Drugs affecting Blood Glucose Levels

• childhood and adolescence
• abrupt

• usually after age 40
• gradual

Loss of pancreatic Beta Cells

Insulin resistance and inappropriate insulin secretion

Type I

• liver
• adipose tissue
• muscle

• Hyperglycemia results when insulin dosage is insufficient.
• Conversely, hypoglycemia results when the insulin dosage is excessive.
• Ketoacidosis develops when hyperglycemia is allowed to persist.

• Macrovascular Damage: Cardiovascular disease mainly due to atherosclerosis, hyperglycemia, and altered lipid metabolism
• Microvascular Damage: Destruction of small blood vessels contributes to kidney damage, blindness, and various neuropathies. Microvascular injury is directly
• related to the degree and duration of hyperglycemia.

• ***Treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) can delay the onset of nephropathy, and can slow progression of nephropathy that is already present
• *** ACE inhibitor (eg, captopril) or an ARB (eg, losartan) can help protect against diabetic nephropathy.

• a fasting plasma glucose (FPG) test,
• a casual plasma glucose test,
• and an oral glucose tolerance test (OGTT).

• Options include oral antidiabetic agents,
• the new injectable hypoglycemic drugs—pramlintide and exenatide—
• and, if needed, daily insulin

• 90 to 130 mg/dL before meals
• 100 to 140 mg/dL at bedtime.

• The principal stimulus for insulin release is a rise in blood glucose.
• ***however, Insulin release may also be triggered by amino acids, fatty acids, and ketone bodies.

beta2-adrenergic receptors in the pancreas

alpha-adrenergic receptors in the pancreas

The metabolic actions of insulin are primarily anabolic (ie, conservative or constructive). Insulin promotes conservation of energy and buildup of energy stores. The hormone also promotes cell growth and division.

• glucose, amino acids, nucleotides, potassium
• glucose is converted into glycogen, amino acids are assembled into proteins, and fatty acids are incorporated into triglycerides.

• glycogen is broken down to glucose
• protiens are broken down into amino acids
• and tryglicerides are broken down into fatty acids

• (1) increased glycogenolysis,
• (2) increased gluconeogenesis,
• (3) reduced glucose utilization. Glycogenolysis, by definition, generates free glucose by breaking down glycogen

Recombinant DNA

—insulin lispro, insulin aspart, and insulin glulisine—

human insulin analog

• rapid acting (insulin lispro, insulin aspart, and insulin glulisine)
• and slower acting (regular or “natural” insulin).

• Humalog
• 15-30 min
• .5-2.5 hr
• 3-6.5 hr
• SQ, IV
• 15 minutes before food

• Novalog
• 10-20 min
• 1-3 hours
• 3-5 hours
• SQ, IV
• 5-10 min before meals

• Apidra
• 10-15 min
• 1-1.5 hr
• 3-5 hr
• SQ, IV
• 15 min before meal, no later than 20 min after starting

• Humulin R, Novolin R
• 30-60 min
• 1-5 hr
• 6-10 hr
• SQ, IV, IM
• 30 min before meals

• NovoLog Mix 70/30
• Rapid
• 1-4 hours
• Up to 24 hours
• SQ
• 15 min before or immediately after

Of the longer acting insulins in current use, NPH insulin is the only one suitable for mixing with short-acting insulins.

• Humulin N, Novolin N
• 60-90 min
• 6-14 hours
• 16-24 hours
• SQ
• used to provide glycemic control between meals

• Humulin 70/30, Novolin 70/30
• 30-60 min
• 1.5-16 hr
• up to 24 hr
• SQ
• Not included.

• Levemir
• Slower than NPH
• 6-8 hrs
• 12-24 hrs
• SQ
• for basal control
• *Do not mix with other insulins. NO IV

• Lantus
• 70 min
• No Peak
• 24 hours
• SQ
• For Basal Control

due to risk of hypoglycemia

To avoid contaminating the stock vial of the short-acting insulin with NPH insulin.

insulin aspart [Novolog], insulin lispro [Humalog], and insulin glulisine [Apidra]

diabetic ketoacidosis

The process of maintaining glucose levels within a normal range, around the clock

• decrease in clinically significant kidney disease
• decrease in neuropathy
• decrease in serious ophthalmic complications.

hypoglycemia

infection, stress, obesity, the adolescent growth spurt, and pregnancy after the first trimester.

exercise and during the first trimester of pregnancy.

• biguanides,
• sulfonylureas,
• glinides (meglitinides),
• thiazolidinediones (glitazones),
• alpha-glucosidase inhibitors,
• gliptins.

• Some of them—notably the sulfonylureas, glitazones, and glinides—actively drive blood glucose down.
• Others—notably metformin (a biguanide) and the alpha-glucosidase inhibitors—don't drive blood glucose down; rather, they simply modulate the rise in glucose that happens after a meal.

• Metformin;
• lowers blood glucose and improves glucose tolerance in three ways. First, it inhibits glucose production in the liver. Second, it reduces (slightly) glucose absorption in the gut. And third, it sensitizes insulin receptors in target tissues

• cause weight loss
• lactic acidosis

• Glyburide (DiaBeta)
• Stimulates insulin release and reduces glucagon levels
• **avoid during pregnancy

• nausea, vomiting, facial flushing, palpations
• low blood sugar
• diminishes effect of sulfonylurea

• repliginide (prandin)
• Stimulates insulin release

• Hypoglycemia
• *patients eat no later than 30 minutes after taking the drug.

• rosiglitazone (Avandia)
• turns on insulin-responsive genes that help regulate carbohydrate and lipid metabolism. As a result, cellular responses to insulin are increased

• fluid retention= edema
• monitor liver function
• Increase in LDL and TG

• acarbose (Precose).
• Delays the digestion of carbohydrates, resulting in a smaller postprandial rise of blood glucose.
• GI: flatulence, cramps, diarrhea, etc

sitagliptin (januvia)

• exenatide (Byetta)
• Slows gastric emptying
• Stimulates glucose dependent release of insulin
• Inhibits post prandial release of glucagon
• Supresses appetite