Hypoglycaemic agents

1. HYPOGLYCAEMIC AGENTS{ANTI
DIABETIC DRUGS}
DR S.O.OLAYEMI, FWACP.

2. DIABETES MELLITUS
METABOLIC SYNDROME OF INSULIN DEFICIENCY
AND GLUCAGON EXCESS.
• ACUTE MANIFESTATION
• DECREASED GLUCOSE UPTAKE
• Hyperglycaemia
• Glycosuria
• Osmotic Diuresis
• Electrolyte Depletion
• Dehydration And Acidosis > Coma And Death As In Dka.

3. DM >METABOLIC SYNDROME OF INSULIN
DEFICIENCY AND GLUCAGON EXCESS.
• ACUTE MANIFESTATION
• INCREASED PROTEIN CATABOLISM
• Increased Plasma Amino Acids And
Nitrogen Loss In Urine
• Hyperglycaemia>osmotic Diuresis >
Electrolyte Depletion > Dehydration And
Acidosis > Coma And Death

4. DM >METABOLIC SYNDROME OF INSULIN
DEFICIENCY AND GLUCAGON EXCESS.
• ACUTE MANIFESTATION
• INCREASED LIPOLYSIS
• Increase plasma FFAs, ketogenesis
>ketonuria > ketonemia > dehydration and
acidosis > coma and death.

5. DM > METABOLIC SYNDROME OF INSULIN
DEFICIENCY AND GLUCAGON EXCESS.
• CHRONIC MANIFESTATIONS
• NON ENZYMATIC GLYCOSYLATION
• Microangiopathy {Retinopathy,
Nephropathy, Neuropathy}
• Macroangiopathy {atherosclerosis, CAD, CVD
and peripheral vascular disease.

6. DM >METABOLIC SYNDROME OF INSULIN
DEFICIENCY AND GLUCAGON EXCESS.
• TYPE 1 > Juvenile onset {IDDM} < 30 years-no
obesity
• Viral or immune destruction of Beta cells
• Decreased Serum insulin level
• Genetic predisposition –Weak/polygenic
• HLA DR3 and DR4 association
• Severe Glucose intolerance
• Ketoacidosis
• Insulin is necessary for treatment

7. DM >METABOLIC SYNDROME OF INSULIN
DEFICIENCY AND GLUCAGON EXCESS
• TYPE 2 {Adult Onset – NIDDM obese and non
obese} – 40 years>
• Increase resistance to insulin
• Beta cells no variable
• OHA drugs/sometimes insulin
• Genetic predisposition -strong/polygenic
• No association with HLA system
• Mild to moderate glucose intolerance
• Ketoacidosis rare except infection etc

8. Glycaemic Goals of Therapy
Prepandial pls glu
90-130mg [5.0-7.2mmol/l [ADA]
<110mg/dl {ACE/AACE
Postprandial pls glu
<180mg/dl[<10mmol/[ADA]
<140mg/dl {ACE/AACE}
HbA1c < 7% (ADA)
HbA1c < 6.5%(ACE/AACE)

9. Diabetic Drugs
• Treatment strategy for type 1 DM
• Low Sugar diet
• Insulin replacement Expire 28 day in Rm temp –
• Rapid acting Insulin (Appearance Clear)
• Insulin lispro (Humalog)
• Insulin aspart (Novolog
• Insulin Glulsine (Apidra)
Their Onset= - 15-30min, Peak -1-2hr,Duration-3-5hr,
Maximum Duration– 5-6hr

10. Diabetic drugs- insulin
Short acting Insulin
Humulin (Regular)
Appearance clear
Onset – 1hr
Peak- 1- 2hr
Duration 3-4hr
Maximum duratin 6-8hr

11. Intermediate acting insulin
Appearance -cloudy
(NPH)Humulin N
Novolin N
Lente (Humulin L)
Their onset- 2-4hr, peak4-6hr,Duration 8-12hr
Maximum duration –14-20hr

12. Long acting Insulin
Apperance cloudy
Ultralente (Humulin U)
Onset 6-10hr, Peak 10-16hr,
Duration 18-20 hr,
Maximum duration 24hr

13. DIABETIC DRUGS- INSULIN
• Pre-mixed insulin Analogs
• Humalog Mix 75/25 (75% neutral
Protamine lispro
25%lispro
Novolog Mix 70/30 (70% aspart protamine
suspension
30% aspart). l

14. Insulin treatment
• Insulin Action – Binds insulin receptor –
{tyrosine kinase activity}
• Liver – Inc glucose stored as glycogen
• Muscle – Inc glycogen and protein
synthesis, K+ uptake
• Aids fat and triglycerides storage

15. Insulin – Clinical use
• Type 1 DM
• Stress induced hyperglycaemia –
sepsis,surgery etc.
• Life threatening hyperkalaemia.
TOXICITY – Hypoglycaemia, Weight gain,
hypersensitivity reactions rarely.

16. Treatment strategy for type 2
• Dietary modification
• Exercise for weight loss
• OHA – Sulphonylureas, Biguanides,
Glitazones and alpha glucosidase
inhibitors

17. Suphonylureas
• First Generation –
• Tolbutamide,Acetohexamide,Chlorpropamide
• Lower potency to 2nd generation
• Second Generation – Glyburide, glimepiride,
glipizide , gliclazide(Reclide) , glibenclimide
• Better tolerability/potency

18. ORAL HYPOGLYCAEMIC DRUGS- SULPHONYUREAS
• 1st Generation
• Acetohexamide 250-500mg (Max dose 1500mg/d (DA-
16hr
• Chlopropamide 100 – 250mg Max dose 500mg/d D.A-
72hr
• Tolbutamide 250-500mg. Max dose 1000mg/d (DA
24hr)
• Metabolixed in the liver and excreted as inactive metab
in the urine.

19. 2nd Generation Suphonlureas
Glipizide 2.5 –10mg (Max dose 20mg)
Glyburide 1.25 – 5mg(Max dose 20mg)
Glimepiride 1-4mg (Max dose 8mg)
Their duration : 20 – 24hr
Metabolized in the liver and excreted as
Inactive metab in the urine.

20. Suphonylureas Action
• Close K+ channel in Beta cell membrane, so cell
depolarizes – triggering of insulin release via
Ca2+ influx
• Stimulate release of endogenous insulin in type
2 DM.
• Require some islet function
• Useless in type 1 DM

21. Suphonylureas Toxicity
• First generation sulphonylureas –
disulfiram like effects
• Second generation - hypoglycaemia

22. Biguanides –Metformin DA-24hr
• Dose 500 – 1000mg (Max dose 2550mg)
• Exact mechanism unknown, ? Decrease
gluconeogenesis,?Increase glycosis,
• Decrease serum glucose levels
• Can be used in patients without islet
function
• TOXICITY – lactic acidosis

23. Glitazones – Rosiglitazone (2-4mg)
Max dose 8mg/d, Pioglitazone (15-
45mg) Max 45mg),Duration –24hr
• Action – Increase target cell response to
insulin

24. Glitazones
They are metabolized in the liver
/excreted in the kidneys
May be used as monotherapy in
type 2 or combined with
sulponylureas/biguanides
Problem – Weight gain
TOXICITY – Hepatoxicity
Troglitazone [no longer used

25. Alpha glucosidase inhibitors-
Acarbose (25-100mg), Miglitol(25-
100mg)
• Action – Inhibit intestinal brush border
alpha glucosidases – delay sugar
hydrolysis and glucose absorption leading
to decrease post prandial hyperglycaemia.
• Used as monotherapy in type 2 DM in
combination with
sulphonylureas/biguanides/glitazones
• TOXICITY – GI disturbances.

26. THE END
•THANK YOU