Diabetes medications: Difference between revisions
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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 | |||
#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 | |||
#stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel. | |||
#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== | ==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 | |||
#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 | |||
#if hypoG- sucrose/ table sugar will not work- use glucose- po or iv | |||
#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 | |||
#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. | |||
#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
- 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
- increase insulin secretion and enhance activity
- second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
- stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
- 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
- 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
- if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
- 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
- rosiglitazone and poiglitazone
- 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
- repaglinide- mono or combo tx c metformin
- 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
6/06 MISTRY