Diabetes Mellitus 2021 PRINT

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ENDOCRINE PHARMACOLOGY DR A.

Diabetes Mellitus (DM)


DM is metabolic disorder due to Absolute or Relative insulin deficiency.

* Characterized by:
1- Glycogenolysis, Gluconeogenesis & ↓Uptake of glucose by tissues →Hyperglycemia → Glycosuria →
Polyuria → Polydipsia.
2- Polyphagia BUT loss of weight.
3- ↑Lipolysis & ↓ Lipogenesis →Hyperlipidemia → Ketonemia (Ketosis) → Ketonuria.
4- ↑Catabolism →Azotemia → Azoturia
5- Weakness, ↓ Immunity & Recurrent infections.

* Classification of DM:

1-Type I (Juvenile-Onset DM, Age of onset<30 Years):


a- Due to ABSOLUTE insulin deficiency = True hypo-insulinism.
b- ALL are Insulin Dependent Diabetics (IDD).
c- Mostly NON-Obese.

2- Type II (Adult or Maturity-Onset DM, Age of onset > 40 Years):


a- Usually due to Insulin resistance + Relative insulin deficiency = Relative hypo-insulinism.
b- Usually, they are Non-Insulin Dependent Diabetics (NIDD).
c- Usually OBESE (85% of patients). Obesity → Down-regulation of insulin Receptors.
Exercise and leanness enhance insulin action while obesity and a sedentary life style oppose its action.
Over-eating → Excess Insulin Release → Excess internalization of receptors →↓Available receptors →
Down regulation. The number of available receptors are inversely proportion to serum insulin.

Type l Type ll

1- Age of Onset: Usually < 30 years Usually> 40 years

2-Insulin deficiency: True (Absolute) Relative

3- Treatment with Insulin: Always necessary = IDD Usually NOT necessary NIDD

4- Body weight: Non-Obese Usually Obese (85%)

5- Ketosis: Marked Absent.

6- Islet cell antibodies: yes No

7- Human Leukocyte Antigen “HLA” Yes No

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ENDOCRINE PHARMACOLOGY DR A.E

3- Type III Diabetes: Due to multiple other specific causes either pancreatic or non- pancreatic,
endocrine diseases and drug therapy e.g.:
1- Alloxan & Streptozotocin: Selective cytotoxic effect on β-Cells.
2- Immunosuppressive: They inhibit insulin synthesis.
3- Inhibitors of Insulin Release: α-Agonists, β2-Antagonists, Thiazide diuretics, Diazoxide & Phenytoin.
4- Counter-regulating hormones e.g. Glucagon, Glucocorticoids, Growth hormone, Thyroxin , Oral
contraceptives & Catecholamines.

4- Type IV Diabetes = Gestational diabetes (GDM) is defined as any abnormality in glucose


levels noted for the first time during pregnancy.

Drugs Used in Treatment of Diabetes Mellitus


1- Insulin.
2- Oral Antidiabetic drugs: Include:

a-Insulin Secretagogues:

1-Sulphonylureas

2-Meglitinides

b-Insulin Sensitizers:

1- Biguanides

2-Glitazones

c-Inhibitors of Glucose Absorption:

1-Acarbose

2-Miglitol

3- New Anti-diabetic drugs:

a- Glucagon Like Peptide-1 (GLP-1) receptor agonist: Exenatide.

b- Di-Peptidyl Peptidase IV ( DPP-IV) inhibitor: Sitagliptin.

c- Amylin analogue: Pramlintide

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ENDOCRINE PHARMACOLOGY DR A.E

Insulin
1-The pancreas contains about one million (1000’OOO) islets of Langerhans.
2-Each islet contains four types of polypeptide hormone-producing cells:
a-A “(α” Cells (20%) → Glucagon → Counter-insulin →Hyperglycemia.
b-B “β” Cells (75%) → Insulin → Synthesis & Storage.
c-D “∞” Cells (3-5%) → Somatostatin →↓↓ A cells > ↓ B cells → ↓Glucagon > ↓Insulin
d-F “PP” Cells (2%) → Pancreatic Polypeptide →↑ Digestive process
e- G Cells (1%) —> Gastrin

* Synthesis, Storage & Release of Insulin:

1- Insulin is synthesized in [β-cells of pancreatic islets of Langerhans as a single chain pro-insulin →


Insulin + C-peptide (Single chain 31 aa). Insulin is a double chain polypeptide of 51 aa (chain A 21 aa &
chain B 30 aa) connected together by 2 bisulphide bridges. The integrity of these bridges, is essential for
activity. A third bridge within chain A

2- Insulin is stored in specific granules in [β-cells].

3- β-cells also synthesize and store Amylin.


a- It is a single chain polypeptide of 37 aa. It is stored and released with insulin.
b- Amylin → Delays gastric emptying.

* Drugs affecting release of insulin:

A-Sulphonylureas & analogues → ↑ Release of insulin.


B-Thiazides & Diazoxide →↑ Open Kt channels →Hyperpolarization→↓Release.
c- Phenytoin →↓ Release.
d- CCB e.g. Verapamil → ↓Release.

* Fate of Insulin:

1- NOT effective orally, used parenterally usually SC. In emergency diabetic coma soluble insulin can be given
IM & IV.
2- Extensive hepatic first pass metabolism (50%), mainly by glutathione-insulin trans-hydrogenase
( Insulinase) enzyme → Break bisulphide bridges → Inactivation.
3- Short t½ of endogenous insulin = 5 minutes.

Insulin Administration Routes

• Subcutaneous: All insulin preparations •Intravenous: Only regular soluble insulin

•New administration routes e.g. intranasal for Alzheimer's dementia or mild cognitive impairment.

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ENDOCRINE PHARMACOLOGY DR A.E

.Sources of insulin

A. Human insulins: made with recombinant DNA technology using yeast or bacteria.

B. Insulin Analogs: These are insulin preparations with modified amino acid sequence or composition
prepared by the use of the recombinant DNA technology and genetic engineer. They are used mainly to
modify the pharmacokinetics of insulin.

C- Animal insulins: are isolated from beef and pig pancreas—> “foreign” proteins—> greater risk of
allergic reactions.

Insulin Strengths: 100 units (U) ml, 40 units/ml

lnsulin preparations

Insulin Preparations

Generic (Trade name) Onset Peak Effect Duration

Rapid acting Insulin Aspart 5-10 min 1-3 hrs 3-5 hrs
analogues
Insulin Lispro <15 min 2-4 hrs

Insulin Glulisine <15 min ½-1½ hrs. 1-2½ hrs.

Regular Inhaled insulin <15 min 1 hr. 3 hrs.

Short acting Regular Soluble insulin 30-60 min 2-3 hrs. 3-6 hrs.

Intermediate- Neutral Protamine Hagedorn NPH 2-4 hrs 4-10 hrs. 10-16 hrs.
acting (isophane) insulin

Long acting Insulin Glargine No peak 24 hrs.


Analogues
Insulin Detemir 1-4 hrs Dose- dependent 6-23 hrs.
peak depending
on dose

Pre-mixed 70%NPH + 30% regular 30-60 min There are 2 peaks:


Insulins (Humulin 70/30)
1-3 hrs. and Up to 24
70% Aspart Protamine + 30% Aspart 5-10 min
4-10 hrs. Hours

50% Lispro Protamine + 50% Lispro There are 2 peaks:

75% Lispro Protamine + 25% Lispro < 15 min ½-1½ hrs. and
4-10 hrs.

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ENDOCRINE PHARMACOLOGY DR A.E

Pharmacodynamics of Insulin:

A) Mechanism of Action:

1- Insulin binds to specific membrane receptors, each receptor has a & β subunits connected together

by 2 bisulphide bridges. The α subunit is outside while the β is trans-membrane and has a tyrosine

kinase activity.

Insulin binds to α subunit → Activation of tyrosine kinase activity of β subunit —> Phosphorylation of

intracellular proteins → Change in enzyme activity, gene expression and translocation of Glut-4

transporter → Glucose uptake by adipose tissue & Skeletal muscles.

2-The insulin receptor complex is then rapidly internalized into the cell → Metabolism of insulin and
recycling of the receptor.
B) Actions of Insulin: see bio

Indications of Insulin :

A) Diabetes Mellitus:

• Insulin is essential & a true replacement therapy in patients with I.D.D.


• Insulin is NOT essential (But NOT Contraindicated) in patients with N.I.D.D.

1- ALL cases of (IDDM):


a- All cases of Type-I diabetics.
b- Some cases of Types-II diabetics after failure of Diet regulation + Exercise + Oral hypoglycemics.

2- Temporary in N.I.D.D. during STRESS periods e.g. Infection, Operation & Pregnancy.

3- Permanently in N.I.D,D. with renal impairment.

4- Emergency treatment of Diabetic Ketoacidosis & Non-ketotic Hyperosmolar Diabetic coma.

B) Other Indications: Hyperkalemia due to renal failure.

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ENDOCRINE PHARMACOLOGY DR A.E

* Adverse Effects of Insulin:

A) Specific reactions:

1- Hypoglycemia:

*causes: *Manifestatios: *Treatment


1- Too much or bad 1- Sympathetic → Sweating, 1- If patient is conscious → Oral glucose
timing of insulin → pallor, tachycardia & tremors. or sweets.
True Hyper-insulinism. 2- Neuro-glycopenia :— Hunger, 2- If patient in Coma = Unconscious →
2- Too little food headache, irritability, weakness, a- I.V. Glucose 50 - 100 ml 25% — Life
intake or missing meal blurring of vision, confusion, saving. Then flush the vein with saline to
→ Relative Hyper- convulsions & coma. If prolonged avoid thrombosis & sclerosis.
insulism → Permanent brain damage & b- Glucagon 1 mg S.C. or I.M. if sterile
3- Too much muscular Death. glucose is not available.
exercise. 3- Laboratory → Low blood sugar c- Adrenaline 1 mg S.C. if No alternative
& Urine is —ve for glucose. & No C.V.S. contraindications.

2- Somogyl Effect : Rebound morning hyperglycemia (due to excess release of counter- regulating
hormones) that follows insulin-induced hypoglycemia during night. Avoided by reducing the evening dose
of insulin .

3- Weight gain.

4- Insulin resistance due to high activity of insulinase enzyme or over production of Insulin
antibodies.

B) Non specific :

1- Hypersensitivity (Allergic) reaction either local at injection site (usually subside spontaneously)
or generalized

a- Change protamine-contaimng insulin to an equivalent non-protamine insulin e g N.P.H. (Isophane) →


Lente Insulin , P.Z.I. → Ultralente Insulin.
b- Change animal species & BETTER use human insulin

c- Immuno-therapy may be required.

2- Secondary infection (Very rare).


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ENDOCRINE PHARMACOLOGY DR A.E

Oral anti-diabetic Drugs


I- Insulin Secretagogues (Oral Hypoglycemic drugs)

A) Sulfonylurea Group :

*Preparations.
A) First Generation:
1- Short acting (6-12 hours) → Tolbutamide
2- intermediate acting (12-24 hours) → Acetohexamide
3- Long acting (up to 60 hours) → Chlorpropamide
Chlorpropamide —> Potentiate ADH on Nephron → Anti diuretic effect.
B) Second Generation:
• More potent & Less side effects
• Intermediate acting → up to 24 hours
1- Glimepiride 2- Glibenclamide = Glyburide 3- Glipizide 4- Gliclazide

*Kinetics.
1- Absorbed orally.
2- Distributed all over the body and pass BBB & placental barrier
3- Metabolized in liver. Acetohexamide →Active metabolite. they should be used in caution in patients
with either renal or hepatic insufficiency
4- Excreted in urine.

*Mechanism of Action:

1- increase the insulin release from the pancreas:

a- It is the main action of sulfonylureas, so their action depends on presence of preformed endogenous
insulin (about 30% functioning -cells)

b-They Block ATP-sensitive K-channel (KATP-Channels) of B-Cells of Pancreas →Depolarization → Influx


of Ca+2→ Exocytosis →↑Release of Insulin.

2- Other actions (Extra-pancreatic): sulfonylureas may reduce hepatic glucose production and increase
peripheral insulin sensitivity.

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ENDOCRINE PHARMACOLOGY DR A.E

*Indications of Sulfonylureas:
1- Type-2 Diabetes (NIDD) after failure of Diet regulation & exercise. They are more effective in mild
diabetics with daily requirements of insulin <30 U / day.
a- Non-Obese (Sulphonylureas ↑ Appetite).
b- Non-Complicated Diabetes:
- No stress e.g. Infection, Operation or Pregnancy.
- No Major organ disease e.g. Cardiac, hepatic or renal.
- No History of diabetic ketoacidosis.
2- Chlorpropamide → Anti-diuretic → Treat Hypothalamo-pituitary Diabetes insipidus.

*Contraindications of Sulfonylureas:

1- Type-I Insulin Dependent Diabetes (I.D.D.).

2- N.I.D.D. during stress periods e.g. Infection, operation & trauma.


3- Pregnancy & Lactation: Sulphonylureas pass placental barrier → Teratogenic & hypoglycemia of neonate.
4- History of diabetic ketoacidosis.
5- Severe hepatic or renal diseases.

NB) Glyburide is most likely to accumulate during renal dysfunction and cause hypoglycemia. Therefore,
glyburide is not recommended for patients with a creatinine clearance less than 50 ml/min.

Glipizide and glimepiride are preferred agents in this setting.

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ENDOCRINE PHARMACOLOGY DR A.E

*Adverse Effects of Sulfonylureas:

A) Specific Adverse Effects:

1-Common adverse effects:

a- Hypoglycemia which may be accompanied with coma especially in overdose, elderly,

b-Weight gain (1-3 kg) due to improvement of glycemic control &T Appetite.

c-Failure:

- Primary failure in 10 -15 % of N.I.D.D.

- Secondary failure after long use (years) due to exhaustion B-Cells.

2-Uncommon:

a- Cholestatic jaundice

b- Hematological: agranulocytosis, aplastic and hemolytic anemias: caution should be used in patients
with G6PD-deficiency and a non sulfonylurea alternative should be considered.

3- Rare Adverse Effects:

a- Hepatic porphyria & Alcohol-induced flush = disulfiram-like reaction

b- Hyponatremia.

4-Teratogenicity and hypoglycemia of fetus.

5-There is a controversial concern whether this class of drugs is associated with an increase in
cardiovascular mortality.

B) Non-specific Adverse Effects:

1-Generalized and dermatological Hypersensitivity & cross-allergy with other sulfonamides e.g. Thiazides

2- GIT upset: Nausea, vomiting, epigastric fullness and heartburn

3-CNS: dizziness, somnolence, tremor & headache (may be due to hypoglycemia)

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ENDOCRINE PHARMACOLOGY DR A.E

*Drug Interactions of Sulfonylureas

1- Aspirin, Phenylbutazone & sulfa → Displace sulfonylureas → Hypoglycemia.


2- Sulphonylureas →Displace Oral anticoagulants → Bleeding.
3- Phenobarbitone, Phenytoin & Rifampicin →↑HME →↑Metabolism of Sulphonylureas.
4- MAO-I, Allopurinol, Cimetidine & Chloramphenicol —> ↓Metabolism of Sulphonylureas.
5- β1ockers e.g. Propranolol:
a- Augment their hypoglycemia & ↓ compensatory hepatic glycogenolysis.
b- Mask sympathetic manifestation of hypoglycemia —÷ Silent coma.
6- Alcohol → hypoglycemia.
7- Thiazides, Corticosteroids & Contraceptives decrease the action of sulphonylureas. Especially
Chlorpropamide.

B) Other Insulin Secretagogues

a- Meglitinides e.g. Repaglinide

b- D-Phenylalanines e.g. Nateglinide

2- No cross-allergy with Sulphonylurea.


3- Pharmacodynamics → Similar to Sulfonylureas.
4- rapid onset of action (Peak = 1 hour) & Short t 1/2 = 2-3 hours.
5- Given before each meal →Control post-prandial hyperglycemia & HbA1c.
6- can be given alone or Better used with Metformin

7- Less liable to produce hypoglycemia & weight gain and no need for dose adjustment in elderly and in
renal impairment especially repaglinide

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ENDOCRINE PHARMACOLOGY DR A.E

II- Insulin Sensitizers ( Euglycemic)


A) Biguanides

* Metformin

*Kinetics:

1- Absorbed orally.

2- Metformin does not bind to plasma protein

3- Fate: Renal excretion as the active drug without hepatic metabolism

4- They can be administered once daily

Mechanism of Action & Pharmacological Effects:

1- The primary effect is to reduce hepatic glucose production by activating the enzyme AMP-
dependent protein kinase (AMPK). This leads to

stimulation of hepatic fatty acid oxidation, glucose uptake, and non-oxidative glucose metabolism

and utilization & reduction of lipogenesis and gluconeogenesis & glycogenolysis.

2-Other effects

a- Increases insulin sensitivity in muscle, improving peripheral glucose uptake and

b- Delays intestinal glucose absorption.

C- Increases anaerobic glycolysis in peripheral tissues→ ↑ Removal of glucose from the blood BUTT
Lactic acid production.

d- Antagonizes the effects of glucagon

Therapeutic Uses of Metformin:

-Type 2 (NIDD), particularly in overweight patients, when dietary management and exercise alone does
not result in adequate glycemic control.

May be used as monotherapy or in combination with other oral anti-diabetic agents, and/or insulin.

A reduction of diabetic complications has been shown in overweight type 2 diabetic patients treated
with metformin as first-line therapy after diet failure
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ENDOCRINE PHARMACOLOGY DR A.E

Adverse Effects of Biguanides


1-GIT: Anorexia, nausea, vomiting, a bdominal discomfort, and diarrhea: occurring in up to 20% of
patients. They are dose related, tend to occur at the onset of therapy, and are often transient. However,
metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea.

2- Lactic Acidosis especially Phenformin in patients with:

a- Hepato-cellular failure &Chronic alcoholism Cannot metabolize lactic acid.

b- Renal insufficiency Cannot excrete lactic acid.

c- Hypoxic states e.g. Cardiac & pulmonary diseases (↑lactic acid production)

d- Advanced age

3- Long use of Metformin ↓absorption of Vitamin B-12.

B) Thiazolidinediones (Glitazones):

1- Examples:
a- Rosiglitazone b- Pioglitazone

2- Kinetics

Absorption: oral and not affected by food and taken once daily

The onset of action of thiazolidinediones is relatively slow; maximal effects on glucose homeostasis
develop gradually over the course of 1-3 months.

Fate: by hepatic metabolism

& should not be used if there is active hepatic disease.

Metabolism is affected by both inhibitors and inducers of the hepatic microsomal enzymes

May be administered to patients with renal insufficiency

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ENDOCRINE PHARMACOLOGY DR A.E

3- Mechanism: Gliltazones decrease insulin resistance.

- They bind to specific nuclear receptor Peroxisome-Prolifrator-Activator-Receptor-Gamma = PPAR-Y) in


insulin-sensitive tissues e.g. adipose, skeletal muscles & liver.

These receptors modulate the expression of genes involved in synthesis of cellular molecules important for
lipid and glucose metabolism, tissues differentiation and insulin signaling e.g. Lipoprotein lipase enzyme &
Glut-4.

- Increase insulin-mediated glucose uptake by adipose tissue and muscles

-Reduce hepatic glucose production and increase hepatic glucose uptake

- Reduces plasma levels of fatty acids by increasing clearance and Reducing lipolysis.

- These drugs also cause a shift of triglyceride stores from non-adipose to adipose tissues and from
visceral to subcutaneous fat depots.

- Pioglitazone reduces plasma triglycerides by 10%-15%, raises HDL cholesterol levels, and both increase
LDL cholesterol.

4-Therapeutic Uses of Glitazones:

Type 2 (NIDD): May be used as monotherapy, in double combination therapy with a biguanide or
sulfonylurea, or in quadruple combination with a biguanide, sulfonylurea, and insulin.

5- -Adverse Effects of Glitazones:


1- The most common are weight gain and edema: weight gain is due to increased body fat and edema
and both are dose-dependent. Adding sulfonylurea or insulin increase both.

2-Increased incidence of heart failure after use of these drugs for several years due to plasma volume
expansion in patients with type 2 diabetes who have an increased risk for heart failure

3- Increase incidence of osteoporosis and fracture of long bones due to decreased osteoblast
formation.

4- Anemia which is mainly due to dilution by fluid retention

5- Although rosiglitazone and pioglitazone have not been reported to cause liver injury, they are not
recommended for use in patients with active liver disease or pretreatment elevation of alanine
aminotransferase (ALT) 2.5 times greater than normal. Liver function should be monitored
intermittently during treatment

6- Teratogenic.

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ENDOCRINE PHARMACOLOGY DR A.E

Alpha-Glucosidase Inhibitors:

1-Examples: a- Acarbose po with the first mouthful. b- Miglitol


Mechanism - ↓α Glucosidase on brush border of intestinal mucosa → ↓Absorption of complex
Carbohydrates→↓ Postprandial hyperglycemia.
- Use: in Type-II N.I.D.D. either alone or with Sulfonylurea but not Metformin.

-Adverse Effects : Flatulence, diarrhea & hypoglycemia with sulfonylurea

May increase liver transaminases that is reversed on stoppage

Give oral glucose (not sucrose) in hypoglycemia, as they impair digestion and absorption of sucrose

The New Antidiabetic Agents

A) Glucagon-like peptide-1 (GLP-1) analogs

1-Examples: a- short duration: Exenatide b-long-acting Liraglutide - Albiglutide

2-Synthetic analogs of Glucagon like Peptide-1(GLP-l), an incretin released from GIT after
a meal → Bind to GLP-1 receptors →
1- delayed gastric emptying 2-↑ insulin release 3-↓secretion of glucagon 4- suppresses appetite
3- Used SC
4- Indicated as an adjunctive therapy to control hyperglycemia in patients with type 2 diabetes who
fail to achieve adequate glycemic control via the use of metformin and/or sulfonylureas.

5-Liraglutide at a dose of 3 mg daily has been approved for weight loss.

6- Disadvantages:
a- Risk of hypoglycemia when used + sulfonylurea
b- Nausea common (about 40% of patients)
c-Pancreatitis, renal impairment and acute renal injury may occur
d- Delayed gastric emptying may ‘↓ absorption of some oral drugs
e- Has to be injected

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ENDOCRINE PHARMACOLOGY DR A.E

B) Di-Peptidyl Peptidase IV inhibitors

1- Members: a- Sitagliptin b- Vildagliptin c- Saxagliptin d-alogliptin

2- Oral(once daily) alternative to Glucagon-like peptide-1 (GLP-l) analogs

3- Inhibit Di-Peptidyl Peptidase IV (DPP-IV) enzyme (DPP-4 is an enzyme that breaks down incretin
hormones e.g. GLP-1) leading to prolongation of the action of endogenously released GLP-1 and GIP (glucose
dependent neurotropic peptide)

4- Adverse Effects:

Rhinitis, upper respiratory infections, headaches, pancreatitis, rare allergic reactions and

saxagliptin may increase risk of heart failure

5- Many of them are now available in combination with insulin sensitizers as metformin and Glitazones
e.g. Janumet ( Sitagliptin + Metformin)

C) Amylin analog: Pramlintide (Symlin)

- A synthetic amylin analog (Amylin is a pancreatic hormone secreted from β-Islet cells and reach to
its receptors in brain by circulation )

1. reduces glucagon release

2. delays gastric emptying (mediated by vagus)

3. decreases appetite

4. reduces postprandial glucose elevation

- Used SC as an adjunct to meal time insulin therapy in patients with Type 1 or Type 2 diabetes who have
problems with post prandial hyperglycemia.

- Adverse effects:

Nausea, anorexia, hypoglycemia, headache

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ENDOCRINE PHARMACOLOGY DR A.E

SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT2) INHIBITORS

Canagliflozin Dapagliflozin Empagliflozin


In the normal individual, the proximal convoluted tubule reabsorbs almost all of the glucose filtered by
the glomeruli.

Sodium-glucose transporter 2 (SGLT2) accounts for 90% of glucose reabsorption, and its inhibition causes
glycosuria and lowers glucose levels in patients with type 2 diabetes

Kinetics:

1. Rapid absorbed from GIT

2. Not recommended in severe renal failure or advanced liver disease

3. Rifampicin reduce its efficacy

Clinical indication:

3rd line in ttt of type 2 DM who are very insulin deficient and prone to ketosis

Adverse Reactions:

1. The main side effects are increased incidence of genital infections and urinary tract infections

2. Dehydration & Hypotension

3. Low incidence of hypoglycemia

4. Mild increase in LDL cholesterol levels

5. May increase the risk of cancer

6. Decrease mineral bone density & increase risk of fractures

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ENDOCRINE PHARMACOLOGY DR A.E

N.B.) Glucagon:

1- Single chain polypeptide of 21 amino-acids.

2- Synthesized, stored & released from α-cells of Islets of Langerhans & from Upper GIT:

3- ↑ Specific membrane receptors →↑ Adenylate cyclase →↑cAMP:

a- ↑ Glycogenolysis & Gluconeogenesis (in liver Not skeletal muscle) →↑Glucose

- ↑ Lipolysis & Catabolic (skeletal muscle) → Counter regulatory to insulin

Useful SC & IM in treatment of Hypoglycemic coma when IV Glucose is not available.

b- ↑Heart → +ve ino & +ve Chrono → Useful in heart failure induced by β-blockers.

c- Smooth muscle relaxation → Useful before radiological examination.

4- Therapeutic Uses:

a- Hypoglycemia coma if the patient could not take oral glucose

b- Assess pancreatic β-cell secretory reserve (Glucagon test)

c- Heart failure due to over dose β-blockers.

d- Used to relax intestine in radiology of bowel

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