Lec 3.5 - Diabetes drugs Flashcards
humilin is made from human insulin _____ in a plasmid expressed in ____
cDNA;
E. coli
Insulin:
name the 3 rapid acting/short action drugs:
lispro, aspart, glulisine;
ie act within 15 min, lasta for 4-8 hours
insulin:
____ has a rapid onset and is short acting.
____ has intermediate action and onset;
which has a cloudy appearance?
regular insulin (ie act within an hour, last 12 hours); NPH (neutral protamine hagedorn) (acts within an hour, lasts 24 hours)
NPH
insulin:
name the 3 slow onset, long acting insulins
glargine, detemir; decludec
last 24 hoiurs, usually taken at bed time or after breakfast
_____ binds insulin and releases insulin after cleavage by tissue proteases, accounting for its slow absorption
NPH
why are the rapid onset insulins so rapid?
what are they used for?
they don’t polymerize into insulin hexamers (due to altered amino acids);
for post-prandial spike (ie administer immediately before meal
insulin detemir and degludec bind _____ extensively = long duration of action
albumin
mixtures of _____ and _____ insulin can give a transient preprandial bolus and a prolonged basal level in a single injection
fast-onset, long acting
routes of administration:
subcutaneous = _____;
insulin infusion pump = ____ _____ and the rapid acting ones
all forms;
buffered regular
____ insulin may be administed via IV for ____ or ____
regular; hyperglycemia, ketoacidosis
_____ is a regular human insulin inhaled as a dry powder. it has a _____ duration of action than regular sub-cu insulin. contradicted in patients with ___ or ____ due to decreased FEV
afrezza; shorter;
asthma, COPD
insulin side effects:
_____ due to too much insulin or not enough food. treat with ____ or _____;
important agent that can increase risk of this side effect?
hypoglycemia;
Glucagon, glucose;
alcohol
other insulin side effects:
____ or _____ at an injection site
lipodystrophy, lipoatrophy
replacement insulin is necessary in treatment of type _____ DM;
oral agents and non-insulin injectables require functional ____ cells and are used in type ___ DM
1 (used in severe type 2);
beta, 2
mechanism of action of sulfonylureas
bind and close K+ channel–>depolarization–>calcium influx and insulin release
what transporter does glucose use to enter a beta cell?
GLUT2
the 1st gen sulfonylureas end in ___. name 2 of them
“-amide”;
chlorpropamide (more potent, longer lasting ie 1-3 days), tolbutamide (12 hr duration)
2nd gen sulfonylureas (3):
glimepiride, glipizide, glyburide;
all have 24 hour duration
name the 2 meglitinides: (end in ____)
mechanism of action?
glinide = nateglinide, repaglinide;
bind K+ channels (similar to sulfonylureas)
sulfonylurea vs meglitinides:
which are used for post prandial insulin release (ie short acting)?
which can cause a sulfa allergy?
which require functional beta cells?
meglitinides;
sulfonylureas;
both
sulfonylurea side effects
risk of _____;
weight ____
hypoglycemia (can be severe);
weight gain
also disulfiram-like effects
sulfonylurea side effects:
hypoglycemia may be exacerbated by salicylates and sulfonamides, which _____ sulfonylureas from _____ binding sites;
_____ has its own hypoglycemic effects = increased risk hypoglycemia
displace, protein;
alcohol
name 2 GLP1 analogs: end in “___”
these are used for type __ DM
tide = exenatide, liraglutide
2;
coadministered with metformin, sulfonylureas, or glitazones
side effects of GLP1 analogs:
nausea, vomiting, ____; increased risk of thyroid tumors with _____
pancreatitis; liraglutide
_____ is a DDP resistant GLP1 dimer that is fused to human serum ____. it is injected once a week.
albiglutde (tanzeum);
albumin
_____ is a GLP1 agonist that is bound to a IgG molecule. injected once a week.
major side effect is increased risk of thyroid ____ tumors
dulaglutide;
C cell
name the 3 gliptins:
what do these molecules do?
lina, saxa, sitagliptan;
inhibit dipeptidyl-peptidase 4 (DDP4), which deactivates GLP1; thus, increase endogenous insulin release
gliptin side effects:
increased ____ or ____ infections due to reduced WBC. severe ____ reactions, increased risk of ____
UTI, respiratory;
skin; cancers
pramlintide is a _____ ____ that blunts the ____ ____ in blood glucose. used in what diabetes?
amylin analog; postprandial rise;p
type 1 and 2
pamlinitde slows ____ ____ and inhibits ___ release;
gastric emptying, glucagon
mechanism of action of acarbose and miglitol:
inhibit alpha glucosidases on brush border (Sucrase, maltase, glucoamylase) = decreased carb absorption
side effects of the alpha glucosidase inhibitors:
____ ferment carbs, leading to ____ disturbances
bacteria;
GI
the “-gliflozins” (name the 3 of them) are _____ inhibitors
cana-, dapa-, empagliflozin; SGLT2
ie block reabsorption in PCT = decrease threshold for glucose excretion
SGLT2 inhibitor side effects:
weight _____;
increased risk of ____ and ____ infections;
contraindicated in patients with _____ impairment
loss; UTI, vaginal;
renal
SGLT2 inhibitor side effects:
volume _____;
____ hypotension;
don’t use _____ in patients with bladder cancer
depletion;
orthostatic;
dapagliflozin (farxiga)
metformin is a _____. it is a _____ agent. it rarely causes ____ or ____, as opposed to sulfonylureas
biguanide, anti-hyperglycemic;
weight gain, hypoglycemia
metformin activates ______. this causes decreased ____ in the liver and increased ____ and _____ in muscle and fat cells. it ____ insulin sensitivity
AMP-activated protein kinase;
gluconeogensis;
glycolysis, glucose uptake;
increases
metformin also decreases serum ____ and decreases serum ____. it is used first line in patients with _____ DM
TG’s, LDL;
Type 2
metformin side effets:
_____ ____, decreased _____ absorption, GI upset
lactic acidosis, vit b12
____ and ____ are thiazolidinediones. they are activators of ____, which is a _____ factor
pioglitazone, rosiglitazone;
PPAR gamma (peroxisome proliferator-activated receptor);
transcription
glitazones:
increase insulin _____ in peripheral tissue. the main target is _____, which enhances differentiation and enhances FA uptake into _____, reducing serum FA
sensitivity;
adipocytes;
sub Q fat
glitazones:
enhance glucose uptake in the ___ and ____. reduce hepatic glucose production
liver, skeletal muscle
glitazone side effects:
weight ____;
contraindicated in patients with ____.
some _____ toxicity.
pioglitazone is associated with increased risk of ____
gain;
CHF;
liver;
bladder cancer
_____ are factors regulated by activation PPAR gamma. they are released by _____ adipose tissue
adipokines;
white
Adipokines in diabetes:
resistin is _____ in type 2 DM. it stimulates insulin ____
elevated, resistance
decreased in response to glitazones
adipokines:
adiponectin is ____ in type 2 DM. it reduces insulin _____
decreased;
resistance;
increased with glitazones
adipokines:
____ inscreased in type 2 DM. it stimulates lipolysis and insulin _____ in skeletal muscle
TNF alpha;
resistance
_____ is elevated in obesity and type 2 DM. it signals the fed state to the brain.
leptin
humans missing leptin or the leptin receptor are ____ and ____
obese, diabetic
with obesity:
____ is elevated and may contribute to prolfieration of white adipose tissue and to ____
angiotensiongen;
HTN;
with obesity:
_____ is elevated and increases the risk of emboli
plasminogen activator inhibitor (PAI 1)
more glitazone side effects:
increased risk of fractures due to _____;
peripheral _____ due to ____ retention
decreased differentiation of stem cells into osteoblasts;
edema, Na
