HOROMONES Of HOMEOSTASIS

Emphasis on Pharmacology o Endocrine Glands

o Pharmacology of Diabetes
Insulin, Hypoglycemic Agents, Glucagon
o Pharmacology of Thyroid Gland

Thryroid Supplements, PTU (Propothiouracil)

o Pharmacology of Corticosteroids
Cortisone, Aldosterone
Hormones of Homeostasis
o Hormones
Secreted by endocrine glands:
pituitary - master gland
thyroid
pancreas
adrenals
parathyroids
gonads
Regulate body functions - homeostasis
Transported by blood to organs
Secretion is often regulated by Negative Feed Back mechanism

o
Two Major Integrating and Modulating Systems of the Body
o Nervous System
o Endocrine System
Hormones - chemical mediators othe endocrine system
Three characteristics ohormones:
o 1. Produced by ductless glands
o 2. Transported by body fluids to target cells
o 3. Interact with specific receptor sites
Endocrine System: Pituitary-Thyroid, Adrenals, Pancreas, Parathyroids, Gonads
o Pituitary control oendocrine gland secretions: e.g. Thyroid and Adrenal cortex
controlled by Pituitary gland
THS (Thyroid Stimulating Hormone)
ACTH (Adrenocorticotropic Hormone)
o Pituitary gland is under control of Hypothalamus
TR(Thyrotropin Releasing Factor)
CR(Corticotropin Releasing Factor)
o Hormones othe Pituitary Gland Master Gland located at base of brain
Anterior Pituitary hormones:
ACTH adrenocorticotropic h. stimulates adrenal cortex
TSH thyroid stimulating h. stimulates thyroid
o stimulating hormone regulated by negative feedback
mechanism
other hormones of the anterior pituitary:
GH growth, FSH follicle stimulating, LH luteinizing, Prolactin
Posterior Pituitary Hormones:
ADH antidiuretic hormone (H2O reabsorption, vasoconstriction)
Oxytocin

Other Hormones of Homeostasis:

Pancreatic Hormones
Insulin---- glucose utilization
Glucagon---increase blood glucose level
Thyroid Hormones
Triiodothyronine (T3)
Thyroxine (T4)-----growth and metabolism
Parathyroid Hormone-----blood calcium levels
Adrenal gland: stress hormones
Adrenal cortex hormones
Steroids:
o Glucocorticoids - carbohydrate and fat
metabolism ,
inflammation
o
Mineralocorticoids water and electrolyte balance
Adrenal Medulla Hormones
Norepinephrine (25%)
o 90% alpha, 10% beta effects
Adrenaline (Epinephrine) -75%
the fight or flight survival
response
o 50% alpha, 50% beta effects
Alpha: Vasoconstriction of blood vessels skin, mucosa, gut,
raises blood pressure
Beta 1: Heart positive Chronotropic and Ionotropic effects
Beta 2: Lungs- dilates bronchioles, dilates skeletal muscle
vasculature
Pancreatic Hormones Insulin and Glucagon
Pancreas - Islets of Langerhans (alpha, beta cells)
Insulin, secreted by beta cells
Necessary for CHO utilization by cells
Facilitates diffusion of glucose through cell membranes
Increases rate of glucose utilization by cell
Increases glycogen stores in liver, heart, muscle, fat
Inhibits gluconeogenesis (new way to make glucose)
o Formation of glucose by breakdown of muscle, fat
o Definition: production of glucose from non- carbohydrate
precursors:
Lactate (formed by skeletal muscle)
Amino acids (from muscle protein)
Glycerol

o
Glucagon secreted by alpha cells
Regulates blood glucose levels
Stimulates glycogenolysis
o Definition: production of glucose from glycogen stores
(these stores are depleted by fasting)
o Glycogen Glucose

Insulin and glucagon secretions are regulated by blood glucose

concentration normally set at 100 mg/dl
High blood glucose causes release of insulin
Low blood glucose causes release of glucagon
Insufficient Insulin Production effects:
1. Blood glucose becomes elevated due to:
a. Decrease in glucose uptake into cells
b. Gluconeogenesis (ketones, fatty acids)
2. Metabolic acidosis (ketoacidosis)
3. End organ, microvascular damage
4. Dehydration
o excess glucose excreted with its solvent (H20)
Frequent urination dehydration
Types of Diabetes Mellitus
Type I - Insulin dependent, insulin insufficiency
o Treatment: Insulin
o Onset in younger age
Type II - Non-insulin dependent, insulin not effective
o Treatment: diet - oral hypoglycemic agent
o May be on insulin also! Review history
Treatment Objectives in DM-- Prevent Hyperglycemia
o Improve carbohydrate metabolism (utilization of
glucose),
this requires insulin + glucose
must have enough insulin and glucose to meet
metabolic demand
o Avoid gluconeogenesis (caused by insulin lack)
o Avoid hypoglycemia (caused by insulin or glucose)
Brittle Diabetes CHO - Insulin balance difficult
Types of Insulin

o
Insulin
Depot alone
Depot Insulin in combination with Regular Insulin
Example:
o Regular + NPH before breakfast
o NPH in evening
The above simulate the normal pattern of insulin
rising after meals
Complications of Insulin Use
Hypoglycemia vs Ketoacidosis
o Hypoglycemia
Insulin levels too high compared to glucose levels
e.g. Patient took insulin but neglected to eat
e.g. Brittle Diabetic
o Ketoacidosis
Insulin levels too low for metabolic requirements
Use of

not enough insulin for facilitated transport

of glucose
body responds by producing glucose
(gluconeogenesis)
e.g. Brittle Diabetic
Oral Hypoglycemic Drugs
Sulfonylureas
o Used when blood glucose control not attained by diet
alone in Type II DM
o Stimulates release of insulin from beta cells of pancreas Type II only
o Tolbutamide ,Orinase
o Chlorpropamide, Diabinese
o Glyburide, Dia Beta
o Glipizide , Glucatrol
Other Oral Antidiabetic Drugs
o Biguanides
Lowers blood glucose
When used alone will not produce
hypoglycemia
production of glucose from liver by
gluconeogenesis
glucose absorption from the GI tract
Metformin ,Glucophage
used alone or in combination with
sulphonylurea or insulin
Dental Treatment Modification
o Avoid hypoglycemia - insulin reaction
o Patient must eat meal prior to appointment
o Infection and surgical stress may affect metabolic
requirements - insulin \CHO
o Antibiotics often prescribed
o Timing of appointment, postop pain, or postop bleeding
may interfere with meals
Hormones which cause Hyperglycemia:
o GLUCAGON and ADRENOCORTICOSTEROIDS
Thyroid Hormones: Triiodothyronine T3 and Thyroxine (tetraiodothyronine) T4
Thyroid gland produces 2 active hormones:
Thyroid production controlled by pituitary TSH
Function: metabolism, growth + development
Normal T4/T3 ratio = 4:1
T3 more potent than T4
because T4 bound to serum proteins
Thyroid Hormone Pharmacology
Increases the BMR (resting Kcal/24hr)
Necessary for normal growth (tadpole
Hyperthyroidism:
o Weight loss, tachycardia, arrhythmias, angina, fatigue,
tremors, sweating, heat intolerance
o Sympathetic NS excess: thyroid hormone sensitizes
adrenergic receptors to catecholamines - Powerful
cardiac stimulant, Caution!
o Hyperthyroidism (Graves Disease)
Heat intolerance, weight loss, excess heat
production, sweating, tremors, anxiety
Increased sympathetic activity:

extreme sensitivity to cathecholamines:

tachycardia, fatal arrhythmias - danger
accelerated tooth eruption, alveolar loss
o rapid periodontal destruction
Exopthalmos (bulging eyes)

Treatment:
Anti-thyroid Drugs
radioactive iodine: destroys gland at high
doses
propylthiouracil: affects synthesis of thyroid
hormone

Beta blockers (to block beta effect on heart)

Thyroidectomy

Iodine and thyroid

Iodine required for T3, T4
o Lack of iodine leads to decreased T3,T4

TSH stimulates Thyroid by negative feedback

Thyroid gland enlarges -but doesnt produce more Thyroxin
This enlargement is called non-toxic Goiter
Hypothyroidism: Deficiency of Thyroid Hormone
1.Cretinism (childhood hypothyroidism)
o mental and physical retardation
o delayed tooth eruption, abnormal teeth
2.Myxedema (adult hypothyroidism)
o cold intolerance, lethargy
o periodontal disease
o Both diseases show decreased response to
catecholamines - often get bradycardia
3.Non-toxic Goiter
Dental Treatment Modification
o Hypothyroidism: minimal modification
CNS depression (narcotics, sedatives)
get exaggerated CNS depression, rare
o Hyperthyroidism: great danger
requires medical management to become
euthyroid
thyroid crisis (storm) triggered by:
catecholamines (epinephrine)
Adrenocorticosteroids: Hormonal Secretion of the Adrenal Cortex
Hormones of the Adrenal Cortex
1. Glucocorticoids - a. affect CHO metabolism
o Cortisol - b. anti-inflammatory effects
o have chiefly metabolic and anti-inflammatory effects
however they do have limited mineralcorticoid effects
o Circadian rhythm of cortisol production

2. Mineralocorticoids - affect H20, electrolytes

o Aldosterone
o - have chiefly sodium retention effects however they do
have limited glucocorticoid effects
3. Androgens
Associated Diseases
Adrenal Excess
o Cushings Disease: excess of adrenocorticosteroids
Glucocorticoid Excess
truncal obesity
moon facies
thin fragile skin
osteoporosis
bruising
hypertension
glucose intolerance
myopathy
exogenous (Iatrogenic)
endogenous, Cushings Disease (excess ACTH),
pituitary adenoma, small cell carcinoma,
adrenocorticol neoplasms

Adrenal Insufficiency
o Primary Adrenal Insufficiency - Addisons Disease
Adrenal cortical insufficiency
Bronze pigmentation
Addisonian crisis: shock, fever,
hypercalcemia, hyponatremia, hyperkalemia
o Secondary Adrenal Insufficiency
Result of steroid (glucocorticoid i.e. cortisol- like)
medications which suppress the adrenal glands by
the negative feedback mechanism
May result in acute adrenal crisis
cardiovascular collapse with stress or
surgery shock

o
Acute Adrenal Crisis - who is at risk?
o Acute adrenal crisis may occur
if a patient is adrenal suppressed because of
steroid medication (on steroid daily, for greater
than two weeks in the past 6 ?months *)
Problem: The adrenal gland does not respond to
stress. The result is adrenal crisis:
weakness, pain
syncope, cardiovascular collapse,
death
* Recovery time is debatable
Patient On Long Term Steroid Therapy

May not be able to produce endogenous corticosteroids

in times of stress.
o Rule of 2s. Consider possibility of corticosteroid
suppression if steroids taken for 2 weeks over last 2
years.
Pharmacologic Activity of the Glucocorticoid - cortisol
o A. Carbohydrate (and protein) metabolism
Anti-insulin effects - diabetogenic
promotes gluconeogenesis (glucose from
amino acids)
inhibits protein synthesis (amino acids used
to make glucose)
inhibition of muscle, connective tissue and
skin (this is an anti-anabolic effect)
prolonged high titers of glucocorticoids
Causes muscle wasting, skin thinning
o Lipid Metabolism
redistribution of fat to central locations on back,
shoulders, abdomen and face called centripetal
obesity
o ANIT-INFLAMMATORY EFFECTS RESULT FROM
their effects on leukocytes (white cells of
inflammation)
their inhibition of phosholipase A
o Anti-allergic effects
suppress immune response
suppresses allergic reactions
o

USES OF STEROIDS
o Replacement
Addisons disease (adrenal insufficiency)
where portions of the adrenals have been surgically
removed e.g. Cushings disease (overactive adrenal
cortex)
o Emergencies:
shock, anaphylaxis
adrenal crisis
o Anti-inflammatory effects:
acute and chronic inflammatory diseases
asthma, allergies, rheumatoid arthritis, Connective
Tissue diseases
Specific Uses in Dentistry
o Apthous ulcers and other ulcerative diseases such as
Lichen Planus often topically applied Exception: Herpes
infections (steroid not used)

o Steroid normally avoided in infection

o Following surgery -decreases inflammation
o TM Joint inflammatory processes
Commonly used Steroids
Hydrocortisone (Hydrocort) = Cortisol
Prednisone 5mg = 20mg Cortisol (4x as potent)
Prednisolone 4mg = 20mg Cortisol (5x as potent
Dexamethasone (Decadron)
0.75 mg=20mg (30x as potent as Cortisol)
Topicals
most potent = Betamethasone
potent =Triamcinolone , (Kenalog)
least potent = Hydrocortisone (Cortaid)
Cortisol Production in 24 hr.= 20 mg Surgical Stress Cortisol
150- 200mg

o
Adverse reactions of Glucocorticoids:
o Metabolic changes - diabetogenic, fat deposits (moon
face, buffalo hump)
o Infections - mask infection, decrease resistance to
infection
o CNS effects - agitation, behavioral effects, PSYCHOSES,
depression
o Peptic ulcer - increase acid and pepsin, impair healing of
ulcer
o Delayed wound healing - (catabolic effect) osteoporosis
o Electrolyte - fluid balance (some mineralocorticoid effect,
weight gain fluid retention)
Hypertension and heart failure
o Adrenal crisis (secondary adrenal insufficiency)
Cautiou with use:
o Gastric Ulcers
o Hypertension
o Infection
o Behavioral disorders
o Osteoporosis
o Glaucoma - may increase intraocular pressure