Part 6: Antidiabetic Agents

Palmyra Prudencia R. Mataberde, RN, MN

GLUCOSE-ELEVATING
AGENTS

Image Source: MOSBY'S pharmacology MEMORY Notecards: Visual, Mnemonic, and memory aids for nurses, 5 th Edition .
OVERVIEW:
Glucose Regulation

The Pancreas
❑ The pancreas has the dual function of secreting hormones into
blood (endocrine) and secreting enzymes through ducts
(exocrine).

❑ Only about 5% of the pancreas is comprised of endocrine cells.

These cells are clustered in groups within the pancreas and look
like little islands of cells when examined under a microscope.
These groups of pancreatic endocrine cells are known as
pancreatic islets or more specifically, islets of Langerhans
Glucose Regulation

The Pancreas
✓ alpha cells release glucagon in response to low
blood glucose levels
✓ beta cells release insulin in response to high blood
glucose levels and when stimulated by incretins
✓ delta cells produce somatostatin (growth
hormone-inhibiting factor) in response to very low
blood glucose levels;
-When levels of other pancreatic hormones, such as
insulin and glucagon, get too high, somatostatin is
secreted to maintain a balance of glucose.
 Glucose Regulation
Functions of Catecholamines
Other Factors Affecting Glucose Control
Adipocytes or fat cells secretes adiponectin. This hormone acts to
regulate insulin sensitivity, it decreases the release of glucose from
the liver, and protect the blood vessels from inflammatory changes.
Endocannabinoid system – Increases food intake by blocking satiety
signals; decrease adiponectin release; decrease insulin sensitivity;
increases fat synthesis; alters gastric emptying to promote greater
nutrient absorption.
The SNS through the effects of Catecholamines – Decreases insulin
release; increases glucose output from liver and muscles; increases
breakdown of fat to free fatty acids (FFAs)
Corticosteroids –Increases glucose output and decrease insulin
sensitivity.
Growth Hormone – causes decreased insulin sensitivity; increases
protein building; increases FFA formation
Glucagon and Insulin Feedback Loop

1. Decreased blood sugar -> pancreas release

glucagon -> causes the liver to release glycogen
which turns into glucose to increase the low
blood sugar level

2.Increased blood sugar -> pancreas releases

insulin -> causes glucose to enter into the cells
to be used or be saved as glycogen for later
(stored mainly in the liver)
Major classifications of diabetes:
1. Type 1 diabetes
2. Type 2 diabetes
3. Gestational diabetes
4. Diabetes mellitus associated
with other conditions or
syndromes (ADA, 2009a).
Pathophysiology of Type 1 Diabetes

• Type 1 diabetes is
characterized by destruction of
the pancreatic beta cells.

Risk Factors:

• Combined genetic,
immunologic, and possibly
environmental (eg, viral) factors
are thought to contribute to beta
cell destruction.
.
Pathophysiology of Type 2 Diabetes
Type 2 Diabetes occurs more commonly among people
who are older than 30 years of age and obese.

Risk Factors:
Lifestyle- being obese, sedentary, poor diet (e.g.
sugary drinks), stress AND genetics

Two main problems related to insulin in type 2

diabetes:

1. Insulin resistance - refers to a decreased tissue

sensitivity to insulin.
2. Impaired Insulin Secretion
 SIGNS AND SYMPTOMS OF HYPOGLYCEMIA AND HYPERGLYCEMIA
CLINICAL EFFECTS HYPOGLYCEMIA HYPERGLYCEMIA
CNS Headache, blurred vision, diplopia, drowsiness Decreased level of consciousness, sluggishness
progressing to coma, ataxia, hyperactive progressing to coma, hypoactive reflexes
reflexes
NEUROMUSCULAR Paresthesias, weakness, muscle spasms, Weakness, lethargy
twitching progressing to seizures
CV Tachycardia, palpitations, normal to high blood Tachycardia, hypotension
pressure
RESPIRATORY Rapid, shallow respirations Rapid, deep respirations (kussmaul); acetone-
like or fruity breath
GI Hunger, nausea Nausea, vomiting, thirst
OTHER Diaphoresis, cool and clammy skin, normal Dry, warm, flushed skin; soft eyeballs
eyeballs
LABORATORY TESTS Urine glucose negative, blood glucose low Urine glucose strongly positive; urine ketone
levels positive; blood glucose levels high
ONSET Sudden; patient appears anxious, drunk; Gradual; patient is slow and sluggish; associated
associated with overdose of insulin, missing a with lack of insulin, increased stress
meal, increased stress.
 INSULIN
• Insulin is the only parenteral antidiabetic
agent available for exogenous
replacement of low levels of insulin.

It is used to treat type 1 and type 2 diabetes

in adults who have no response to diet,
exercise, and other agents.

JoAnn, Z. (2019). Types of Insulin. In MOSBY'S PHARMACOLOGY MEMORY

NOTECARDS: Visual, mnemonic, and memory aids for nurses (5th ed., p.
196). St. Louis, Missouri: Mosby.
Therapeutic Actions and Indications
• Insulin is a hormone that promotes the storage of
the body’s fuels, facilitates the transport of various
metabolites and ions across cell membranes, and
stimulates the synthesis of glycogen from glucose,
fats from lipids, and of proteins from amino acids.
• Insulin does these things by reacting with specific
receptor sites on the cell.
Pharmacokinetics
• Insulin is available in various preparations
with a range of peaks and duration of
action.
• The types of insulin used are determined by
the anticipated eating and exercise
activities of any particular patient.
• Insulin glargine (Lantus, Toujeo) and insulin
Detemir (Levemir) cannot be mixed in
solution with any other drug, including
other insulins.
 3 Characteristics of Insulin:

✓ Onset - refers to the length of time

before insulin reaches the bloodstream
and begins lowering blood sugar.

✓ Peak time - the time during which

insulin is at maximum strength in terms
of lowering blood sugar.

✓ Duration - how long insulin continues to

lower blood glucose.
JoAnn, Z. (2019). Types of Insulin. In MOSBY'S PHARMACOLOGY MEMORY
NOTECARDS: Visual, mnemonic, and memory aids for nurses (5th ed., p. 196). St.
Louis, Missouri: Mosby.
*Selected Drugs:

JoAnn, Z. (2019). Types of Insulin. In MOSBY'S

PHARMACOLOGY MEMORY NOTECARDS: Visual,
mnemonic, and memory aids for nurses (5th ed., p.
196). St. Louis, Missouri: Mosby.

From JoAnn, Z. (2019). Types of Insulin. In MOSBY'S PHARMACOLOGY MEMORY NOTECARDS: Visual, mnemonic, and memory aids
for nurses (5th ed., p. 198). St. Louis, Missouri: Mosby.
 Parts of an
Insulin Pen

• https://www.researchgate.net/figure/Parts-of-an-Insulin-Pen6_fig6_319555151
Example:

The doctor’s order calls for:

HRI 12 units + 30 units NPH per subcutaneous injection
AC breakfast
 Source:
https://www.endocrineweb.com/conditions/typ
e-1-diabetes/type-1-diabetes-treatments

* NPH means neutral protamine hagedorn

 Contraindications and Cautions
• No contraindications other than episodes of
hypoglycemia
✓ (check blood sugar levels before giving insulin)

• Insulin does not cross the placenta; therefore, it is

the drug of choice for managing diabetes during
pregnancy.

• Insulin does not enter breast milk, but it is destroyed

in the GI tract and does not affect the nursing infant.
✓ Care should be taken during pregnancy and lactation to
monitor glucose levels closely and adjust the insulin dose
accordingly.
• Patients using inhaled insulin are at risk for
impairment of respiratory function; this route is
contraindicated in people with asthma or COPD and
in people with lung cancer or history of lung cancer.
Adverse Effects
• Most common: hypoglycemia
and ketoacidosis
(can be controlled with proper dose
adjustments)

• Local reactions at injection sites

(can be lessened by rotation of
injection sites)
General rules
•Never use the same injection spot more than once
consecutively.
•Place the injections 1-2 centimeters apart.
•Never inject close to navel.
Clinically Important Drug-Drug Interactions
❑Caution should be used when giving patient stabilized on insulin any
drug that decrease glucose levels (e.g. monoamine oxidase
inhibitors, beta-blockers, salicylates).
✓ Dose adjustments are needed when any of these drugs is added or
removed.

❑Care should be taken when combining insulin with any beta-blocker.

• The blocking of the SNS also blocks many of the signs and symptoms
of hypoglycemia, hindering the patient’s ability to recognize
problems.
Nursing Implications
✓ Draw up clear (e.g. regular, lispro, aspart, and glulisine—short acting)
before the cloudy (e.g. NPH) insulin to prevent contaminating a short-
acting insulin with a longacting insulin.
✓ Inject subcutaneously; aspiration is not necessary.
✓ Avoid massaging the site after injection.
✓ Rotate sites within anatomic area; the abdomen is preferred for more
rapid, even absorption.
✓ Only NPH (Humulin) can be mixed with short-acting insulins.
✓ Only the short-acting insulins may be administered intravenously (IV).
✓ Hypoglycemia is the primary drawback in maintaining tight control of
glucose level.
✓ Store unopened vials of insulin in the refrigerator; vial currently in use
should be stored at room temperature for 1 month.
✓ Prefilled syringes should be stored vertically with the needle pointing up
to avoid clogging the needle; gently agitate the syringe to resuspend the
insulin before use. May be stored in refrigerator for at least 1 week,
perhaps 2 weeks.
Oral antidiabetic drugs
and non-insulin
injectable agents:

Oral Antidiabetic Drugs

1. sulfonylureas
2. biguanides
3. meglitinides (glinides)
4. thiazolidinediones (glitazones)
5. alpha-glucosidase inhibitors
6. dipeptidyl peptidase-4 (DPP-4)
inhibitors (gliptins)
7. sodium-glucose cotransporter 2
(SGLT-2) inhibitors.
-Used for type 2 diabetes

JoAnn, Z. (2019). Oral Antidiabetic Drugs & Non-insulin Injectable Agents. In MOSBY'S
PHARMACOLOGY MEMORY NOTECARDS: Visual, mnemonic, and memory aids for nurses (5th ed.,
p. 199). St. Louis, Missouri: Mosby.
 Sulfonylureas
Therapeutic Actions and Indications

• Indicated as an adjunct to diet and exercise to

lower blood glucose levels in type 2 diabetes
mellitus.
• Stimulate insulin release from the beta cells
in the pancreas. Improves insulin binding to
insulin receptors and may actually increase
the number of insulin receptors.
• They have the off-label use of being an
adjunct to insulin and metformin and
improve glucose control in type 2 diabetes.

JoAnn, Z. (2019). Sulfonylureas. In MOSBY'S PHARMACOLOGY MEMORY NOTECARDS: Visual,

mnemonic, and memory aids for nurses (5th ed., p. 202). St. Louis, Missouri: Mosby.
 Pharmacokinetics
• Sulfonylureas are rapidly absorbed from the
GI tract and undergo hepatic metabolism.
They are excreted in the urine.

• Peak Effects and Duration of effects differ

JoAnn, Z. (2019). Sulfonylureas. In MOSBY'S PHARMACOLOGY MEMORY NOTECARDS: Visual,

mnemonic, and memory aids for nurses (5th ed., p. 202). St. Louis, Missouri: Mosby.
Contraindications and Cautions
• Contraindicated in the presence of known allergy to any
sulfonylureas to avoid hypersensitivity reactions
• In diabetes complicated by fever, severe infection, severe
trauma, major surgery diabetic Ketoacidosis, severe renal or
hepatic disease, pregnancy or lactation which require tighter
control of glucose levels using insulin.
• Contraindicated in Type 1 diabetes who do not have
functioning beta cells and would have no benefit from the
drug.
• Not for use during pregnancy and lactation
✓ Insulin should be used if an antidiabetic agent is needed during
pregnancy.
JoAnn, Z. (2019). Sulfonylureas. In MOSBY'S PHARMACOLOGY MEMORY
NOTECARDS: Visual, mnemonic, and memory aids for nurses (5th ed., p.
202). St. Louis, Missouri: Mosby.
Adverse Effects
• Most common: hypoglycemia
• GI distress including nausea, vomiting, epigastric
discomfort, heartburn, and anorexia
• Allergic skin reactions
• Increased risk of cardiovascular disease

Clinically Important Drug-Drug Interactions

• Caution with beta blockers which may mask the signs of
hypoglycemia,
• Caution with alcohol which can lead to altered glucose
levels when combined with sulfonylureas
• Any Drug that acidifies the urine because excretion of
the sulfonylurea may be decreased.
JoAnn, Z. (2019). Sulfonylureas. In MOSBY'S PHARMACOLOGY
MEMORY NOTECARDS: Visual, mnemonic, and memory aids for nurse
(5th ed., p. 202). St. Louis, Missouri: Mosby.
 Selected Drugs:

First Generation Sulfonlyureas:

▪ chlorpropamide (Diabinese)
▪ tolazamide (generic
▪ tolbutamide (generic)

Second Generation Sulfonlyureas:

▪ glimepiride (Amaryl)
▪ glipizide (Glucotrol)
▪ glyburide (DiaBeta, Micronase, Glynase
PresTab)

JoAnn, Z. (2019). Sulfonylureas. In MOSBY'S PHARMACOLOGY MEMORY NOTECARDS: Visual,

mnemonic, and memory aids for nurses (5th ed., p. 202). St. Louis, Missouri: Mosby.
Karch, A. M. (2017). Other Antidiabetic Agents. In Focus on Nursing Pharmacology (7th ed., p. 642). Philadelphia: Wolters Kluwer Health.
Oral Antidiabetic Drugs and Non-insulin Injectable agents:

Oral Antidiabetic Drugs

1. *sulfonylureas
2. *alpha-glucosidase inhibitors
3. *Biguanides
4. *dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins)
5. *meglitinides (glinides)
6. *sodium-glucose cotransporter 2 (SGLT-2) inhibitors
7. *thiazolidinediones (glitazones)

With asterisk(*): Drugs Used to treat type 2 diabetes

Non-insulin injectable agents:

1. Human Amylin – used both in DM type 1 and type 2
2. Incretin Mimetics - Used to treat type 2 diabetes
3. GLP-1 Agonists - Used to treat type 2 diabetes
JoAnn, Z. (2019). Oral Antidiabetic Drugs & Non-insulin Injectable Agents. In MOSBY'S
PHARMACOLOGY MEMORY NOTECARDS: Visual, mnemonic, and memory aids for nurses (5th ed.,
p. 199). St. Louis, Missouri: Mosby.
Karch, A. M. (2017). Other Antidiabetic Agents. In Focus on Nursing Pharmacology (7th ed., p. 642). Philadelphia: Wolters Kluwer Health.
Karch, A. M. (2017). Other Antidiabetic Agents. In Focus on Nursing Pharmacology (7th ed., p. 642). Philadelphia: Wolters Kluwer Health.
Karch, A. M. (2017). Other Antidiabetic Agents. In Focus on Nursing Pharmacology (7th ed., p. 642). Philadelphia: Wolters Kluwer Health.
 GLUCOSE-ELEVATING
AGENTS
DRUG NAME DOSAGE/ROUTE USUAL INDICATIONS
Glucose-elevating agents as the name Diazoxide Adult and pediatric: Oral management of
implies, raise the blood level of glucose (Proglycem, 3-8 mg/kg/d PO in two to hypoglycemia; intravenous
when severe hypoglycemia occurs Hyperstat) use for management of severe
three divided doses q8-
hypertension to counteract
(<40mg/dl). 12h
severe hypoglycemic
reactions)
Glucagon Adult and pediatric
(GlucaGen) (>20kg): 0.5-1mg
subcutaneous, IM or IV
Pediatric(<20kg):0.5 mg,
subcutaneous, IM or IV
 GLUCOSE-ELEVATING AGENTS

Therapeutic Actions and Recommendations

Increases the blood glucose level by decreasing insulin
release and accelerating the breakdown of glycogen in
the liver to release glucose.
Pharmacokinetics
Diazoxide is given orally.
Glucagon is given parenterally only and is the preferred
agent for emergency situations.
Both drugs are rapidly absorbed throughout the body and
excreted in urine.
GLUCOSE-ELEVATING AGENTS
Contraindications and Cautions

• Diazoxide – associated with adverse effects on the fetus including

pulmonary hypertension and should not be used during pregnancy

• Glucagon- Use of glucagon during pregnancy should be reserved for

those situations in which the benefits to the mother outweigh any
potential risks to the fetus. Caution should be used during lactation
because the drugs may cause hyperglycemic effects in the baby.

Adverse Effects

• Glucagon – GI upset, nausea, vomiting

• Diazoxide – vascular effects including hypotension, headache,
cerebral ischemia, weakness, heart failure, and arrhythmias (diazoxide
relaxes arteriolar smooth muscle)
 Clinically Important Drug-Drug Interactions
• Diazoxide in combination with thiazide diuretics causes an increased
risk of toxicity because diazoxide is structurally similar to these
diuretics
• Increased anticoagulation effects when glucagon is combined with oral
anticoagulants.
SEE YOU IN MODULE 2:

DRUGS AFFECTING THE

MALE AND FEMALE
REPRODUCTIVE SYSTEM