Civility Clause….Students are expected to behave toward lecturers and fellow students with courtesy and consideration. This means that talking and disruptive behavior will be kept to a minimum. Cell phones, pagers, and other electronic devices should be silenced in the classroom. I reserve the right to end a class at any time, for any reason, including the disruptive or rude behavior of anyone in the classroom.

Starting with insulin

Figure 3 The feedback loops of the insulin axis involve a number of different tissues.

Maloney C A , and Rees W D Reproduction 2005;130:401-410

© 2005 Society for Reproduction and Fertility

Goals of therapy in diabetes

• To normalize blood sugar levels to minimize risk of long-term complications

• To avoid instances of hypoglycemia• To promote normal carbohydrate, fat and

protein metabolism

Non-insulin drugsInsulins

Drugs for diabetes

biguanides

secretagogues

sulfonylureas meglitinides

-glucosidaseinhibitors

TZDs

amylinanalogues

incretinmodulators

GLP-1analogues

DPP-4inhibitors

Others

Therapy with insulin

• Insulin is the PRIMARY treatment for Type 1 diabetes – insulin administration replaces insulin that is not produced by B cells

• Also used in Type 2 as B cells fail and disease progresses

Therapy with insulin

• USED TO TREAT– Type I or type 2 diabetes

• CONTRAINDICATED IN– Allergy to a specific insulin product– hypoglycemia

Types of insulin

• Ultra short acting or rapid acting– Rapid onset, short duration

• Short-acting– Rapid onset

• Intermediate-acting• Long-acting

– Slow onset

Insulins Insulin aspart (Novolog®) - CInsulin lispro (Humalog®) - BInsulin glulisine (Apidra®) - C

Pharmacology (Mechanism of action)

Replaces insulin;

Promotes cellular uptake of glucose, fatty acids and amino acids;

Promotes storage of glycogen, triglycerides and proteins

Adverse Effects Pharmacokinetics

Insulins Regular insulin (Humulin-R®, Novolin-R®)

Pharmacology (Mechanism of action)

Replaces insulin;

Promotes cellular uptake of glucose, fatty acids and amino acids;

Promotes storage of glycogen, triglycerides and proteins

Adverse Effects Pharmacokinetics

Insulins Isophane insulin suspension (NPH®, Novolin-N®, Humulin-N)

Insulin zinc suspension (Lente) (Humulin-L®; Novolin-L®)

Pharmacology (Mechanism of action)

Replaces insulin;

Promotes cellular uptake of glucose, fatty acids and amino acids;

Promotes storage of glycogen, triglycerides and proteins

Adverse Effects Pharmacokinetics

Insulins Insulin glargine (Lantus®)Insulin detemir (Levemir®)

Pharmacology (Mechanism of action)

Replaces insulin;

Promotes cellular uptake of glucose, fatty acids and amino acids;

Promotes storage of glycogen, triglycerides and proteins

Adverse Effects Pharmacokinetics

Insulins - MixturesNPH70% + regular insulin 30% (Humulin 70/30 ®; Novolin 70/30®)NPH50% + regular insulin 50% (Humulin 50/50®)

Insulin lispro protamine suspension 75% + insulin lispro 25% (Humalog Mix 75/25®)

Pharmacology (Mechanism of action)

Replaces insulin;

Promotes cellular uptake of glucose, fatty acids and amino acids;

Promotes storage of glycogen, triglycerides and proteins

Adverse Effects Pharmacokinetics

http://forecast.diabetes.org/files/images/InsulinChart_4.pdf

http://www.ourdiabetes.com/insulin-therapy.htm

Adverse Effects of Insulin

• Hypoglycemia– Sympathatic activation produces palpitations,

sweating, nervousness, weakness– Serious hypoglycemia produces CNS effects,

including mental confusion, incoherent speech, blurred vision, coma

• Weight gain

Role of the nurse (Abrams, pp. 726-730)

• Teach the patient how to administer insulin correctly– Choice of administration techniques– Using a syringe– Choice of injection sites– When and how often to inject– How to store

Non-insulin drugsInsulins

Drugs for diabetes

biguanides

secretagogues

sulfonylureas meglitinides

-glucosidaseinhibitors

TZDs

amylinanalogues

incretinmodulators

GLP-1analogues

DPP-4inhibitors

Others

SulfonylureasGlyburide (Diabeta®, Micronase®)Glipizide (Glucotrol®) Glimepiride (Amaryl®)

Pharmacology (Mechanism of action)

Stimulate insulin release from the pancreas;

Increases the number and sensitivity of insulin receptors;

Decreases glycogenolysis and gluconeogenesis

Adverse Effects Pharmacokinetics

K+

B cellbasal state

insulin

glucose

K+

Sulfonylureas

• Inhibits (closes) a K+-ATP channel, leading to• Decreased K+ efflux from B-cells which• Depolarizes the B-cell membrane, leading to• Increased Ca++ influx and• Increased exocytosis of insulin from B-cells

glipizide

sulfamethoxazole

Sulfonylureas

• Serious adverse effects– Hypoglycemia– Hematological effects (thrombocytopenia, aplastic

anemia, others)

• Common adverse effects– Weight gain– Rash– Hypoglycemia

Biguanidesmetformin (Glucophage®)

metformin / glipizide (Metaglip®) rosiglitazone / metformin (Avandamet®)Others….

Pharmacology (Mechanism of action)

Decrease hepatic glucose production;

Decrease glucose absorption from GI tract;

Increases insulin receptor sensitivity

Adverse Effects Pharmacokinetics

Biguanides

• USED TO TREAT– Type 2 diabetes

• CONTRAINDICATED IN– Hypersensitivity to biguanides– Hepatic or renal disease– Alcoholism– Cardiopulmonary disease

Biguanides

• Serious adverse effects– Lactic acidosis (due to the inhibition of

gluconeogenesis and the buildup of fatty acids) - rare

• Common adverse effects– Nausea, vomiting– Flatulence

Thiazolidinediones (Insulin Sensitizers; glitazones; TZDs)Rosiglitazone (Avandia®) - CPioglitazone (Actos®) - C

Pharmacology (Mechanism of action)

Enhances the effects of circulating insulin;

Stimulates peripheral glucose uptake and storage

Inhibits hepatic glucose production

NO increase in insulin levels

Adverse Effects Pharmacokinetics

http://www.fda.gov/Drugs/DrugSafety/ucm255005.htm

Thiazolidinediones (TZDs)• Serious adverse effects

– Congestive heart failure (new or exacerbated) due to increasing blood volume –

BLACK BOX WARNING– Hepatic dysfunction or failure

• Common adverse effects– Mild anemia– Moderate weight gain– Upper respiratory infection– Headache and myalgia

Secretagogues (meglitinides)Repaglinide (Prandia®)Nateglinide (Starlix®)Pharmacology (Mechanism of action)

Stimulates insulin release from B-cell through inhibition of ATP-sensitive K+ channels;

Adverse Effects Pharmacokinetics

Alpha-glucosidase inhibitorsAcarbose (Precose®)

Pharmacology (Mechanism of action)

Reversibly inhibit alpha glucosidase

Delays absorption of glucose in the intestine;

Blunts postprandial elevations in glucose

Adverse Effects Pharmacokinetics

Glucagon-like peptide 1 (GLP-1)Exenatide (Byetta®; Bydureon®) – CLiraglutide (Victoza®)Pharmacology (Mechanism of action)

Incretin mimetic that binds to GLP receptors;

Increases glucose-dependent secretion of insulin from pancreatic B cells

Adverse Effects Pharmacokinetics

Injected sc

Synthetic amylin analogpramlintide (Symlin®)

Pharmacology (Mechanism of action)

Amylin slows gastric emptying;

suppresses glucagon;

Modulates appetite in the CNS

Adverse Effects Pharmacokinetics

Injected sc

DPP-4 inhibitorSitagliptin (Januvia®)Saxagliptin (Onglyza®)Pharmacology (Mechanism of action)

Inhibits DPP-4, which slows inactivation of incretin hormones GLP-1 and GIP

Adverse Effects Pharmacokinetics

Oral

Figure 1. Key sites of action of diabetes medications.

Martin C L The Diabetes Educator 2007;33:6S-13S

Copyright © by American Association of Diabetes Educators; Published by SAGE Publications