LECCTURE OF PHARMACOLOGY

MADE BY NURSING ZONE TEAM

L12. Endocrine System drugs

THIRD YEAR

@Nursing_Zone39

• Pancreas: is a mixed exocrine (secrets digestive enzymes) & endocrine

Oral
of Langerhans) glands. Rectal SC

Hmmmm

(islets

• Islets
or ofEasy
Langerhans secrets:

1.orInsulin:
Verity from B or cells

2. Glucagon: from A or cells Bypasses liver
(hyperglycemic effect) Patient can
or Compact

3. Somatostatin: from DErratic

or cellsabsorption low
/ hypothalamus administer

Convenient

4. Amylin: from B or cells compliance Complete
First pass effect

absorption

Sometimes inefficient

Small does
difficultly in swallowing

Differentiate between glucose, glycogen & glucagon Pain full

• Sublingual-Buccal
Glycogen is a stored form of energy. IV IM

• Glucagon signals the body to convert the stored glycogen back into glucose.

TI Rapid absorption

Stability of drug
I Rapid TI Large volume

GBBBEmMgm

E

Higher bioavailability
I Accurate K Sustained release
E Can’t be retrieved (DM) possible

Inconvenient
IXHyperglycemia

XI Expensive Trained personnel

Small doses
only

& Glucagon
EXRequires trained personnel Erratic absorption

Can’t be swallowed

Insulin

Work as a team (opposite to each other), and they’re the most

important regulators of normal fuel metabolism (glucose).

Complementary interaction of glucagon and insulin

Best of luck

Blood glucose Blood glucose

β-cell
α-cell α-cell β-cell

Glucagon Insulin Glucagon Insulin

Blood glucose to normal

Blood glucose to normal

• Somatostatin: inhibits both glucagon & insulin secretion by a paracrine

Oral Rectal SC

Hmmmm

mechanism.

or Easy inhibits both glucagon
• Somatostatin:
& insulin secretion by a paracrine

or Verity
mechanism. Patient can

Bypasses liver
or Compact

• Amylin: delays gastric emptying, and opposes insulin by stimulating

Erratic absorption low administer

Convenient
glycogen breakdown.

compliance Complete
First pass effect

absorption

Sometimes inefficient

Small does
difficultly in swallowing

Inappropriate glucose homeostasis Pain full
Diabetes Mellitus

Sublingual-Buccal IV IM

TI Rapid absorption

• The most common

Stability of drug
I Rapid
endocrinological disorder. TI Large volume

GBBBEmMgm

E

• IsHigher
a group I Accurate
of syndromes characterized
bioavailability by: K Sustained release
E

◦Hyperglycemia
Inconvenient
IX Can’t be retrieved possible

XI Expensive Trained personnel

◦Altered metabolism of lipid, carb., protein

What is Diabetes Mellitus

Small doses only

◦ risk of complicationsEXRequires trained personnel

from vascular Erratic absorption
diseases (include

Can’t be swallowed
atherocalarosis)

• Differentiated from Diabetes insipidus (deficiency/imbalance of ADH)

• Complications:

◦Autonomic neuropathy.

◦Hypertension.

Best of luck

◦Cardiovascular disease.

◦Dyslipidemia.

◦Gastropathy.

◦Peripheral vascular disease.

◦Erectile dysfunction.

◦Renal disease.

◦Peripheral neuropathy.

Retinopathy/Macular edema.

Insulin dependent DM (IDDM)

Oral Rectal Type I

SC

Hmmmm

Sever / absolute lack of insulin

(10-20%)

or Easy

Verity with insulin
orTreated

Bypasses liver Patient can
or Compact

Erratic absorption low administer

Convenient Type

compliance Complete
First pass effect Diabetes Mellitus

absorption

Sometimes inefficient

Small does
difficultly in swallowing

Pain full

Non-insulin dependent DM (NIDDM)

Sublingual-Buccal
Type II IV IM

(80-90%) Insulin resistance (⬇ sensitivity to its action)

TI Rapid absorption + lack of insulin

I Rapid TI Large volume

E Stability of drug

GBBBEmMgm

Accurate

ITreated K Sustained release

E Higher bioavailability by a range of drugs

IX Can’t be retrieved possible

XI Inconvenient
Diagnosis Diabetes Expensive Trained personnel

Small doses only

EXRequires trained personnel Erratic absorption

Can’t be swallowed
Test Fasting Plasma Glucose (FPG)*

Oral Glucose Tolerance Test*

(Preferred Test) Informal Plasma Glucose *

before taking food (no calories (common during pregnancy) after

Stage for at least 8h) taking food

Casual plasma glucose Two-hour plasma glucose

Diabetes FPG >126 mg/dl

Best of luck

>200 mg/dl (2hPG) >200 mg/dl

Impaired Impaired Glucose Tolerance

Impaired Fasting Glucose

Glucose (IGT) = 2HPG >140 ; and

(IFG)=FPG >100 and <126

Homeostasis <200 mg/dl

Normal FPG <100 mg/dl 2 hPG <140 mg/dl

• In absence of unequivocal hyperglycemia (=no confirmed diagnosis), these need to

be repeated on the second day

• All results are confirmed by the existence of symptoms

Glycated hemoglobin (Hb-A1c)

Oral
• Used to monitor the average Rectal
plasma glucose concentration & SC
HB over

Hmmmm

prolonged

or Easy periods of time (2-6months)

or Verity Patient can

HbA1c Bypasses
mmol/mol liver %
or Compact

Normal Below 42 mmol/mol Belowadminister
6.0%
Erratic absorption low

Convenient

Prediabetes compliance
42 to 47 mmol/mol Complete
6.0% to 6.4%
First pass effect

Diabetes 48 mmol/mol or over 6.5% absorption
or over

Sometimes inefficient

Small does
difficultly in swallowing

A1c (%) Pain full
Average Blood

Sugar (mg/dL)

Sublingual-Buccal IV 4 IM68

5 97
TI Rapid absorption Rapid

I TI Large volume
E Stability of drug
6 126

GBBBEmMgm

Accurate

I K Sustained152
release
E Higher bioavailability 7

IX Can’t be retrieved possible

XI Inconvenient Expensive 8 183

Trained personnel

Small doses only

EXRequires trained personnel Erratic absorption

Can’t be swallowed

Treatment of

Hyperglycemia

Treatment

Best of luck

Diet & Physical exercise

Anti-diabetic drugs

A. Parentral agents B. Oral hypoglycemic

agents

(Insulin)

A. Parentral agents (Insulin)

Oral
• Chemistry: Rectal SC

Hmmmm

◦A protein

or Easy
‣ MW ~6000

Verity
or ‣ C-poly-peptide (chain): A & B

Bypasses liver Patient can
◦A
or Compact
hormone: 51 a.a

Erratic absorption low administer

Convenient

compliance Complete
First pass
• Action effect
& MoA:

absorption

◦Carb, inefficient
Sometimes fat, and protein metabolism

◦Storage of glucose (as glycogen in Small does
difficultly in swallowing

liver & skeletal muscles, and as Pain full

triglycerides in fat cells)

Sublingual-Buccal IV IM

• So insulin;
TI Rapid absorption

I Rapidin blood by:

◦Lowers concentration of glucose
Stability of drug
TI Large volume

GBBBEmMgm

E Accurate (in liver).

Higher
‣ Stimulating glycogenI synthesis
bioavailability K Sustained release
E ‣ Increase glucose Can’t be
(inretrieved possible

Inconvenient
IXuptake muscle) by

XI glucose transporter type 4 (GLUT-4).

Expensive Trained personnel

Small ‣doses only gluconeogenesis (in liver).

Inhibiting

EXRequires trained personnel Erratic absorption

Can’t be swallowed
◦Stimulates DNA, RNA, and protein synthesis

(essential for growth).

◦Facilitates the storage of triglyceride in

adipose tissue.

Best of luck

• Pharmacokinetics:

◦Not active orally (broken down in stomach)

◦Inactivated by insulinase in liver & kidney

◦50% is destroyed in a single passage to liver

◦IV has a t1/2 of less than 9min, so slow release preparations

◦Dose reduced in renal impairment

• Sources of Insulin:

1- Beef pancreas/ Pork pancreas

2- Human insulin: recombinant DNA origin

• Insulin preparations:

1-Oral Rectal
Very short, Rapid acting insulin (ultra-short, 3-5h):
SC

Hmmmm

Insulin Lispro, insulin Aspart
Easy

2-orShort acting insulin (6-10h):
Regular soluble insulin

Verity
3-orIntermediate acting insulin (10-12h):

Bypasses liver Patient can
or Compact

Neutral Protamine Hagedorn insulin (NPH)

Erratic absorption low administer

4-Convenient
Long acting insulin (24h): Ultra-Lente insulin, insulin Glargine.

compliance Complete
First pass effect

absorption

• Sometimes
Situations inefficient
in which short and long acting insulins should be used

together:in swallowing Small does
difficultly

1- for old and young patients where frequent injections are Pain
notfull
easy.

2- Before long flights.

Sublingual-Buccal IV IM

• Clinical uses of insulin:
TI Rapid absorption

1- life long IDDM.

Stability of drug
I Rapid TI Large volume

GBBBEmMgm

E 2- NIDDM which is not controlled

Higher bioavailability
I Accurate K Sustained
by oral hypoglycaemic release
agents.

E 3- Gestational diabetes. Can’t be retrieved possible

Inconvenient
IX

XI4- Diabetic ketoacidosis (life Expensive

threatening). Trained personnel

Small doses only

5- Hyperosmolar coma.

EXRequires trained personnel Erratic absorption

Can’t be swallowed
6- Before major operations.

• Adverse effects:

◦Hypoglycemia.

◦Insulin allergy and insulin resistance.

Best of luck

◦lipodystrophy: Lipo-hypertrophy (accumulatio

of fat); and lipo-atrophy (repeated injections

in specific area).

◦Insulin edema.

◦Weight gain.

B. Oral hypoglycemic agents

Oral Rectal SC

Hmmmm

1st generation:
Easy Chlorpropamide (t 1⁄2 60 hrs).
1- Sulfonylureas (oldest used Type II DM drug)

or
2nd generation: Glipizide.

or Verity
3rd generation: Glimiperide
Bypasses liver Patient can
Compact
◦Action and MoA:
or

Erratic absorption low administer

Convenient
‣ I.Decrease blood glucose level by:

compliance Complete
First pass•effectIncrease of insulin release from functioning pancreatic β cell

• Increase in insulin receptors. absorption

Sometimes inefficient

• Reduction of serum glucagon concentration. Small does

difficultly‣ inII.swallowing
chlorpropamide has antidiuretic effect.

Pain full

◦Clinical uses of sulfonylureas:

Sublingual-Buccal
‣ Mainly for Type II DM patients. IV IM
‣ Chlorpropamide: promotes ADH release, used to treat diabetes insipidus.
TI Rapid
◦Adverse absorption
effects:
‣ Weight
Stability of drug
I Rapidin obese patients), TI
gain (not recommended
Large volume
hypoglycemia,

GBBBEmMgm
E

Higher bioavailability
I Accurate
cholestatic jaundice, allergic K Sustained
skin reaction, hemopoietic release
changes.

E ‣ Cross placenta. IX Can’t be retrieved possible

Inconvenient
XI ‣ Disulfiram-like reaction with

Expensive
alcohol. Trained personnel

Small‣ doses only

Chlorpropamide can cause water retention by increase release of ADH

EXRequires trained personnel Erratic absorption

Can’t be swallowed

2- Meglitinides (Repaglinide, Nateglinide)

• Action and MoA:

Lowers blood glucose, and stimulates insulin release from B cells, causing

potassium k+ channel to close.

Best of luck

• Abs/Dist/Elim:

More rapidly acting and has shorter duration compared to sulfonylurea.

• Clinical uses:

◦Taken with each meal to stimulate insulin release.

◦Useful in patients with: type 2 DM and impaired renal function.

• Adverse effects:

◦Hypoglycemia.

◦Less weight gain

•
Action and MoA: Lowers blood glucose, increase of GLUT-4.
Oral Rapid oral absorption, Rectal SC

Hmmmm

Abs/Dis/Elim: • short t 1⁄2 7h.

Clinical EasyType 2 DM.
or use:•

Adverseor •
effects:
Verity

◦Weight gain, fluid retentionBypasses
which could Patient can
liver lead to heart failure.
or Compact

◦Low risk of hypoglycaemia. Erratic absorption low administer

Convenient

compliance Complete
First pass effect 3- Thiazolidinediones (Pioglitazone, Rosiglitazone)

absorption

Sometimes inefficient
& Metformin) Small does

difficultly in swallowing • Action and MoA: Lowers blood glucose

Pain full

5- Metformin (Glucophage)
4- Biguanide compounds (Phenformin

• Action and MoA: concentration, via inhibiting

◦Inhibition of hepatic
Sublingual-Buccal IV
gluconegenesis by activating AMP.
IM
gluconeogenesis. • Abs/Dist/Elim: Given orally t 3 1⁄2 h.
◦Direct stimulation of
TI Rapid absorption avoided in patients with renal
Rapid
glycolysis.
Stability of drug
I insufficiency TI Large volume

GBBBEmMgm
E

◦Decrease of
Higher bioavailability
I Accurate
• Clinical uses: K Sustained release
E intestinal absorption IX Can’t be retrieved possible

◦patients with refractory obesity .

Inconvenient
XI of glucose.

Expensive
◦certain non-obeseTrained
adult personnel
diabetics.

Small doses only

◦Inhibition of plasmaRequires trainedItpersonnel

EX does not causeErratic absorption

hypoglycemia.

Can’t be swallowed
glucagon levels. • Adverse effects:

◦Up-regulation of ◦lactic acidosis.

insulin receptors. ◦Anorexia, GIT disturbances,

including diarrhea weight loss.

Best of luck

• Action and MoA: Delays carboydrate absorption from intestine; via decrease

intestinal absorption by inhibiting the action of intestinal brush border α-

glucosidase, slows the absorption decrease the postprandial (after meals) rise in

plasma glucose in both normal and diabetic subjects.

• Abs/Dis/Elim: Metabolized in GIT by bacteria and digestive enzymes.T 1⁄2 2h.

• Clinical use: Type 2 DM not controlled by other drugs.

• Adverse effects: Flatulence & diarrhea.

6- Glucosidase inhibitors (acarbose and miglitol)

Treatment of hypoglycaemia
Oral Rectal SC

Hmmmm

or Easy

or Verity(IV).
1- Glucose Patient can

Bypasses liver
or Compact

Erratic absorption low administer

Convenient
2- Glucagon:

compliance Complete
First pass effect

◦Action: Increase blood glucose con. absorption

Sometimes inefficient

Small does
difficultly in swallowing

◦MoA: Glucagon activates adenylate cyclase = stimulatingPain full
hepatic

gluconeogenesis

Sublingual-Buccal IV IM

◦Abs/Dist/Elim: Given by injection t 5 1⁄2 min.
TI Rapid absorption

Stability of drug
I Rapid TI Large volume

GBBBEmMgm

E ◦Clinical use: Emergency treatment

Higher bioavailability
I Accurate of K Sustained release
E

Inconvenient
IX Can’t
hypoglycaemic (caused be retrieved
by insulin possible

XI overdose),. Expensive Trained personnel

Small doses only

Hypoglycaemia

EXRequires trained personnel

gtfo Erratic absorption

Can’t be swallowed
◦Adverse effects: uncommon

Best of luck

MADE BY NURSING ZONE TEAM

Pharma references

A- Basic and Clinical Pharmacology 13 E Paperback

Bertram Katzung (Author), Anthony Trevor (Author) Publisher: McGraw-Hill Medical; 13 edition
(December 23, 2014)
Language: English
ISBN13:97 0071825054
ISBN 10:0071825053
B. Lippincott Illustrated Reviews: Pharmacology 6th edition (Lippincott Illustrated Reviews Series)
Paperback
Karen Whalen PharmD BCPS (Author) Edition: Sixth, North American.
Edition Language: English. ISBN-13: 978-1451191776 ISBN-10: 1451191774
2. List Essential References Materials (Journals, Reports, etc.) British National Formulary (BNF)