THE ENDOCRINE PANCREAS & THE CONTROL OF BLOOD

GLUCOSE
• The endocrine portion of the pancreas, the islets of Langerhans, contains four
main cell types:
1. A-cells (20%):
▪ They secrete glucagon →  blood glucose.
▪ Excessive secretion (in glucagonomas) → moderate hyperglycemia & profound
catabolic effects on muscle protein.
2. -cells (75%):
▪ They secrete insulin, which controls the metabolism of carbohydrates, fat, and
protein and normally determines blood glucose concentration.
▪ Deficiency of insulin → diabetes mellitus while increased secretion (functioning -
cell tumors known as insulinomas) is characterized by profound metabolic
disturbances.
3. D-cells (3-5%):
▪ They secrete somatostatin, which has an indirect paracrine role as it inhibits
secretion of insulin and glucagon.
▪ It is widely distributed outside the pancreas and is also released from the
hypothalamus (which inhibits the release of GH from the anterior pituitary).
4. PP-cells ( 2%):
▪ They secrete a pancreatic polypeptide, which is facilitates digestive processes

1
2
 DIABETES MELLITUS

▪ It is a chronic metabolic disorder characterized by a high blood glucose

concentration due to insulin deficiency (or relative insulin deficiency) and/or insulin
resistance.

Complications:

▪ The most common complications of diabetes are atherosclerosis and diabetic

retinopathy, nephropathy, neuropathy & comas.

3
▪ Hyperglycemia occurs because liver and skeletal muscles
can not store glycogen and the tissues are unable to take
up and utilize glucose.

▪ Glucose  beyond the renal threshold → appearance of

glucose in urine (glucosouria) with osmotic diuresis →
polyuria → dehydration, thirst and  drinking (polydepsia).

▪ Protein wasting is due to metabolic derangement of

protein metabolism.

▪ Ketosis is due to  fat breakdown and  acetyl CoA →

acetoacetic acid, -hydroxy burterate and acetone (ketone
bodies).
▪ Polyogagia and loss of weight

4
 Forms of diabetes mellitus
Type 1 diabetes Type 2 diabetes
(insulin-dependent (non-insulin-dependent
diabetes mellitus, IDDM or diabetes mellitus, NIDDM
juvenile-onset diabetes) or maturity onset diabetes)

Age of onset Usually below 35 years Usually over 35 years

(Usually obese)
Cause Absolute deficiency of insulin Both insulin resistance and
resulting from autoimmune impaired regulation of insulin
destruction of -cells. secretion.

Treatment ✓ Diet control ✓ Diet

✓ Insulin ✓ Oral anti-diabetics and if
failed shift to insulin.
5
6
 Gestational diabetes:
Carbohydrate intolerence with onset during pregnancy.

-When uncontrolled---→ fetal macrosomia. •

shoulder dystocia. •
neonatal hyperglymia •

-Treated by------→Diet , exercise and insulin

7
 HbA1c
Glycosylated hemoglobin

~
-The rate of formation of HbA1c average blood •
glucose concentration over previous 3 months.

↑↑average glucose ---→↑↑ HbA1c.

-The goal HbA1c is usually < 7%

8
 INSULIN

➢ Insulin is Polypeptide hormone consiting of two peptide chains and a B-chain

linked by two disulfide bonds).

➢ It is synthesized as proinsulin successive proteolytic cleavage to insulin & C-

peptide. These are stored in granules in the -cells and are normally co-
secreted by exocytosis in equimolar amounts together with smaller amounts of
proinsulin.

-As insulin undergoes significant hepatic and renal extraction----→

plasma insulin levels may not accurately reflect insulin production--→
measurement of C-peptide provides a better index of insulin levels.]

9
INSULIN SECRETION

▪ ATP-sensitive K+ channels (KATP) determine the resting membrane potential in -

cells. In the resting cell with normal (low) ATP levels, K+ diffuses down its
concentration gradient through ATP-gated K+ channels (ATP closes the
channels) maintaining the intracellular potential at a fully polarized, negative level
(insulin release is minimal).

▪ Glucose enters -cells via a membrane transporter called Glut-2, and its
subsequent metabolism via glucokinase (the rate-limiting enzyme that acts as
the “glucose sensor” linking insulin secretion to extracellular glucose) and, by
glycolysis, glucose →  intracellular ATP → closure of the KATP → membrane
depolarization. Voltage-gated Ca2+ channels open in response to depolarization
→ Ca2+ influx →  intracellular Ca2+ →  insulin secretion. Sulfonylurea
hypoglycemic drugs → blocking of the KATP → depolarization of the membrane
→  insulin secretion.

▪ About 1/5 of insulin stored in the pancreas of the human adult is secreted daily,
and the mean plasma concentration after an overnight fast is 20-50 pmol/l.

10
 KATP Channel Structure and Function
ATP-sensitive K+ Channel (KATP Channel)
Sulfonylurea Receptor Inwardly Rectifying
glucose K+ Channel Voltage-dependent
Ca2+ Channel

Membrane
Depolarization

ADP
ATP
ADP
ATP Ca2+
NBF
K+ Influx
ATP NBF
glucose
metabolism
insulin secretion

NBF
Nucleotide Binding Fold = site of ATP/ADP binding

Four copies of each subunit combine to form an active KATP channel

11
http://www.musc.edu/~rosenzsa
12
PHARAMACODYNAMICS
▪ Signal transduction is mediated through insulin-regulated transmembrane
receptors whose intracellular enzyme activity is tyrosine kinase, which is
controlled by binding of insulin to the extracellular portion of the receptor.

▪ .

13
ACTIONS

✓ Insulin is the main hormone controlling intermediary metabolism, having actions

on liver, muscle and fat.

✓ The overall effect of insulin is to conserve fuel by facilitating the uptake, utilization
& storage of glucose, amino acids & fats after a meal. It  blood sugar.

✓ A fall in plasma insulin →  cellular glucose uptake and mobilization of

endogenous sources of fuel.

Short-term effects of insulin

A. Rapid transport effects:

1. It  entry of glucose, amino acids, K+, Mg2+, Ca2+, nucleosides and PO43- into the
cells.

2. It facilitates glucose uptake by all tissues except brain, renal tubules, intestinal
mucosa and RBCs.

3. Insulin  glucose uptake in adipose tissue and muscle by  facilitated transport of

glucose via a transporter called Glut-4.
14
B. Gradual (anabolic effects):

1. CHO metabolism: Insulin  glycogen storage and  glycogenolysis.

2. Lipid metabolism: ↓ lipolysis.

3. Protein metabolism: Insulin  protein synthesis and  protein catabolism and

gluconeogenesis.

15
 INSULIN PREPARATIONS

1.According to the origin:

◆ Insulin may be prepared from animals (pork and beef) which differ
from human insulin by one and three amino acid residues,
respectively. Therefore, human insulin is the least immunogenic
insulin preparation followed by porcine insulin followed by bovine
insulin.

◆ Human insulin is produced by recombinant DNA technology form E.

coli or yeast. It is less immunogenic than animal insulin → 
incidence of therapeutic complications as allergy, resistance and
local lipodystrophy.

2. According to the impurities:

◆ Immunological reactions are due to impurities present in insulin

such as residual C-peptide and proinsulin.
◆ .

16
 Duration Peak Onset Insulin preparation

Rapid-Acting
Aspart 5-15 min 30-90 min <5 h

Lispro 5-15 min 30-90 min <5 h

Glulisine 5-15 min 30-90 min <5 h

Short-Acting
Regular 0.5-1 h 2-3 h 5-8 h

Intermediate, )
Basal
Neutral protamine 2-4 h 4-10 h 10-16 h
Hagedorn (NPH)

Long-Acting,
Basal
Insulin glargine 2-4 h No peak 20-24 h

Insulin detemir 3-8 h No peak 17-24 h

Premixed
Insulin lispro protamine/ insulin 5-15 min Dual 10-16 h
lispro

Insulin lispro protamine/insulin 5-15 min Dual 10-16 h

aspart

NPH/regular 0.5-1 h Dual 10-16 h

 Insulin Delivery Systems

◆ The standard mode of insulin therapy is s.c. injection using disposable

syringes.

◆ New means of administration include:

1. Portable Pen Injector: They facilitate multiple s.c. injection of insulin.

2. Closed-Loop Systems: Automated administration of soluble insulin by

“closed loop” systems (blood glucose-controlled insulin infusion systems) used
in acute situations such as management of diabetic ketoacidosis or in patients
undergoing surgery. They are not used for a long period because of the need
for uninterrupted aspiration of blood to reach an external glucose sensor and
by the size of the computerized insulin pumps used in present models.

3. Open-Loop Systems (Insulin Pumps): They are composed of a small

reservoir and a pump programmed to deliver regular insulin at a calculated
rate without a glucose sensor. They are convenient for s.c., i.v. and i.p.
administrations. They are useful in the management of IDDM.

4. Nasal Insulin Delivery: Insulin is combined with a detergent and

administered as an aerosol to the nasal mucosa.

5. Inhaled Insulin: Rapid-acting inhaled insulin is approved by the FDA for use
before meals

18
 INSULIN PHARMACOKINETICS
◆ Insulin is not administered by the oral route.

◆ Administration of crystalline insulin (s.c.) → rapid absorption and

distribution within minutes. It can be detected in the cells of liver,
kidney and muscle. These tissues, particularly liver and kidney,
contain insulinase enzyme which inactivates insulin.

◆ It is inactivated enzymatically in the liver and kidney and 10% is

excreted in the urine. Renal impairment reduces insulin
requirement.

◆ The fate of injected insulin (exogenous) is different from secreted

insulin (endogenous). More than 50% of endogenous insulin is
secreted into the portal vein is degraded in the liver and never
reaches the general circulation. This creates a marked differential
concentration gradient between the liver and the periphery,
resulting in a greater effect of endogenously secreted insulin on
hepatic function.

◆ Attempts to control hepatic gluconeogenesis with injected insulin

do not mimic the effects of secreted insulin because there is no
concentration gradient. Adequate levels of insulin for hepatic
effect may result in peripheral hyperinsulinemia → hypoglycemia.
19
 INDICATIONS OF INSULIN

1. Insulin-dependent diabetes mellitus (IDDM).

2. Non-insulin dependent diabetes mellitus (NIDDM) not controlled

by diet and oral hypoglycemic drugs.

3. NIDDM with pregnancy, infection, lactation, stress, surgery,

myocardial infarction or development of complication of
diabetes (e.g., diabetic ketoacidosis, retinopathy and
nephropathy).

20
 COMPLICATIONS OF INSULIN THERAPY
1. Hypoglycemia:
◆ Causes: Missed meal, insulin overdose or due to strenuous muscular work.

◆ Symptoms: sweating, tachycardia, tremor, weakness, hunger, “being ill at

ease”, blurred vision and mental confusion; severe cases may present with
convulsions and coma.

◆ Treatment: In conscious patients, give a sweet drink or a snack. In

comatose patient, give glucose (50% solution, i.v.) or glucagon (s.c. or
i.m.) or Adrenaline (SLOWLY diluted IV).
◆ .

2. Insulin allergy:
◆ Manifestations: The most common manifestation is a cutaneous reaction
at the site of injection, e.g. rash or hives due to IgE-mediated histamine
release from mast cells.
◆ Rarely, there is severe allergy with urticaria, angioneurotic edema &
anaphylaxis.
◆ Treatment: antihistaminics, glucocorticoids, desensitization regimens and
the use of highly purified or human insulin.

21
 COMPLICATINS OF INSULIN THERAPY
3. Insulin lipodystrophies:
Atrophy or hypertrophy of subcutaneous fatty tissue at the site of
injection.
Insulin lipoatrophy: it is due to immunogenic components of
insulin. It is treated by injecting highly concentrated pure
neutral insulin at the center or edge of the atrophic skin.
Insulin lipohypertrophy: it is due to repeated injection at the same
site. High local concentration of insulin stimulates lipid
synthesis. It is prevented by proper rotation of injection site.

◆ 4. Insulin resistance:
A totally insulin-deficient diabetic usually requires from 30-50
units of insulin/day for control. A requirement of  200
units/day indicates that the patient is resistant to insulin
therapy (A need for  1.5 units/kg/day may be also considered
resistance).
Causes: Obesity, surgery, infection, hormones (cortisol and
GH), -adrenoceptor agonists, etc.
Mechanisms of resistance:
Prereceptors: immune insulin resistance due to insulin-binding
IgG antibodies.
Receptors: insulin receptor down-regulation.
Post-receptors: genetic mutations in components of the insulin-
signaling pathway (insulin receptor, IRS-1, glucokinase, GLUT-4
glucose transporter) that rarely occur.

22
 COMPLICATINS OF INSULIN THERAPY
5. Pseudo-insulin resistance (Somogyi phenomenon):
➢ Somogyi phenomenon (rebound hyperglycemia):
◆ It follows excessive insulin administration.
◆ It is hyperglycemia in the early hours of the morning, before
breakfast, following an unrecognized insulin-induced hypoglycemic
attack during sleep.
◆ It is caused by release of insulin-opposing or counter-regulatory
hormones (adrenal steroids, GH, glucagon & epinephrine) in
response to hypoglycemia.
◆ It is an indication to decrease insulin dosage.
➢ Dawn phenomenon:
◆ It is morning hyperglycemia due to inadequate insulin therapy.
◆ It is an indication to increase insulin dosage.
◆ To differentiate between Somogyi and Dawn phenomena, do 4 a.m.
blood glucose sample.

◆7.Edema:
◆ Edema lasting for a few weeks may occur on initiation of insulin
therapy. This effect results in part from insulin-dependent sodium
retention by the kidney.

23
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
MECHANISM OF ACTION
A. A. Pancreatic action:
● SUs stimulate -cells of the islets of Langerhans to secrete insulin.
For a proper action, at least 30% of the islets should be functioning.
Consequently, these drugs are ineffective in IDDM.

● High-affinity receptors for SUs are present on the KATP channels in -

cell plasma membrane, and binding of various SUs parallels their
potency in stimulating insulin release. They inhibit K+ efflux by
blocking the KATP channels in the -cells → cellular depolarization,
Ca2+ influx and Ca2+-stimulated release of insulin from the pancreas.

24
 Mechanism of Sulfonylurea Action

Sulfonylurea Receptor Inwardly Rectifying

ATP-sensitive K+ Channel (KATP Channel) + Channel
K
Sulfonylurea Receptor Inwardly Rectifying
K+ Channel Voltage-dependent
Ca2+ Channel

Membrane
Depolarization

ADP
ATP Ca2+
ADP
ATP Influx
NBF
NBF
K+ NBF
NBF insulin secretion

25
http://www.musc.edu/~rosenzsa
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
MECHANISM OF ACTION
B. Extrapancreatic actions (less contribution to hypoglycemic
effects):

i. They  tissue sensitivity to insulin by  # of insulin receptors (up-

regulation) &  glucose transporters.

ii. On the liver, they  glucose output and  hepatic gluconeogenesis.

iii. They  glucagon secretion.

26
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
PREPARATIONS

Generic Name Trade Name Plasma t1/2 Dose

(Hour) (mg/day)
First
Generation
Tolbutamide Rastinon 6 500-3000
Acetohexamide Dimelor 2-6 250-1500
Tolazamide Tolinase 7 100-1000
Chlorpropamide Diabenes 36 100-400

Second
Generation
Daonil, Euglocon
Glibenclamide 10 2.5-20
Gliclazide Diamicron
Minidiab 10 - 12 40-240
Glipizide 2-4 2.5-30
Glimepiride Amaryl
0.5-8 27
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
PREPARATIONS
➢ Notes on chlorpropamide

✓ Chrlorpropamide has a long duration of action. A substantial fraction

is excreted in urine and consequently, it can cause severe
hypoglycemia in elderly patients in whom there is progressive decline
in glomerular filtration rate.

✓ It causes flushing after alcohol because of a disulfiram-like effect. It

potentiates the action of ADH on the distal convoluted tubules →
dilutional hyponatremia and water intoxication.

28
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
PREPARATIONS
Notes on the second generation

✓ They are approximately 100X more potent than first

generation ones but their maximum hypoglycemic effect is
no greater.

✓ Glibenclamide is best avoided in the elderly and in patients

with even mild renal impairment because of the risk of
hypoglycemia since several of its metabolites are
moderately active and are excreted in urine.

✓ Glimepiride produces less nocturnal hypoglycemia and no

weight gain.

✓ Glyburide --→ used in pregnancy as alternative to insulin

29
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
PHARMACOKINETICS

▪ They are well absorbed after oral administration and most

reach peak plasma concentrations within 2-4 hours.

▪ Short acting SUs should be taken 1/2 hour before meals.

Food and hyperglycemia impair absorption (hyperglycemia
→  gastric & intestinal motility → delayed absorption of
many drugs).

▪ All SUs bind strongly to plasma proteins (mainly albumin)

(90-99%) → interactions with other drugs as aspirin &
sulfonamides that compete for the same binding sites → 
hypoglycemic effects.

30
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
PHARMACOKINETICS
▪ The second generation SUs t1/2 is about 3-5 hours but their
hypoglycemic actions are evident for 12-24 hours allowing once
daily dosing.

▪ Tolbutamide and tolazamide are exclusively metabolized in the

liver → they are preferred in patients with renal disease.

▪ All SUs are metabolized in the liver and all metabolites (including
active ones) are excreted in urine, so their action is increased in
elderly patients with renal disease.

▪ SUs cross the placenta and stimulate fetal -cells to release insulin
causing → severe hypoglycemia in the newborn. So, their use is
contraindicated in pregnancy. Gestational diabetes is managed by
diet  insulin.

31
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)

INDICATIONS
◆ Treatment of NIDDM.

ADVERSE EFFCTS

◆ Hypoglycemia, which can be severe leading to coma.

◆ Skin rash.
◆ Weight gain.
◆ Gastrointestinal upset.

32
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
Drug interactions
 Hypoglycemic action of SUs  Hypoglycemic
action of SUs
anti-inflammatory drugs (e.g. salicylates ), diuretics (thiazide
antibacterials ( sulfonamides) and loop
antifungals (Ketoconazole) diuretics),
antiCoagulant ( warafarin). hormones
(corticosteoids,
thyroid hormones
The probable bases of interaction include and contraceptive
mainly competition for metabolizing enzymes, pills),
interference with plasma protein binding or
with excretion.
Diazoxide, and
phenytoin.

33
 ORAL ANTIDIABETIC DRUGS
1. SULFONYLUREAS (SUs)
CONTRAINDICATIONS

1. IDDM.

2. Patient of NIDDM with critical conditions (pregnancy, surgery,

stress and ketoacidosis).

3. Patients of NIDDM with renal, hepatic and cardiac disease.

34
 ORAL ANTIDIABETIC DRUGS
2. MEGLITINIDES

➢ Meglitinides were approved for use in 1997.

➢ They are oral insulin-secretagogues. They stimulate insulin release by

blocking KATP in the pancreatic -cells of islets of Langerhans.

◆ Members: repaglinide, nateglinide.

◆ Similar to sulphonylureas with less hypoglycemia .

35
 ORAL ANTIDIABETIC DRUGS
3. BIGUANIDES
MECHANISM OF ACTION
✓ They are orally active hypoglycemic agents that do not
need functioning -cells.

1. They  glucose absorption from the gut.

2. stimulate anaerobic metabolism of glucose to lactate.

3. They  glucose uptake by the muscles.

4. They  hepatic gluconeogenesis.

5. They  plasma glucagon level.

6. They  receptor responsiveness by  # insulin receptors.

7. Metformin →  plasma LDL & VLDL →  atheroma.

36
 ORAL ANTIDIABETIC DRUGS
3. BIGUANIDES
PREPARATIONS

▪ Only metformin is present in the market.

▪ It does not stimulate appetite and is useful in the

majority of type 2 diabetic patients who are obese and
who fail treatment with diet. It can be combined with
SUs.

37
 ORAL ANTIDIABETIC DRUGS
3. BIGUANIDES
INDICATIONS
1. NIDDM.

2. Adjuvant to SUs: to decrease the incidence of

hypoglycemia.

3. Type 1 diabetes: to smoothen the effect of insulin and to

decrease insulin requirements in some cases of insulin
resistance.

38
 ORAL ANTIDIABETIC DRUGS
3. BIGUANIDES
ADVERSE EFFECTS & CONTRAINDICATIONS
ADVERSE EFFECTS

1. Transient gastrointestinal disturbances: anorexia, metallic

taste, vomiting, diarrhea and malabsorption of vitamin B12.

2. Lactic acidosis with phenformin.

CONTRAINDICATIONS

1. Patient with renal disease or severe pulmonary or cardiac

disease should never take metformin (because of reduced
drug elimination or increased anaerobic metabolism).

2. Pregnancy.

39
 ORAL ANTIDIABETIC DRUGS
4. THIAZOLIDINEDIONES

◆ They are selective agonists for nuclear peroxisome proliferators-

activated receptor gamma (PPAR) → stimulation of insulin-
responsive genes that regulate carbohydrates and lipid
metabolism. They require insulin for their actions.

◆ They  glucose production by the liver (a direct action).

◆ They  glucose transport into muscles and adipose tissue by 

synthesis and translocation of transporter proteins (Glut-4).

◆  tissue sensitivity.

◆ They lower insulin resistance in peripheral tissues.

40
 ORAL ANTIDIABETIC DRUGS
4. THIAZOLIDINEDIONES

Pioglitazone (Actos)

◆ They are administered once daily. They are absorbed within 2

hours.

◆ Metabolized by the liver → (regular monitoring of liver

functions + safe in renal diseases).

◆ They can be combined with insulin or other oral hypoglycemic

drugs.

Side effects:
◆Anemia, weight gain, edema and  plasma volume (contraindicated
in heart diseases).
◆ ↑ the risk of bladder cancer.

41
 Pramlintide

◆Pramlintide is a synthetic form of amylin

Which is cosecreted with insulin from β cells.

-it delay gastric emtying, ↓ glucagon, improves satiety.

◆ Uses: It is approved only as an adjunctive

therapy with insulin, but it can be used
both T1DM and T2DM.
◆ Administerd S.C

42
what are Incretins?

43
 Incretins
Glucagon-like peptide 1 (GLP-1) and Gastric
inhibitory peptide (GIP) are intestinal incretin
hormones, released in response to food
ingestion
Actions of GLP-1:
◆ ↑release of insulin.
◆ ↓ Appetite.

◆ Delay gastric emptying.

◆ E.g., exenatide ----- used SC.
44
45
 Incretins
Endogenously released GLP-1 has a short
t1/2 of 1.5–5 min

-Upon secretion, GLP-1 and GIP are rapidly

degraded and inactivated by DPP-4.

-Incretin effect’ is reduced in patients -

with T2DM
46
To extend the half-life
DPP-4 inhibitors
to prevent degradation of
endogenous incretins

enhancing plasma level

of active incretins in
circulation, prolonging
the actions of the incretin

increased
insulin
level
47
Dipeptidylpeptidase-IV (DPP-4) inhibitors

◆ The effects of endogenous incretins are short-lived because

of rapid degradation and inactivation by the enzyme DPP-4.

Mechanism of action
◆ Inhibitors of DPP-4 have been developed to prevent the
inactivation of GLP-1 and prolong the activity of the
endogenously released hormone.

E.g., sitagliptin used orally

48
 Sodium Glucose co-transporter-2
inhibitors

◆ It is the newest group of medications approved for

treatment of diabetes mellitus.

◆ Main function of sodium-glucose co-transporter in the

kidney’s proximal tubules is reabsorption of the filtered
glucose from the urine back into the circulation. It is
responsible for about 90% of total glucose reabsorption.
Inhibition of this protein leads to the excretion of the
glucose in the urine.

◆ Uses: NIDDM.

◆ e.g., canagliflozin.

49
50
 Sodium Glucose co-
transporter-2 inhibitors
Main side effects

1- Polyurea
2-Vaginal infections
3-Urinary tract infections

51
 ORAL ANTIDIABETIC DRUGS
5. OTHER ORAL HYPOGLYCEMIC DRUGS
1. -Glucosidase inhibitors (Acarbose "precose" & Miglitol
"glyset"):
◆ They reduce GI absorption of complex carbohydrates (which
udergoes breakdown into glucose that can be absorbed).

◆ They lower blood glucose and cause weight loss especially if post-
prandial hyperglycemia is a problem.

◆ Adverse effects include flatulence, loose stools, diarrhea, abdominal

pain and bloating.

▪ It stimulates peripheral glucose utilization and inhibits triglycerides and

cholesterol synthesis.

2. Bromocriptine colesevelam---------→ reduce HA1C

52
53
 ◆

1- Alndronate is used in:

a) bronchial asthma.

b)hypercalcaemia

c)peptic ulcer
54
2-Only one of the following drugs can
cause failure of oral contraceptives if
co-administered with them:
a)Rifampicin
b)Aspirin
c) Morphine
d) Progestin

55
3-Mechanism of action of
Etodronate which is used in the
treatment of osteoporosis:
A. Inhibition of receptor activator of
nuclear factor-kappa ligand
(RANKL).
B. it is a recombinant segment of
human parathyroid hormone.
C. It increases tubular reabsorption of
calcium within the kidney.
D. They are incorporated into the bone
and promote osteoclast apoptosis.
56
4- corticosteroids are used
in

a) osteomalacia

b)
osteoarthritis

57
5-Tamoxifin is used in treatment of
breast cancer due to:
A. It has estrogenic activity on bone
and breast.
B. It is a selective receptor
modulator in breast and
endometrium.
C. It block estrogen receptors in
hypothalamus.
D. It inhibits estrogen synthesis
58
6-Radioactive iodine is
contraindicated in treatment of
young patients with
hyperthyroidism, due to:
A. It exerts a powerful cytotoxic action
that is not restricted to the cells of the
thyroid follicles.
B. The risk of thyroid cancer following the
treatment.
C. It has contraceptive effect in females.

D. It has depressive effect on the bone

marrow.
59
◆ 4- pioglitazone is used in
treatment of type II diabetes
mellitus because it:
A. Blocks peroxisome proliferator-
activated receptor-γ (PPARγ).
B. Decreases hepatic
glucneogenesis
C. Decreases insulin resistance.
D. Depends on presence of insulin
in its action.

60
◆ 15- Which one of the following
compounds is matched with its
mechanism of action?
A. Clomiphine citrate : Selective
estrogen receptors modulators.
B. Finastride: competitively block
testosterone receptors.
C. Flutamide: inhibits 5αreductase
enzyme.
D. Letrozole: inhibit estrogen
synthesis (Aromatase
Inhibitors). 61
◆ In a patient of diabetes mellitus
maintained on insulin therapy,
administration of the following
drug can inhibit hypoglycemic
action of insulin:
A. Paracetamol.

B. Exanetid.

C. Prazocin

D. Prednisone

62
◆ Which one of the following
compounds is matched with its
mechanism of action?
A. Gliclazide: opening the KATP
channels in the -cells
B. Diazoxide: blocking the KATP
channels in the -cells.
C. Sitagliptin: inhibits
Dipeptidylpeptidase enzyme.
D.Canagliflozin; Sodium Glucose .D
co-transporter-2 inducers 63