Endocrine
Drugs that Affect the
Endocrine System 2.1.7
Trevonne M. Thompson, MD
2.1.7 Drugs that affect the endocrine system
2.1.7.1 Antidiabetic drugs
2.1.7.1.1 Insulin
2.1.7.1.2 Oral hypoglycemics
2.1.7.1.2 Others
2.1.7.2 Bone active drugs
2.1.7.3 Electrolytes and minerals
2.1.7.4 Glucocorticoids
2.1.7.5 Sex hormones, growth hormones, anabolic steroids
2.1.7.6 Thyroid drugs
2.1.7.7 Vasopressin and somatostatin analogues
Antidiabetic Drugs
2.1.7.1
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Endocrine
Insulin
• Released from pancreas, binds to receptors
on cell surface of insulin-sensitive tissue
• Hepatocytes, myocytes, adipocytes
Sulfonylureas
• Stimulate pancreatic insulin release
• Bind to receptors that result in closure of
the KATP channels
• Results in multistep process that
increases insulin release
Meglitinides
• Structurally different from sulfonylureas
• Bind to same receptors that result in
closure of the KATP channels
• Results in multistep process that
increases insulin release
2
Endocrine
Biguanides
• Inhibits gluconeogenesis, decreasing hepatic
glucose output
• Also enhances peripheral glucose uptake
Thiazolidinediones
• Decrease insulin resistance by potentiating
insulin sensitivity in the liver, adipose, and
skeletal muscle
• Also reduce hepatic glucose production
Glucosidase Inhibitors
• Acarbose, miglitol
• Oligosaccharides that inhibit alpha-
glucosidase enzymes in small intestine
• Blunts postprandial blood glucose
concentration
3
Endocrine
Goldfrank’s Toxicologic Emergencies, 8th ed
Goldfrank’s Toxicologic Emergencies, 8th ed
Goldfrank’s Toxicologic Emergencies, 8th ed
4
Endocrine
Pharmacokinetics
• Many sulfonylureas have long durations of
action
Clinical Manifestations
• Insulin, sulfonylureas, meglitinides
• All cause hypoglycemia
• CNS effects predominate with
hypoglycemia
• Brain uses glucose almost exclusively as
energy source (ketones in starvation)
Management
• Supportive care
• Reversal of hypoglycemia
• Insulin
• Titrate dextrose infusion as needed
5
Endocrine
Management
• Sulfonylureas
• Feed patient when appropriate,
• Octreotide
• Somatostatin analogue, blocks insulin
release from pancreas
Special Consideration
• Metformin associated lactic acidosis
(MALA)
• Metformin inhihibits hepatic lactate update
and conversion of lactate to glucose
• 2 entities
Special Consideration
• MALA
• Lactic acidosis associated with underlying
medical disease (especially renal
insufficiency)
• Metformin overdose
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Endocrine
Bone Active Drugs
2.1.7.2
Bone Active Drugs
• Calcitonin & bisphosphonates
Calcitonin
• Inhibits osteoclast activity, reduces bone
reabsorption
• Used to treat hypercalcemia
• Can cause hypocalcemia
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Endocrine
Bisphosphonates
• Inhibits osteoclast activity, reduces bone
reabsorption
• Can be used to treat hypercalcemia,
osteoporosis
• Associated with osteonecrosis of the jaw
Electrolytes & Minerals
2.1.7.3
Calcium
• Ca++ homeostasis is regulated by the
endocrine system
• Interaction between vitamin D,
parathyroid hormone, and calcitonin
• Ca++ essential in maintaining function of
heart, vascular smooth muscle, skeletal
muscle and nervous system
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Endocrine
Calcium
• Hypocalcemia
• Paresthesias, muscle cramps, carpopedal
spasm, tetany, seizures, prolonged QTc
• Hypercalcemia
• Lethargy, muscle weakness, nausea,
vomiting, constipation, altered mental
status, dysrhythmias
Glucocorticoids
2.1.7.4
Glucocorticoids
• Class of steroid hormones that bind to the
glucocorticoid receptor (present in nearly
all vertebrate animal cells)
• Both metabolic and immunologic effects
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Endocrine
Adverse Effects
• Immunosuppression
• Hyperglycemia
• Skin fragility
• Osteoporosis
• Weight gain
• Adrenal insufficiency
• Anovulation
• Irregular menses
• Growth retardation
• CNS excitation
• Cararacts
• Many others
Sex Hormones,
Growth Hormones,
and Anabolic steroids
2.1.7.5
Anabolic Steroids
• Androgenic anabolic steroids (AAS)
• Increase muscle mass, lean body weight,
cause nitrogen retention
• Responsible for secondary sex
characteristics (hair, voice, etc)
• Testosterone is the prototype
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Endocrine
Anabolic Steroids
• 1990 Anabolic Steroid Control Act
• Amended the Substance Control Act
• Made AAS schedule III
• 2004 Anabolic Steroid Control Act
• Added certain precursors (like
androstenedione) to the list of
substances
Anabolic Steroids
• Testosterone is rapidly degraded in the
liver
• For clinical usefulness:
• Esterify the 17-hydroxy position to form
a hydrophobic compound suitable for
injection
• Alkylate the 17-hydroxy position for an
oral preparation
Goldfrank’s Toxicologic Emergencies, 8th ed
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Endocrine
Goldfrank’s Toxicologic Emergencies, 8th ed
Terminology
• Cycling
• AAS use intervals (2 months on/2 off)
• Stacking
• Combining several AAS at one time
• Plateauing
• Developing tolerance
Terminology
• Pyramiding
• Start with low dose, increase, then
decrease
• Bridging
• Changing to short acting agents just prior
to drug testing
12
Endocrine
Clinical Manifestations
• Musculoskeletal
• Increase muscle mass and size
• Hepatic
• Hepatic subcapsular hematoma, peliosis
hepatis
Clinical Manifestations
• Infectious
• Local complications from injecting
• Dematologic
• Keloids, sebaceous cysts, comedones,
seborrheic furunculosis, folliculitis, striae
Clinical Manifestations
• Endocrine
• Gynecomastia, testicular atrophy,
reduced spermatogenesis, breast atrophy
in women
13
Endocrine
Clinical Manifestations
• Cardiovascular
• Acute MI, sudden cardiac death,
biventricular hypertrophy, myocardial
fibrosis, contraction band necrosis
• Psychiatric
• Depression, mania, delirium, insomnia,
aggression
Clenbuterol
• Beta-2 agonist with anabolic properties
• Overdose will have beta-2 agonist
characteristics
Human Growth
Hormone
• Anabolic peptide hormone
• Stimulates protein synthesis
• Adverse effects
• Myalgias, arthralgias, carpel tunnel
syndrome, edema, acromegaly,
hyperglycemia
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Endocrine
Thyroid Drugs
2.1.7.6
Thyroid Function
• Influenced by hypothalamus, pituitary gland,
thyroid gland, and target organs
Thyroid Function
• Hypothalamus releases thyrotropin
releasing hormone (TRH)
• TRH causes pituitary gland to release
thyroid stimulating hormone (TSH)
• TSH causes thyroid to release T3 and T4
• T3 and T4 affect end organs (metabolic
consequences)
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Endocrine
Thyroid Function
• 95% of circulating hormone is T4
• T3 has 3x hormonal activity
• T4 is de-iodinated intracellulary to T3
Pharmacology
• Desiccated thyroid
• Animal derived, contains T3 and T4
• Levothyroxine
• Synthetic T4
• Most widely used for hypothyroidism
Toxicity
• 7-10 day delay
• Most remain asymptomatic or only mildly
symptomatic
• Treatment
• Supportive care, beta-blockers
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Endocrine
Thioamides
• PTU and methimazole
• Used to treat hyperthyroidism
• Both inhibit T3/T4 release
• PTU also blocks peripheral deiodination of
T4 to T3
• Little data on overdose
Iodides
• Iodide salts were used before Thioamides
were available
• Inhibit T3/T4 release
Iodism
• Rash, laryngitis, bronchitis, esophagitis,
conjunctivitis, drug fever, metallic taste,
salivation, headache, bleeding diathesis
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