Diabetes Lec 4-5 Flashcards by Jeff Lattman

SC insulin takes about __ hours before reaching a max, therefore it should be injected about ___ min before meals

2, 30

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How does zinc change the diffusion of SC insulin?
a. increases diffusion
b. decreases diffusion
c. inhibits diffusion
d. limits diffusion

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______ insulin is what is secreted in response to elevated blood glucose

mature

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The structure of insulin is comprised of?

along helix B chain and 2 short helices of A chain

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what are the three short acting insulins called?
what are the advantages of this form of insulin?

lispro (humalog), insulin aspart (novolog), and glulisine
-more rapid onset than regular insulin
-reduces risk of hypoglycemia

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what is the structural significance of the short-acting insulins?

they prevent formation of oligomers

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what are the long-acting insulin called?

glargine (lantus, toujeo)
detemir (levemir)
degludec (tresiba)

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why does glargine (lantus, toujeo) have a pl (isoelectric point) that is more basic than insulin and why is this important?

Because of 21-G on A chain and (mainly) 2 arginine at the C-terminus of the B chain. They increase basicity to precipitate at injection site. this makes it act for a longer period of time

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For detemir (levemir), __________ is bound to B chain K29 which allows it to bind to ______ and slowly dissociate

myristic acid, albumin

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for degludec (tresiba), it’s structure has a deletion of ________ and an addition of a __________ attached to B-Lys29 via a glutamic acid spacer. It self-associates into multi-_______ resulting in an ultra-long peak

B-Thr30, 16-carbon fatty diacid, hexamers

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Rank the order of insulin meds from longest acting to shortest acting

Glargine -> Detemir -> NPH -> Regular -> lispro/ aspart/glulisine

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Once a glucagon emergency kit is reconstituted, how long can it be used for?

not long, it should be used immediately after reconstitution

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what is the mechanism of action of sulfonylureas?
what gives them their hypoglycemic effect?

close K+ channels located on beta cells to promote insulin release from beta cells
modification of the structure to contain a urea group

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List the drugs classified as sulfonylureas

-drugs ending in amide
-glipizide
-glyburide
-gliclazide
-glimepiride

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what is the mechanism of action of meglitinides?

same as sulfonylureas: close K+ channels located on beta cells to promote insulin release from beta cells

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List the drugs classified as meglitinides

nateglinide, repaglinide, and mitiglinide

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which sulfonyureas/meglitinides are selective for SUR1-type channels?

tolbutamide, chlorpropamide, nateglinide, and mitiglinide

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which sulfonyureas/meglitinides are non-selective for SUR1/SUR2-type channels?

glibenclamide, glimepiride, and repaglinide

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what is the mechanism of action of biguanides?

indirectly activates AMPK and reduces cytosolic dihydroxyacetone phosphate while raising cytosolic NADH/NAD+ ratio
-decreases hepatic glucose production by inhibiting gluconeogenesis and intestinal absorption of glucose, and improves insulin sensitivity

what drugs are classified as biguanides?
what is a potential adverse reaction of biguanides?

metformin and buformin (can cause toxic lactic acidosis), and phenformin (withdrawn due to toxic lactic acidosis)

what drug is co-administered with metformin?

glyburide

what can toxic lactic acidosis cause? (adverse rxn to biguanides)

death, hypothermia, hypotension, and resistant bradyarrhythmias

why does phenformin have a greater risk of toxic lactic acidosis than metformin?

because it is more lipophilic and and may bind more strongly to mitochondria to inhibit oxygen consumption causing a shift to anaerobic glycolysis

why is metformin formulated with hydrochloride?

because it has a nearly permanent positive charge

what is the mechanism of action of thiazolidinediones (glitazones)? they are approved as combo therapy with?

improve insulin sensitivity by agonizing PPARy and reduce insulin resistance in T2DM. sulfonylureas, metformin, and insulin

what are the names of the thiazolidinediones (glitazones)? dosing? adverse reactions?

pioglitazone: 15-45mg qd rosiglitazone: 4-8mg qd -> has adverse cardiovascular effects Troglitazone: withdrawn due to drug induced hepatitis Lobeglitazone -all drugs have warnings of monitoring liver function

thiazolidinediones should not be used in pts with ______ impairment because they may cause _____ retention leading to possible cardiac failure a common side effect from these drugs is?

renal, fluid weight gain

what are the names of the 2 aminocyclitols (a-glucosidase inhibitors) and their dosing MOA? common SEs?

acarbose: initial: 25mg tid at start of each meal maintenance: 50-100mg tid miglitol: same dosing inhibit a-glucosidase and pancreatic amylase to prevent glucose absorption flatulence and diarrhea

describe the "incretin effect"

higher lvl of insulin secretion when carb load is given orally than when given parentally which is caused mainly by GLP-1 and GIP

what drugs are increatin based?

amylin agonists, GLP-1 agonists (the glutides +xenatide), DPP-4 inhibitors (gliptins)

what is the MOA of pramlintide (aka Symlin)? SEs?

it's a synthetic analog of amylin: activates amylin receptors to extend gastric emptying to slow glucose absorption and potential appetite reduction N/V, HA

GLP-1 is derived from a larger peptide named ______

proglucagon

what are the 2 forms of GLP-1 in bloodstream?

GLP-1 (7-37) and GLP-1 (7-36)

Exenatide is a GLP-1 agonist that is a synthetic version of ______ it stops the liver from making too much ______ it reduces ______ it slows down ______ absorption it slows _________ and stimulates ___________ secretion

exendin-4 glucose appetite glucose GI emptying, glucose-dependent insulin

Exenatide comes in two forms: Byetta and Bydureon, what is the dosing/administration of both?

Byetta: bid injection Bydureon: qw injection

Liraglutide is a GLP-1 agonist Dosing? what is an advantage of this med? what is an associated risk? what hormone can be monitored to determine this risk?

qd injection causes weight loss thyroid C-cell hyperplasia and C-cell tumors calcitonin

what is semaglutide's dosing? (GLP-1 agonist)

qw injection

what are common SEs of GLP-1 R agonists?

heartburn, N/V, diarrhea, and constipation

All DPP-4 inhibitors name's end in?

gliptin

which DPP-4 inhibitors are class 1? (i played the SAX for Veronica) which binding substrates do they inhibit?

saxagliptin and vigdagliptin S2 and S1

which DPP-4 inhibitors are class 2? (I put some Aloe on to Lin) which binding substrates do they inhibit?

linagliptin and alogliptin S2,S1,S2', and S1'

which DPP-4 inhibitors are class 3? (go SIT with the TENors) which binding substrates do they inhibit?

sitagliptin (januvia) and tenegliptin S2 extensive, S2, and S1

MOA of SGLT2 inhibitors? why is this drug class more beneficial than the others?

block SGLT2 to increase renal glucose excretion to reduce plasma glucose levels and decrease weight they don't cause significant SEs

what are the drug names of the SGLT2 inhibitors?

phlorizin, and all drugs ending in (gliflozin)

which of the following is not a SE of SGLT2 inhibitors? a. vaginal odor/discharge/itching b. nausea/vomiting/diarrhea/constipation c. UTI/polyuria d. rhinorrhea/polydipsia/rash

which drug classes are labeled as biologics?

amylin analogs, GLP-1 mimics, and DPP-4 inhibitors

In summary: what effect(s) do GLP-1 mimics have? Sulfonylureas/meglitinides? Biguanides? Thiazolidinediones? Symlin? a-glucosidase inhibitors? SGLT2 inhibitors?

stimulate insulin release and inhibit glucagon release stimulate insulin release improve insulin sensitivity and reduce hepatic glucose production improve insulin sensitivity by targeting PPARy lower blood glucose by activating amylin receptors lower blood glucose by inhibiting a-glucosidase and pancreatic amylase lower blood glucose by inhibiting reabsorption of glucose from kidney via inhibition of SGLT2 receptors