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Flashcards in Diabetes Deck (43):

Amylin analog

Adjunct therapy


Oral antidiabetics may

Increase insulin secretion (known as secretagogues) • Increase insulin sensitivity • Work via other mechanisms



Insulin (often is needed eventually)
Amylin Analogues: e.g. Pramlintide (Symlin®) -
Incretin GLP-1 Mimetics: e.g. Exenatide (Byetta®


Insulin human (Afrezza®)

rapid-acting insulin inhalation powder, administered before meals. Action peaks in 12-15 minutes. Must be used in combination with long-acting insulin in Type 1 diabetics. Contraindicated in asthma, COPD and lung cancer. Can cause acute bronchospasm.


Amylin analogue MOA

slows gastric emptying, promotes
satiety, suppresses glucagon secretion,. The
hormone amylin is normally co-secreted with insulin.


Incretin GLP-1 Mimetics

glucose-dependent insulin secretion, inhibits
post-prandial release of glucagon, slows gastric
emptying, suppresses appetite



increase sensitivity of insulin receptors, decrease
liver gluconeogenesis



stimulate insulin release (secretagogue) ...watch for hypoglycemia



increase insulin release (secretagogue)


α-Glucosidase Inhibitors

α-qGlucosidase Inhibitors: inhibit enzymes at GI brush border →
inhibits absorption of ingested carbohydrates


Thiazolidinediones (TZDs)

Insulin sensitizers


Dipeptidyl peptidase-4 (DPP-4) inhibitors

slow incretin
inactivation by DPP-4 enzyme → stimulate glucose-dependent
insulin release and inhibit post-prandial glucagon release


Sodium-glucose co-transporter-2 (SGLT2) inhibitors

Reduce reabsorption of glucose by the kidneys



Indication – DM1, DM2, acute hyperglycemia
MOA – binds to insulin receptor, stimulating
translocation of glucose transporters (e.g., GLUT4 on
muscle and adipose cells), thereby facilitating glucose
movement into cells.

Adverse effects – hypoglycemia, lipohypertrophy, more
rarely lipoatrophy; weight gain, allergic reaction. •

Interactions - alcohol (inc. risk of hypoglycemia), oral DM
medications (inc. risk of hypoglycemia), β-blockers
(hypoglycemic unawareness)


Hypoglycemia risk factors

Mismatch of insulin timing, amount or type for carbohydrate
intake, Oral secretagogues, without sufficient carbohydrate intake, Reduction in nutrient intake, Nausea/vomiting

Geriatric patients at higher risk for hypoglycemia


Rapid acting

Aspart (NovoLog®) Lispro (Humalog®) Glulisine (Apidra®)


Short acting

Regular/Human (Humulin® R, Novolin® R)


Intermediate acting

NPH (Humulin® N, Novolin® N) Detemir (Levemir®) (lower doses)


Long acting

Glargine (Lantus®, Toujeo®, Basaglar®) Detemir (Levemir®) (higher doses) Degludec (Tresiba®) – ultra-long-acting


Keep in mind about insulin mixes

The rapid- or short-acting portion will generally determine the onset
• The intermediate-acting portion will generally determine the duration


Rules for mixing insulins

Of the intermediate- and long-acting insulins
(NPH, detemir, glargine and degludec) ONLY
NPH can be mixed in the same syringe with rapid-
and short-acting insulins.

Do not mix detemir, glargine or degludec in the same syringe with rapid or short-acting insulin.


Insulin needs are decreased by

by exercise (generally speaking), first trimester of pregnancy and immediate post-partum period


Define basal and bolus

Basal: The steady, low level of insulin constantly
secreted by the pancreas

Bolus: The spikes in insulin secretion stimulated by
glucose ingestion, especially at meals


Correctional insulin

is often given at mealtimes (in addition to carb-related), to account for the actual blood glucose reading prior to the meal.


In patient scenarios requiring insulin

Type 1 diabetics may require more than their
normal dose
– Type 2 diabetics who are not insulin-dependent
may need it
– Patients receiving total parenteral nutrition may
require it
– Even people who do not have a history of diabetes
may require insulin and they or their families will
be asking you why you are giving it to them.


Somogyi Effect

Undetected hypoglycemia followed by rebound
hyperglycemia in AM


Dawn Phenomenon

Rise in BG between 2-8 AM secondary to rise in counterregulatory hormones (inc. glucagon, growth hormone, cortisol) that are normally released, even by healthy people → patient will be hyperglycemic in AM



(Remember TIDE - gastric water jug)

Indication – For Type 1 & insulin-using Type 2 patients (Used as supplement to Insulin)
Mechanism – mimetic of human amylin. Slows gastric
emptying, suppresses glucagon secretion, promotes satiety (prevents postprandial hyperglycemia)

ADE: nausea, headache, hypoglycemia (due to concomitant insulin administration); caution if gastroparesis



Class: Biguanide
• Indication – Type 2 DM (First-line therapy in T2DM).
• Mechanism – increases sensitivity of insulin receptors AND
decreases liver gluconeogenesis (weight-neutral, very low risk
of hypoglycemia)

Adverse effects – A/N/V/D (esp. first 2-3 weeks), lactic acidosis; avoid in significant hepatic or renal dysfunction, alcoholism; long-term use associated with B contribute to neuropathy.

Interactions: alcohol (increases risk of lactic acidosis), caution
with sulfonylureas, other DM medications (may enhance
hypoglycemia risk)


Metformin contraindications

Contraindicated in patients with an eGFR < 30. Test eGFR before initiating treatment with metformin.
– Supplement with B12 if testing indicates deficiency


Metformin consideration

If eGFR < 60 or if the patient has a
history of liver disease, alcoholism,
or heart failure, metformin should be
discontinued immediately prior to
and for 48 hours after any radiologic
procedure involving IV iodinated
contrast material.


Glipizide (sulfonylurea swan)

Class: Sulfonylurea
• Indication – Type 2 DM
• Mechanism – stimulates insulin release by blocking ATP-sensitive potassium channels → Ca++ influx → insulin release. Secretagogue.

Take 30 mins. prior to first meal of the day and another
meal if taking BID. Important to teach about taking with meals!
ADE: hypoglycemia, weight gain – hepatotoxicity, rash; avoid in late pregnancy (1 month prior to delivery);
Interactions: alcohol (potentiates hypoglycemic effects), β-blockers (may mask hypoglycemia Sx, can also suppress insulin release); DPP-4 inhibitors


Sulfonyurea MOA

This mechanism of insulin release by blocking
ATP-sensitive potassium channels works the same as
if endogenous glucose had stimulated insulin release.
However, oral secretagogues do not require the
presence of glucose to work. This is the main reason
they can cause hypoglycemia.


Repaglinide (think gliding swan)

Class: Meglitinide (also known as glinides)
• Indication – Type 2 DM
• Mechanism – same as sulfonylureas. Secretagogue


Adverse effects – hypoglycemia, weight gain (fat lady by tree)
Interactions: Gemfibrozil can inhibit metabolism of repaglinide → inc. risk of hypoglycemia; alcohol, β-blockers.


Considerations for:

Secretagogues (sulfonylureas, meglitinides)

Stimulate insulin release regardless of food intake. → Risk of hypoglycemia.
• Take them with (or right before) meals.
• If N/V/A, skip the secretagogue until able to eat again!



• Class: α-Glucosidase inhibitor
• Indication – Type 2 DM
• Mechanism – inhibit α-Glucosidase enzyme at GI brush
border → slowed absorption & digestion of carbohydrates.


• Adverse effects – abdominal distension, cramps,
flatulence, and diarrhea; hepatic dysfunction with long-term
use, (monitor LFTs), decreased iron absorption → anemia;
caution if bowel obstruction
• Interactions – metformin (additive GI side effects), oral iron



• Class: Thiazolidinedione (TZD)
• Indication – Type 2 DM
• Mechanism – PPAR (peroxisome proliferator-activated
receptor) gamma agonist; increases tissue insulin
sensitivity, decreases hepatic glucose production
• Adverse effects – fluid retention, edema, HF, anemia,
↑ LDL-C but ↑ HDL-C and ↓TGs, risk for bladder cancer, fractures in women; hepatotoxicity
• Interactions: combination with insulin increases risk for
hypoglycemia; CYP2C8 inhibitors (atorvastatin, ketoconazole) and CYP2C8 inducers (rifampin, cimetadine)



• Class: DPP-4 Inhibitor
• Indication – Type 2 DM – third-line drug, usually used in combo with other anti-diabetic medications
• Mechanism – inhibits DPP-4 enzyme and prevents inactivation of

Interaction: Sulfonylureas

Adverse effects: low risk of hypoglycemia when used alone.
Increased risk of hypoglycemia when combined with
sulfonylurea. Headache, edema, acute renal failure, upper
respiratory infection, rare risk of pancreatitis, serious
hypersensitivity reactions, Stevens-Johnson Syndrome.
Reduce dose in renal disease.


Incretin function

Incretin hormones found in the gut (such as GLP-1) normally
increase insulin synthesis and release and also inhibit
glucagon. DPP-4 enzyme normally inactivates incretins.
Sitagliptin inhibits DPP-4,thus increasing and prolonging
action of incretins → ↑insulin and ↓ post-prandial glucagon.


Benefit to DPP-4 inhibitors on hypoglycemia

Risk of hypoglycemia when used alone is low because
sitagliptin extends the action of incretins, which require the
presence of glucose to increase insulin secretion, as we will
see shortly.



Class: SGLT2 inhibitor
• Indication – Type 2 DM
• Mechanism: Sodium-glucose co-transporter-2 (SGLT2)
inhibitor in the kidney. Newest type of oral diabetes
medication, first approved in 2013. Prevents reuptake of most
filtered glucose by the kidney → glucose is diuresed and
not returned to circulation.
• Dose: 100 – 300 mg daily if eGFR > 60, 100 g daily of eGFR
between 45-60; do not give to patients with eGFR < 45

Adverse effects: increased urination (osmotic diuresis), hypotension (potential for volume depletion), hypoglycemia (when used with insulin or secretagogues), hyperkalemia, decreased renal function (increased creatinine and decreased eGFR), acute kidney injury, urinary tract infection, genital yeast infections, bone fractures (as early as 12 weeks after initiating the drug) and atypical

Interactions: Drug interactions: rifampin, phenytoin, phenobarbital,
ritonavir (all decrease effectiveness of canagliflozin), digoxin (serum concentration of digoxin will be increased).

– BBW: In 2017, FDA required BBW regarding increased
risk of leg and foot amputation with this mediction.


Exenatide (think witch with stomach)

Class: Incretin mimetic/GLP-1 receptor agonist
• Indication – Type 2 DM
• Mechanism: incretin-mimetic, analog of GLP-1 hormone, activates
pancreatic receptors for GLP-1, increases glucose-dependent
insulin secretion AND decreases post-prandial glucagon, slows
gastric emptying, suppresses appetite
• Administer: injectable only - prefilled pen formulation
• Adverse effects: N/V/D, pancreatitis, nephrotoxicity, bile duct
and gallbladder disease, hypoglycemia when combined with some
oral DM medications, renal impairment, avoid in pregnancy
(animal studies show fetal harm)
Interaction: Can slow absorption of oral drugs, give oral drugs 1
hour before exenatide.


Warnings with incretin mimetics

All incretin mimetics/GLP-1 analogs come with a BBW about
thyroid C-cell tumors, including medullary thyroid carcinoma,
due to increased incidence of these tumors in animal studies.