Insulin and Diabetes Therapeutics Flashcards by Paige Tustanowsky

What are the short-acting insulins?

Lispro (Humalog), Aspart (Novolog), Glulisine (Apidra)

How well did you know this?

Not at all

Perfectly

What are the long-acting insulins?

Glargine (Lantus), Detemir (Levemir), Degludec (Tresiba)

How well did you know this?

Not at all

Perfectly

What GLUT transporter is Insulin-induced?

GLUT 4
Km= 5 mM
-expressed in skeletal muscles, adipocytes

How well did you know this?

Not at all

Perfectly

What GLUT transporter has the fastest Km?

GLUT 2
Km= 15-20 mM
-constitutive
-expressed in B-cells. liver

How well did you know this?

Not at all

Perfectly

What are the mechanisms of cell damage initiated by hyperglycemia?

-Polyol pathway
-Hexosamine pathway
-Protein Kinase C pathway
-AGE pathway

How well did you know this?

Not at all

Perfectly

How is NPH absorbed?

Neutral Protamine Hagedorn
-complexed with Protamine when injected; tissue proteases break it down to just free insulin
-slow absorption, long duration of action

How well did you know this?

Not at all

Perfectly

How is Lispro & Aspart absorbed?

-reversed position of Proline 28 and Lysine 29 (Aspart-switched to aspartate) on insulin B chain; prevents dimer and hexamer formation
-faster onset than regular insulin (5-15 minutes)

How well did you know this?

Not at all

Perfectly

How is Glulisine absorbed?

-Asn(Asparagine) 3 and Lys 29 in B chain are switched to Lys & Glutamate
-faster onset than regular insulin (5-15 minutes)

How well did you know this?

Not at all

Perfectly

How is Glargine absorbed?

Asn(Asparagine) 21 of a-chain is changed to Gly(Glycine)
2 Arg residues are added to end of B chain -changes pKa of the peptide and solubility
-slowly and steadily released from injection site over 24 hours (inject once daily)

How well did you know this?

Not at all

Perfectly

How is Detemir/Degludec absorbed?

Thr 30 of b-chain is deleted, and Lys 29(y-Glu/C16 FA in Degludec) is modified with insulation peptides to bind serum albumin extensively
-long acting 1 or 2 injections/day

How well did you know this?

Not at all

Perfectly

Which insulin preparation is not genetically modified?

NPH

How well did you know this?

Not at all

Perfectly

What are the sulfonylureas?

Tolbutamide, Chlorpropamide, Tolzamide
Glipizide, Glyburide, Glimepiride

How well did you know this?

Not at all

Perfectly

What are the Meglitinides “Glinides”?

Nateglinide (Starlix)

How well did you know this?

Not at all

Perfectly

What are the GLP-1 analogs?

Exenatide, Liraglutide (Victoza), Dulaglutide (Trulicity), Lixisenatide (Adlyxin), Semaglutide (Ozempic)

How well did you know this?

Not at all

Perfectly

What are the GIP receptor agonist and Biased GLP-1 receptor?

Tirzepatide (Mounjaro)

How well did you know this?

Not at all

Perfectly

What are the DPP-4 inhibitors?

Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta), Alogliptin (Nesina)

What are the a-glucosidase inhibitors?

Acarbose (Precose), Miglitol (Glyset)

What are the SGLT2 inhibitors?

canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro), Bexagliflozin (Benzavvy)

What are the Thiazolidinediones?

Rostiglitazone (Avandia), Pioglitazone (Actos)
-restricted prescribing due to cardiac toxicities
-contradindicated in heart failure later stages
-check liver function

How does metformin reduce blood glucose levels?

Molecular Target: Complex 1 (ETC)
Cellular effect: Elevates [AMP], activates AMPK
Physiological effect: liver- reduced glucose export
skeletal muscle- increased glucose uptake

How do TzDs reduce blood glucose levels?

Molecular target: PPARy
Cellular effect: regulation of transcription in adipose cells
Physiological effect: reduces adipokines that induce insulin resistance (resistin and TNFa)

The toxicity of hyperglycemia results from:
A. the chemical reactivity of glucose
B. Shunting of excess glucose into the polyol and hexosamine pathways
C. Formation of AGEs and activation of receptors for AGEs
D. All of the above

All of the above

How do you optimize glucose control in patients with T2DM + kidney disease (UACR >200mg/g)?

-SGLT2 Inhibitor w/evidence of CKD progression if eGFR > 20mL/min
-GLP-1 agonist with CV benefit if SGLT2I CI or not tolerated

How do you manage patients with CVD/HF + T2D?

1st line: SGLT2 Inhibitors + GLP-1 agonists

What are the preffered antihypertensive agents for patients with T2D?

ACEIs or ARBs -use at max tolerated dose -do not use in combo due to risk of AEs 2nd line: HCTZ, chlorthalidone, amlodipine, spironolactone

What indicates use of antiplatelet agents in patients with diabetes?

-aspirin indicated as use for secondary prevention in patients with diabetes and history of past CVD (or clopidogrel 75mg/day) -aspirin indicated as use for primary prevention in patients 50+ years old with 1 major risk factor + not at increased risk of bleeding

What are the fasting blood glucose target and random blood glucose target?

Fasting: 80-130 mg/dL (ADA); <110mg/dL (AACE) Random/postprandial: <180 mg/dL (ADA); <140mg/dL (AACE)

What is the Egregious Eleven?

-factors that cause B cell damage and decrease insulin production -B-Cell is final common denominator of B-Cell damage Includes: Incretin effect, a-cell defect, adipose, muscle, liver, brain, colon/biome, immune dysregulation/inflammation, stomach/small intestine, kidney

What is the diagnostic criteria for diabetes?

FBG: >126 mg/dL AIC: greater than or equal to 6.5% random glucose: 200mg/dL + symptoms 2hr postprandrial glucose: >200mg/dL during an OGTT

What class of drugs enhance insulin secretion?

Sulfonylureas, Meglitinides "Glinides"

What class of drugs enhance the incretin effect?

GLP-1R agonists, GLP-1 analogs, GIP receptor agonist, DPP-4 inhibitors

What class of drugs reduce glucose absorption or increase glucose excretion?

a-glucosidase inhibitors, SGLT2 inhibitors

What class of drugs reduce insulin resistance/lipotoxicity?

metformin (Biguanides), Thiazolidinediones (TzDs)