Endocrine 1 Exam 1: Witt-Enderby Drugs (p12-17)

Drugs can be hypoglycemic (impacts ___)

insulin

Drugs can be anti-hyperglycemic (inhibits ___)

gluconeogenesis

What 2 drug classes close ATP-sensitive K+ channels?

Sulfonylureas, Meglitinides

Sulfonylureas (SURs)

1. ____ (Diabeta, Micronase, Glynase)

2. _____ (Glucotrol)

3. _____ (Amaryl)

Glyburide, Glipizide, Glimepiride

Meglitinides/Glinides

1. _____ (Prandin), which is a derivative of benzoic acid

2. Nateglinide (Starlix)

Repaglinide

are drugs that close ATP-sensitive K+ channels hypoglycemic or anti-hyperglycemic?

hypoglycemic

By closing ATP-sensitive K+ channels:

-this causes a ____ and Ca2+ ___ through voltage-gated Ca2+ channels

depolarization, influx

By closing ATP-sensitive K+ channels:

-stimulate insulin ___ and reduce hepatic___ of insulin

release, clearance

What drug class increases insulin action in peripheral tissues?

Biguanides

Biguanides

1. _____ (Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet)

Metformin

Metformin is also used in combination with ____ (glyburide, glipizide, repaglinide)

sulfonylureas

is Metformin (increases insulin action in peripheral tissues) hypoglycemic or anti-hyperglycemic?

anti-hyperglycemic

Biguanides

-anti-hyperglycemic, which means metformin does NOT cause insulin release from beta cells/____

hypoglycemia

Biguanides MOA

-activates adenosine monophosphate kinase (____)

AMPK

AMPK is normally activated by high levels of ____

AMP

AMPK is activated when AMP levels are high, which signals that ATP is being ____ down and the cell’s energy level is low

broken

remember that a ratio of ATP:AMP that is __:__ means the cell is happy

10:1

A cell is not happy in DM because hyperglycemia causes capillaries to narrow (poor perfusion), which can lead to ___ (low O2)

hypoxia

Remember oxygen is the driving force of the electron transport chain to make ATP. So a patient with hypoxia will have ____ ATP

decreased

Decreased ATP will cause an ___ in AMP (bc cell needs energy)

increase

In DM, decreased ATP causes an increase in AMP. A ratio of ATP:AMP that is ___:____ results

1:10

In DM, decreased ATP causes an increase in AMP. A ratio of ATP:AMP that is 1:10 results, resulting in activation of ____

AMPK

When AMPK is activated:

1. ____ is inhibited (bc this pathway uses ATP, and we are trying to save ATP bc we r low)

gluconeogenesis

When AMPK is activated:

2. ____ is stimulated (breakdown TG into glycerol + fatty acids!)

lipolysis

Lipolysis breaks down TGs into glycerol and fatty acids. Fatty acids undergo beta-oxidation to produce lots of ___ :)

ATP

When AMPK is activated:

3. increased ___ insertion into membrane

GLUT

Increased GLUT insertion into membrane increases glucose "____"

utilization

glucose "utilization" = convert glucose to ____ :)

ATP

Metformin stimulates AMPK in the ___ and periphery (___ and ___)

liver, fat, muscle

AMPK located in the muscle is stimulated by ____ (this is why you should counsel patient to do exercise that involves muscular contraction)

contraction

When AMPK inhibits gluconeogenesis, this decreases glucose in the ___ and ___

liver, blood

What drug class modulates signaling proteins involved in insulin receptor signaling?

Thiazolidinediones

Thiazolidinediones

1. ____ (Actos)

2. ____ (Avandia)

pioglitazone, rosiglitazone

Thiazolidinediones MOA

-selective agonists for nuclear peroxisome proliferator-activated receptor gamma (____)

PPAR-γ

PPARs are ___ receptors (3 subtypes are PPAR-α, PPAR-β, and PPAR-γ, but only PPAR-γ are involved in managing T2D)

nuclear

Thiazolidinediones

-require ___ to be present for their action

insulin

Thiazolidinediones

1. increase #____ transporter genes that regulate lipid and carbohydrate metabolism

2. increase glucose _____ (to make more ATP)

GLUT, utilization

Dipeptidyl Peptidase-4 Inhibitors

1. ____ (Januvia)

2. _____ (Tradjenta)

3. _____ (Nesina)

4. _____ (Onglyza)

sitagliptin, linagliptin, alogliptin, saxagliptin

DPP-4 is expressed on the ___ tract and prevents the ___ of incretin hormones like GLPs

GI, inactivation

DPP-4 prevents the inactivation of incretin hormones like GLPs, therefore ___ incretin levels by ___ their half life

increasing, increasing

Glucagon-like peptides (GLPs) have effects on the brain which lead to ___ appetite

decreased

Glucagon-like peptides (GLPs)

-___ gastric emptying

-____ glucagon

decrease, decrease

Glucagon-like peptides (GLPs)

-____ glycemic control in liver

-____ liver lipids

increase, decrease

____ drugs → activate both GLP-1 and GIP pathways simultaneously

twincretin

GLP-agonists

1. ____ (Victoza)

2. ____ (Trulicity)

3. Lixisenatide (Adlyxin)

4. _____ (Rybelsus, Ozempic, Wegovy)

5. Exenatide/Exenatide ER

liraglutide, dulaglutide, semaglutide

____ (Mounjaro) is a twincretin (GLP-1 and GLP agonist)

tirzepatide

GLP-agonists MOA

-____ actions of GLP-1 to reduce fasting and postprandial glucose levels

mimics

α-Glucosidase Inhibitors

1. ____ (Precose)

2. _____ (Glyset)

acarbose, miglitol

α-Glucosidase Inhibitors MOA

-inhibit α-Glucosidase → slow the absorption of ____ through the intestine

carbohydrates

We want to slow the absorption of carbohydrates through the intestine to prevent glucose ____ (which can cause insulin receptor desensitization)

spikes

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

1. _____ (Invokana)

2. _____ (Farxiga)

3. ______ (Jardiance)

4. Ertugliflozin (Steglatrol)

5. Bexagliflozin (Brenzavvy)

canagliflozin, dapagliflozin, empagliflozin

are SGLT2 inhibitors hypoglycemic or anti-hyperglycemic?

anti-hyperglycemic

remember cotransporters move two molecules in the ___ direction across a membrane.

same

SGLT2 Inhibitors MOA

-inhibit ____ of glucose from the proximal tubules located in the kidneys (so glucose stays in urine, so increases ____)

reabsorption, excretion

Synthetic analog of humin amylin

1. ____ (Symlin)

Pramlintide

Amylin = a neuroendocrine hormone

-secreted by β-cells of the pancreas along with insulin

-Secretion ratio: ~ ___ amylin : ___ insulin molecules

1, 20

Amylin affects glucose concentrations by 3 different mechanisms

1. ___ gastric emptying without altering the overall absorption of nutritents (to prevent glucose spikes)

slow

Amylin affects glucose concentrations by 3 different mechanisms

2. suppresses postprandial ____ secretion (to decrease glucose in blood)

glucagon

Amylin affects glucose concentrations by 3 different mechanisms

3. modulates ___ centrally leading to decreased caloric intake

appetite

Levels of amylin are ___ in T1D and ___ in T2D

absent, low

If someone is in a hypoglycemic state, then they are given ____ (Glucagen)

glucagon

Remember that glucagon is a hormone released from the alpha cells of the islets of langerhan to increase blood glucose by stimulating ____ (breakdown of glycogen into glucose)

glycogenolysis