Endo exam 1

You can do it, I swear

Metformin drug class

Biguanide

Metformin brand names

Glucophage and Glucophage XR, Glumetza, Riomet, Fortamet

How is metformin cleared

Renally eliminated

Metformin's MOA

Inhibits mitochondrial complex one and decreases the production of ATP

This increases intracellular AMP, leading to the activation of AMP kinase. (Also decreases pyruvate and increases lactate)

AMP kinase increases function of insulin receptor, and transport of glucose.

Decreases gluconeogenesis

"insulin sensitizer"

metformin med chem

2 guanidine residues

what are the Sulfonylureas

Glyburide, Glipizide, Glimepiride

Glyburide brands

DiaBeta, Glynase, Micronase

Glipizide brand

Glucotrol

Glimepiride brand

Amaryl

How do sulfonylureas exist in the bloodstream

90% plasma protein bound

Sulfonylureas MOA

"Insulin Secretagogue"

binds to SUR which is a coreceptor for Beta cell KIR (potassium inward rectifying) channel, inhibiting the inward flow of potassium, leading to depolarization which facilitates activation of voltage gated calcium channels leading to influx of calcium into the cell leading to calcium dependent exocytosis of insulin

Sulfonylureas medchem

Conserved sequence of a sulfa group and a urea group

Examples of Meglitinides

Nateglinide, and Repaglinide

Nateglinide brand

Starlix

Repaglinide brand

Prandin

Meglitinides moa

Bind to same receptor on a different spot as sulfonylureas (allosteric site), (SUR) which is a coreceptor for Beta cell KIR (potassium inward rectifying) channel, inhibiting the inward flow of potassium, leading to depolarization which facilitates activation of voltage gated calcium channels leading to influx of calcium into the cell leading to calcium dependent exocytosis of insulin

Meglitinides medchem

Structural similarity to sulfonylureas, but lack sulfonylurea moiety

Thiazolidinedione example

Rosiglitazone, Pioglitazone

Pioglitazone brand

Actos

Rosiglitazone brand

Avandia

How are TZDs cleared

CYP2C8 and CYP3A4 metabolism

TZDs MOA

Insulin sensitizers

Makes cells respond better to insulin by increasing the transcription and protein production of insulin receptors (PPAR-gamma agonist/activator)

Primary action in adipocytes increased insulin receptors on surface increased glucose uptake/storage in peripheral tissues

TZDs CTX

NYHA Class III or IV HF
Osteoporotic in high fracture risk individuals

TZD medchem

Thiol - sulfur
Thiazole - 5-member ring with both N and S
Dione - 2 ketone groups

GLP-1 Receptor Agonists examples

Semaglutide, Dulaglutide, Exenatide, Lisizenatide, Liraglutide

Semaglutide IV brand

Ozempic

Semaglutide oral brand

Rybelsus

Oral GLP1A

Semaglutide (Rybelsus)

Dulaglutide brand

Trulicity

Exenatide brands

Byetta, Bydureon

What GLP1A has a long acting release dosage form

Exenatide (Bydureon)

Lisizenatide brand

Adlyxin

Liraglutide brand

Victoza

What GLP1 agonist are given daily

Liraglutide (Victoza), and Lisizenatide (Adlyxin)

What GLP1 agonis is given BID

Exenatide (Byetta)

What GLP1 agonists are given weekly

Semaglutide (Ozempic), Dulaglutide (Trulicity), Exenatide (bydureon)

Compare the efficacy of BID, QD, and weekly GLP1As

Weekly \> QD&BID

GLP1 agonists moa

Insulin secretagogue

Bind to GLP-1 receptor activating cascade production of cAMP leading to activation of PKA (Gs pathway) activation of enzymes necessary for biosynthesis of insulin and docking/release of insulin containing vesicles

Long term improved CV outcomes

Potential for weight loss due to lipolysis

What is the chemical structure of GLP1As

peptide

Med chem of Liraglutide

16 carbon palmitoylation which leads to increased duration of effect

DPP-4 Inhibitors examples

Saxagliptin, Alogliptin, Linagliptin, Sitagliptin

DPP-4 inhibitors MOA

Competitive enzyme inhibition

Noncovalent bonding within the DPP-4 enzyme to prevent GLP or GIP from binding increased insulin secretion because of increased incretin effect

Reduced fasting and postprandial levels of glucose

Weight neutrality

Saxagliptin brand

Onglyza

Alogliptin brand

Nesina

linagliptin brand

Tradjenta

sitagliptin brand

Januvia

What DPP4 inh touches the smallest area of the enz

saxagliptin (Onglyza) (S1&21)

What DPP4 inh touches S'1 and S'2 in the enz

alogliptin (Nesina)
linagliptin (Tradjenta)

What DPP4 inh touches the largest area of the enz, and what modifiaction allows it to reach into the extended S2 pocket

Sitagliptin (Januvia), fluorine containing ring

SGLT2 Inhibtiors examples

canagliflozin (Invokana)
dapagliflozin (Farxiga)
empagliflozin (Jardiance)
ertugliflozin (Steglatro)

canagliflozin brand

Invokana

dapagliflozin brand

Farxiga

empagliflozin brand

Jardiance

ertugliflozin brand

Steglatro

SGLT2 inhibitors MOA

Binds to the glucose domain on the SGLT2 transporter in the renal proximal tubule which leads to decreased glucose reuptake (but SGLT1 can still take in glucose no worries) so most of the glucose gets excreted in the urine

Normalizes Na+ delivery and restores GFR

Should have glycosuria

SGLT2 medchem

Glucose like moiety (chair formation)

Amylin Analogues examples

Pramlintide (Symlin)

Amylin Analogues MOA

Three proposed mechanisms
- Neuro-endocrine appetite suppression (brain)
- Slowed gastric emptying (stomach)
- Inhibit glucagon release (pancreas)

Pramlintide brand name

Symlin

Amylin Analogues med chem

Proline substituted amylin

α-Glucosidase Inhibitors examples

Acarbose (Precose)
Miglitol (Glyset)

α-Glucosidase Inhibitors MOA

Decreases the absorption of glucose from the diet into circulation by blocking galactosidase

Acarbose brand

Precose

Miglitol brand

Glyset

Bile Acid Sequestrant (BAS) example

Colesevelam

Colesevelam brand

Welchol

Bile Acid Sequestrant (BAS) MOA

Not 100% known - modulates FXR and TGR5 activity leading to improvement in hepatic glucose metabolism, an increase in incretin hormone secretion, and increased insulin secretion

Increasing morning hypothalamic dopamine levels leads to decreased SNS activity, decreased HGP, decreased lipolysis of FFA and decreased lipogenesis of TG. These lead to increased glucose tolerance, increased insulin sensitivity, decreased plasma FFA/TG and decreased vascular pathology

Bile Acid Sequestrant medhem

Polymer backbone with hydrophobic side chains

Binds bile acids

Dopamine Receptor Agonist example

Bromocriptine (Cycloset)

Bromocriptine brand

Cycloset

Dopamine Receptor Agonist MOA

Increasing morning hypothalamic dopamine levels leads to decreased SNS activity, decreased HGP, decreased lipolysis of FFA and decreased lipogenesis of TG. These lead to increased glucose tolerance, increased insulin sensitivity, decreased plasma FFA/TG and decreased vascular pathology

Dopamine Receptor Agonist med chem

Ergot alkaloid

Short-Acting Insulin examples

Lispro
Aspart
Glulisine

insulin aspart brand

NovoLog

fast acting insulin aspart brand

Fiasp

insulin glulisine brand

Apidra

insulin lispro brand

Humalog, Admelog

insulin lispro-aabc brand

Lyumjev

inhaled insulin

Afrezza

regular insulin brands

Humulin R, Novolin R,

What insulins inlcude zinc

short acting

Why is zinc added to short acting insulins

to form a pentameric structure

Intermediate-Acting Insulins

Neutral Protamine Hagedorn

NPH insulin brands

Humulin N, Novolin N

Long-Acting Insulins

insulin glargine, insulin detemir, concentrated glargine, degludec

insulin glargine brands

Lantus, Basaglar, Rezvoglar, Semglee

What is substitutable for Lantus

semglee

insulin detemir brand

Levemir

cencentrated glargine band

Toujeo

degludec brand

Tresiba

Detemir medchem

Adds myristic acid to Lsy29 to enhance association with albumin

Glargine medchem

adds 2 Arg after B30 and changes Asp21 to Gly21

First line choices for T2D

Metformin, SGLT2 inh, GLP1A

Diabetes diagnosis (Fasting, 2 hr PP, Random, A1C)

\>126
\>200
\>200
\>6.5

Pre-Diabetes diagnosis (Fasting, 2 hr PP, Random, A1C)

100-125
140-199
N/A
5.7-6.4

No diabetes diagnosis (Fasting, 2 hr PP, Random, A1C)

Avg blood sugar for A1C 6

120

Avg blood sugar for A1C 10

240

Methods of auto immune beta cell destruction

- Islet cell cytoplasmic autoantibodies
- Insulin autoantibodies
- Autoantibodies to glutamic acid decarboxylase
- Zinc transporter 8 autoantibodies
- Tyrosine phosphatases islet cell antigen 2 and 2B