Antidiabetics Flashcards
1
Q
What are the 2 agents that are used to INCREASE blood sugar?
A
Glucagon
Diazoxide (Proglycem)
2
Q
Which cell types do NOT need insulin to get glucose?
A
Brain
Liver
RBCs
3
Q
What happens to levels when you inject insulin (in anyone)
Blood glucose:
Pyruvate and lactate:
Inorganic phosphate:
Plasma potassium:
A
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)
4
Q
Which GLUT receptors are on the B-cells in the pancreas?
A
GLUT-2
5
Q
Which GLUT transporter is in muscle and adipose?
A
GLUT 4 (needs insulin)
6
Q
Do we use insulin for Type 1 or Type 2
A
Both
7
Q
What are the adverse reactions of insulin?
A
HYPOGLYCEMIA**
Weight gain***
Cough (inhaled only)
Local reactions (allergy)
Lipodystrophy and lipohypertrophy
8
Q
What are some symptoms of hypoglycemia
A
Tachycardia
Confusion
Vertigo
Sweating
Cognitive dysfunction/ death
9
Q
What kinds of things can cause hypoglycemia in a patient who uses insulin?
A
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🍻🍸🥃🍾🍷🥂🍺🍹
10
Q
How do you treat hypoglycemia in someone who is unconscious?
A
Give 50% glucose solution IV until they wake up
Could also theoretically give glucagon but no one does that
11
Q
Do we give oral glucose to unconscious patients
A
No
12
Q
Why do patients get local allergic reactions to insulin?
A
Because they get lazy with their injection technique. Reusing needles, injecting through clothes etc
13
Q
What kinds of things increase insulin requirement?
A
ANYTHING that increases stress**
….Like SURGERY, preganncy, thyrotoxicosis, infection
Acromegaly and Cushings
14
Q
If your patient is having surgery, what do you need to do to their insulin dose?
A
Increase it! (Surgery is stressful)
15
Q
What are the 4 preparation types of insulin?
A
Rapid
Short (Regular)
Intermediate
Long acting
16
Q
What are the 4 types of rapid acting insulin available
A
Lispro
Aspart
Glulisine
Inhaled*
17
Q
Which insulins are clear solutions and can be given in an IV (like you would do for an unconscious patient)
A
Rapid acting
Short acting
18
Q
What kind of insulin is used in insulin pumps?
A
Rapid acting
19
Q
Which insulin’s have been modified to provide prolonged action?
A
NPH (Turbid)
Glargine (low pH)
Detemir (myristoylated)
I DONT KNOW WHAT THIS MEANS
20
Q
What kind of insulin is used first in type II DM?
A
Long-acting (basal)
21
Q
What do you need to do if you’re going to inject your insulin yourself (instead of have a pump)
A
Create an insulin profile and eat to fill it
22
Q
How do you take insulin if you use a pump?
A
Adjust insulin blouses according to what you eat
More similar to a natural insulin release pattern
23
Q
What is necessary for glucagon to work to increase blood glucose?
A
You must have glycogen stores!**
NOT EVERYONE DOES
24
Q
What are two uses for glucagon that are not to increase blood sugar
A
Beta blocker overdose- will increase heart rate and contractility
Radiology- relaxes the intestine
25
What is Diazoxide (Proglycem)?
It is a thiazide (no diuretic effect though) that vasodilators and RAISES blood sugar by inhibiting insulin secretion, decreasing peripheral glucose utilization, and stimulating hepatic glucose production
26
Who do we give Diazoxide (Proglycem) to?
Patients with insulinoma (insulin secreting tumor)
Diazoxide inhibits insulin secreting and raises blood sugar
27
What are some of the things you need to consider before giving a patient an anti diabetic agent?
Effect on cardiovascular disease (CVD is the #1 killer of diabetics!)
Hypoglycemia risk
Impact on weight
Glucose reduction efficacy
Side effects, cost, patient preferences
28
What are the 4 rapid acting insulins?
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Insulin, inhaled (Afrezza)
29
What are the short acting insulin’s
Regular Insulin (Novolin R, Humulin R)
30
What are the intermediate acting insulins?
NPH or Isophane Insulin (Humulin N, Novolin N)
31
What are the long acting insulins?
Insulin glargine (Lantus)
Insulin detemir (Levemir)
Insulin degludec (Tresiba)
32
What is the #1 killer of diabetics
cardiovascular disease
33
What is the initial drug of choice for Type 2 diabetics, as long as their A1C is under 10%?
Metformin
34
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)
35
What glycemic effects does metformin have?
Decreases A1C a LOT! (1-1.5%)
Promotes a euglycemic state ***!!!** (as opposed to hypoglycemic)
36
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
37
What are the cardiovascular effects of metformin?
Lower triglycerides by 15-20%
Decrease Macrovascular events (aka heart attacks)*********
38
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**
39
What drug should prediabetics take to prevent diabetes?
Metformin
40
Will metformin cause weight gain
No
41
How is metformin excreted?
Through the kidneys
| Remember the whole contrast and holding metformin thing?
42
What are the adverse effects of metformin?
Lactic Acidosis********** LETHAL
Diarrhea*** (53% of patients!)
Hypoglycemia rarely
43
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
44
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)
45
What is the MOA of GLP-1 agonists?
They are GLP-1 agonists that are ~resistant~ to DPP-4 degradation
46
What are the 5 GLP-1 agonists?
Exenatide (Byetta, Bydureon)
Liraglultide (Victoza)
Dulaglutide (Trulicity)
Albiglutide (Tanzeum)
Lixisenatide (Adlyxin)
47
How are GLP-1 agonists administered?
SC injections 2x/day or 1x/week
48
What are the effects of GLP-1 agonists?
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**
49
Which GLP-1 agonist is only approved for weight loss?
Liraglutide (Sandexa)
🏝👙 (take it before you hit the SAND)
50
What are the adverse effects of GLP-1 agonists?
ACUTE PANCREATITIS*** ON TEST*****!!
Hypoglycemia (low risk)
GI
Hypersensitivity
51
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
52
What are the 4 DPP-4 inhibitors?
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
the gliptins
53
What is the MOA of DPP-4 inhibitors?
Potentiates the effects of endogenous incretins by inhibiting their breakdown by DPP-4
54
How are DPP-4 inhibitors administered?
Oral
55
What are the therapeutic effects of DPP-4 inhibitors?
Decrease A1C a medium amount (0.5-1%)
Weight neutral
Neutral CV effects (at least its not bad)
56
What are the adverse effects of DPP-4 inhibitors?
Hypoglycemia*
Acute pancreatitis*
Severe joint pain*
57
What are the contraindications/precautions of DPP-4 inhibitors?
Pancreatitis now or ever*
Slow GI
Renal impairment
58
What are the 4 SGLT-2 inhibitors?
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)
“Gli” -> glucose
“Flozin” -> flowing (kidney)
59
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
60
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
61
Do SGLT-2 inhibitors do anything to address the insulin resistance problem
No
62
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)
63
What are the adverse effects of SGLT-2 inhibitos?
Vaginal yeast infections, UTIs and increased urinary frequency****** You’re pissing out glucose 🧁🚽
Hypoglycemia rarely
Hyponatremia***Increased urinary Na+ excretion due to increased H2O in proximal tubule
Osmotic diuresis**
Hypotension, dizziness, syncope, dehydration due to diuresis
Increased LDL (not addressing insulin problem)
Increased bone fractures
Renal impairment
64
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
65
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
66
What are the 2 thiazolidinediones (TZDs)?
Pioglitazone (Actos)
Rosiglitazone (Avandia)
the glitazones
67
What is the MOA of thiazolidinediones (TZDs)?
Bind to PPARγ receptor which causes post-receptor insulin-mimetic action:
Increased GLUT4
Decreased hepatic gluconegenesis
68
What antilipid drug class are Thiazolidinediones (TZDs) similar to?
Fibrates (PPAα ligands)
69
Do thiazolidinediones (TZDs) specifically target insulin resistance?
YES. They are “Insulin sensitizers”**
70
How long does it take for thiazolidinediones to work?
Weeks to months
| Half life is 100-150 hours
71
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
72
What are the adverse effects of thiazolidinediones?
Edema (can cause HF in patients with CHF!!**)
Weight gain **
Bone fracture risk** (no one knows why)
Back pain, fatigue, headache
Rosiglitazone had a troubled history CV issues, but it’s all made up
73
What are the contraindications/precautions for thiazolidinediones?
Hepatic disease (1st TZD was taken off the market for this!*)
Contraindicated in heart failure ** due to edema
74
What are the 2 α-glucosidase inhibitors?
Acarbose (Precose)
Miglitol (Glyset)
75
What is the only Class of antidiabetic agent that is used in type 1 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)
76
What is the MOA of α-glucosidase inhibitors?
Inhibit α-glucosideases in small intestine= delayed carb digestion and absorption
77
How do you take α-glucosidase inhibitors?
Orally, pre-prandially
78
What are the therapeutic effects of α-glucosidase inhibitors?
Decrease postprandial glucose (can lower A1C)
No effect on weight (?!?!)
79
What are the adverse effects of α-glucosidase inhibitors?
GI effects- diarrhea and flatulence****** (all those undigested carbs make your gut bacteria very happy!)💩💨
High liver enzymes, jaundice
80
What are the contraindications to α-glucosidase inhibitors?
Contraindicated in: GI disease, GI obstruction, lieu’s, IBD, hiatal hernia
Be careful with Liver/kidney probs
81
Left off on slide 51
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82
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
83
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
84
What are the adverse effects of sulfonylureas?
HYPOGLYCEMIA** the worst drug for this
Weight gain
85
What are the contraindications of sulfonylureas?
SULFA ALLERGY!!!!!*****
86
Which diabetic drug class has the highest risk of causing hypoglycemia (other than insulin)
Sulfonylureas
87
Why dont we use sulfonylureas very much anymore?
They have the highest risk of hypoglycemia
88
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
89
What are the 1st generation sulfonylureas, and what are the points you need to know about them?
Tolbutamide- short acting (less hypoglycemia)
Chlorpropamide- long acting, disulfiram-like effect, WORST hypoglycemia
Tolazamide
90
What are the 3 second generation sulfonylureas, and which ones has the highest risk of hypoglycemia?
Glyburide- most hypoglycemia
Glipizide-worst hypoglycemia
Glimepiride
91
Which sulfonylureas generation is the most potent: 1st or 2nd?
2nd
92
What are meglitinides?
Almost the same thing as sulfonylureas, but they are NOT sulfonamides= can be used in a sulfa allergy
93
What are the 2 Meglitinides?
Repaglinide (Prandin)
Nateglinide (Starlix)
94
What are the adverse effects of meglitinides?
Nateglinide: a little bit of hypoglycemia
Repaglinide: hypoglycemia
95
What is Colesevelam (WelChol)?
A bile acid binding resin that will lower A1C in combo with other antidiabetic drugs
96
What is Bromocriptine (Cycloset)?
It is a dopamine agonist that suppresses hepatic glucose production
97
What are the therapeutic effects of Bromocriptine (Cycloset)?
Lowers FFA and TG’s
Lowers CV end point problems
98
What is Pramlintide (Symlin)?
A synthetic analog of amylin (a hormone cosecreted with insulin)
99
Can we give Pramlintide (Symlin) alone?
No, it is only an adjunct to insulin therapy in Type 1 AND Type 2 diabetes!!!!!***!!
100
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
101
What are the only two classes of diabetes drugs that can cause hypoglycemia?
Sulfonylureas
Meglitinides
(+ insulin of course)
102
What are the only two classes of drugs that can cause hyperinsulinemia?
Sulfonylureas
Meglitinides
103
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
