Transcript Adverse effects

Drugs for Thyroid
Disorders
Burchum & Rosendahl,
Chapter 58
Thyroid
Thyroid Hormone Actions
• 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 Hormones
• The thyroid gland produces:
• Tri-iodothyronine (T3) - highly active
• Tetra-iodothyronine (T4) - more abundant,
but much less active (prohormone)
• 99.5% plasma-protein bound
•
T4  T3 in cells
• Most abnormalities of thyroid function can be
treated effectively
Figure 58-2
Steps in thyroid hormone synthesis.
Regulation of thyroid function:
when levels of T3 and T4
hormones rise in the bloodstream,
negative feedback inhibits
production of more T3 and T4.
(Figure 58-3)
Hypothalamus is the major neuroendocrine gland
Hypothalamus produces a variety of “Releasing
Factors” which cause the pituitary, in turn, to
secrete hormones.
Lab Tests
• Thyroid Stimulating Hormone (TSH) is an
exquisitely sensitive indicator of thyroid status
(when hypothalamus and anterior pituitary function
are normal.)
• The free T4 (thyroxin) assay is usually done at the
same time as the TSH assay.
Thyroxine level is used to
confirm a thyroid disorder
in the event that the TSH
is abnormal.
Thyroid Problems
Hypo
• Weakness/ Fatigue
• Skin changes (dry,
coarse, cold)
• Slowed speech
• Eyelid (or facial) edema
• Increased sensitivity to
cold
• Constipation
• Low HR
• Weight gain
• Hoarseness
• Depression
• Forgetfulness
Hyper
• Increased sensitivity
to heat
• Skin warm and moist
• Elevated HR
• Weight loss
• Increased BM
• Increased appetite
• Nervousness, anxiety,
irritability, INSOMNIA
• Possible tremor
• Possible sweating
GOITER
• A goiter can occur in a gland that is producing:
– too much hormone (hyperthyroidism)
– too little hormone (hypothyroidism)
– or the correct amount of hormone (euthyroidism).
A goiter indicates there is a condition present which
is causing the thyroid to grow abnormally.
“Beauty” in ancient times
TOO LITTLE
thyroid hormone
Hypothyroidism: epidemiology
• #2 most common endocrine disorder in US
• Prevalence 0.5% in the general US population.
• increasingly common with advancing age,
affecting about 2 to 3 percent of older women
• May be misdiagnosed as depression, postpartum “blues” , constipation, etc
Hypothyroidism
• Top Causes
– Autoimmune (Hashimoto’s thyroiditis)
– Iodine deficiency (goiter)
• in countries without iodinated salt,
and where soil doesn’t get rainfall from
ocean clouds
Thyroid Hormone Replacement: Preparations
• Therapeutic strategy for hypothyroid: hormone
replacement
– Most common treatment is T4 replacement
– Levothyroxine = synthetic preparation of thyroxine (T4)
– Liothyronine (T3)
– “Armor thyroid”
“natural”, from animal
source (?))
– Historically,
dessicated animal
thyroid was used
Before
After
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?
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 separate
administration of levothyroxine and these drugs.
• Levothyroxine can intensify the anticoagulant
effects of warfarin.
Hypothyroidism
• Severe deficiency of thyroid hormone
– Myxedema (adults)
– Cretinism (infancy)
– Extremes help teach hormone functions
Puffy face
TOO MUCH
thyroid hormone
Hyperthyroidism: two forms
• Much less common
• Two major forms:
– Graves’ disease (most common)
• Symptoms can often be unnoticed, resulting in
severe hyperthyroid manifestation of “thyroid storm”
– Toxic nodular goiter (Plummer’s disease)
Hyperthyroidism: Grave’s Disease
• Cause of Grave’s disease: autoimmune
– Thyroid-stimulating immunoglobulins (TSIs)
– Attack TSH receptors on thyroid gland
resulting in overstimulation
• Treatment
– Suppression of thyroid hormone synthesis
(eg drug therapy with methimazole, PTU)
– Surgical removal of thyroid tissue
– Destruction 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
•
•
•
•
Propylthiouracil (PTU)
“antithyroid medication”:
Inhibits thyroid hormone synthesis and release
Short half-life (about 75 minutes)
Drug is given with radiation treatment (thyroid destroyed);
pt becomes hypothyroid; then thyroid replacement therapy
• Therapeutic uses
– Graves’ disease
– Adjunct to radiation therapy
– Preparation for thyroid gland surgery
• Adverse effects
– Skin problems = most common
– Agranulocytosis (loss of granulocytes, decreased
ability to fight infection) = most serious
– Hypothyroidism
 Caution in Pregnancy and lactation (Category D) ;
evidence of risk
Radioactive Iodine-131 (131I)
• Radioactive isotope of stable iodine
– Emits gamma and beta rays
• Half-life is 8 days
• Full effects of 131I require 2 to 3 months to develop.
• 131I is contraindicated during pregnancy and lactation.
• Used in Graves’ disease
• Action
– Produces clinical remission with destruction of thyroid
gland
Exophthalmos (Uncommon) &
Goiter (common)
Case
A 25-year-old, previously healthy woman
presents with 1 month of anxiety, palpitations,
loose stools, fine tremors, and hair loss. She has
had a 20-pound weight loss over past 4 months,
despite increased appetite.
HR 115 to 130 BPM, T 37.5C. Exam notable for
mild bilateral proptosis, thin hair, and moist skin.
Goiter visible with audible bruit. Hyperreflexia and
fine tremors. EKG – normal sinus tachycardia.
Question
A client is prescribed levothyroxine (Synthroid)
daily. The most important instruction to give her is…
• Taper dose & dc if mental or emotional states
stabilize
• Take it at bedtime to avoid side effects of nausea
and flatus.
• Call the doctor immediately at the onset of
palpitations or nervousness.
• Decrease intake of juices and fruits with high
potassium and calcium contents.
Drugs for Disorders
of the Adrenal Cortex
Chapter 60: Endocrine Gland Dysfunction
- hypERsecretion or hypOsecretion
Chapter 72: Glucocorticoids for Non-endocrine
Disorders
Corticosteroids are key regulators of whole-body
homeostasis; provide capacity to resist environmental
changes and invasion of foreign substances
Physiology of the Adrenocortical Hormones
• The adrenal cortex produces over 20 hormones
• “Corticosteroids” refers to the glucocorticoids and the
mineralocorticoids.
• NURS 310 will examine the following three classes of
adrenocortical steroid hormones:
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
1. Glucocorticoids:
Physiologic Effects and mechanism of production
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Affect all of the major systems of the body
Carbohydrate , protein and lipid metabolism
Inflammation, immunity, wound healing
Myocardial and skeletal muscle integrity
Central nervous system
Cardiovascular system
Musculoskeletal system
Stress response
Respiratory system in neonates
Figure 60-2
Negative feedback regulation of
glucocorticoid synthesis and secretion.
Physiologic Effects and mechanism of production
Glucocorticoids:
2. Mineralocorticoids:
Physiologic Effects and mechanism of production
Mineralocorticoids
– Circulatory
balance;
Hemodynamic
stability
– Retention of
sodium (Na+) &
water
– Excretion of
potassium (K+)
3. Androgens:
Physiologic Effects and mechanism of production
Androgens are male hormones. Androgens are used for
several reasons, such as:
• To replace the hormone when the body is unable to
produce enough on its own.
• To stimulate the beginning of puberty in certain boys
who are late starting puberty naturally.
• To treat certain types of breast cancer in females.
• Development of male features in transsexuals
• Lichen sclerosus (a skin problem of the vulva)
• Microphallus (underdevelopment of the penis)
Exogenous corticosteroids
(ie glucocorticoids with or without
mineralocorticoids) are used to treat
seemingly “opposite” conditions:
excessive and insufficient hormone
secretion by the adrenal cortex.
Why?
Excess or Insufficiency of
Adrenocortical Hormones
• Two most familiar forms of adrenocortical
dysfunction
• Adrenal hormone excess
= Cushing’s syndrome
• Adrenal hormone deficiency
= Addison’s disease
TOO MUCH
ADRENAL HORMONE
Cushing’s syndrome
Cushing’s syndrome
Cushing’s syndrome
Adrenal Hormone Excess =
Cushing’s Syndrome
Cushing’s syndrome
– Causes
• Hypersecretion of adrenocorticotropic
hormone (ACTH)
• Hypersecretion of glucocorticoids
• Administering glucocorticoids in large
doses
– Treatment
• Surgical removal of the adrenal gland
• Replacement therapy
TOO LITTLE
ADRENAL HORMONE
Addison’s Disease
Addison’s
Disease
Addison’s Disease
Adrenal Hormone Insufficiency
(Addison’s Disease): causes
Primary Adreno-cortical Insufficiency:
 Causes
— most often caused by autoimmune disease
Acute adrenal insufficiency (adrenal crisis)
• Causes
– Adrenal failure
– Pituitary failure
– Inadequate doses of corticosteroids
Adrenal Hormone Insufficiency
(Addison’s Disease): Symptoms & Tx
Symptoms
• Hypoglycemia
• Malaise
• Loss of appetite
• Reduced capacity to respond to stress
Treatment: lifelong
• Replacement of fluid, salt, and glucocorticoids
• Hydrocortisone is the drug of choice
– Increase in time of physiologic stress – 3x3 rule
• In adrenal insufficiency:
– All people require glucocorticoid replacement
– Some people require mineralocorticoid
Glucocorticoids in tx of adreno-cortical hormone
insufficiency: hydrocortisone is drug of choice
• Synthetic steroid
– Primarily glucocorticoid effects, but also has some
mineralocorticoid effects
– Must take entire daily dose upon wakening
– Doses for endocrine hormones are SMALLER than
when dosed for anti-inflammatory or other
purposes. In times of stress, MUST increase dose
by a magnitude of 3, for 3 days (otherwise
potentially fatal)
• Therapeutic uses
– Adrenal insufficiency
– Allergic reactions to inflammation to cancer
• Adverse effects
– 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
Question
A nurse knows the clinical manifestations of
a client with Addison’s disease include
which of the following?
• Weight gain
• Hypertension
• Melanosis
• Hypotension
• Hyponatremia
Answer
A nurse knows the clinical manifestations of
a client with Addison’s disease include…
• Weight gain
• Hypertension
• Melanosis
• Hypotension
• Hyponatremia
CASE
•Ms. J is diagnosed with primary adrenocortical
insufficiency, or Addison’s disease. She is prescribed
corticosteroid therapy. She wonders how she will fit
taking pills into her busy schedule.
•Glucocorticoid replacement therapy may be done by (1)
giving the entire daily dose in the morning or (2) splitting
the daily dose, giving two-thirds in the morning and onethird in the afternoon.
•She asks the nurse if she really has to take pills for this
condition for the rest of her life. She insists that she
works hard and loves to go on vacation and that she will
not take pills every day for the rest of her life.
• What is the nurse’s most appropriate response?
Same case, one week later
Ms. J is started on corticosteroid replacement therapy.
One week later, she is admitted to the emergency
department with hypotension, dehydration,
hypoglycemia, weakness, lethargy, vomiting, and
diarrhea.
What is the most probable cause of these
signs and symptoms?
Which treatment measures are likely to be
used to resolve the cause of Ms. J’s signs
Glucocorticoids in
non-endocrine disorders
Burchum & Rosenthal, Chapter 72
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 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
Pharmacology of the Glucocorticoids:
(to decrease risk of adverse effects)
• Prolonged glucocorticoid use (may) cause adrenal
insufficiency/ adrenal suppression
– Due to negative feedback/ suppression
– Exogenous vs. endogenous
• 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.
• Taper depends on duration and dose of GC therapy:
might be very slow taper over a LOOONG time
– Taper the dosage to 50% of physiologic values
– Monitor for adrenal crisis: nausea, vomiting, shock
 People with adrenal suppression MUST have
supplemental GC during physiologic stress (surgery,
trauma); potentially fatal if no increased dose
Things to Know
• Similarities among corticoids are striking: no prototype
• Doses are highly individualized
• Duration of treatment & withdrawal/ taper of therapy are
somewhat subjective
• 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)
• Different steroids (eg topical) vary considerably in
strength of effect/potency. Concentration differences/
doses meaningful if comparing the SAME medication.
Glucocorticoids
Drug
Physiologic
dose
Nonendocrine
dose
Hydrocortisone
(half-life 8-12 hours)
20-25 mg
Up to 240 mg
(up to 800 mg
in MS!)
Prednisone
(half-life 18 – 36 hours)
5-10 mg
Up to 60-80
mg
Dexamethasone
(half-life 36-54 hours)
0.25- 0.75 mg
Up to 9 mg
GC = glucocorticoid
MC = mineralocorticoid
Relative
GC
efficacy
Relative MC
efficacy
Pharmacology of Glucocorticoids: General
• widely used through many routes: PO IV IM SUBCUT
TOPICAL INHALE INTRANASAL INTRA-ARTICULAR
RECTAL and more
• TEACH: do not stop taking suddenly; confer with PCP
• TEACH: psyche effects
• Daily therapy: administer before 9:00 am
– Minimizes SE such as insomnia
– Often tolerated better if taken with food
• Multiple drug intx: examples
– GC + NSAIDS  PUD
– Hypokalemia  ↑risk of digoxin toxicity, some diuretic
• PK:
− Oral absorption is rapid and complete
– Metab by liver, metabolites are not active
– Excreted by kidneys
Prednisone: oral synthetic corticosteroid
• Effects similar to other corticosteroids;
• mimic the action of cortisol (hydrocortisone)
• Used in low doses to treat symptoms of low corticosteroid levels
• More commonly used at higher doses (to tx acute, chronic , or
remit/relapse conditions) for its potent anti-inflammatory effects:
− arthritis, colitis, asthma, bronchitis, skin conditions, allergies,
or inflammatory conditions of the nose and eyes;
− multiple sclerosis ; lupus; and a multitude of other
conditions that affect the lungs, skin, eyes, kidneys blood,
thyroid, stomach, and intestines; including symptoms of
certain types of cancer
− these patients may have normal adrenocortical function
• Prednisone is inactive; must be converted to prednisolone
by hepatic enzymes. May not be effective in people with liver
disease.
Case: 30 yr old man post-transplant
As a nursing student, you are assigned to the transplant
clinic. Mr. M, 30 years old, received a heart and lung
transplant 6 weeks ago. He is single with a large
extended family. He tells you, “I have six nieces and
nephews. The oldest is 10, and the youngest is 8
months. I was so glad to see all of them when I went
home. They really cheer me up.”
Mr. M is taking multiple drugs to manage his health,
including glucocorticoids.
Develop a plan of care to minimize adverse effects of
long-term glucocorticoid therapy.
What do you identify as a priority teaching points related
to glucocorticoid therapy?
What side effects should you inform Mr. O about?
References and resources for
further learning
• National Institute of Diabetes and Digestive
and Kidney Diseases- excellent endocrine section
• http://www.niddk.nih.gov/health-information/healthtopics/endocrine/Pages/default.aspx
• Medline Plus: library on drugs, herbs and
supplements. See also videos and cooltools
• https://www.nlm.nih.gov/medlineplus/druginform
ation.html
• https://www.nlm.nih.gov/medlineplus/videosand
cooltools.html