Diabetius Mellitus

Symptoms:- polydipsia, polyphagia, polyuria, dry skin, vaginal

infection.

Types:-
Type 1 IDDM.
Type 2 NIDDM.
Gestational DM.
2nd diatetius
Diabetius insipidus " ADH"
Insulin secreted from B-cells of langehans in pancreas.

Insulin structure:-
Proinsulin -C chain insulin
86 amino acid 51 amino acid
proinsulinUsed to check purity of insulin products.

Modern Pharmacy Academy

Differentiate bet type 1,2
Type 1 Type 2
Insulin dependent D.M. Non-insulin dependent D.M
IDDM. "NIDDM"

- Full destruction of B-cells - Partial destruction of B-cells or

insulin resistance.
- Juvenile onset occur in adult < - Occur in adults > 30 years.
30 years.
- Wt loss - Wt gain

- Auto – immune disease - Not auto – immune.

- Prone to ketoacidosis. - Not prone to ketaacidosis.

- TTT Insulin Except "surgery, trauma,

infection".
- Diabetic ketosis. "DK" - TTT oral tab.

- Hyperglauncmic, hyperosmolar
non-ketonic syndrome "HHNK"

Gestational diabetius:- occur in pregnancy.

And it is considered glaucose intolerance.
Mainly the BGL back to normal after labour.

. female < 25 year

. not obese no gestational D.M.
. no family history

Modern Pharmacy Academy

2nd D.M. :- due to disease or drug
- Niacin, loop, thiazide diurctic.
- Sympathiomimetic
- Cushing disease ( cortisone).
- Phenytoin

Diabetius insipidus . not related to BGL . ADH

TTT : vasssopressin, desmopressin (oral).
Lypressin (nasal).
20 Liter / day normal 1 – 2 l/day

Insulin effect:-
1- Increase Glaucose uptake by the cell
From blood vessel.
glycogensis
2- Glaucose Glycogen.
3- Amino Acid protein.
4- Fatly Acid Fats.
glycogenolysis
5- Glycogen glaucose.
glauconeogenesis
6- Amino Acid & fatly acid glaucose.

:. Insulin is anabolic hormone.

Glauconeogensis: Formation of glaucose from non-carbohydrate
source.

Note:-
prescence even low amount of insulin, prevent formation of the
ketonebodies.

Modern Pharmacy Academy

Formation of ketone bodies:-
In absence of insulin:-
- Cell consume all glaucose content
To produce energy.
- Then cell break glycogen to glaucose
To consume it in producing energy.
- Then cell break its own protein into amino acid then to glaucose
to consume it in producing energy.
- Then cell consume its own Fats.

Fats fatty acid + glycerol

Ketone Glucose
bodies Consumed

Ketone bodies:-

Acetone Acetoacetic acid

Excreted W breathing excreted in urine

"Fruity odor" :. Ketonuria

Modern Pharmacy Academy

After time the urine is saturated with Ketone bodies so the Ketone
bodies appear in blood so ketonemia
So the bodies make rapid, deep respiration "kussmal respiration".
To excrete acetone.
After time kussmal respiration stopped then ketonemia increased
:. Ketoacidosis (PH )
:. Coma & death.
Note that the Ketone bodies formation occur when BGL is
more than 250 Mm/dl

Counter – regulatory hormone:

Insulin . EPI
. NEPI
. Cortisol
. GH "growth Hormone"
. glaucagon (from α- cell of pancreas)

TTT of hyperglaucemia TTT of hypoglaucemia

In Type 1 D.M
Anion gap .
Na [cl + Hco3].

Normal range 14 – 18

Urine sample + Na+ nitroprusside + ammonia purple So

Ketone bodies in urine

Modern Pharmacy Academy

Glucosuria:- apper of glaucose in urine occur BGL > 180 mg/dl
Called renal threshold

.
Lab test:- random BG test :- not used.

Normal impaired D.M.

Fasting BG 80-110 110-125 Above 125
Fasting 8 hr Mg/dl Mg/dl mg/dl
Oral glucose Up to 140 140-200 Above 200
tolerance mg/dl Mg/dl Mg/dl
test
“OGGT”

OGTT:- 75 gram anhydrous glucose in water and then after 2 hr..

50gram .
1 hr.
75gram .
2 hr.
100gram .
3 hr.

ሺ۶‫܍ܛܗ܋ܝܔ܏ – ܊‬ሻ
۵‫ ܌܍ܜ܉ܔܝܛܗ܋ܡܔ‬۶‫ ܊‬ሺ۶‫ۯ܊‬૚‫܋‬ሻ =
۶‫ ܊‬ା ۶‫܍ܛܗ܋ܖ܉ܔ܏ – ܊‬

Normal = 7% 125 mg/dl %6

.This test is done by every 7-16 week "120 days"

"
.long term Monitorin

Glycosulated fractosamine test

Every 3 weeks .
short term monitoring.
.
Used in pregnancy.

Note:- BMI 27 :. Risk of D.M

‫ ܜ܅‬ሺ‫܏ܓ‬ሻ
۰‫ۻ‬۷ =
ሺ ‫ ܜܐ‬ሺ‫ܕ‬ሻሻ

Modern Pharmacy Academy

 Hyperglucemia

Mild Moderat Severe

Up to 250-500 > 500
250mg/dl mg/dl mg/dl

Somagyi effect "rebound hyperglaucemia-:

Hypoglaucemia at night due to insulin Release followed by
hyperglaucemia at morning due to glucagon
.
Release.

Drugs: BGL cortisone, EPI, NEPI, Thiazide, Loop, niacin, ,

.
Phenytoin, isoniazid, antiviral.
.
Drugs: BGL - MAO-I, fluxetine, salicylate ( dose), alcohol.
Masking of hypoglaucemi symptoms Propranolol, nadolol and
timolol

Hypoglucemia
Mild Moderate Severe
Tachycardin CNS effect
Unconscious
Sweating Confusion BGL < 40 mg/dl
CNS No unconsciousness Coma
seizires
 ‫
ا  ا‬ TTT give
Glaucagon 1 mg I.M / I.V / S.C
TTT by
Oral if unconsious
Glaucose I.V. glaucose

.
Pseudo – hypoglaucemic:- symptoms appear but BGL is normal.

Modern Pharmacy Academy

 TTT
1-Non-pharmacological TTT:
• Fat, carbohydrate in diet, Fiber
• Aerobic:- swimming, walking BGL..
• Anaerobic:- wt-lifting has .
no effect on BGL.
-Ve affect heart

Diet Balance Exercise

Drug

Note -:
.
Starvation, vomiting, low CHO in diet ketone bodies formation.

Pharmacological TTT

1-Insulin
• Used in type 1 and given SC
• Used in uncontrolled type 2..
Types
Short Acting: - semilent, regular, (Mixed Freely Clear, soluble,
S.C. &
I.V)
.
aspart, glulisine, lispro.
Intermediate Acting:- lente (70% ultra + 30% semi) , NPH
"neutral
protamine hegadron (isophane) ).
Long Acting:- ultralente, protamine – zn insulin

Modern Pharmacy Academy

 )
Garline(clear)
Duration of insulin depends on -:
• Zn content
• Protamin content
Semi lente < lente < ultra lente in zn content
Glargine:- contain No zn
No zn
Its long duration is due to PH = 4
Mixing in insulin product-:
1-Lente W other Lente semi ultra
2-Regular W other insulin product. .
S.E. of insulin:- hypokalemia. .
S.E. of insulin injection:- lipodystrophy
Lipohypertrophy lipohypotrophy
To avoid lipodystrophy .
rotate site of injection.
Note -:
Don't inject insulin near an excersicing muscle as it will cause
hypoglaucemia. .
.Least absorption site abdomen. .
Note -:
Insulin pump (S.C. PUMP ). .

Oral tablet
Oral hypoglaucemic antihyperglaucemic
S.E. - hypoglaucemia No hypoglaucemia but may
Hypoglaucemia of The oral
hypoglaucemic
Insulin
Secretagoges
"sulfonylurea"
"

Modern Pharmacy Academy

 Antihyperglaucemic

Insulin sensitizer α – glaucosidose inhibitor DPP-4 Inhibitor

Biguanide
"
Thiazolidendione “glitazone"

Insulin secretagogues
Drugs (all acidic):
Sulfonyrlureas:
First gen: chlorpropamide, tolbutamide, acetohexamide,
,more potent.
tolazamide, more lipid-soluble,

. Also repaglinide.
Second gen: glyburide, glipizide, glimperide.

Mechanism:block ATP-sensitive potassium channels insulin

Pancreatic release (primary), and also as sensitizers with time
(Secondary).

Use: Type 2 (useless in type 1, require functioning beta cells).

Chlorpropamide: longest duration of action.

CI : in liver and kidney disease.

↑ SE: severity and frequency, disulfiram-reaction (also with

Tolbutamide).

Use: insulin instead during stressful conditions (↑ risk of

Hyperglycemia due to ↑ counter-regulatory hormones release).

SE: severe / prolonged hypoglycemia (esp. in the elderly, w/

glipizide /glyburide), GI upset, sulfa sensitivity, sun sensitivity,
headache, rash, Tachycardia, hematologic problems,
cholestatic jaundice.

CI: allergy to sulfa drugs, pregnancy, lactation.

Modern Pharmacy Academy

Altered protein binding of sulfonylureas: alcohol, salicylates,
NSAID’s, methyldopa, chloramphenicol, MAO-I, clofibrate,
probenecid.

Therapy failure: due to ↓number of funcLoning beta cells.

Primary: failure to control BG within 4 weeks.
Secondary: initial control of BG, but fails to maintain control,
due to progression of DM.
Repaglinide: less hypoglycemia. .

Insulin sensitizers
Drugs: biguanides (metformin, basic drug), thiazolidinediones
(rosiglitazone, pioglitazone).
Mechanism: anti-hyperglycermic not hypoglycemic.
↑ sensiLvity to insulin, (metformin work on liver, ↓ hepaLc
glucose production, gluconeogenesis), (glitazones ↑ sensiLvity
/ ↓ insulin resistance in muscle and adipose tissue).
Thiazolidinediones bind to PPARs.
Use: significant insulin resistance. Biguanides

SE: fatal lactic acidosis, metallic taste, GI upset, ↓ vitamin B12,

no hypoglycemia.
May be fatal if at ↑ risk of lacLc acidosis (liver / kidney disease,
hypoperfusion, hypoxia, radiography).
Phenformin was d/c.
Glitazones

SE: liver toxicity / failure (monitor), weight gain, edema, GI

upset, no hypoglycemia. Troglitazone was d/c due to liver
toxicity.
CI: liver disease. May resume ovulation in premenopausal
women. Highly protein bound (99%).

Modern Pharmacy Academy

Alpha-glucosidase inhibitors
Drugs: acarbose (polysaccharide), miglitol (basic
monosaccharide)
Mechanism: inhibit intestinal enzyme alpha-glucosidase ↓
absorption of complex carbohydrates (starch, dextrins,
disaccharides).

Use only glucose or lactose for correcting hypoglycermia if it

occurs.

Use: significant post-prandial hyperglycemia. Minimal effect on

preprandial or fasting BG. Good combination with insulin
.
secretagogues. Take with first bite of meal.

SE: GI (diarrhea, abdominal pain, flatulence) due to undigested

carbohydrates in the lower GI, no hypoglycemia.

CI: GI conditions (inflammatory bowel, colonic ulcer,

obstructive bowel, intestinal gas), liver cirrhosis (monitor liver
, pregnancy.
function), .

Complications of DM-:
• Nephropathy. .
• Neropathy. Microvascular. .
• Retinopathy..
Macrovascular system. (Supply Leg W blood)

Modern Pharmacy Academy

DPP-4 Inhibitor:
• Incretin is intestinal enzyme that stimulate insulin release.
• Amylin: neurohormone co-secreted w insulin by B-cells of
pancreas.
• Incretin mimetics: Exenatide which may be used w
Metformin or sulfonylurea only. Taken S.C
• Dipeptidyl peptidase 4 inhibitor (DPP-4 Inhibitor)
X-gliptin
1- Used in type 2 “antihyperglaucemic “
2- Fasting & postprandial BGL
3- Hbn1c
Category B in Pregnancy
S.E: Angioedema and Anaphylaxis

Lipase
Fats Fatty acid “absorbed”
Orlistat is lipase inhibitor which inhibit the fat absorption so
Fats excretion in stool “Steatorrhea”

Modern Pharmacy Academy