Pharmacology of Endocrine
Disorders
Diabetes and Hypothyroidism
Endocrine System

Consists of ductless glands that secrete hormones into
the bloodstream
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Two categories:
 Steroids (from adrenal glands & gonads)
 Proteins or small peptides (all others)
Endocrine System
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Include:
 Pancreas
 Pituitary
 Thyroid
 Parathyroid
 Adrenal
 Gonads
Hormone Drug Therapy

Used for replacement, diagnostic purposes, hormone inhibiton,
hormone secretion.
Pancreas
The beta cells in the pancreas produce a
peptide called insulin. Lower the blood glucose
levels.
 The alpha cells produce glucagon. Increase
blood glucose levels.
 the delta cells somatostatin
 Before administering insulin check glucose
levels.

Diabetes Mellitus
Type I- juvenile
diabetes insulin
dependent
Types:
Type II- adult onset
diabetes insulin
independent
Gestational
Secondary
Type 1 Diabetes Mellitus
Characterized by the absolute absence of
endogenous insulin
 May be triggered by an autoimmune process, possibly
triggered by viral infection destroying beta cells
(insulin production)
 Require exogenous insulin for the rest of their lives, no
cure at this time
 Oral hypoglycemics do not manage blood glucose in a
type one diabetes mellitus because of the absolute
insulin deficit
 Pancreatic transplant or islet cell transplant can
typically cure type 1

Type 2 Diabetes Mellitus
Characterized by inadequate endogenous insulin and the
body’s inability to properly use insulin (insulin resistance)
 range from predominant insulin resistance with insulin
deficiency to a predominant secretory defect with insulin
resistance
 May be controlled by diet and exercise alone or may
require oral hypoglycemic agents and/or exogenous insulin
 Type 2 can develop autoimmune type 1.
 Increase in beta cell activity which results in
hyperinsulinemia which results in beta cell exhaustion
which produces a decrease in insulin
 Genetically predisposed.

Gestational Diabetes Mellitus
Diagnosed when a woman is found to have
glucose intolerance for the first time during
pregnancy
 After delivery, the condition resolves

Chronic Complications of Diabetes
Mellitus
Microvascular
Retinopathy – pathological changes to the retina that can
lead to blindness
 Nephropathy - end-stage renal disease
 PVD – peripheral vascular disease
Macrovascular
 CVD – cardiovascular disease
High glucose damages the wall of the vessels. Goal is to
manage the disease and keep the glucose in range
Neuropathy – pathological changes in nerve tissue, ranging
from tingling, numbness, and burning sensations to
complete loss in sensations (usually legs/feet)
Treatment Goals of Diabetes
Mellitus
To prevent the chronic and acute complications by
maintaining physiological normal blood glucose levels
 It is supported by research that decreasing blood
glucose concentrations slows or prevents microvascular
complications
 A1C – Hemoglobin carries glucose in the blood. A RBC
lives for approx. 3 months.
 BGM Control:
 Fasting 4-7 mmol
 2 hrs pc meal: 5-10 mmol
Types of drugs for Diabetes
Mellitus
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Insulin
 It is an anabolic and anti-catabolic hormone
 Stores glucose,energy,fat and many more
 Make insulin by modifying endogenous insulin
 Insulin preparations primarily are different in the onset and duration of activity.
 Subcutaneous administration can be intermittently or continuously (insulin pump)
Oral hypoglycemic agents
 Only used on Type 2 diabetics. Must have beta cell function to be used
 GLP-1 agonists are oral hypoglycemic agents and only used on type 2 diabetes.
Insulin Preparations
Rapid acting
 Short acting
 Intermediate acting
 Long acting
 Insulin combinations
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Rapid acting insulin
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preparations that fall in this category:
 Insulin lispro (Humalog)
 Insulin aspart (NovoRapid)
 Insulin glulisine (Apidra)
Due to modifications of the amino acid chain it allows for rapid absorption, faster
onset, and a shorter duration
Greater flexibility of lifestyle because it can be injected shortly before eating
Decreases the risk of nocturnal hypoglycemia and less need for snacks
Can also be used when quick correction of hyperglycemia is required
Rapid acting insulin
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Analog insulin refer to rapid acting and long acting
Rapid acting is most physiologically similar to endogenous insulin
Base level of insulin release means some insulin is always available
Long acting and intermediate
Bolus release of insulin is when you have food it is rapid acting
Combination of basal and bolus is given
Rapid acting provides a bolus dose
Onset is 3-15 mins
Peak is 45-75 mins
Duration is 2-4 hrs
Rapid onset and do not contaminate the fastest acting insulin.
Short Acting/Regular Insulin
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preparations that fall in this category:
 Humulin R
 Novolin ge Toronto
Often the one chosen for use for IV
administration
 Often used in conjunction with intermediate or
long-acting insulin
 Onset is 30-60 min. peak is 1-5 hrs. duration is
10 hrs. used in IV. USED AS A BOLUS DOSE.
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Intermediate acting Insulin
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preparations that fall in this category:
 Humulin N
 Novolin ge NPH (neutral protamine Hagerdorn)
The addition of the protamine or excess zinc delays the onset, peak, and
duration
NPH and all suspension insulins (cloudy) should be inverted or rolled at least
10 times to ensure fully suspended insulin before drawing
Basal level of insulin
Modifies to delay onset peak and duration
The higher the dose the later the peak and duration.
Long Acting Insulin
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preparations that fall in this category:
 Insulin detemir (Levemir)
• Neutral pH
• Give once or twice daily (type 1 is more likely to require twice a day
dosing)
 Insulin glargine (Lantus)
• Acidic pH (some pain at the injection site)
• More absorption variability than Levemir
Provide a basal glycemic control
Some are no peak and some are less peak.
Levemir peak is 17 hrs.
Lantus is not a peak.
Only given subq.
Can administer any time of the day but needs to be same time each day
INSULIN DEGLUDEC 40 hrs duration has no nocturnal hypoglycemia.
Mixing insulins
Do not mix long-acting insulins with other preparations
 Regular (short-acting insulins) can mix will all insulins
 NPH with regular
 Rapid acting with NPH as long as it is administered shortly
after mixing
 Always draw up the short or rapid-acting first to prevent
contamination with the longer-acting
 Avoid giving at bedtime
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 Some insulins come premixed (regular/intermediate ratio)
 Humulin 30/70
 Novolin GE 30/70
 Novolin GE 40/60
 Novolin GE 50/50
Adverse effects of Insulin
Administration
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Hypoglycemia
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More common in type 1 diabetics
Need to educate the pt on the signs and symptoms of hypoglycemia
•
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Tachycardia, tremulousness and sweating
Initial symptoms are often neurological in nature
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Weight gain
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Insulin facilitates the storage of adipose tissue
Mostly truncal
Irritation at the injection site
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Confusion, agitation, loss of consciousness
Lipodystrophy is less common
Raised fat mass at the injection site
Rotating sites help prevent it
The acidic preparations such as Lantus may cause more pain at the injection site
Hypokalemia
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Facilitates the intracellular uptake of potassium-depleting potassium in the blood
Oral Anti-diabetic - Biguanides
Significantly decrease hepatic glucose production decrease in
gluconeogensis.
 Favourable cardiovascular outcomes
 Decrease un LDL and increase in HDL
 Adverse effects are gi symptoms nausea diarrhea and cramping
 Increase insulin sensitivity and cellular glucose uptake and utilization
 Does not promote insulin secretion therefore hyperinsulinemia is not a
concern
• *** does not by itself cause hypoglycemia***
 Possible weight loss (drug of choice with obesity)
 Possibly avoided with decreased renal function (GFR <30mls/hr)
 Not metabolized
Example: metformin (Glucophage) – DOC (drug of choice in T2DM)
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T2DM - GLP-1 Receptor Agonists
Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)
are hormones that are released following a meal
Increase the feeling of fullness
Works in centre that manages vomit.
Rare adverse effects are sore bladder, pancreatitis, thyroid cancer
Mechanism of action:
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Promote glucose-dependent insulin secretion,
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slowed gastric emptying, and
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reduction of postprandial glucagon and food intake
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Do not usually independently cause hypoglycemia
GLP-1 Receptor Agonists
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GLP-1 is produced in the small intestine. It binds to
a specific GLP-1 receptor found in multiple tissues
including pancreatic beta cells. GLP-1 promotes
insulin, slows gastric emptying, inhibits inappropriate
post-meal glucagon release, and reduces food
intake.
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GLP-1 short half-life of one to two minutes.
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Synthetic GLP-1 receptor agonists have a longer
half-life and can be administered once daily or once
weekly.
GLP-1 Receptor Agonists
GLP-1 receptor agonists can be used:
 combination with metformin (and/or another oral agent) for
patients with (CVD) atherosclerosis.
 liraglutide, semaglutide, or dulaglutide
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For weight loss or when hypoglycemia is a concern
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Medications: liraglutide, semaglutide, dulaglutide,
tirzepatide, exenatide (once a week)
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There are cost and injection considerations.
GLP-1 receptor agonists may also be used in combination
with basal insulin.
 Adverse Effects: Gastrointestinal - nausea, vomiting, and
diarrhea Hypoglycemia risk is low.
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Oral Anti-diabetic - Sulfonylureas
Promote beta cell insulin release
 Increase peripheral insulin sensitivity
 Decrease hepatic gluconeogenesis
 Metabolized by the liver and excreted by the kidneys
 Requires regular food intake to decrease the
problems with hypoglycemia
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Adverse Effects
 Hypoglycemia
 Weight gain
Oral Anti-diabetic - Sulfonylureas
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Examples
 Gliclazide (Diamicron)
 Glyburide (Diabeta)
 Tolbutamide (Orinase)
Dipeptidyl peptidase-4 (DPP4)
Inhibitors
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Site of action – pancreas
Ex Sitagliptin, Linagliptin
Oral meds glucose dependent increase insulin
Increase in GLP-1
Lowers glucagon
Well tolerated hypoglycaemia is rare.
Sodium-glucose Co-transporter-2
“flozin”
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Works in the kidney to increase glucose secretion and decrease glucose
reabsorption.
Inhibits SGLT2 in the proximal tubule
BP may also be lowered as glucose is osmotically active
AE: Increase urinary output (and frequency) therefore hypovolemia; increased risk of
DKA (diabetic ketoacidosis)
Interacts with all diuretics
Monitor volume status and electrolyte status Examples
 Empagliflozin (Jardiance)
 Dapagliflozin (Forxiga)
Glucose acts like sodium
Oral Anti-diabetic Thiazolidinediones (TZD)
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Decrease hepatic release of glucose
Increase peripheral uptake of glucose
Increases glucose utilization in the muscle
4-6 weeks before effective
Does not by itself cause hypoglycemia
Adverse Effects
 Hepatotoxicity
 Anemia
 Weight gain
 Decre in gluconeogenesis increase in insulin action
Oral Anti-diabetic Thiazolidinediones (TZD)
Examples:
 Pioglitazone (actos)
 Rosiglitazone (Avandia)
Meglitinides (GTN)
Binds to the beta cells to stimulate insulin release
 Sometimes called glinides
 Rapid onset and shorter duration of action (greater
flexibility)
 Adverse effect
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 Mild hypoglycemia if they skip a meal
 Oral meds
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Examples
 Repaglinide
• Gluconorm
 Nateglinide
• Starlix
Pharmacotherapy of Endocrine Disorders –
Thyroid Disorders
Hypothyroidism and Hyperthyroidism
What does this gland regulate?
Thyroid Gland - Hormones
 thyroxine (T4),
 triiodothyronine (T3) (liothyronine)
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Affect nearly every tissue and organ be
controlling their metabolic rate and activity
Hypothyroidism
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Results from a deficiency of thyroid hormone
Increased incidence with age.
More common in women
Commonly caused by an autoimmune (Hashimoto’s thyroiditis)
 The destruction of thyroid cells by circulating thyroid AB
Other causes radioiodine therapy, surgery
Signs and symptoms:sluggish cold intolerance weight gain muscle aches
Hypothyroidism – Drug Therapy
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Thyroid hormone replacement therapy – T4
 Eg. levothyroxine sodium (Synthroid, Eltroxin)
Thyroid hormone replacement therapy – T3
 Eg. liothyronine sodium (Cytomel)
S/E – mimic hyperthyroidism (if in excess)
Therapeutic doses monitored by TSH levels
Goal for this med is to return the person to luthyroid levels normal levels
T3 often given with t4
Adverse mimic hyperthyroidism
1.6-1.7 mcg/kg/day is normal dose
Hypothyroidism – levothyroxine (Lthyroxine)
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Preferred treatment is levothyroxine (l-thyroxine)
 Thyroid replacement of choice
 Stability, uniformed potency, lack of foreign protein
content
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Adverse Effects tachycardia arrhythmias
 Half life is 7 days