Lecture 8: Diabetes (cont.) Flashcards
Adverse reactions to insulin
Hypoglycemia - blood glucose < ___ mg/dL
- too much insulin and/or not enough food (glucose)
- symptoms are ___ in nature
- treated with ___ or ___
60 mg/dL
- neurologic
- glucose, glucagon
Adverse reactions to insulin (cont.)
Lipodystrophy - changes of fat at ___ injection site
Lipohypertrophy - ___ of fat in subcutaneous tissue
Lipoatrophy - ___of fat in subcutaneous tissue
- inflammatory response
rarely occurs (mostly in animal insulin)
- over-used
- accumulation
- loss
factors and agents which may alter insulin action
agents that increase blood glucose (esp in diabetics)
- catecholamines
- glucocorticoids
- oral contraceptives
- thyroid hormone
- calcitonin
- somatropin
- isoniazid
- phenothiazines
- morphine
factors and agents which may alter insulin action
agents that increase risk of insulin hypoglycemia
- ethanol
- ACE inhibitors
- somatostatin
- beta adrenergic blockers
- fluoxetine anabolic steroids
- MAO inhibitors
- vigorous, unaccustomed exercise
Overview of treatment of type I and type II
Type I: ___, diet, exercise
Type II:
1) diet + exercise
2) diet + exercise + ___ drugs
3) diet + exercise + ___
- insulin
- antidiabetic, insulin
Insulin secretion defects in type II DM
___ phase not defined
First
Patho of Type II
Type II is a combo of insulin ___ and reduced insulin ___
- tissues that normally respond to insulin become less and less ___
resistance, secretion
- responsive
Agents that enhace insulin secretion
___ - tolbutamide, tolazamide, chlorpropamide, glyburide, glipizide, glimepiride
___ - nateglinide, repaglinide
Sulfonylureas
Meglitinides
Type 2 diabetes and sulfonylureas
must have functioning ___
increased release of insulin
- may restore ___ phase insulin release
- increase beta cell ___ to glucose and ___ glucose stimulated insulin release
beta cells
- first
- sensitivity, increase
effects of sulfonylureas on beta cell insulin release
1) binds to ___ receptors
2) inactivated ___ channel
3) decreases cell ___
4) activates voltage sensitive ___ channels
5) increases ___ and activity of ___
6) increased exocytosis of ___ containing granules
- sulfonylurea
- K
- polarization
- Ca
- Ca, microfilaments
- insulin
insulin release from pancreatic beta cells
High glucose: K channel ___ , Ca channel ___ , insulin ___
Low Glucose: K channel, Ca channel ___, insulin ___
- closed, open, released
- open, closed, trapped
drug class: ___
drug 1 name: ___
drug 2 name: ___
- sulfonylureas
- tolbutamide
- glyburide
1st generation sulfonylureas
in order of increasing potency and duration
not really used anymore
1) tolbutamide
2) tolazamide
3) chlorpropamide
not really used anymore
2nd gen sulfonylureas
- ____ (Glucotrol)
- ___ (DiaBeta, Glynase)
- ___ (Amaryl)
- glipizide
- glyburide
- glimepiride
Meglitinides “Glinides”
____ (Prandin)
- MOA: like ___
- quick onset, ___ duration of action
- tablet taken ___ each meal (preprandial)
Repaglinide
- sulfonylureas
- short
- before
Meglitinides “Glinides”
____ (Starlix)
- MOA: non-sulfonylurea ____ channel blocker
- very ____ for K-ATP channels
- in ___ vs cardiovascular tissue
- shorter t1/2 than ___ (less risk of ___ )
- synergistic with ___
Nateglinide
- K-ATP
- specific
- pancreas
- Repaglinide (Prandin), hypoglycemia
- metformin
AE of sulfonylureas
- ____ due to long t1/2
- glipizide, glimepiride < ___
- ___ problems: N/V
- weight ___ and increased numbers of ___ failures
- hypoglycemia
- glyburide
- GI
- gain, secondary
Drug interactions (sulfonylureas)
drugs which enhance the action of sulfonylureas and increase the risk of ____ (4 examples)
- displacement of sulfonylureas from ___ binding
hypoglycemia
- salicylates
- phenylbutazone
- sulfonamides
- clofibrate
- plasma protein
T or F: GLP-1 amplifies insulin secretion without glucose being present
F: glucose dependent
T or F: the incretin effect is enhanced in type II diabetics
F: it is diminished
GLP-1 Analogs
___ (Victoza)
hGLP-1 aa7-37
- ___ linker
- ___ instead of alanine
- t1/2 of ___ hours
- SE: N/V, pancreatitis, risk of thyroid tumors, monitor ___ levels
- can be co-administered with metformin, TzDs, and sulfonylureas
- ___ injection
liraglutide
- fatty acid
- valine
- 13
- calcitonin
- daily
GLP-1 Analogs
___ (Trulicity)
- GLP-1 agonist peptides are slowly released from ___ domain by reduction of ___ bonds in linker region
- SE: N/V, pancreatitis
- containdicated in pts with family history of medullary ___ cancer
- ___ injection
Dulaglutide
- IgG Fc, disulfide
- thyroid
- weekly
GLP-1 Analogs
___ (Adlyxin)
- ___ amino acid peptide
- ___ instead of alanine
- injected ___ before breakfast
- ___ with a polylysine tail
Soliqua
- 100 U ___ + 33 micro grams lixisenatide/mL
- injected ___
- SE: N/V, pancreatitis
- Contraindicated in pts with family history of medullary ___ cancer
Lixisenatide
- 44
- glycine
- GLP-1
- daily
- exenatide
- glargine
- daily
- thyroid
GLP-1 Analogs
___ (Ozempic)
- ___ amino acid peptide
- Injected once ___
- extensively bound to ___
- vulnerable alanine is replaced with ____
- t1/2 about a ___
- has ___ spacer and ___
- SE: N/V, pancreatitis
- Contraindicated in pts with family history of medullary ___ cancer
- 31
- weekly
- serum albumin
- 2-aminoisobutyrate
- week
- hydrophillic, fatty acid
Inhibiting incretin proteolysis - DPP-4
DPP stands for ___
- if we inhibit it, there will be more ___ and ___
dipeptidyl peptidase
- GLP-1, GIP
DPP-IV inhibitors
inhibitors of ___
(4 examples)
- ___ (Januvia)
- ___ (Onglyza)
- ___ (Tradjenta)
- ___ (Nesina)
DPP-4
- sitagliptin
- saxagliptin
- linagliptin
- alogliptin
