Diabetic Drugs

Diabetes Insipidus

deficiency of, or lack of response to, ADH

salty urine — Na+ comes out, taking water with it, since ADH can't reabsorb the water back in

Diabetes Mellitus

deficiency of, or lack of response to, insulin

sweet urine — glucose can't get into tissues, so it stays in bloodstream or exits via urine

Insulin Preparations

any manufactured, pharmaceutical formulation containing the protein hormone insulin—or its chemically modified analogs—used as a medical treatment to regulate glucose metabolism and lower blood sugar levels

Insulin Structure

A and B chains joined by two disulfide bridges

A chain has ___ amino acids, while B chain has ___ amino acids

31

30

What is basal insulin secretion rate? How about stimulated rate?

5-15 mcU/mL

60-90 mcU/mL

What is the half-life of insulin?

3-5 minutes

How can insulin secretion be regulated — think more 'adjunct' —>

food products (glucose)

GI peptides (CCK, glucagon, GIP, GLP-1)

neural regulation (beta2 inc, alpha2 inh)

What is a drug that promotes insulin release by blocking hyperpolarization efforts (K+ leave)?

sulfonylurea

Sulfonylurea is a type of ___ agent

oral hypoglycemic

= lowers blood sugar levels

What are some types of sulfonylureas?

Glyburide

Glipizide

Glimepiride

Which receptors, exactly, do sulfonylurea drugs bind to in order to block hyperpolarization & increase secretion of insulin?

ATP-sensitive potassium channels

Sulfonylurea AE:

hypoglycemia

GI

muscle weakness

weight gain

mental confusion

Back to the concept... what ion enters to depolarize the cell even further after you block hyperpolarization?

Ca2+

Calcium also aids the ___ efforts of insulin

exocytosis

Where does insulin act, after it is released?

intestine

pancreas

fat

muscle

liver

Insulin facilitates the ___, ___, and ___ of glucose, amino acids and fatty acids

uptake

metabolism

storage

Diabetes Mellitus Type I

absence of insulin production

may be autoimmune

Diabetes Mellitus Type II

subnormal insulin production OR reduced tissue sensitivity

associated with diabetes

Which is more popular?

type II

Which is more severe?

I

What are some other causes of diabetes mellitus?

drug-induced

gestational

Let's go back to the topic of insulin preparations... these are designed to be given to patients with ___

diabetes

Insulin preparations that are 'rapid acting' have onset within ___

30 minutes

What was used for older, rapid preps?

crystalline zinc

New rapid preps often feature:

Lispro insulin

Inhaled insulin

Insulin aspart

Insulin glulisine

'Intermediate' and 'long' acting preps often have ___

NPH insulin

There are also ___ preparations, which have times of onset between rapid and intermediate/long acting

regular

What are some of the adverse effects of taking insulin (via prep)?

hypoglycemia

local/systemic allergic reactions

What are some factors that alter insulin dosage?

hyperthyroidism

stress

cessation of physical exercise

increased food intake

drug therapy

Another way to treat diabetes (type II) is via oral hypoglycemic agents, such as sulfonylurea... what is another type of OHA that decrease blood glucose levels?

metformin

also decreases hepatic glucose production and increases secretion of GLP-1

GLP-1

- Glucagon like peptide 1- Secreted from the small intestine after a meal

- increases insulin secretion

- inhibits glucagon secretion

- signals satiety in the CNS

- delays gastric emptying

Metformin AE:

metallic taste

GI

anorexia

lactic acidosis

Another OHA is ___, which works by inhibiting alpha-glucosidase

Acarbose/Miglitol

= delay in absorption of glucose

Miglitol AE:

bloating, flatulence, cramps, diarrhea

Yet another type of OHA is ___, which binds to PPAR-gamma receptor, thus reducing gluconeogensis and increasing glucose uptake out of the blood

Pioglitazone

Pioglitazone AE:

weight gain, edema, increased risk heart failure, increased risk bone fracture

not taken much, anymore

ANOTHER OHA is ___, which stimulates insulin secretion and is taken with meals

Repaglinide

Repaglinide AE:

weight gain

hypoglycemia, but not as much as other drugs

Yup, there's more... ___ is an OHA that serves to inhibit DPP4... this increases incretin hormones, as well

Sitagliptin

Incretin

a hormone produced by the intestine which increases insulin synthesis and release from the pancreas

GLP-1, GIP

Sitagliptin AE:

GI upset

hypersensitivity rxns

does not lead to weight gain!

minimal hypoglycemia!

One more OHA..... ___ inhibits SGLT2 in the kidney, thus reducing glucose reabsorption

Canaglifozin

Canaglifozin AE:

dehydration, orthostatic hypotension, hypoglycemia, infections

Canaglifozin may also be preferred for patients with ___ and ___, as well as in general, because it conveys ___

heart failure and CKD

modest weight loss

That was a bunch of OHAs... now we need to cover the injectable hypoglycemic drugs (cause this)... these are approved for ___

chronic weight management **

Which injectable drugs act as GLP-1 receptor agonists (incretin mimetics)?

Liraglutide **

Semeglutide **

Dulaglutide **

Exenatide

Lixisenatide

As aforementioned, incretin stimulates ___ and suppresses ___

insulin

glucagon

Injectable 'tides' AE:

nausea

vomit

diarrhea

headache

mild hypoglycemia

Which injectable drug can also be given orally?

Semegutide

Another injectable drug that works to decrease appetite is the amylin analog ___

Pramlintide

Pramlintide AE:

GI

significant hypoglycemia

One more!! ___, a peptide hormone, is an injectable agonist at both GIP and GLP-1 receptors

Tirzepatide

Tirzepatide is great for ___ and ___

glycemic control

weight loss

Tirzepatide AE:

GI

lowered appetite

diarrhea, constipation

dyspepsia