- given with meals - Acts quickly and wears off quickly

- not quite as quick as rapid; lasts slightly longer

Pharm 39 - DB Flashcards by Heather McKnight

what is T1DM

i. Destruction of beta cells results in an inability to produce insulin
1) Usually autoimmune
2) Require around the clock insulin supplementation
ii. Typical, usual patient
1) Underweight, child/adolescent

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what is T2DM

i. Resistant to the effects of insulin
1) A progressive loss of insulin secretion starts to result in beta cells that do not function properly and ultimately stop producing insulin as well
2) Usually present originally with cells that do not respond to the insulin and eventually will end up with cells that do not respond to insulin and cells that cannot produce insulin
ii. Typical, usual patient
1) Overweight, adult
2) Can see metabolic syndrome, CVD

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Amylin: increases _____ secretion

Pharmacologic congener: _________

Amylin: increases insulin secretion

Pharmacologic congener: Pramlintide

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This drug reduces appetite, decreases gastric motility/slows gastric emptying, lowers post-prandial glucose peak, and decrease glucagon release

amylin

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A satiety hormone - tells the body that they are full

amylin

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Produced in and released by the pancreatic beta cell and is co-secreted with insulin
Only other FDA approved med for T1DM other than insulin

amylin

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Glucagon - increases ______ secretion

Pharmacologic congener: ________

Glucagon - increases insulin secretion

Pharmacologic congener: Glucagon

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glucagon administration

ii. Given in subQ, IM, or IV preps

1) Used IV for hypoglycemic emergencies

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Secreted by the pancreatic alpha cells to oppose insulin

Glucagon

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1) Causes an increase in blood glucose levels through glycogenolysis
2) Breaks down glycogen stores to glucose

Glucagon

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MOA: Glycogenolysis: breaks down glycogen stores of glucose

Glucagon

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Note about Glucagon use

only effective if glycogen stores are available in that individual
must replenish stores after administering this medication

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Glucagon-like peptide - increases _____ secretion

Pharmacologic congener: _______

Glucagon-like peptide - increases insulin secretion

Pharmacologic congener: GLP-1’s

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Secreted by the L cells in the intestines

Glucagon-like peptide (GLP-1)

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1) Potent stimulator of insulin synthesis and release
2) Inhibits glucagon secretion
3) Slows gastric emptying

Glucagon-like peptide (GLP-1)

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Somatostatin - decreases _____ secretion

Pharmacologic congener: ________

Somatostatin - decreases insulin secretion

Pharmacologic congener: Octreotide

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uses:

1) Treats acromegaly
i) Decreases GH, IGF-1
2) Metastatic, carcinoid tumors
i) Inhibits serotonin release
3) Vasoactive intestinal peptide-secreting tumor

Glucagon-like peptide (GLP-1)

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Similarities among the various insulin preparations:

i. All products on the market now are human forms of insulin
1) All equipotent (equal serum concentrations)
2) Given by injection (usually SubQ)
1) Only insulin-R is given IV route

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Differences among the various insulin preparations:

Based on their PKs, onset, and duration of action only

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Rapid-acting insulin

given with meals

- Acts quickly and wears off quickly

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Short-acting insulin

not quite as quick as rapid; lasts slightly longer

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Intermediate-acting insulin

Acts slower; lasts longer

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Long-acting insulin

Slowest onset; longest duration

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what modifications are made to make a rapid-acting insulin faster acting than regular insulin?

a. Longer lasting insulin has a hexagonal shape that forms a hexamer
i. When the insulin breaks down into monomers and dimers, the body’s circulation can absorb it from the subcutaneous tissues and the insulin is then considered active

b. Insulin-R does not have a hexamer form and is not altered
i. Makes it a very active IV insulin form

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List the diabetes medication classes most likely to incite hypoglycemia (in order of risk)

1. Insulin 2. Sulfonylureas: first generation 3. Insulin's combined with amylin 4. Oral agents of antihyperglycemic

Hypoglycemic reactions are most common complication of _____ therapy

Hypoglycemic reactions are most common complication of insulin therapy

Excessive insulin causes hypoglycemia in a dose-dependent fashion, esp if:

1) Inadequate carb consumption 2) Unusual physical exertion 3) Too larger of a dose of insulin

Drug that causes severe hypoglycemia, esp. in elderly

Sulfonylureas: first generation

How do you treat a patient with a hypoglycemic episode that is conscious? Administer what? Monitor what? Dosage? How does that effect the labs?

i. 15 grams oral glucose 1) Monitor blood glucose 1) 1 tablet: 4 grams; 4 tablets = 16 grams of glucose i) Glucose levels will increase 16 points 2) Repeat dose if necessary after 15 minutes

How do you treat a patient with a hypoglycemic episode that is unconscious? Drug of choice? If in hospital, what is used?

i. Glucagon is treatment of choice | ii. If in hospital, give IV glucose

Explain the MOA of the sulfonylureas

a. Secretagogues that close the ATP K+ pump of the beta cells to prevent the release of K+ from the cells 1) This causes massive depolarization of the cells and over stimulation of the release of insulin 2) This allows the cell to skip over the step of increasing the ATP : ADP ratio from the increasing levels of glucose 1) Bypasses the necessary glucose to trigger insulin release 1) Results in hypoglycemia

1) Activates the AMP-activated protein kinase to reduce hepatic resistance to insulin 1) Makes liver respond better to insulin i) Decreased hepatic and perhaps renal, glucose production and release 2) Slows glucose absorption from GI tract to slow and evens out glucose absorption during meals What drug has this MOA?

metformin

How is metformin eliminated?

renally

Contraindications to metformin?

1) Renal disease 1) eGFR < 45 mL/min at new onset of use of this drug 2) STOP the drug if eGFR is < 30 mL/min 2) Acute/unstable heart failure 1) Can increase risk of lactic acidosis

ADE of metformin

GI complaints: 1) N/D, cramping 2) GI upset: take at end of meal 3) Titrate dose over days to weeks May reduce B12 absorption

i. MOA: insulin sensitizer 1) Agonist of PPAR-gamma receptor 1) Receptor is found in adipose tissue i) Secondarily on cardiac, skeletal, and smooth muscle Insulin sensitizers at peripheral insulin responsive tissues

Thiazolidinediones

How long do you need to wait with Thiazolidinediones to see an A1C change?

at least one month

Contraindications to Thiazolidinediones

1) Heart failure patients 2) Bladder cancer 3) Liver disease

ADE of _____: 1) Can promote new growth of adipose tissue 2) Macular edema 3) Anemia 4) Bone mineral density loss (Increased fracture risk in women) 5) Weight gain 6) Water retention (Can worsen heart failure signs/symptoms) 7) Must monitor liver enzymes (If increases 2.5x the normal limits, must D/C this drug)

Thiazolidinediones

Thiazolidinediones drugs (2)

"-litazone"s Pioglitazone Rosiglitazone

MOA: Stops the release of K+ from the beta cell to cause depolarization of the cell and release of insulin

Sulfonylureas | Glinides

Primary contraindications of sulfonylureas

can induce sulfa allergies

Glyburide is ___ as likely as glipizide or glimepiride to induce ___________

Glyburide is 2x as likely as glipizide or glimepiride to induce hypoglycemia

Glinides drugs (2)

Non-sulfonylureas/short-acting secretagogues: repaglinide, nateglinide

Perk of glinide drugs

1. Patients with sulfa allergies can take these medications

when do are glinides taken

Used postprandially

glinides require how many doses

Require 3 to 4 doses a day

a less potent drug than SUs and has a shorter duration of action than SUs

glinides

Can you use short acting secretagogues (like the glinides) with the long-acting secretagogues (SUs)?

NO - contraindicated as severely hypoglycemic and the MOAs are too similar

MOA: 1) Stimulates insulin synthesis and release 2) Inhibits glucagon secretion 3) Slows gastric emptying 4) Produces an anorectic effect (suppresses appetite)

Glucagon-like-peptide (GLP)-1 agonists

Glucagon-like-peptide (GLP)-1 agonists drugs (3)

"-tide"s exenatide exenatide ER liragultide dulaglutide

Primary contraindications: 1) Possible thyroid C cell tumors 2) Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome, Type 2 3) Patient on a DPP-4 inhibitor

Glucagon-like-peptide (GLP)-1 agonists drugs

ADE of GLIP-1 agonists (5)

1) Significant nausea 2) HA and infections 3) Anorectic effects can cause too much weight loss 4) Can slow absorption of oral drugs 5) Must watch sugars when added to insulin or secretagogues

Severe, serious ADE of GLIP-1 agonists (4)

Pancreatitis, immunologic reactions, AKI, angioedema

This drug inhibits an enzyme that enhances endogenous GLP-1 activity. This subsequently increases the cleaving of polypeptide pro-glucagon to make more GLP-1 to stimulate insulin synthesis and release.

Dipeptidyl peptidase (DPP)-4 inhibitors

A specific drug class that works exceptionally well in combo with Metformin to reduce A1C up to 1.5 - 2%.

Dipeptidyl peptidase (DPP)-4 inhibitors

ADE of Dipeptidyl peptidase (DPP)-4 inhibitors

Hypoglycemia with concurrent SU use

SGLT-2 inhibitors reduce risk of...

heart failure and worsening renal dysfunction

MOA: Increase urinary excretion of filtered glucose by inhibiting the reabsorption of glucose at a specific cell membrane channel in the proximal convoluted tubules

Sodium Glucose co-Transporter-2 inhibitors (SGLT-2 inhibitors)

A DB drug that has a low risk of inducing hypoglycemia but is only able to work if the blood glucose level is > 100 or so

Sodium Glucose co-Transporter-2 inhibitors (SGLT-2 inhibitors)

- Slight weight loss effect due to osmotic release of water/sodium - Also helps to reduce BP this way!

Sodium Glucose co-Transporter-2 inhibitors (SGLT-2 inhibitors)

Sodium Glucose co-Transporter-2 inhibitors (SGLT-2 inhibitors) contraindications hint: remember MOA!

1) Renal disease (individuals less than 30mL/min eGFR) | 2) Hypotensive patients

ADE of ____ are: 1) Hyponatremia as the drug inhibits the reabsorption of glucose AND sodium 2) Increased GU infections (UTI's and candidiasis) 3) Diabetic ketoacidosis with euglycemia 4) Increased risk of amputation, fournier gangrene, fracture risk

Sodium Glucose co-Transporter-2 inhibitors (SGLT-2 inhibitors)

Best drugs to reduce A1C when treating DB: (think of two)

1. Metformin | 2. Metformin + GLP-1

Best drug to use when avoiding hypoglycemia

SGLT-2 inhibitors

Insulin is first choice in these situations: (5)

i. Hospitalized for hyperglycemia or outpatient with severe hyperglycemia ii. Pregnancy iii. Chronic kidney disease iv. Heart failure v. Contraindications to metformin or other oral agents

A specific drug that has the following problems: i. Drug seemed to have a higher MI and liver risk - sanction was later removed ii. Bladder cancer possible risk - not able to discern iii. requires liver enzyme monitoring (if see a 2.5x increase, must D/C)

Pioglitazone (Thiazolidinediones drug class)

A specific drug that was associated with an increased MI risk (there's actually two of them)

Pioglitazone (Thiazolidinediones drug class) Rosiglitazone (Thiazolidinediones drug class)

Moderate intensity statin therapy is indicated in...

People with DB and aged 40 - 75

High intensity statin therapy is indicated in...

People with DB and: i. Anyone with atherosclerotic CV disease ii. Anyone with a > 7.5% 10 year CV disease risk

List the two most commonly used antiplatelet drugs used in patients with diabetes.

1. ASA (81mg) | 2. Clopidogrel