Difference between revisions of "Diabetes medications"

(Source)
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 +
==Background==
 +
 
Hypoglycemics- sulfonylureas, benzoic acid derivatives
 
Hypoglycemics- sulfonylureas, benzoic acid derivatives
  
 
Antihyperglycemics- biguanides, alpha glucosidase inhibitors and thiazolidinediones
 
Antihyperglycemics- biguanides, alpha glucosidase inhibitors and thiazolidinediones
  
+
#type 2 dm- overproduction and under utilization of glucose
 
+
#diet and exercise best
==Gen==
+
#if sugar not controlled with one agent, add bedtime insulin or second agent
 
+
#if still not controlled p 2 meds either do 2 orals + nighttime insulin, or mixed split insulin regimen or third oral agent
 
 
- type 2 dm- overproduction and under utilization of glucose
 
 
 
- diet and exercise best
 
 
 
- if sugar not controlled with one agent, add bedtime insulin or second agent
 
 
 
- if still not controlled p 2 meds either do 2 orals + nighttime insulin, or mixed split insulin regimen or third oral agent
 
 
 
 
  
 
==Sulfonylureas==
 
==Sulfonylureas==
 
+
#increase insulin secretion and enhance activity
 
+
#second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
- increase insulin secretion and enhance activity
+
#stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
 
+
#Decrease hepatic insulin clearance= increase insulin conc
- second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
+
#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
- stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
+
#Sulfon has hepatic metab, renal exretion and prolonged activity
 
+
#Toxicity related to hypoglycemia
- Decrease hepatic insulin clearance= increase insulin conc
+
#Risk factors for hypoG- elderly, poor diet, alcohol, renal/ hepatic dz, polypharmacy
 
+
#Time to peak effect and duration of effect important in OD
- Elevated insulin level feeds back to liver and causes decrease hepatic gluc prod
+
#Chlorpropamide, glyburide and glypizide most likely to cause hypoG
 
+
#Do not use glyburide in pt with CRI since renally excreted
- Secondary treatment failure from noncompliance, wt gain, desensitized beta cells, and escalating insulin resistance and increased insulin deficiency
+
#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
- Sulfon has hepatic metab, renal exretion and prolonged activity
+
#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
- 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==
 
==Biguanides==
 
+
#metformin, phenformin and buformin
 
+
#phenformin no longer used due to lactic acidosis
- metformin, phenformin and buformin
+
#metformin does not cause wt gain like sulfonyls
 
+
#effect is to decrease hep glucose prod, inhibit intestinal glucose absorption
- phenformin no longer used due to lactic acidosis
+
#also decreases fatty acid oxidation
 
+
#increases insulin sensitivity and decreases insln resis
- metformin does not cause wt gain like sulfonyls
+
#decrease sugar of dm pt not normal person- so is antihyperglycemic agent not hypoglycemic agent
 
+
#100% renal excretion
- effect is to decrease hep glucose prod, inhibit intestinal glucose absorption
+
#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
- also decreases fatty acid oxidation
+
#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
- increases insulin sensitivity and decreases insln resis
+
#OD- hypoglycemia rare, can get lactosis- obs for 6-8 hr and tx c bicarb and consider hemodialysis
 
 
- 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
 
+
#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
- acarbose, miglitol, voglibose
+
#does not affect lactose absorption
 
+
#if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
- 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
+
#take these meds with each meal with first bite
 
+
#since limited aborption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
- does not affect lactose absorption
+
#contraindications- cirrhosis, IBD, malabsorption synd
 
+
#alpha glucs do not cause hypoG when used as monotx
- if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
+
#acarbose- can cause transaminitis/ liver inj
 
+
#since min absorption- systemic tox from OD unlikely
- take these meds with each meal with first bite
 
 
 
- since limited aborption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
 
 
 
- contraindications- cirrhosis, IBD, malabsorption synd
 
 
 
- alpha glucs do not cause hypoG when used as monotx
 
 
 
- acarbose- can cause transaminitis/ liver inj
 
 
 
- since min absorption- systemic tox from OD unlikely
 
 
 
 
  
 
==Thiazolidinediones==
 
==Thiazolidinediones==
 
+
#rosiglitazone and poiglitazone
 
+
#enhance insulin effect on muscle, fat, liver without increasing panc insulin secretion
- rosiglitazone and poiglitazone
+
#protein bound and hep metab- not good if liver dz
 
+
#side effects- induce ovulation, increase plasma vol bad if CHF, decrease effectiveness of OCP's
- enhance insulin effect on muscle, fat, liver without increasing panc insulin secretion
 
 
 
- protein bound and hep metab- not good if liver dz
 
 
 
- side effects- induce ovulation, increase plasma vol bad if CHF, decrease effectiveness of OCP's
 
 
 
 
  
 
==Benzoic Acid Derivatives==
 
==Benzoic Acid Derivatives==
 
+
#repaglinide- mono or combo tx c metformin
 
+
#binds to atp dependent potassium channel like sulfonyls but at different site.
- repaglinide- mono or combo tx c metformin
+
#Unlike sulfonyls, it decreases insulin lvls
 
+
#Dose 30 min before meal to decrease post prandial hyperglycemia
- binds to atp dependent potassium channel like sulfonyls but at different site.
 
 
 
- Unlike sulfonyls, it decreases insulin lvls
 
 
 
- Dose 30 min before meal to decrease post prandial hyperglycemia
 
 
 
 
  
 
==Source ==
 
==Source ==

Revision as of 05:22, 13 March 2011

Background

Hypoglycemics- sulfonylureas, benzoic acid derivatives

Antihyperglycemics- biguanides, alpha glucosidase inhibitors and thiazolidinediones

  1. type 2 dm- overproduction and under utilization of glucose
  2. diet and exercise best
  3. if sugar not controlled with one agent, add bedtime insulin or second agent
  4. if still not controlled p 2 meds either do 2 orals + nighttime insulin, or mixed split insulin regimen or third oral agent

Sulfonylureas

  1. increase insulin secretion and enhance activity
  2. second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
  3. stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
  4. Decrease hepatic insulin clearance= increase insulin conc
  5. Elevated insulin level feeds back to liver and causes decrease hepatic gluc prod
  6. Secondary treatment failure from noncompliance, wt gain, desensitized beta cells, and escalating insulin resistance and increased insulin deficiency
  7. Sulfon has hepatic metab, renal exretion and prolonged activity
  8. Toxicity related to hypoglycemia
  9. Risk factors for hypoG- elderly, poor diet, alcohol, renal/ hepatic dz, polypharmacy
  10. Time to peak effect and duration of effect important in OD
  11. Chlorpropamide, glyburide and glypizide most likely to cause hypoG
  12. Do not use glyburide in pt with CRI since renally excreted
  13. If pt well and young, will not get hypoG during fast due to counterregulatory hormones for glucose homeostasis
  14. Chlorpropamide can cause hyponatremia regardless of dose- induces ADH secretion- risk increases with elderly and if on thiazide diuretics
  15. Chlorpropamide can also give cholestatic jaundice, resolves with discontinuation
  16. Glypizide- enterohepatic recirculation- prolonged action if liver dz. Long duration of action since metabolite still active. All metabolites renally cleared

Biguanides

  1. metformin, phenformin and buformin
  2. phenformin no longer used due to lactic acidosis
  3. metformin does not cause wt gain like sulfonyls
  4. effect is to decrease hep glucose prod, inhibit intestinal glucose absorption
  5. also decreases fatty acid oxidation
  6. increases insulin sensitivity and decreases insln resis
  7. decrease sugar of dm pt not normal person- so is antihyperglycemic agent not hypoglycemic agent
  8. 100% renal excretion
  9. most serious side effect is lactic acidosis- aerobic type by increased lactate production- not tissue hypoxia
  10. signs of lactic acidosis- nonspecific- nvd, abd pain, sleepy, tachypnia, lethargy- seen mostly if renal/ liver dz, alcohol, heart dz, infection
  11. metformin exclusion criteria- CRI, cardiac/ pulm insuff, h/o lactosis, profound infc, liver dz, alcohol, iv contrast agents
  12. fatality from metformn lactosis not related to lactate levels or metformin level but rather to concomitant condition (hypoxia) resulting in elevated lactate
  13. OD- hypoglycemia rare, can get lactosis- obs for 6-8 hr and tx c bicarb and consider hemodialysis

Alpha Glucosidase Inhibitors

  1. acarbose, miglitol, voglibose
  2. 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
  3. does not affect lactose absorption
  4. if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
  5. take these meds with each meal with first bite
  6. since limited aborption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
  7. contraindications- cirrhosis, IBD, malabsorption synd
  8. alpha glucs do not cause hypoG when used as monotx
  9. acarbose- can cause transaminitis/ liver inj
  10. since min absorption- systemic tox from OD unlikely

Thiazolidinediones

  1. rosiglitazone and poiglitazone
  2. enhance insulin effect on muscle, fat, liver without increasing panc insulin secretion
  3. protein bound and hep metab- not good if liver dz
  4. side effects- induce ovulation, increase plasma vol bad if CHF, decrease effectiveness of OCP's

Benzoic Acid Derivatives

  1. repaglinide- mono or combo tx c metformin
  2. binds to atp dependent potassium channel like sulfonyls but at different site.
  3. Unlike sulfonyls, it decreases insulin lvls
  4. Dose 30 min before meal to decrease post prandial hyperglycemia

Source

6/06 MISTRY