Antidiabetics (wait is this pharm or clin med?? 🤔) Flashcards
What are the 2 agents that are used to INCREASE blood sugar?
Glucagon
Diazoxide (Proglycem)
What happens to levels when you inject insulin (in anyone)
Blood glucose:
Pyruvate and lactate:
Inorganic phosphate:
Plasma potassium:
Glucose decreases
Pyruvate and Lactate: increase (metabolism)
Phosphate: decrease (metabolism)
Potassium- decreases. Glucose in cells makes Na-K pumps work more
(PROBABLY not on test)
Do we use insulin for Type 1 or Type 2
Both
What are the adverse reactions of insulin?
HYPOGLYCEMIA**
Weight gain***
Cough (inhaled only)
Local reactions (allergy)
Lipodystrophy and lipohypertrophy
What kinds of things can cause hypoglycemia in a patient who uses insulin?
Taking too much insulin
Change in insulin type preparation
Too many insulin secreting drugs
Spontaneous decreases in insulin requirements (no longer pregnant or stressed out)
Vigorous exercise ⛹️♂️
Failure to eat
Overindulgence in alchol🍻🍸🥃🍾🍷🥂🍺🍹
How do you treat hypoglycemia in someone who is unconscious?
Give 50% glucose solution IV until they wake up
Could also theoretically give glucagon but no one does that
What kinds of things increase insulin requirement?
ANYTHING that increases stress**
….Like SURGERY, preganncy, thyrotoxicosis, infection
Acromegaly and Cushings
If your patient is having surgery, what do you need to do to their insulin dose?
Increase it! (Surgery is stressful)
What are the 4 preparation types of insulin?
Rapid
Short (Regular)
Intermediate
Long acting
What are the 4 types of rapid acting insulin available
Lispro
Aspart
Glulisine
Inhaled*
What kind of insulin is used first in type II DM?
Long-acting (basal)
What is necessary for glucagon to work to increase blood glucose?
You must have glycogen stores!**
NOT EVERYONE DOES
What is Diazoxide (Proglycem)?
It’s used to INHIBIT insulin secretion.
Does so by acting on K+ channels so no insulin can be released.
Who do we give Diazoxide (Proglycem) to?
Patients with insulinoma (insulin secreting tumor)
Diazoxide inhibits insulin secreting and raises blood sugar
NOT patients with diabetes
What are the 4 rapid acting insulins?
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Insulin, inhaled (Afrezza)
What are the short acting insulin’s
Regular Insulin (Novolin R, Humulin R)
What are the intermediate acting insulins?
NPH or Isophane Insulin (Humulin N, Novolin N)
What are the long acting insulins?
Insulin glargine (Lantus)
Insulin detemir (Levemir)
Insulin degludec (Tresiba)
What is the #1 killer of diabetics
cardiovascular disease
What is the initial drug of choice for Type 2 diabetics, as long as their A1C is under 10%?
Metformin
What is the MOA of Metformin?
Decreases glucose in an insulin-INDEPENDENT matter:
Removes glucose from blood (AMPK)
Secretion of GLP-1
Decrease glucose absorption from GI
Decrease glucagon levels
Decreased gluconeogenesis (mitochondrial enzyme inhibition)
notice that not one of these says that it INCREASES insulin***
What glycemic effects does metformin have?
Decreases A1C a LOT! (1-1.5%)
Promotes a euglycemic state *!!! (as opposed to hypoglycemic)
Why is it ok to give metformin to women with PCOS that DONT have diabetes?
Because metformin promotes a euglycemic state and NOT a hypoglycemic state
What are the cardiovascular effects of metformin?
Lower triglycerides by 15-20%
Decrease Macrovascular events (aka heart attacks)*******
What are some “other” effects of metformin?
Weight neutral (does NOT increase insulin release, so it has no effect on weight!)***
Decrease all-cause mortality events
BEST pharmacologic therapy for diabetes prevention in prediabetics**
Will metformin cause weight gain
No*****
How is metformin excreted?
Through the kidneys
Remember the whole contrast and holding metformin thing?
What are the adverse effects of metformin?
Lactic Acidosis** LETHAL
Diarrhea*** (53% of patients!)
Hypoglycemia almost NEVER
What are the contraindications/precautions for metformin?
Anything that can cause lactic acidosis:
Kidney disease (contraindicated in renal failure or GFR <30)
Liver disease
Alcoholism
Diseases that predispose to tissue hypoxia: COPD, CHF
What are incretins?
GLP-1 and GIP that get released when you take glucose ORALLY
They increase insulin release and inhibit glucagon release (decreased hepatic gluconeogenesis)
What is the MOA of GLP-1 agonists?
They are GLP-1 agonists that are ~resistant~ to DPP-4 degradation
What are the 5 GLP-1 agonists?
Exenatide (Byetta, Bydureon)
Liraglutide (Victoza)
Dulaglutide (Trulicity)
Albiglutide (Tanzeum)
Lixisenatide (Adlyxin)
How are GLP-1 agonists administered?
SC injections 2x/day or 1x/week
What are the effects of GLP-1 agonists?
Increase the effects of insulin
Large A1C decrease (1-1.5%)
Liraglutide (Victoza) will decrease macrovascular events**
Lower BP (maybe)
Slows gastric emptying= eating less***
Weight loss**
Increased B cell number and function**
Which GLP-1 agonist is only approved for weight loss?
Liraglutide (Sandexa)
🏝👙 (take it before you hit the SAND)
What are the adverse effects of GLP-1 agonists?
ACUTE PANCREATITIS* ON TEST***!!
Hypoglycemia (low risk)
GI
Hypersensitivity
What are the contraindications/precautions of GLP-1 agonists?
Pancreatitis (now or ever)***
Thyroid Cancer BLACK BOX WARNING it is thought that it exacerbates thyroid cancer when it increases the # of B cells
What are the 4 DPP-4 inhibitors?
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
the gliptins
What is the MOA of DPP-4 inhibitors?
Potentiates the effects of endogenous incretins by inhibiting their breakdown by DPP-4
How are DPP-4 inhibitors administered?
Oral
What are the therapeutic effects of DPP-4 inhibitors?
Decrease A1C a medium amount (0.5-1%)
Weight neutral
What are the adverse effects of DPP-4 inhibitors?
Hypoglycemia (rare)
Acute pancreatitis***
Severe joint pain
What are the contraindications/precautions of DPP-4 inhibitors?
Pancreatitis now or ever*
Slow GI
Renal impairment
What are the 4 SGLT-2 inhibitors?
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)
“Gli” -> glucose
“Flozin” -> flowing (kidney)
What is the MOA of SGLT-2 inhibitors?
Inhibits the sodium-glucose cotransporter (SGLT-2) in the kidney= makes you pee out a lot of glucose
What are the 2 antidiabetic drugs that are FDA approved too treat Cardiovascular Disease’?
Liraglutide (Victoza)
Empagliflozin (Jardiance)
This is probably due to their weight loss effect
Do SGLT-2 inhibitors do anything to address the insulin resistance problem
No
What are the therapeutic effects of SGLT-2 inhibitors?
Medium A1C decrease (0.5-1%)
Empagliflozin decreases CV events****
Lower BP*
Weight Loss** (you’re pissing out glucose)
What are the adverse effects of SGLT-2 inhibitos?
Vaginal yeast infections, UTIs and increased urinary frequency**** You’re pissing out glucose 🧁🚽
Hyponatremia***Increased urinary Na+ excretion due to increased H2O in proximal tubule
Osmotic diuresis**
Hypotension, dizziness, syncope, dehydration due to diuresis**
Hypoglycemia rarely
What are the contraindications/precautions for SGLT-2 inhibitos?
Contraindicated in severe kidney disease or on dialysis (these drugs wont work if your kidneys are shitty)
Prone to UTIs or other GU infections
How would an SGLT-2 inhibitor affect someone with an overactive bladder?
It would be made WORSE due to the osmotic diuresis and increased need to pee
What are the 2 thiazolidinediones (TZDs)?
Pioglitazone (Actos)
Rosiglitazone (Avandia)
the glitazones
What is the MOA of thiazolidinediones (TZDs)?
They are “insulin sensitizers”= specifically target insulin resistance**
Bind to PPARγ receptor which causes post-receptor insulin-mimetic action*****
Increased expression of GLUT4 transporter
What antilipid drug class are Thiazolidinediones (TZDs) similar to?
Fibrates (PPAα ligands)
Do thiazolidinediones (TZDs) specifically target insulin resistance?
YES. They are “Insulin sensitizers”*****
What are the therapeutic effects of thiazolidinediones?
High A1C decrease (1-1.5%)
Lower triglycerides in long-term use (insulin is getting glucose into cells, so there’s less FFA’s)
Increase HDL
Lower insulin resistance**
May help prediabetics prevent development of DM
What are the adverse effects of thiazolidinediones?
Hypoglycemia **(sometimes)
Edema (can cause HF in patients with CHF!!)
Weight gain ** (maybe due to edema)
Bone fracture risk** (no one knows why)
What are the contraindications/precautions for thiazolidinediones?
Contraindicated in heart failure ** due to edema***
Hepatic disease (1st TZD was taken off the market for this!)
What are the 2 α-glucosidase inhibitors?
Acarbose (Precose)
Miglitol (Glyset)
What is the only Class of antidiabetic agent that is used in type 1 and Type 2 diabetes?
α-glucosidase inhibitors
Used off-label in type 1 becasue if they eat too many carbs than the amount of insulin they took for their insulin profile, they can take this to prevent the absorption of the carbs)
What is the MOA of α-glucosidase inhibitors?
Inhibit α-glucosideases in small intestine= delayed carb digestion and absorption
How do you take α-glucosidase inhibitors?
Orally, pre-prandially
What are the therapeutic effects of α-glucosidase inhibitors?
Decrease postprandial glucose (can lower A1C)
No effect on weight (?!?!)
What are the adverse effects of α-glucosidase inhibitors?
GI effects- diarrhea and flatulence**** (all those undigested carbs make your gut bacteria very happy!)💩💨
Do α-glucosidase inhibitors cause hypoglycemia?
NEVER**
How do Sulfonylureas work?
They float over to the β-cells and bind to a K+ channel, which depolarizes the membrane and increases Calcium influx into the cells= big fat insulin release
What are the therapeutic effects of sulfonylureas?
Lower A1C a lot (1-1.5%)
Decrease risk of MI and microvascular disease
Decrease mortality
Decrease glucagon= lower hepatic glucose production
Potentiate action of insulin on target tissues
What are the adverse effects of sulfonylureas?
HYPOGLYCEMIA** the worst drug for this
Weight gain*****
What are the contraindications of sulfonylureas?
SULFA ALLERGY!!!!!*****
Which diabetic drug class has the highest risk of causing hypoglycemia (other than insulin)
Sulfonylureas
Why dont we use sulfonylureas very much anymore?
They have the highest risk of hypoglycemia
A guy went on a trip to the Himalayan Mountains, and he got Acute mountain sickness. The doctor there gave him a drug to treat this and he had an allergy! What drug class can we not use to treat his Type II diabetes
Sulfonylureas, because they are SULFAS
He was treated with acetzolamide- a sulfa
What are the 1st generation sulfonylureas, and what are the points you need to know about them? (Maybe???)
Tolbutamide- short acting (less hypoglycemia)
Chlorpropamide- long acting, disulfiram-like effect, WORST hypoglycemia
Tolazamide
What are the 3 second generation sulfonylureas, and which ones has the highest risk of hypoglycemia?
Glyburide- most hypoglycemia
Glipizide-least hypoglycemia
Glimepiride
Which sulfonylureas generation is the most potent: 1st or 2nd?
2nd
What are meglitinides?
Almost the same thing as sulfonylureas, but they are NOT sulfonamides= can be used in a sulfa allergy***
What are the 2 Meglitinides?
Repaglinide (Prandin)
Nateglinide (Starlix)
What is Colesevelam (WelChol)?
A bile acid binding resin that has some hypoglycemic effect when combined with other antidiabetic agents
What is Bromocriptine (Cycloset)?
It is a dopamine agonist that inhibits excessive SNS tone which suppresses hepatic glucose production
What is Pramlintide (Symlin)?
An amylin-like peptide**
How is Pramlintide (Symlin) administered?
It is injected because it is a PEPTIDE
Can we give Pramlintide (Symlin) alone?
No, it is only an adjunct to insulin therapy in Type 1 AND Type 2 diabetes!!!!!***!!
What is the MOA of Pramlintide (Symlin)?
It works with insulin to Lower post-prandial glucose by:
Slowing gastric emptying
Suppressing glucagon
Centrally-mediated appetite suppression
What are the only two classes of diabetes drugs that can cause hypoglycemia?
Sulfonylureas
Meglitinides
(+ insulin of course)
What are the only two classes of drugs that can cause hyperinsulinemia?
Sulfonylureas
Meglitinides
Some guy rolls into the ER and you can tell right away he has way too much insulin flowing through his system. How can you tell if it’s from taking too much insulin or if he took too much of a sulfonylurea or Meglitinide?
C-peptide.
Sulfonylureas and Meglitinides will increase endogenous insulin production
How long do short acting insulin take to kick in and how long does it last?
Starts in 1 hour
Lasts 4-5 hours
How long does intermediate acting insulin take to reach peak effect and how long does it last?
Peaks in 4 hours and lasts 15 hours
When do long acting insulins reach peak effect?
They don’t peak. They have a sustained effect for 24 hours or longer
Which type of insulin is best to start type 2 diabetics on since it will fix their fasting glucose?
Basal/long acting
How long does rapid acting insulin take to kick in and how long do they last?
Start in 30 min
Lasts 2-3 hrs
