1. Antidiabetic drugs

8. Genetically Engineering Insulin DNA strands can be separated and used as templates for new DNA synthesis An 18 base synthetic piece of DNA will hybridise to strand 2 and form the primer for complete synthesis of a new strand 1 An 18 base synthetic piece of DNA with an altered 4 th codon will hybridise to strand 1 which will tolerate the mistake. This will form the primer for complete synthesis of a new strand 2. When next this DNA replicates then a new ‘engineered’ gene for the B-chain will be formed that codes for ASP in position 9 instead of SER.

9. The bacteria that contain the plasmid that carries this engineered gene for the B chain will now produce insulin that cannot form dimers or hexamers. This monomeric insulin has proved effective for diabetics

10. Substitution in the B chain of His (B10) with Asp(B10), produced a genetically engineered human insulin ‘Insulin Asp(B10)’ that was absorbed twice as rapidly. However, it illustrated a potential problem in that it changed the 3D structure of insulin and increased its affinity for the IGF-I receptor and therefore had increased growth and mitogenic effects compared with native insulin. The analog Asp(B10) has been demonstrated to lead to increased mitogenic activity, and cause a dose- dependent increase in the incidence of adenocarcinomas in laboratory animals. Further clinical studies with this analog were therefore halted. ‘Insulin Lispro’ was the first genetically engineered rapid-acting insulin analog to become available clinically in 1996. The normal sequence of Pro (B28) and Lys (B29) is reversed (LysB28,ProB29; Lispro). This reversal inhibits self-association, and thus faster absorption, higher peak serum levels, and shorter duration of action. Importantly, these amino acid sequence changes do not affect its receptor- binding domain and the affinity to the insulin receptor of insulin Lispro is similar to that of regular insulin, whereas Lispro's affinity for the IGF-I receptor is slightly higher but not enough to cause a difference in its cell growth-stimulating activity compared. In clinical studies, as expected from a short-acting analog, insulin Lispro achieved significant improvements in postprandial glucose levels with a lower rate of hypoglycemic events compared with regular insulin.

12. glulisine is a rapid-acting insulin analogue that differs from human insulin in that the amino acid asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid.

14. Longer lasting formulations. Avoids concentration fluctuations Insulin Lente - mixed with zinc; hexamers that must dissociate. - 70%Zn insulin crystals:30% amorphous insulin -Ultra lente is longest acting-solid dissolution, then hexamer. NPH Insulin - Regular insulin mixed with protamine to delay absorption - NPH=neutral protamine Hagedorn - Long acting; crystalline dissolution, then hexamer dissociation. Insulin Glargine (Lantus) (ip shifted from pH 5.4 to 6.7) -avoids Zn and protamine -amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. - low aqueous solubility at neutral pH, but is completely soluble at pH 4. After sc injection, the acidic solution diffuses and is neutralised leading to formation of microprecipitates from which insulin is slowly released in a relatively constant concentration/time profile over 24 h with no pronounced peak.

15. Schematic Time–Activity Curves for Selected Insulin Formulations. The graph depicts time–activity profiles for selected insulin formulations. For simplicity, the known dose-dependent variability in duration of action and the wide variability in hypoglycemic effect for the selected formulations among patients are not represented. Biphasic insulin preparations are not shown.

16. The goal of subcutaneous insulin therapy is to mimic both the normal prandial insulin secretion and the basal between-meal insulin levels. Most current regimens use at least two different insulin analogs. Long-acting insulins to provide basal insulin levels, and rapid, short-acting insulins to correct the transient hyperglycemia associated with meals. Another available option is the use of an insulin pump, in the form of a battery powered pump controlled by a microprocessor.

30. Classification:

31. The psychoactive drugs are classified as ; 1. Antipsychotic drugs 2. Anti depressant drugs 3. Anti anxiety drugs

32. Anti psychotic drugs are used to treat psychoses like schizophrenia, mania, senile dementia and behaviour disorders in children. These drugs act by depressing the central nervous system (by decreasing dopamine levels) and by producing sedation without producing sleep. Thus the antipsychotics are employed to reduce excitation, agitation, agressiveness and impulsiveness. Hence they are also known as antischizophrenic drugs or neuroleptic drugs or major tranquilizers.

66. STEROIDS

69. Classification