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drugs affecting glucose metabolism Insulin Glucagon Oral hypoglycemics Acarbose Somatostatin Diazoxide IDDM lack of insulin due to destruction of beta cells dogs & cats NIDDM insulin may be lower or higher than normal but their is hyperglycemia assoc w/ obesity *cats* stimulation of insulin secretion glucose, aa, FAs, ketone bodies GI hormones stim of B2 adrenergic rec vagal stim (M3 rec) inhibition of insulin secretion stim of a2 adrenergic rec somatostatin MOA of insulin binds to insulin rec activating tyrosine kinase->phosphorylation of rec & proteins effects of insulin anabolic: inc glycogenesis, lipogenesis, protein syn, uptake of K into cells dec glycogenolysis, lipolysis **rapid/short acting insulin preps** Regular (crystalline) Semilente (onset <1hr, DOA 5-16hr) **Intermediate insulin preps** NPH (isophane) Lente (onset 1-2 hr, DOA 18-24hr) **slow/long acting insulin preps** Ultralente Protamine zinc (PZI) (onset 4-6, DOA 24-36) Only insulin prep given IV in emergency **Regular (crystalline) ** Tx IDDM: Diabetic ketoacidosis Emergency-inappetence & vomiting -Regular insulin IV infusion or svl IM inj -fluid therapy-correct acidosis -high fiber diet (1/2 caloric needs) Tx IDDM: uncomplicated intermediate or long-acting insulin high fiber diet Tx NIDDM dietary management (high fiber diet) Oral hypoglycemics Insulin Acarbose (adjunctive therapy) Adverse effects of insulin hypoglycemia & insulin shock hypoK IR HS rxns rebound hyperglycemia tx of hypoglycemia & insulin shock dextrose-orally(best)/IV(unconscious) glucagon-IM(slow effect) drug interactions that dec hypoglycemic effect of insulin (may need to inc dose) Sympathomimetics a2 agonists Diuretics (CAI, loop, thiazide) Hormones (corticosteroids, GH, progestins, estrogens, glucagon, thyroid agents) Phenytoin (anticonvulsant) Phenothiazines drug interactions that inc hypoglycemic effect of insulin B-blockers Oral hypoglycemics Androgens Anabolic steroids ACE inhibitor Alcohol MAOI Aspirin & phenylbutazone Sulfonamides Tetracyclines ORAL hypoglycemics (sulfonylureas) Glipizide Glyburide Glimepiride MOA of oral hypoglycemics inc basal insulin secretion (close K channels-depolarize cell) inc glucose mediated insulin secretion inc insulin binding dec glucagon use of oral hypoglycemics Tx NIDDM in cats ***may exhaust beta cells->IDDM** contraindications for oral hypoglycemic use renal/hepatic insuf pregnancy antihyperglycemic used in diabetic dogs/cats with mild hyperglycemia Acarbose MOA of Acrabose **slow elevation of blood glucose levels** -competitively inhibit pancreatic alpha-amylase/glucosidases -delay CHO digestion -dec GI glucose absorption stimulation of glucagon secretion low glucose & FAs protein intake GI hormones & NTs MOA of glucagon G protein coupled rec->activate adenylyl cyclase->inc CAMP->protein kinase->substrate phos glucagon effects -inc hepatic glycogenolysis, gluconeo & lipolyis -stim heart -relax smooth mm in gut therapeutic uses of glucagon insulin induced hypoglycemia (dextrose not available) cardiac stimulant (B-blocker OD) Tx peri-parturient bovine ketosis release of somatostatin hypothalamus D cells of islets of Langerhans effects of somatostatin inhibit release of insulin, glucagon, GH, GI hormones management in dogs of: insulinoma glucagonoma acromegaly gastrinoma Octreotide acetate (syn analog of somatostatin) nondiuretic thiazide used in oral tx of insulinomas Diazoxide MOA of Diazoxide inhibit insulin release from beta cells stim catecholamine release