Diabetes medications: Difference between revisions

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
Drug	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

Glipizide, glyburide
Increase insulin secretion
Hypoglycemia is the major adverse effect (especially with glyburide)

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

References

Authors:

@@ Line 1: / Line 1: @@
-Hypoglycemics- sulfonylureas, benzoic acid derivatives
+==Background==
+*Hypoglycemics
+**Sulfonylureas
+**Benzoic acid derivatives
+*Antihyperglycemics
+**Biguanides
+**Alpha glucosidase inhibitors
+**Thiazolidinediones
-Antihyperglycemics- biguanides, alpha glucosidase inhibitors and thiazolidinediones
+{{Common Anti-hyperglycemic Drugs and Pharmacology}}
+==[[Insulin]]==
-==Gen==
+==Biguanides (Metformin)==
+Suppresses liver glucose production
+===Dose===
-- type 2 dm- overproduction and under utilization of glucose
+[[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
-- diet and exercise best
+*Should be withheld for 48hr after IV contrast
+===Side Effects===
-- if sugar not controlled with one agent, add bedtime insulin or second agent
+*Lactic acidosis (due to increased lactate production)
+**Seen almost exclusively in patients with renal failure
-- if still not controlled p 2 meds either do 2 orals + nighttime insulin, or mixed split insulin regimen or third oral agent
+*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==
+*[[Glipizide]], [[glyburide]]
+*Increase insulin secretion
-- increase insulin secretion and enhance activity
+*[[Hypoglycemia]] is the major adverse effect (especially with glyburide)
-- 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
-- acarbose, miglitol, voglibose
+*Taken with first bite of each meal
+*Since limited absorption, stays in gut and side effects mostly GI- bloating, gas, [[diarrhea]]
-- 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- can cause transaminitis/ liver inj
+*Contraindications- [[cirrhosis]], [[IBD]], malabsorption syndrome
-- does not affect lactose absorption
+*Do not cause [[hypoglycemia]] when used as monotherapy
+**If [[hypoglycemia|hypoglycemic]]- sucrose/ table sugar will ''not'' work- use glucose- PO or IV
-- if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
+*Since minimal absorption- systemic toxicity 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==
+*Rosiglitazone and poiglitazone
+*Enhance insulin effect on muscle, fat, liver without increasing pancreatic insulin secretion
-- rosiglitazone and poiglitazone
+*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)
-- 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- 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
-- repaglinide- mono or combo tx c metformin
+==[[DPP-4 inhibitors]]==
+*Sitagliptin, saxagliptin, linagliptin, alogliptin
-- binds to atp dependent potassium channel like sulfonyls but at different site.
+*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]]
-- Unlike sulfonyls, it decreases insulin lvls
-- Dose 30 min before meal to decrease post prandial hyperglycemia
-==Source ==
-/06 MISTRY
+==[[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)]]
+==References==
+<references/>
-[[Category:Endo]]
+[[Category:Endocrinology]]
+[[Category:Pharmacology]]