INSULIN AND ANTI DIABETIC DRUGS DR K K

INSULIN AND ANTI DIABETIC DRUGS DR. K. K. MISHRA ASSISTANT PROFESSOR S. K. M. C. H. MUZAFFARPUR

INSULIN ANALOGUE(DESIGNER INSULIN): �The animal insulin has limitation like antigenicity, resistance, hypoglycemia. �To overcome these s/e highly purified (monocomponent) insulin is now using frequently. �Hypoglycemia is still persisting, this is due to delayed onset & peak effect of insulin. �So there was need of insulin that act promptly so that can be administered with meal or within 5 -10 minutes of meal. �They should not produce peak (peakless insulin) thus minimize hypoglycemia. �To achieve these goals insulin analogue were developed.

�Insulin lisipro was the first insulin analogue introduced which has rapid onset but short duration of action but peak effect is present. �Later on other short acting insulin aspart & insulin glulisine were developed. �Long acting analogues like insulin glargine & insulin detemir also introduced, which have no peak. �There is no intermediate acting analogue but when short acting analogue is mixed with long acting intermediate acting is prepared. �The main disadvantage of insulin analogue is their high cost.

CLASSIFICATION OF INSULIN ANALOGUE: -

ONSET & DURATION OF ACTION OF DIFFERENT INSULIN TYPE: -

RAPIDLY & SHORT ACTING INSULIN ANALOGUE: � 1. INSULIN LISPRO- 1 st insulin analogue introduced & is similar to human insulin except change at position B 28 & B 29 , so that it does not self associate. It exists as hexamer but soon dissociate into monomer & rapidly absorbed with onset of action 5 -15 minutes , peak reaches 60 -90 minutes, effect lasts for 4 hours. It is used just before or within 5 minutes of meal.

Advantage of insulin lispro 1. More effective in reducing post prandial glucose level 2. Less hypoglycemic incidence 3. Uniform absorption on s. c. administrtion 4. Suitable for those patients in which blood sugar is not effectively controlled 5. Suitable for continuous subcutaneous insulin infusion (CSII) pumps.

� 2. INSULIN ASPART: - The proline of B 28 of human insulin is replaced by aspartic acid It more closely mimics the physiological insulin release pattern after meal longer acting than insulin lispro little faster acting must be administered just before the meal It can be used in place of intermediate acting insulin like semilente or isophane insulin

�INSULIN GLULISINE: - it is recently introduced short acting insulin property similar to other rapidly acting insulin It is administered either 15 minutes before or 15 minutes after meal Safety in pregnancy is not yet established

LONG ACTING ANALOGUES: �INSULIN GLARGINE: - it is very long acting insulin similar to ultra lente when injected it precipitates at injection site in s. c. tissue at neutral p. H and slowly dissolves to provide continuous low level of insulin Ø Advantages— 1. absorption is uniform even if site of injection is changed 2. no peak plasma concentration (peakless insulin)

3. Provides continuous prolonged low plasma level of insulin for maintaining normal blood glucose level. 4. Hypoglycemic episodes are very less as it is peakless insulin it is generally used in combination with short acting insulin once a day before meal. The reason behind acting short acting insulin is that it does not control meal time glycemia.

�INSULIN DETEMIR: - Recently introduced long acting analogue The amino acid at 30 th position is replaced by myristic acid (fatty acid) with B-29 terminal , due to this there is increased binding with albumin. There is self aggregation in s. c tissue & binding with albumin its action is prolonged. The effect is similar to older long acting insulin with less chance of hypoglycemia.

INSULIN DELIVERY SYSTEMS: � 1. CONVENTIONAL INJECTION BY S. C. ROUTE: Ø Frequent injection of insulin given by s. c. route Ø Increase chance of hypoglycemia, chance of missing the dose are the main problem Ø Thus there was need to develop such device which is convenient, affordable, prevent hypoglycemia & 24 hour euglycemia. Ø Various devices were developed to meet these objectives, still try to develop.

� 2. PORTABLE PEN INJECTION: Ø These are portable pen size injectors Ø Prefilled replaceable cartridges of insulin are available to use with these injectors Ø Different insulin formulation ( regular / insulin lispro / various combinations / mixtures) are available as cartridges. Ø Advantage is that it is convenient to use at work place, during travel, no need to carry drug vial/ syringe/needle separately Ø Disadvantage is that it is costly.

� 3. INHALED INSULIN: Ø It is powdered form of r. DNA human insulin & used by inhaler device in finely powdered & aerosolized form. Ø It is readily absorbed but only 10% of inhaled amount reaches the circulation. Ø Onset is rapid achieving peak level in 30 minutes & action last for upto 6 -8 hours Ø the above timing effect is comparable to regular insulin & there is less chance of postprandial hypoglycemia.

Ø Disadvantage is that control of blood glucose level is satisfactory in only 1/3 rd of patients. Ø Not suitable for children Ø Avoided in patients with respiratory disease like asthma, emphysema , bronchitis etc. due to s/e on lungs like pulmonary fibrosis, reduced lung volume, excess insulin antibody formation. Ø Used three times a day with meal , but for nocturnal control intermediate acting injectable insulin is required Ø Not cost effective, efficacy inferior in comparison to injectable insulin

�CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII) PUMPS: Ø It is an external open loop pump having size of a pager that can be placed on belt or pocket. Ø Its components are insulin reservoir, programme chip, key pad, display screen. Ø Insulin is delivered from time to time as per the programme through plastic tubing which is connected to subcutaneously implanted infusion set at abdomen. Ø Advantage is that no injection is required so convenient , insulin is released during meal as programmed

Ø Disadvantage is that can not find out the insulin requirment Ø Clinician has to calculate the amount of insulin delivered phase wise Ø Food must be taken as per the schedule, failing which may result into hypoglycemia as insulin is released as per programme irrespective of blood glucose level Ø Needle may be blocked so faulty or no release of insulin Ø Pump failure may occur Ø Very high cost not affordable to maximum people

�ORAL INSULIN (RECOSULIN): - Recently developed & marketed It is liposomal encapsulated Insulin is protected from degradation in stomach. Much expensive

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