating
Hormone (TSH) is used to
determine thyroid status
(when hypothalamus and
anterior pituitary function
are normal.)
• A LOW TSH level
indicates
HYPERTHYROID
• A HIGH TSH level
indicates HYPOTHYROID
Regulation of thyroid function:
when levels of T3 and T4
hormones rise in the bloodstream,
negative feedback inhibits
production of more T3 and T4.
Hypothyroidism:
• #2 most common endocrine disorder in US
• Top Causes
– Autoimmune (Hashimoto’s thyroiditis)
– Iodine deficiency (goiter)
• in countries without iodinated salt,
and where soil doesn’t get rainfall from ocean clouds
• Treatment = hormone replacement
– Most common treatment is T4 replacement
– Levothyroxine = synthetic preparation of thyroxine (T4)
Thyroid Hormone Therapy
Levothyroxine (T4) [Synthroid]
– Used for all forms of hypothyroidism
• Use caution in elderly or if heart disease
• monitor vital signs
– Half-life is 6-7 days
– Takes FIVE WEEKS for plateau to be reached
– Starting dose titrated up/down based on TSH
– Recheck TSH 6 - 8 weeks after every dose change
– Absorption decreased with food (varies 40-80%):
Give 30 - 60 minutes before breakfast with a full glass of water
(empty stomach)
– best for patients to not switch brands
Adverse effects from too much levothyroxine are the signs of
hyperthyroidism
Levothyroxine: interactions
• Many drugs, including cholestyramine [Questran], colestipol
[Colestid], sucralfate [Carafate], H2 receptor blockers, proton
pump inhibitors, aluminum-containing antacids, iron
supplements, and calcium supplements can significantly reduce
levothyroxine absorption.
***At least 4 hours should lapse between the administration of
levothyroxine on an empty stomach and these drugs.
• Levothyroxine can intensify the anticoagulant effects of
warfarin.
Hyperthyroidism: Grave’s Disease
• Most common cause of hyperthyroid is Grave’s disease
– Autoimmune
– antibodies called thyroid-stimulating immunoglobulins attack
TSH receptors on thyroid gland resulting in overstimulation
• Treatment
– Suppression of thyroid hormone synthesis, if possible
– If suppression of overactive thyroid tissue is not possible,
then:
• the overactive thyroid tissue is destroyed
• Surgical removal of thyroid tissue
• Followed by hormone replacement therapy
Methimazole
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First line drug
Inhibits thyroid hormone synthesis
Is safer and more convenient than PTU
Oral med taken once daily,
minimal plasma protein binding,
crosses membranes more easily,
Half life is 6 – 13 hours
Full benefits of methimazole may take 6 to 12 months to
develop
contraindicated during pregnancy and breastfeeding
Main adverse effect is agranulocytosis
– Decreased ability to fight off infection
Key concepts – Drug Therapy r/t Metabolism: ADRENAL CORTEX
• Adrenocortical steroid hormones produced by the adrenal cortex
(glucocorticoids, mineralocorticoids, androgens) & their principal
actions
• Glucocorticoids
– Physiologic effects
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– Exogenous glucocorticoids: physiologic vs pharmacologic doses
Changing glucocorticoid needs in response to stress
Pharmacologic treatment that may be indicated for…
Cushing’s syndrome
Addison’s disease
Mineralocorticoids (fludrocortisone)
– Therapeutic use, MOA
• Overlap of glucocorticoid and mineralocorticoid properties in drugs
used for corticosteroid replacement
• Feedback regulation of glucocorticoid synthesis and secretion; impact
of stress, development of adrenal suppression.
• Drugs to know for Metabolism r/t Adrenocortical
• Hydrocortisone
• Fludrocortisone (Florinef)
Use of glucocorticoids in nonendocrine diseases:
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Mechanism (why it works)
Therapeutic uses
Adverse effects
Guidelines for withdrawing glucocorticoid
therapy and WHY this needs to be.
• Other general uses of glucocorticoids
(discussed in class)
Adrenocortical Hormones
• Three main classes of adrenocortical hormones, the natural
exemplar hormone in the body, and principal actions
1. Glucocorticoids- cortisol
 Homeostasis (metabolism, immune, inflammation and more
 In times of stress, glucocorticoids are essential for survival.
2. Mineralocorticoids- aldosterone
→ Salt and water balance
3. Androgens- androstenedione
→ Sexual hormones and sexual balance
Glucocorticoids (GC): physiologic effects
• Affect all of the major systems of the body (wide array of effects)
• Natural steroids possess both glucocorticoid and mineralocorticoid
activity to some extent.
• Essential roles in:
– carbohydrate, protein & lipid metabolism
– Important to normal inflammation, immune responses, and
wound healing (at normal endocrine physiologic levels.)
– Cardiovascular system- GC promote efficient CV function and
tone
– Important to myocardial and skeletal muscle integrity
– Important to central nervous system
• In the following roles, glucocorticoids are ESSENTIAL for surviva
– help the body respond to stress
– help the body respond to environmental change
Glucocorticoids (GC): physiologic effects
• Cortisol levels naturally vary over a 24-hour period: GC peak in th
body during early-morning hours just before waking. It helps
produce a wake-up signal, turning on appetite and physical
activity.
• When fasting, cortisol mobilizes energy sources such as glucose
fatty acids, and amino acids
• In acute stress, GC enhance memory, increase activity of the
immune system, and help protect the body from pathogens.
Cortisol and epinephrine facilitate the movement of immune cells
from the bloodstream and storage organs, such as the spleen,
into tissue where they are needed to defend against infection.
• Glucocorticoids have multiple effects on fetal development, eg:
respiratory system in neonates
Therapy with Glucocorticoids: for hormone replacement
 GC are administered at LOW (“physiologic doses”) to treat
Adrenal Hormone Insufficiency (aka Addison’s Disease)
 Hydrocortisone is the drug of choice
– In people with insufficient adrenal hormone production,
it is absolutely essential to increase glucocorticoid
doses at times of stress (e.g., surgery, infection,
trauma). Failure to do so may prove fatal.
 Treatment: lifelong
 Fludrocortisone, a pure mineralocorticoid, may be added if the
mineralocorticoid actions of hydrocortisone are inadequate.
 Glucocorticoid replacement therapy may be done by
– (1) taking the entire daily dose in the morning , or
– (2) splitting the daily dose, taking two-thirds in the morning
and one-third in the afternoon
 When used in the low (physiologic) doses needed for hormone
replacement therapy, glucocorticoids have no adverse effects.
Therapy with Glucocorticoids: for anti-inflammation or
anti-immune purposes
 GC are administered at HIGH (“pharmacologic doses”) to
treat a huge array of non-endocrine disorders/ conditions
related to the potent anti-inflammatory and anti-immune
properties
 ranging from severe allergic reactions to inflammatory
conditions to autoimmune diseases and even cancer
 MANY adverse effects can result when GC are
administered at HIGH (“pharmacologic doses”) including:
– Adrenal suppression
– Cushing’s syndrome
 See next slides
Glucocorticoid: Hydrocortisone
• Synthetic steroid (closely resembles cortisol)
• Primarily glucocorticoid effects, but some mineralocorticoid effects
May take the entire daily dose in the morning , or
Split the daily dose, taking two-thirds in the morning and one-third in
the early afternoon (close to noon)
THERAPEUTIC USES:
LOW (“physiologic doses”) are used to treat adrenal hormone
insufficiency (aka Addison’s Disease)
–In times of stress, MUST increase dose by a magnitude of 3, for 3
days (otherwise potentially fatal)
HIGH (“pharmacologic doses”) are used to treat a huge array of
non-endocrine disorders/ conditions related to potent antiinflammatory and anti-immune properties
ranging from severe allergic reactions to inflammatory conditions to
autoimmune diseases and even cancer
MANY adverse effects can result when GC are administered at
HIGH (“pharmacologic doses”) including:
–Adrenal suppression
–Cushing’s syndrome
Mineralocorticoid:
Fludrocortisone [Florinef]
• Potent mineralocorticoid
• Therapeutic uses
– Addison’s disease
– Primary hypoaldosteronism
– Congenital adrenal
hyperplasia
• Adverse effects
– Hypertension
– Edema
– Cardiac enlargement
– Hypokalemia
Pharmacology of Glucocorticoids:
therapeutic uses
→ Effects on metabolism and electrolytes
(physiologic dose- LOW)
→ Anti-inflammatory and immunosuppressant effects
(pharmacologic dose- HIGH),
Therapeutic uses in non-endocrine disorders:
− Rheumatoid arthritis
– Systemic lupus erythematosus
– Inflammatory bowel disease
– Miscellaneous inflammatory disorders
– Allergic conditions
– Asthma
– Dermatologic disorders
– Neoplasms
– Suppression of allograft rejection
– Prevention of respiratory distress syndrome
Pharmacology of glucocorticoids:
anti-inflammatory mechanism
• Glucocorticoids reduce inflammation by multiple
mechanisms, including suppressing synthesis
of inflammatory mediators (prostaglandins,
leukotrienes, histamine), infiltration of
phagocytes, release of lysosomal enzymes,
and proliferation of lymphocytes.
Pharmacology of the Glucocorticoids:
adverse
effects
• Adverse effects
– Thinning of the skin- pts notice
– Adrenal insufficiency with prolonged use- next slide
– Osteoporosis
– Increased risk of infection, cancers
– Glucose intolerance
 increased BG, may develop diabetes
– Myopathy
– Fluid and electrolyte disturbance
– Growth retardation
– Psychologic disturbances- insomnia, racing thoughts
steroid-induced psychosis (“wig out”)
– Cataracts and glaucoma
– Peptic ulcer disease
– Iatrogenic Cushing’s syndrome
Guidelines for withdrawing glucocorticoid
therapy and WHY
• Prolonged glucocorticoid use (may) cause adrenal
insufficiency/ adrenal suppression
– Due to negative feedback/ suppression
– Depends on duration of therapy and dose
• When GC are discontinued, withdrawal of therapy must
allow time for adrenal glands to regain function:
– TAPERING DOSE TO OFF will ↓risk of adrenal insufficiency
– Duration of taper, and rate at which doses are decreased are
(subjectively) determined by provider… based on duration
and dose of GC therapy
– TEACH: do not stop drug suddenly
– TEACH signs, and monitor for adrenal crisis
Things to Know
• Similarities among corticoids are striking: no prototype
• Doses are highly individualized
• Duration of treatment & withdrawal/ taper of therapy are
somewhat subjective
• All corticoids have some degree of glucocorticoid effect
and some degree of mineralocorticoid effect.
See comparison tables.
• GC vary in half-lives; potency; degree of GC vs MC
 Short-acting (typically acute, time-limited conditions)
 Intermediate acting
 Long-acting (typically used for chronic conditions)
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