Drugs for DM
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| Stimuli for Insulin Secretion | Glucose, Amino Acids (esp. leucine, arginine), Sulfonyl urea drugs, Vagal stimulation (acetylcholine on M3 receptors)
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| Mechanism for Insulin Release | ^ Glucose -> ^ATP in beta cells -> closure of ATP-dependent K channels -> depolarisation of cell membrane -> Ca channels open -> influx of Ca -> trigger insulin release.
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| Actions of insulin | ^ glycogenesis in liver and muscles, decreases glycogenolysis and lipolysis. ^lipogenesis in adipose tissue, ^ activity of GLUT-4 transporters.
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| Types of insulin replacement (7) | Insulin lispro, Insulin aspart, Insulin glulisine, Regular insulin, Neutral protamine Hagedorn (Isophane), Insulin detemir, Insulin glargine.
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| Insulin lispro | Rapidly acting drug with a short duration (3-6h) which can be administered IV & mixed with other insulin drugs (eg. NPH). Available as Humalog Pen and administered subcutaneously 15min before a meal.
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| Insulin aspart | Rapidly acting drug with short duration (4-5h), can be administered IV & mixed with other insulin drugs (NPH). Available as NovoRapid Flexpen & administered 15min before a meal.
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| Insulin glulisine | Rapidly acting drug with a short duration (1.5h) which can be administered IV & mixed with other insulin drugs (eg. NPH). Administered subcutaneously 15min before a meal or 20 min after, as it appears in blood earlier with higher conc than reg insulin.
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| Regular insulin | Short duration(5-8h) & slower acting (. Can be administered IV and mixed with other insulin (NPH) at varying concentrations for different patients (Mixtard).
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| Neutral Protamine Hagedorn (NPH)/Isophane | Intermediate duration (~15h) and usually mixed with short duration insulin. Has an added component protamine to form dipole prep w/ insulin, releasing it slowly. Have varying pre-mixed preperations.
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| Insulin detemir | Intermediate duration (12-24h), available as Levamir Flexpen. Contains a fatty acid side chain which enhances affinity to plasma albumin. This provides a delayed, reproducible absorption.
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| Insulin glargine | Long duration (>20h), given once daily.
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| Adverse effects of insulin | Hypoglycemia, lipodystrophy (lipoatrophy or lipohypertrophy). Factitious hypoglycemia in non-diabetics who inject a high dose of insulin. Redness at injection site
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| Sulfonylureas: mode of action | Increases secretion of insulin by causing depolarisation of K+ channels in pancreatic B cells, promoting insulin release.
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| Sulfonylureas: examples | 1st gen: tolbutamide, 2nd gen: glibenclamide, glipizide. 3rd gen: glimepiride
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| Sulfonylureas: toxicity | GIT related (nausea, cramps, diarrhea), dizziness, hypoglycemia, occasional rash (due to sulphur), teratogenicity in animals. Drug interation with salicylates.
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| Meglitinide: mode of action | Same as sulfonylureas, just different receptors bound
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| Meglitinide: toxicity | Headache, hypoglycemia.
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| Meglitinide: example | Repaglinide, not commonly used.
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| Biguanide: mode of action | Insulin sensitiser, increases insulin receptor density and sensitivity at tissue level, effect dependent on circulating insulin. Also: stimulates glycolysis, hepatic gluconeogenesis, decreased glucose absorp from GIT, reduced plasma glucagon.
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| Biguanide: clinical uses | main drug for type 2 DM, also reduces hyperlipidemia. mixed with rosiglitazone (thiazolidinedione, another insulin sensitiser. (Avandamet).
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| Biguanide: toxicity | GIT related (nausea,anorexia,diarrhea,vomiting), metallic taste, folate and vB12 def -> pernicious anemia (treated w supplements), lactic acidosis due to inhibition of hepatic gluconeog (seen by hypervent, myalgia, malaise).
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| Biguanide: contraindications | liver disease, due to the reduced ability to undergo gluconeogenesis and breakdown lactic acid (a substrate), excessive alcoholism and shock.
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