thyroid and Parathyroid pharmacology

1. Dr. Maria Idrees; PT
MS (RIU)
DPT (TUF)
Pancreatic Hormones and the
Treatment of Diabetes Mellitus

2.  The pancreas functions uniquely as both an
endocrine and an exocrine gland.
 The gland’s exocrine role consists of excretion
of digestive enzymes into the duodenum via
the pancreatic duct.
 Pancreatic endocrine function consists of the
secretion of two principal hormones— insulin
and glucagon—into the bloodstream
 Problems with the production and function of
insulin cause a fairly common and clinically
significant disease known as diabetes
mellitus.

3. Structure and Function of the
Endocrine Pancreas
 The bulk of the gland consists of acinar cells that
synthesize and release pancreatic digestive
enzymes (thereby providing the exocrine function).
 Interspersed within the acinar tissues are smaller
clumps of tissue known as the islets of
Langerhans. These islets contain cells that
synthesize and secrete pancreatic hormones, thus
constituting the endocrine portion of the gland.
 The pancreatic islets consist of four primary cell
types: alpha (A) cells, which produce glucagon;
beta (B) cells, which produce insulin; delta (D)
cells, which produce somatostatin; and (F) cells,

4. Insulin
 The primary effect of insulin is to lower
blood glucose levels by facilitating the
entry of glucose into peripheral tissues.

5. Effects of Insulin on Carbohydrate
Metabolism.
 Following a meal, blood glucose sharply
increases.
 Insulin is responsible for facilitating the
movement of glucose out of the bloodstream
and into the liver and other tissues, where it
can be stored for future needs.
 Most tissues in the body (including skeletal
muscle cells) are relatively impermeable to
glucose and require the presence of some
sort of transport system, or carrier, to help
convey the glucose molecule across the cell
membrane.

6.  Hepatic cells are relatively permeable to
glucose, and glucose enters these cells quite
easily, even when insulin is not present.
 Insulin stimulates the activity of the
glucokinase enzyme, which phosphorylates
glucose and subsequently traps the glucose
molecule in the hepatic cell.
 Insulin also increases the activity of enzymes
that promote glycogen synthesis and inhibits
the enzymes that promote glycogen
breakdown.
 Thus, the primary effect of insulin on the liver
is to promote the sequestration of the glucose
molecule and to increase the storage of

7. Effects of Insulin on Protein and
Lipid Metabolism.
 In general, insulin promotes storage of protein
and lipid in muscle and adipose tissue,
respectively Insulin encourages protein synthesis
in muscle cells by stimulating amino acid uptake,
increasing DNA/RNA activity related to protein
synthesis, and inhibiting protein breakdown.
 In fat cells, insulin stimulates the synthesis of
triglycerides (the primary form of lipid storage in
the body), and inhibits the enzyme that breaks
down stored lipids (hormone-sensitive lipase).
 Consequently disturbances in insulin function
(diabetes mellitus) will affect the storage and use

8. Cellular Mechanism of Insulin
Action

9. Glucagon
 Glucagon is considered to be the hormonal
antagonist of insulin.
 The primary effect of glucagon is to increase
blood glucose to maintain normal blood glucose
levels and to prevent hypoglycemia.
 Glucagon produces a rapid increase in
glycogen breakdown glycogenolysis) in the liver,
thus liberating glucose in the bloodstream from
hepatic glycogen stores.
 Glucagon then stimulates a more prolonged
increase in hepatic glucose production
(gluconeogenesis).
 This gluconeogenesis sustains blood glucose

10.  Glucagon appears to exert its effects on liver
cells by a classic adenyl cyclase–cyclic
adenosine monophosphate (cAMP) second
messenger system
 Glucagon binds to a specific receptor located
on the hepatic cell membrane. This stimulates
the activity of the adenyl cyclase enzyme that
transforms adenosine triphosphate (ATP) into
cAMP.
 Then, cAMP acts as an intracellular second
messenger that activates specific enzymes to
increase glycogen breakdown and stimulate
gluconeogenesis.

11. Control of Insulin
and Glucagon Release
 An adequate level of glucose in the bloodstream
is necessary to provide a steady supply of
energy for certain tissues, especially the brain.
 Normally, blood glucose is maintained between
80 and 90 mg of glucose per 100 mL of blood. A
severe drop in blood glucose (hypoglycemia) is
a potentially serious problem that can result in
coma and death. Chronic elevations in blood
glucose (hyperglycemia) have been implicated
in producing pathologic changes in neural and
vascular structures.

12.  The level of glucose in the bloodstream is the
primary factor affecting pancreatic hormone
release.
 As blood glucose rises (e.g., following a
meal), insulin secretion from pancreatic beta
cells is increased.
 Insulin then promotes the movement of
glucose out of the bloodstream and into
various tissues, thus reducing plasma glucose
back to normal levels.
 As blood glucose levels fall (e.g., during a
sustained fast), glucagon is released from the
alpha cells in the pancreas.

13.  Cells located in the pancreatic islets are
bathed directly by the blood supply
reaching the pancreas.
 These cells act as glucose sensors,
directly monitoring plasma glucose
levels.
 In particular, the beta cells or insulin-
secreting cells act as the primary
glucose sensors.
 When the beta cells sense an increase
in blood glucose, they release insulin,
which in turn inhibits glucagon release

14. Diabetes Mellitus
 Diabetes mellitus is a disease caused by
insufficient insulin secretion or a
decrease in the peripheral effects of
insulin.
 This disease is characterized by a
primary defect in the metabolism of
carbohydrates and other energy
substrates.
 These metabolic defects can lead to
serious acute and chronic pathologic

15.  Diabetes insipidus is caused by a lack of
antidiuretic hormone (ADH) production
or insensitivity to ADH.
 Consequently, the full terminology of
“diabetes mellitus” should be used when
referring to the insulin-related disease.
 Most clinicians, however, refer to
diabetes mellitus as simply “diabetes.

16. COMPARISON OF TYPE I AND
TYPE II DIABETES MELLITUS

17. Type 1 Diabetes
 Patients with type 1 diabetes are unable
to synthesize any appreciable amounts
of insulin.
 There appears to be an almost total
destruction of pancreatic beta cells in
these individuals.
 Because these patients are unable to
produce insulin, type 1 diabetes has
also been referred to as insulin-
dependent diabetes mellitus (IDDM);

18.  The onset of type 1 diabetes is usually
during childhood, so this form of
diabetes has also been referred to as
juvenile diabetes.
 Patients with type 1 diabetes are
typically close to normal body weight or
slightly underweight.

19.  Specifically, a virus or some other
antigen may trigger an autoimmune
reaction that selectively destroys the
insulin-secreting beta cells in
susceptible
 Genetic predisposition, environmental
factors
 The idea that type 1 diabetes may have
an autoimmune basis has led to the use
of immunosuppressant agents in the

20. Type 2 Diabetes
 Type 2, also known previously as non–
insulin-dependent diabetes mellitus
(NIDDM), accounts for 90 to 95 percent
of persons with diabetes mellitus.
 This form of diabetes usually occurs in
adults, especially in older individuals.
 Genetic predisposition combined with
poor diet, obesity, and lack of exercise
all seem to contribute to the onset of
type 2 diabetes.

21.  Whereas insulin cannot be produced in type
1
 diabetes, the problem in type 2 diabetes is
somewhat more complex.
 In most patients with type 2 diabetes,
pancreatic beta cells remain intact and are
capable of producing insulin.
 Therefore, the primary problem in type 2
diabetes is a decreased sensitivity of
peripheral tissues to circulating insulin; this
is referred to as insulin resistance.
 For instance, tissues such as the liver and
skeletal muscle fail to respond adequately to

22.  The resistance may be caused by a
primary (intrinsic) defect at the target
cell that results in a decreased response
of the cell to insulin.
 Problems in postreceptor signaling, such
as decreased protein phosphorylation,
impaired production of chemical
mediators, and a lack of glucose
transporters, have all been suggested
as intracellular events that could help
explain insulin resistance
 Therefore, even though insulin binds to

23.  A defect in pancreatic beta cell function
may also contribute to the manifestations
of type 2 diabetes.
 As indicated, type 2 diabetes is often
associated with plasma insulin levels that
are normal or even slightly elevated.
 Insulin release, however, does not follow a
normal pattern in people with type 2
diabetes.
 Normally, insulin is released from the beta
cells following a meal, and release
decreases substantially during fasting.

24.  Following a meal, beta cells also fail to
adequately increase insulin release in
proportion to the increased glucose
levels in the bloodstream.
 This abnormal pattern of insulin release
suggests that beta cell function has
been impaired in people with type 2
diabetes.
 Hence, the combination of peripheral
tissue resistance and inappropriate beta
cell response creates the fundamental

25. Effects and Complications
of Diabetes Mellitus
 The most common symptom associated with
diabetes mellitus is a chronic elevation of blood
glucose (hyperglycemia).
 Hyperglycemia results from a relative lack
 of insulin-mediated glucose uptake and use by
peripheral tissues.
 Glycosuria is caused by an inability of the
kidneys to adequately reabsorb the excess
amount of glucose reaching the nephron.
 Increased glucose excretion causes an osmotic
force that promotes fluid and electrolyte
excretion, thus leading to dehydration and
electrolyte imbalance.

26.  Also, the loss of glucose in the urine
causes a metabolic shift toward the
mobilization of fat and protein as an
energy source.
 Increased use of fats and protein leads
to the formation of acidic ketone bodies
in the bloodstream.
 Excessive accumulation of ketones
lowers plasma pH, producing acidosis
(ketoacidosis), which can lead to coma

27.  Microangiopathy -Small vessels may undergo a
thickening of the basement membrane, which can
progress to the point of vessel occlusion.
 The progressive ischemia caused by small-vessel
disease is particularly damaging to certain structures
such as the retina (leading to blindness) and the
kidneys (leading to nephropathy
 and renal failure).
 Damage to cutaneous vessels results in poor wound
healing that can lead to ulcer formation.
 Problems with large blood vessels
(macroangiopathy) can also occur in diabetes
because of defects in lipid metabolism that lead to
atherosclerosis, hypertension, myocardial infarction,
and cerebral vascular accident in diabetic patients.
 Finally, peripheral neuropathies are quite common

28. Use of Insulin in Diabetes
Mellitus
 Exogenous insulin is administered to
replace normal pancreatic hormone
production in type 1 diabetes (IDDM).
 Insulin may also be administered in
some cases of type 2 diabetes to
complement other drugs (oral
antidiabetic agents) and to supplement
endogenous insulin release

29. Insulin Preparations
 In the past, insulin used in the treatment
of diabetes mellitus was often derived
from animal sources; that is, beef and
pork insulin.
 These sources were obtained by
extracting the hormone from the
pancreas of the host animal.
 Even though pork insulin has one amino
acid that is different from the human
insulin sequence, and beef insulin differs

30.  Biosynthetically produced insulin that is
identical to regular human insulin has
advantages over the animal forms,
including more rapid absorption after
subcutaneous injection and a lower risk
of immunologic (allergic) reactions.

31. INSULIN PREPARATIONS

32. Administration of Insulin
 Insulin, a large polypeptide, is not suitable for
oral administration.
 Even if the insulin molecule survived
digestion by proteases in the stomach and
small intestine, this compound is much too
large to be absorbed through the
gastrointestinal wall.
 Consequently, insulin is usually administered
through subcutaneous injection.
 emergency situations (diabetic coma)-
intravenous route
 In particular, a form of insulin (Exubera) has

33. Intensive Insulin Therapy
 Goal in the treatment of diabetes mellitus is
to maintain blood glucose in the normal
physiologic range as much as possible.
 To achieve this goal, an administration
strategy known as intensive insulin therapy
has been developed for persons who
require exogenous insulin.
 The idea of intensive insulin therapy is that
the patient frequently monitors his or her
blood glucose level and self administers
several (three or more) dosages of insulin

34. Adverse Effects of Insulin Therapy
 Hypoglycemia
 Strenuous physical activity may promote
hypoglycemia during insulin therapy
 Exercise generally produces an
insulinlike effect, meaning that exercise
accelerates the movement of glucose
out of the bloodstream and into the
peripheral tissues (skeletal muscle)
where it is needed
 Initial symptoms of hypoglycemia
include headache, fatigue, hunger,

35. Oral Antidiabetic Drugs
 Several agents are now available that
can be administered by mouth to help
control blood glucose levels in people
with type 2 (NIDDM) diabetes mellitus.

36. Sulfonylureas
 These drugs act directly on pancreatic
beta cells and stimulate the release of
insulin, which is released directly into
the hepatic portal vein and subsequently
travels to the liver, inhibiting hepatic
glucose production.
 Increased plasma levels of insulin also
help facilitate glucose entry into muscle
and other peripheral tissues

38. Other Drugs Used in the
Management of Diabetes Mellitus
Glucagon
 Glucagon is sometimes used to treat
acute hypoglycemia induced by insulin
or oral hypoglycemic agents
 When used to treat hypoglycemia,
glucagon is administered by injection
(intravenous, intramuscular,
subcutaneous)

39. Glucagon-like Peptide 1
 Glucagon-like peptide 1 is a hormone
that is normally released from the GI
tract after eating a meal.
 This hormone increases the ability of
blood glucose to stimulate insulin
release from pancreatic beta cells.
 Hence, a synthetic form of this hormone
can be administered by injection to help
provide better glycemic control following
a sudden rise in blood glucose.

40. Immuno suppressants
 Most cases of type 1 diabetes are caused by an
autoimmune response that selectively attacks
and destroys pancreatic beta cells in susceptible
individuals.
 Therefore, drugs that suppress this autoimmune
response may be helpful in limiting beta cell
destruction, thereby decreasing the severity of
this disease.
 cyclosporine, azathioprine, cyclophosphamide,
methotrexate, and glucocorticoids

41. Aldose Reductase Inhibitors
 This enzyme, which is located in
neurons and other cells, is responsible
for converting glucose to another sugar
known as sorbitol.
 The excessive accumulation of sorbitol
within the cell may lead to structural and
functional changes that are ultimately
responsible for the complications
associated with diabetes mellitus,
especially peripheral neuropathies.

42. Nonpharmacologic Intervention in
Diabetes Mellitus
1. Dietary Management and Weight Reduction
2. Exercise
3. Tissue Transplants and Gene Therapy