Pancreatic hormones and anti diabetic drugs Flashcards
insulin dependent DM
Type 1
4 categories if Diabetes Mellitus
Type1 insulin dependent
Type 2 non insulin dependent
Type 3 juvenile
Type 4 Gestational DM
non insulin dependent DM
Type 2
juvenile DM
Type 3
Gestational DM
Type 4
4 main cell types in pancreas
glucagon
insulin
somatostatin
pancreatic polypeptide
alpha pancreatic cells secrete
glucagon
beta pancreatic cells secrete
insulin
gamma pancreatic cells secrete
somatostatin
effects of insulin on liver
inhibit glycogenolysis
inhibit conversion of AA and FA to keto acids
inhibit AA to glucose
anabolic action
effects of insulin on muscle
increase CHON. synthesis, AA transport, ribosomal synthesis
increase glycogen synthesis, glucose trasport
inhibits phosphorylase
effects of insulin on adipose tissue
increase triglyceride stores
lipoprotein lipase induced
glucose transport into cells
inhibits intracellular lipase
rapidly acting insulin
Lispro
Aspart
Glulisine
rapidly acting insulin (1) onset of action and (2) peak
ONSET: 15 minutes
PEAK: 30-90minutes
taken before meals
duration of action is 3-5 hours
rapidly acting insulin
crystalline zinc insulin that is now made by recombinant DNA techniques
short acting insulin
short acting insulin onset of action
within 30 min
peak of short acting insulin
2-4 hours after SQ
short acting insulin duration of action
5-8 hours
regular insulin / short acting insulins
Novolin
Humulin
regular insulin should be administered within
30-45 mins
intermediate acting insulin which combines insulin and protamine
Neutral Protamine Hagedorn or isophane insulin
intermediate acting insulin onset of action
1-2 hours
intermediate acting insulin peak
8 hours
duraton of action is 12-16 hours
intermediate acting insulin
usually mixed with regular, lispro, aspart, or glulisine insulin
NPH or isophane intermediate acting insulin
duration of action >24 hours
onset of actin 1-2 hrs
DETEMIR long acting insulin
soluble “peakless” insulin given once daily
GLARGINE Long acting insulin
insulin glargine onset of action
slow onset of action 1-1.5 hrs
insulin lispro, aspart, glusine acutely mixed with NPH
Pre-mixed insulin (doesnt affect rapid absorption)
available concentration of insulin
100 U/ml
external open loop pump for insulin delivery
Continuous SQ insulin infusion device (abdomen, flank, thighs)
most recently developed long scting insulin
DOSE dependent
DETEMIR insulin
insulin therapy formula
(wt in lbs) / (4) or
0.55) x (wt in kg
conventional insulin therapy
for DM type 2
fixed dose of intermediate or long acting
vary dos of short or rapidly acting
condition caused by inadequate or absent insulin replacement
Diabetic Ketoacidosis (DKA)
Tx for DKA
regular insulin IV 0.1IU/kg/h + IV hydration
DM type 2 characterized by HYPERGLYCEMIA and DEHYDRATION
Hyperosmolar Hyperglycemic Syndrome (HHS)
Tx for Hyperosmolar Hyperglycemic Syndrome (HHS)
aggressive rehydration and restoration of glucose
LOW DOSE Insulin therapy
most common complication of insulin therapy
HYPOGLYCEMIA
2 major disorders of insulin therapy
insulin allergy
immune insulin resistance
immediate type hypersensitivity, rare condition
insulin allergy
disorder where low titer IgG anti insulin antibodies neutralize the action of insulin
immune insulin resistance
abnormal or degenerative conditionof the body’s adipose tissue
Lipodystrophy
oral anti diabetic agents
Secretagogues BIGuanides Thiazolidinediones Alpha-glucosidase inhibitors Incretin based therapies Amylin analogs
insulin secretagogues
Sulfonylureas
sulfonylureas MOA
increase insulin release
reduce serum glucagon levels
closure of K channels in extrapancreatic tissure
first generation of Sulfonylureas
Tolbutamide
Chlorpropamide
Tolazamide
safest sulfonylureas for elderly diabetics, short halflife
TOLBUTAMIDE
rapidly metabolized in liver
first gen sulfonylurea prolonged hypoglycemic reactions
Chlorpropamide
ADR of CHLORPROPAMIDE if given >500mg daily
Jaundice
more slowly absorbed than other sulfonylureas
half life: 7hours
duration: 10-14 hours
TOLAZAmide
Second generation sulfonylureas
Glyburide (aka Glibenclamide)
gLIPizide
gLIMEpiride
Second gen sulfonylureas used with caution on Px with CV DISEASE and the ELDERLY
gLIMEpiride
2nd gen sulfonylurea with very loew hypoglycemic effect
Glyburide (aka Glibenclamide)
dose of Glyburide (aka Glibenclamide)
starting dose: 2.5mg/day
maintainance: 5-10 mg/day
contraindicated in Glyburide (aka Glibenclamide) therapy
hepatic and renal impairment
alcohol intake
ADR of Glyburide (aka Glibenclamide) with alcohol intake
Flushing
2nd gen sulfonylurea with delayed absorption when taken with food (take 20min before breakfast)
gLIPizide
2nd gen sulfonylurea single dose 1mg use as MONOTHERAPY or in combination with insulin
gLIMEpiride
1st member of MEGLITINIDE group of insulin secretagogue
REPAglinide
Used for controlling pstprandial glucose excursion
REPAGLINIDE
latest insulin secretagogue available clinically
NATEGLINIDE
insulin secretagogue D phenylalanine derivative
NATEGLINIDE
stimulates very rapid insulin release from beta cells thru CLOSURE of ATP-sensitive K channel
NATEGLINIDE
Nateglinide metabolism
via liver CYP2C9 and CYP3A4
reduces glucose production thru AMPK
BIGuanides
BIGuanide minor MOA
IMPAIR renal gluconeogenesis, SLOWS GIT glucose abs
direct stimulation of glycolysis in tissues
INCREASE glucose removal in blood
REDUCE glucagon
first line therapy for DM type 2
METFORMIN
insulin sparing drug
METFORMIN
METFORMIN dosage
500mg to 2.55g daily
METFORMIN toxicity
GIT disorders (anorexia, NV, abd pain, diarrhea) DECREASE vit B12 abs
METFORMIN contraindication
renal, hepatic disease, alcoholism
predispose to ANOXIA ( bec inc risk of LACTIC ACIDOSIS)
they act to decrease insulin resistance
THIAZOLIDINEDIONE
major site of THIAZOLIDINEDIONE
adipose tissue
In, THIAZOLIDINEDIONE ligands of peroxisomes proliferatior activates what receptor?
Receptor GAMMA
current available THIAZOLIDINEDIONE
PIOglitazone
ROSIglitazone
other THIAZOLIDINEDIONEs pulled from the market due to LIVER TOXICITY
TROglitazone
REZULIN
insulin sensitizer THIAZOLIDINEDIONE
PIOglitazone
attaches to insulin receptors throughout the body
PIOglitazone (insulin sensitizer!)
rapidly absorbed and highly protein bound THIAZOLIDINEDIONE
ROSIglitazone
not recommended for type 1 DM
MONOTHERAPY for type 2 DM
ROSIglitazone
ROSIglitazone adverse effects
Fluid retention (presented as MILD ANEMIA, EDEMA) Bone fracture (decrease osteoblast formation)
alpha glucosidase inhibitors
ACARBOSE
MIGLITOL
competitive inhibitors of of intestinal Alpha GLUOSIDASES
ACARBOSE
MIGLITOL
Alpha GLUOSIDASES moa
reduces post meal glucose excursions
sugars that can only be transported out of the GIT
glucose and fructose
Alpha GLUOSIDASES with side effect of FLATULENCE and DIARRHEA
ACARBOSE
Synthetic analog of AMYLIN
PRAMLINTIDE
hyperglycemic agent modulates POST PRANDIAL GLUCOSE LEVEL
rapidly absorbed SQ admin
PRAMLINTIDE
synthetic analog of Glucagon-like polypeptide 1 (GLP-1 agonist)
Exenatide
1st INCRETIN therapy for Diabetes
EXENATIDE
Adjunctive therapy in persons with type 2 DM
EXENATIDE
EXENATIDE moa
potentiation of INSULIN SECRETION supression of POSTPRANDIAL GLUCAGON release DECREASE gastric emptying REDUCE appetite REDUCES liver fat content
EXENATIDE adr
Nausea, vomiting, diarrhea
risk for THYROID CA, ACUTE PANCREATITIS
inhibitor of dipeptidyl petidase 4 (DPP-4)
SITAglipin
SITAglipin MOA
increase GLP-1 and GIP
decreases post prandial glucose excusion
SITAglipin common side effects
Nasopaharyngitis, URTI, headaches
other DPP4 inhibitors
SAXAgliptin
LINAgliptin
ALOgliptin
VILDAgliptin
What do you give in combination therapy?
Initial therapy: BIGuanide
2nd line: Sulfonylureas or insulin (cost-efficient) ; EXENATIDE (aggressive control)
for concurrent mealtime administration in type 2 DM for early post prandial glucose excursion
combination therapy with PRAMALINTIDE
for adjunct to oral anti diabetic therapy in type 2 DM
Bedtime insulin
NOT approved for Tx of type 1 DM
insulin secretagogues, Tzds, biguanides, alpha glucosidase and incretin
insulin secretagogues
Sulfonylureas, Meglitidines, D phenylalanine derivatives
For concurrent meal time administration with type 1 DM who have POOR control despite optimal insulin therapy
Combination therapy with PRAMLINTIDE
synthesized in alpha cells of pancreas, degraded in liver and kidney
Glucagon
GLUCAGON is a precursor intermmediate of 69 AA peptide called
GLUCENTIN
Glucentin immuno reactivity found in small intestine and alpha cells
Gut Glucagon
predominant form of GLP in human intestine
glucagon like peptide GLP-1
potential therapeutic agent in type 2 D
GLP-1 aka INSULINOTROPIN
Metabolic effects of glucagon
increase gluconeogenesis and ketogenesis
clinical uses of glucagon
severe hypoglycemia (for emergency) endocrine diagnosis beta adrenoceptor blocker overdose radiation of bowel
glucagon adverse reactions
NV
drug interaction with glucagon which result to greater risk of bleeding
WARFARIN
standard mode of insulin therapy
SQ