Pharm 39 - DB Flashcards
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
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
Amylin: increases _____ secretion
Pharmacologic congener: _________
Amylin: increases insulin secretion
Pharmacologic congener: Pramlintide
This drug reduces appetite, decreases gastric motility/slows gastric emptying, lowers post-prandial glucose peak, and decrease glucagon release
amylin
A satiety hormone - tells the body that they are full
amylin
- 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
Glucagon - increases ______ secretion
Pharmacologic congener: ________
Glucagon - increases insulin secretion
Pharmacologic congener: Glucagon
glucagon administration
ii. Given in subQ, IM, or IV preps
1) Used IV for hypoglycemic emergencies
Secreted by the pancreatic alpha cells to oppose insulin
Glucagon
1) Causes an increase in blood glucose levels through glycogenolysis
2) Breaks down glycogen stores to glucose
Glucagon
MOA: Glycogenolysis: breaks down glycogen stores of glucose
Glucagon
Note about Glucagon use
- only effective if glycogen stores are available in that individual
- must replenish stores after administering this medication
Glucagon-like peptide - increases _____ secretion
Pharmacologic congener: _______
Glucagon-like peptide - increases insulin secretion
Pharmacologic congener: GLP-1’s
Secreted by the L cells in the intestines
Glucagon-like peptide (GLP-1)
1) Potent stimulator of insulin synthesis and release
2) Inhibits glucagon secretion
3) Slows gastric emptying
Glucagon-like peptide (GLP-1)
Somatostatin - decreases _____ secretion
Pharmacologic congener: ________
Somatostatin - decreases insulin secretion
Pharmacologic congener: Octreotide
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)
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
Differences among the various insulin preparations:
Based on their PKs, onset, and duration of action only
Rapid-acting insulin
- given with meals
- Acts quickly and wears off quickly
Short-acting insulin
- not quite as quick as rapid; lasts slightly longer
Intermediate-acting insulin
Acts slower; lasts longer
Long-acting insulin
Slowest onset; longest duration
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
List the diabetes medication classes most likely to incite hypoglycemia (in order of risk)
- Insulin
- Sulfonylureas: first generation
- Insulin’s combined with amylin
- 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
- 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)
- 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.
- ASA (81mg)
2. Clopidogrel
