Antidiabetic Drugs Flashcards
Insulin’s MOA
Insulin binds to receptor on cell and GLUT 4 transported moves to cell surface and brings glucose into the cell
* without insulin, glucose cannot enter the cell
Insulin actions
⬆️ glucose, aa, fatty acid and K uptake ⬆️ glycogenolysis ⬆️ protein synthesis ⬆️ TG synthesis Gluconeogenolysis
How much do insulins lower HBa1c levels?
2% decrease
Adverse effects of all insulins
Hypoglycemia
Lipodystrophies
Hypokalemia
Hypoglycemia and hyperglycemia cause problems for diabetics?
Hypoglycemia: can kill you
Hyperglycemia: DKA, increase fluid loss, dehydration
Rapid acting and long acting insulins have a Lower risk of hypoglycemia versus what?
Regular human insulin and NPH
Slow acting/long duration insulin
Modified chain of amino acids of human insulin
- huddle after SQ for a long time and are released slowly over time into blood
- onset slow
- duration: up to 24hrs
Lispro (humalog)
Aspart (novalog)
Glusine (apidra)
Rapid acting short duration insulin
Detemir (levimir)
Glargine (lantus)
Slow acting long duration insulin
NPH
Suspension in injected liquid- NO IV only SQ
- available for aspart and lispro
- 2% ⬇️ in Hba1c levels with insulin
- ⬆️ risk of hypoglycemia
- must be gently mixed
What kind of insulin can be given IV or mixed with other insulin?
Short duration/rapid acting
- when mixing draw short duration first
- lispro, aspart, glusine
Insulin: rapid acting/short duration
Modified chain of amino acids of human insulin
- rapid onset shirt duration (3-5 HR)
- no huddle after SQ-straight to blood stream
- preferred over regular/human insulin bc of fast onset and lower risk of hypoglycemia
Non insulin drug therapy
-1% Hba1c levels
All similiar in effectiveness
Duration varies by drug
*none of these are shown to have positive effects on macrovascular outcomes
Metformin (glucophage) Sulfonylures Meitinides Thiazolineadiones TZDs Alpha-glucoside inhibitors SGLT2 inhibitors GLP analogs DPP-IV inhibitors Pramlintide (symlin)
Non-insulin diabetic therapy
Metformin (glucophage)
MOA
⬇️ hepatic glucose production, ⬇️ intestinal glucose absorption: sensitizes target cells to insulin
*stops gluconeogenesis and glycogenolysis
Metformin (glucophage)
MOA
⬇️ hepatic glucose production, ⬇️ intestinal glucose absorption: sensitizes target cells to insulin
- stops gluconeogenesis and glycogenolysis
- superior to sulfonylureas: low risk of heart attack, no weight gain, improved lipids
Metformin (glucophage)
Adverse effects
Stinky Lactic acidosis- lower risk: high with phenformin-low with metformin * renal dysfunction- do not give!! Diarrhea Anorexia Dyspepsia *B12 folate deficiency -GI low absorption
Metformin (glucophage)
Inx
*Cimetidine: H2 receptor antagonist
Sulfonylureas -“ide”
MOA
Indirectly ⬆️ insulin release/levels
Long duration
-two generations (1 old, 2 new)
Sulfonylureas
Adverse effects
* hypoglycemia Impaired B-cell fxn * cardiovascular toxicity- ⬆️ heart attack risk Weight gain Increase BP * risk of disulfiram rxn
Sulfonylureas
Disulfiram rxn
Disulfiram (anabuse): anti alcoholic drug
Makes body intolerant to alcohol
*mimic disulfiram with OLD sulfonylureas
-N/V
-sweating
-severely sick
Tolbutamide (orinase) Acetohexamide (dymelor) Tolazamide (tolinase) Chlorpropamide (diabinese) * old- 1st generation Glipizide (glucotrol, glucotrol XL) Glyburide -nonmicronized (diabeta, micronase) -micronized (glynase prestab) Glimepride (amaryl) * second generation-new
Sulfonylureas
Meglitinides (new)
MOA
Promote insulin release- control postprandial hyperglycemia
- short duration (1-4 HR)
- dosed 30 min prior to meal (few times a day)
- cannot skip meals!!!!
Meglitinides
Adverse effects
- hypoglycemia
- many drug inx risks
Repaglinide (prandin)
Nateglinide ( starlix)
Meglitinides
Thiazolidinediones-2
MOA- decrease insulin sensitivity
-almost never used
AE: fluid retention, edema, weight gain
1) Pioglitazone (actos)
2) Rosiglitazone (arandia)
Thiazolidinediones
1) worsens HF, 2012 bladder cancer
2) MI, cardiovascular related deaths, DC in 2010
Alpha Glucosidase inhibitors-2
MOA
Reduce post prandial rise in glucose
Delays carb absorbtion
* prevent gut from breaking down big sugars into small Sugars
Absorb sugar slowly-delayed
-given at start of a meal
* do not use oral sucrose for treatment of hypoglycemia-use glucose
Alpha Glucoside inhibitors
AE
Flatulence Cramps Bloating Constipation * hepatic dysfunction with long term use
Acarbose (precose)
Miglitol (glyset)
Alpha Glucoside inhibitors
Sodium glucose cotransporter 2 inhibitors
(SGLT2)
-“flozin”
MOA
Increase urinary excretion of glucose; blocks kidneys ability to reabsorb filtered glucose
* blocks SGLT2 pump= pee out glucose = lower blood sugar
- newest class
- favorable on wt and BP
- BS of 150-180= kidney cannot filter anymore sugar conc too high
SGLT2 inhibitors
AE
High risk of UTI High risk of vaginal yeast infections Hypotension Orthostatic hypotension Low BP Dehydration * will not work if renal fxn is impaired -not reccomeneded for PTs with renal dysfunction
Drugs working via incretins
1) GLP-1 analogs
2) DPP-IV inhibitors
Hormones that are released from the GI tract for gastric emptying, glucose absorbtion, tells pancreas how quickly to make insulin
GLP-1 analogs
Incretins
MOA
Stimulate insulin release in a glucose dependent manner
Act like GLP
* injectable
-⬆️ satiety and ⬇️ food intake: weight loss or neutral effect on WT
Preserve B cell fxn
* control post prandial glucose concentration: ⬇️ glucagon ⬆️ insulin
DPP-IV inhibitors -“gliptin”
Incretins
MOA
Stimulate insulin release in a glucose dependent manner
* slows down the breakdown of GLP1 and GIP
* effectiveness is half of GLP analogs (less potent)
* PO 1x a day
-well tolerated
-⬆️ satiety and ⬇️ food intake: weight loss or neutral effect on WT
Preserve B cell fxn
* control post prandial glucose concentration: ⬇️ glucagon ⬆️ insulin
GLP-1 analogs
AE
N/V Diarrhea Caution with some orally admin drugs * acute pancreatitis Low risk of hypoglycemia when used with a sulfonylureas
DPP-IV inhibitors
AE
Low risk of hypoglycemia
Low risk of GI effects
Low risk regarding pancreatitis
-theoretical concerns regarding cancer
Exenatide (byetta): avoid in severe renal dysfunction
Liraglutide (victoza)
Albiglutide (tanzem)
Dulaglutide (triulicity)
GLP-1 analogs
Incretins
Sitagliptin (januvia)
Saxagliptin (anglyza): high drug inx risk
Linagliptin (trajenta): not sensitive to renal fxn
Alogliptin (nesina)
* all available in combo with metformin
DPP-IV inhibitors
Incretins
GLP1 analogs and DPP-IV inhibitors
Low risk of hypoglycemia Slows the rate of gastric emptying Increase satiety N/V Impairs body ability to absorb other drugs
Pramlintide (symlin)
An amylin mimetic- pancreas
- lowers postprandial glucagon
- slows gastric emptying- increase satiety
- can be used for type 1 and type 2 DM
- dosed prior to meals
- SQ injection
- acts like a GLP-1: decreases GI absorbtion of glucose
- may increase insulin related hypoglycemia
- caution with drugs that slows down gastric emptying
Canagliglozin (invokana)
Dapagliflozin (farxiga)
Empagliflozin (jardiance)
SLGT2 inhibitors
