Difference between revisions of "Diabetes medications"

 
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==Background==
 
==Background==
 +
*Hypoglycemics
 +
**Sulfonylureas
 +
**Benzoic acid derivatives
 +
*Antihyperglycemics
 +
**Biguanides
 +
**Alpha glucosidase inhibitors
 +
**Thiazolidinediones
  
Hypoglycemics- sulfonylureas, benzoic acid derivatives
+
{{Common Anti-hyperglycemic Drugs and Pharmacology}}
  
Antihyperglycemics- biguanides, alpha glucosidase inhibitors and thiazolidinediones
+
==[[Insulin]]==
  
#type 2 dm- overproduction and under utilization of glucose
+
==Biguanides (Metformin)==
#diet and exercise best
+
Suppresses liver glucose production
#if sugar not controlled with one agent, add bedtime insulin or second agent
+
===Dose===
#if still not controlled p 2 meds either do 2 orals + nighttime insulin, or mixed split insulin regimen or third oral agent
+
[[Metformin]] 500mg PO BID is first-line agent for type II diabetics
 +
*Do not prescribe if creatinine > 1.4 (GFR <40), CHF, hepatic insufficiency, ETOH abuse
 +
*Should be withheld for 48hr after IV contrast
 +
===Side Effects===
 +
*Lactic acidosis (due to increased lactate production)
 +
**Seen almost exclusively in patients with renal failure
 +
*Nausea, diarrhea, crampy abdominal pain
 +
===Toxicity===
 +
*Almost never causes hypoglycemia when taken alone, but can exacerbate hypoglycemia when taken in combination with hypoglycemic agents
 +
*Toxic dose unknown
 +
*Management: Supportive care
  
 
==Sulfonylureas==
 
==Sulfonylureas==
#increase insulin secretion and enhance activity
+
*[[Glipizide]], [[glyburide]]
#second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
+
*Increase insulin secretion
#stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
+
*[[Hypoglycemia]] is the major adverse effect (especially with glyburide)
#Decrease hepatic insulin clearance= increase insulin conc
 
#Elevated insulin level feeds back to liver and causes decrease hepatic gluc prod
 
#Secondary treatment failure from noncompliance, wt gain, desensitized beta cells, and escalating insulin resistance and increased insulin deficiency
 
#Sulfon has hepatic metab, renal exretion and prolonged activity
 
#Toxicity related to hypoglycemia
 
#Risk factors for hypoG- elderly, poor diet, alcohol, renal/ hepatic dz, polypharmacy
 
#Time to peak effect and duration of effect important in OD
 
#Chlorpropamide, glyburide and glypizide most likely to cause hypoG
 
#Do not use glyburide in pt with CRI since renally excreted
 
#If pt well and young, will not get hypoG during fast due to counterregulatory hormones for glucose homeostasis
 
#Chlorpropamide can cause hyponatremia regardless of dose- induces ADH secretion- risk increases with elderly and if on thiazide diuretics
 
#Chlorpropamide can also give cholestatic jaundice, resolves with discontinuation
 
#Glypizide- enterohepatic recirculation- prolonged action if liver dz. Long duration of action since metabolite still active. All metabolites renally cleared
 
 
 
==Biguanides==
 
#metformin, phenformin and buformin
 
#phenformin no longer used due to lactic acidosis
 
#metformin does not cause wt gain like sulfonyls
 
#effect is to decrease hep glucose prod, inhibit intestinal glucose absorption
 
#also decreases fatty acid oxidation
 
#increases insulin sensitivity and decreases insln resis
 
#decrease sugar of dm pt not normal person- so is antihyperglycemic agent not hypoglycemic agent
 
#100% renal excretion
 
#most serious side effect is lactic acidosis- aerobic type by increased lactate production- not tissue hypoxia
 
#signs of lactic acidosis- nonspecific- nvd, abd pain, sleepy, tachypnia, lethargy- seen mostly if renal/ liver dz, alcohol, heart dz, infection
 
#metformin exclusion criteria- CRI, cardiac/ pulm insuff, h/o lactosis, profound infc, liver dz, alcohol, iv contrast agents
 
#fatality from metformn lactosis not related to lactate levels or metformin level but rather to concomitant condition (hypoxia) resulting in elevated lactate
 
#OD- hypoglycemia rare, can get lactosis- obs for 6-8 hr and tx c bicarb and consider hemodialysis
 
  
 
==Alpha Glucosidase Inhibitors==
 
==Alpha Glucosidase Inhibitors==
#acarbose, miglitol, voglibose
+
*Acarbose, miglitol, voglibose
#competitively and reversibly inhibit alpha glucosidase brush border hydrolase enzyme- makes postprandial decrease in carbohydrate absorption since complex polysaccharides not broken down into absorbable monosaccharides
+
*Competitively and reversibly inhibit alpha glucosidase brush border hydrolase enzyme- makes postprandial decrease in carbohydrate absorption since complex polysaccharides not broken down into absorbable monosaccharides. Does not affect lactose absorption
#does not affect lactose absorption
+
*Taken with first bite of each meal  
#if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
+
*Since limited absorption, stays in gut and side effects mostly GI- bloating, gas, [[diarrhea]]
#take these meds with each meal with first bite
+
**acarbose- can cause transaminitis/ liver inj
#since limited aborption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
+
*Contraindications- [[cirrhosis]], [[IBD]], malabsorption syndrome
#contraindications- cirrhosis, IBD, malabsorption synd
+
*Do not cause [[hypoglycemia]] when used as monotherapy
#alpha glucs do not cause hypoG when used as monotx
+
**If [[hypoglycemia|hypoglycemic]]- sucrose/ table sugar will ''not'' work- use glucose- PO or IV
#acarbose- can cause transaminitis/ liver inj
+
*Since minimal absorption- systemic toxicity from OD unlikely
#since min absorption- systemic tox from OD unlikely
 
  
 
==Thiazolidinediones==
 
==Thiazolidinediones==
#rosiglitazone and poiglitazone
+
*Rosiglitazone and poiglitazone
#enhance insulin effect on muscle, fat, liver without increasing panc insulin secretion
+
*Enhance insulin effect on muscle, fat, liver without increasing pancreatic insulin secretion
#protein bound and hep metab- not good if liver dz
+
*Protein bound and hepatic metabolism - avoid in patients with liver disease
#side effects- induce ovulation, increase plasma vol bad if CHF, decrease effectiveness of OCP's
+
*Side effects- induces ovulation, decreases effectiveness of OCP's, increases plasma volume (bad if CHF)
  
 
==Benzoic Acid Derivatives==
 
==Benzoic Acid Derivatives==
#repaglinide- mono or combo tx c metformin
+
*Repaglinide- monotherapy or combined with metformin
#binds to atp dependent potassium channel like sulfonyls but at different site.
+
*binds to ATP dependent potassium channel like sulfonyls but at different site.
#Unlike sulfonyls, it decreases insulin lvls
+
*Unlike sulfonyls, it ''decreases'' insulin levels
#Dose 30 min before meal to decrease post prandial hyperglycemia
+
*Dose 30 min before meal to decrease postprandial hyperglycemia
 +
 
 +
==[[GLP-1 agonists]]==
 +
*Exanatide (Byetta and Bydureon), Liraglutide (Victoza)
 +
*Synthetic glucagon-like peptide-1 (GLP-1) receptor agonists
 +
*Stimulates insulin release from pancreatic islet cells
 +
*May promote weight loss by slowing gastric emptying and increasing satiety
 +
 
 +
==[[DPP-4 inhibitors]]==
 +
*Sitagliptin, saxagliptin, linagliptin, alogliptin
 +
*Block DPP-4, which leads to increased activity of incretins, which inhibit glucagon release, which in turn increase insulin secretion and slow gastric emptying, ultimately decreasing blood glucose levels
 +
*Potential serious adverse events include acute [[pancreatitis]], [[anaphylaxis]]/[[angioedema]], [[SJS]]
 +
 
 +
==[[SGLT-2 inhibitors]]==
 +
*Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance)
 +
*Inhibit sodium-glucose cotransporter 2, decreasing glucose reabsorption in the proximal tubule
 +
*Potential serious adverse event: euglycemic [[DKA]]
 +
 
 +
==See Also==
 +
*[[Diabetes Mellitus (Main)]]
  
==Source ==
+
==References==
6/06 MISTRY
+
<references/>
  
[[Category:Endo]]
+
[[Category:Endocrinology]]
[[Category:Drugs]]
+
[[Category:Pharmacology]]

Latest revision as of 15:44, 28 September 2019

Background

  • Hypoglycemics
    • Sulfonylureas
    • Benzoic acid derivatives
  • Antihyperglycemics
    • Biguanides
    • Alpha glucosidase inhibitors
    • Thiazolidinediones

Common Anti-hyperglycemic Drugs and Pharmacology

Drug Pharmacology
Onset Peak Duration
Rapid-acting insulin

  • Aspart (Novolog)
  • Lispro (Humalog)
15-30min 1-2h 3-5h
Short-acting insulin

  • Regular
30-60min 2-4h 6-10h
Intermediate-acting insulin

  • NPH (Humulin, Novolin)
1-3h 4-12h 18-24h
Long-acting insulin

  • Glargine (Lantus)
2-4h None 24h
Sulfonylurea

  • Glimepiride
  • Glipizide (Glucotrol)
  • Glyburide (Glycron, Micronase)
2-6h 12-24h

Insulin

Biguanides (Metformin)

Suppresses liver glucose production

Dose

Metformin 500mg PO BID is first-line agent for type II diabetics

  • Do not prescribe if creatinine > 1.4 (GFR <40), CHF, hepatic insufficiency, ETOH abuse
  • Should be withheld for 48hr after IV contrast

Side Effects

  • Lactic acidosis (due to increased lactate production)
    • Seen almost exclusively in patients with renal failure
  • Nausea, diarrhea, crampy abdominal pain

Toxicity

  • Almost never causes hypoglycemia when taken alone, but can exacerbate hypoglycemia when taken in combination with hypoglycemic agents
  • Toxic dose unknown
  • Management: Supportive care

Sulfonylureas

Alpha Glucosidase Inhibitors

  • Acarbose, miglitol, voglibose
  • Competitively and reversibly inhibit alpha glucosidase brush border hydrolase enzyme- makes postprandial decrease in carbohydrate absorption since complex polysaccharides not broken down into absorbable monosaccharides. Does not affect lactose absorption
  • Taken with first bite of each meal
  • Since limited absorption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
    • acarbose- can cause transaminitis/ liver inj
  • Contraindications- cirrhosis, IBD, malabsorption syndrome
  • Do not cause hypoglycemia when used as monotherapy
    • If hypoglycemic- sucrose/ table sugar will not work- use glucose- PO or IV
  • Since minimal absorption- systemic toxicity from OD unlikely

Thiazolidinediones

  • Rosiglitazone and poiglitazone
  • Enhance insulin effect on muscle, fat, liver without increasing pancreatic insulin secretion
  • Protein bound and hepatic metabolism - avoid in patients with liver disease
  • Side effects- induces ovulation, decreases effectiveness of OCP's, increases plasma volume (bad if CHF)

Benzoic Acid Derivatives

  • Repaglinide- monotherapy or combined with metformin
  • binds to ATP dependent potassium channel like sulfonyls but at different site.
  • Unlike sulfonyls, it decreases insulin levels
  • Dose 30 min before meal to decrease postprandial hyperglycemia

GLP-1 agonists

  • Exanatide (Byetta and Bydureon), Liraglutide (Victoza)
  • Synthetic glucagon-like peptide-1 (GLP-1) receptor agonists
  • Stimulates insulin release from pancreatic islet cells
  • May promote weight loss by slowing gastric emptying and increasing satiety

DPP-4 inhibitors

  • Sitagliptin, saxagliptin, linagliptin, alogliptin
  • Block DPP-4, which leads to increased activity of incretins, which inhibit glucagon release, which in turn increase insulin secretion and slow gastric emptying, ultimately decreasing blood glucose levels
  • Potential serious adverse events include acute pancreatitis, anaphylaxis/angioedema, SJS

SGLT-2 inhibitors

  • Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance)
  • Inhibit sodium-glucose cotransporter 2, decreasing glucose reabsorption in the proximal tubule
  • Potential serious adverse event: euglycemic DKA

See Also

References