Lec 3.5 - Diabetes drugs

Question 1

humilin is made from human insulin _____ in a plasmid expressed in ____

Answer 1

cDNA;

E. coli

Question 2

Insulin:

name the 3 rapid acting/short action drugs:

Answer 2

lispro, aspart, glulisine;

ie act within 15 min, lasta for 4-8 hours

Question 3

insulin:
____ has a rapid onset and is short acting.
____ has intermediate action and onset;

which has a cloudy appearance?

Answer 3

regular insulin (ie act within an hour, last 12 hours);
NPH (neutral protamine hagedorn) (acts within an hour, lasts 24 hours)

NPH

Question 4

insulin:

name the 3 slow onset, long acting insulins

Answer 4

glargine, detemir; decludec

last 24 hoiurs, usually taken at bed time or after breakfast

Question 5

_____ binds insulin and releases insulin after cleavage by tissue proteases, accounting for its slow absorption

Answer 5

NPH

Question 6

why are the rapid onset insulins so rapid?

what are they used for?

Answer 6

they don’t polymerize into insulin hexamers (due to altered amino acids);

for post-prandial spike (ie administer immediately before meal

Question 7

insulin detemir and degludec bind _____ extensively = long duration of action

Answer 7

albumin

Question 8

mixtures of _____ and _____ insulin can give a transient preprandial bolus and a prolonged basal level in a single injection

Answer 8

fast-onset, long acting

Question 9

routes of administration:
subcutaneous = _____;
insulin infusion pump = ____ _____ and the rapid acting ones

Answer 9

all forms;

buffered regular

Question 10

____ insulin may be administed via IV for ____ or ____

Answer 10

regular; hyperglycemia, ketoacidosis

Question 11

_____ 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

Answer 11

afrezza; shorter;

asthma, COPD

Question 12

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?

Answer 12

hypoglycemia;
Glucagon, glucose;

alcohol

Question 13

other insulin side effects:

____ or _____ at an injection site

Answer 13

lipodystrophy, lipoatrophy

Question 14

replacement insulin is necessary in treatment of type _____ DM;

oral agents and non-insulin injectables require functional ____ cells and are used in type ___ DM

Answer 14

1 (used in severe type 2);

beta, 2

Question 15

mechanism of action of sulfonylureas

Answer 15

bind and close K+ channel–>depolarization–>calcium influx and insulin release

Question 16

what transporter does glucose use to enter a beta cell?

Answer 16

GLUT2

Question 17

the 1st gen sulfonylureas end in ___. name 2 of them

Answer 17

“-amide”;

chlorpropamide (more potent, longer lasting ie 1-3 days), tolbutamide (12 hr duration)

Question 18

2nd gen sulfonylureas (3):

Answer 18

glimepiride, glipizide, glyburide;

all have 24 hour duration

Question 19

name the 2 meglitinides: (end in ____)

mechanism of action?

Answer 19

glinide = nateglinide, repaglinide;

bind K+ channels (similar to sulfonylureas)

Question 20

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?

Answer 20

meglitinides;
sulfonylureas;
both

Question 21

sulfonylurea side effects
risk of _____;
weight ____

Answer 21

hypoglycemia (can be severe);
weight gain

also disulfiram-like effects

Question 22

sulfonylurea side effects:
hypoglycemia may be exacerbated by salicylates and sulfonamides, which _____ sulfonylureas from _____ binding sites;

_____ has its own hypoglycemic effects = increased risk hypoglycemia

Answer 22

displace, protein;

alcohol

Question 23

name 2 GLP1 analogs: end in “___”

these are used for type __ DM

Answer 23

tide = exenatide, liraglutide
2;

coadministered with metformin, sulfonylureas, or glitazones

Question 24

side effects of GLP1 analogs:

nausea, vomiting, ____; increased risk of thyroid tumors with _____

Answer 24

pancreatitis; liraglutide

Question 25

_____ is a DDP resistant GLP1 dimer that is fused to human serum ____. it is injected once a week.

Answer 25

albiglutde (tanzeum); | albumin

Question 26

_____ is a GLP1 agonist that is bound to a IgG molecule. injected once a week. major side effect is increased risk of thyroid ____ tumors

Answer 26

dulaglutide; | C cell

Question 27

name the 3 gliptins: what do these molecules do?

Answer 27

lina, saxa, sitagliptan; inhibit dipeptidyl-peptidase 4 (DDP4), which deactivates GLP1; thus, increase endogenous insulin release

Question 28

gliptin side effects: | increased ____ or ____ infections due to reduced WBC. severe ____ reactions, increased risk of ____

Answer 28

UTI, respiratory; | skin; cancers

Question 29

pramlintide is a _____ ____ that blunts the ____ ____ in blood glucose. used in what diabetes?

Answer 29

amylin analog; postprandial rise;p | type 1 and 2

Question 30

pamlinitde slows ____ ____ and inhibits ___ release;

Answer 30

gastric emptying, glucagon

Question 31

mechanism of action of acarbose and miglitol:

Answer 31

inhibit alpha glucosidases on brush border (Sucrase, maltase, glucoamylase) = decreased carb absorption

Question 32

side effects of the alpha glucosidase inhibitors: | ____ ferment carbs, leading to ____ disturbances

Answer 32

bacteria; | GI

Question 33

the "-gliflozins" (name the 3 of them) are _____ inhibitors

Answer 33

cana-, dapa-, empagliflozin; SGLT2 ie block reabsorption in PCT = decrease threshold for glucose excretion

Question 34

SGLT2 inhibitor side effects: weight _____; increased risk of ____ and ____ infections; contraindicated in patients with _____ impairment

Answer 34

loss; UTI, vaginal; | renal

Question 35

SGLT2 inhibitor side effects: volume _____; ____ hypotension; don't use _____ in patients with bladder cancer

Answer 35

depletion; orthostatic; dapagliflozin (farxiga)

Question 36

metformin is a _____. it is a _____ agent. it rarely causes ____ or ____, as opposed to sulfonylureas

Answer 36

biguanide, anti-hyperglycemic; | weight gain, hypoglycemia

Question 37

metformin activates ______. this causes decreased ____ in the liver and increased ____ and _____ in muscle and fat cells. it ____ insulin sensitivity

Answer 37

AMP-activated protein kinase; gluconeogensis; glycolysis, glucose uptake; increases

Question 38

metformin also decreases serum ____ and decreases serum ____. it is used first line in patients with _____ DM

Answer 38

TG's, LDL; | Type 2

Question 39

metformin side effets: | _____ ____, decreased _____ absorption, GI upset

Answer 39

lactic acidosis, vit b12

Question 40

____ and ____ are thiazolidinediones. they are activators of ____, which is a _____ factor

Answer 40

pioglitazone, rosiglitazone; PPAR gamma (peroxisome proliferator-activated receptor); transcription

Question 41

glitazones: increase insulin _____ in peripheral tissue. the main target is _____, which enhances differentiation and enhances FA uptake into _____, reducing serum FA

Answer 41

sensitivity; adipocytes; sub Q fat

Question 42

glitazones: | enhance glucose uptake in the ___ and ____. reduce hepatic glucose production

Answer 42

liver, skeletal muscle

Question 43

glitazone side effects: weight ____; contraindicated in patients with ____. some _____ toxicity. pioglitazone is associated with increased risk of ____

Answer 43

gain; CHF; liver; bladder cancer

Question 44

_____ are factors regulated by activation PPAR gamma. they are released by _____ adipose tissue

Answer 44

adipokines; | white

Question 45

Adipokines in diabetes: | resistin is _____ in type 2 DM. it stimulates insulin ____

Answer 45

elevated, resistance decreased in response to glitazones

Question 46

adipokines: | adiponectin is ____ in type 2 DM. it reduces insulin _____

Answer 46

decreased; resistance; increased with glitazones

Question 47

adipokines: | ____ inscreased in type 2 DM. it stimulates lipolysis and insulin _____ in skeletal muscle

Answer 47

TNF alpha; | resistance

Question 48

_____ is elevated in obesity and type 2 DM. it signals the fed state to the brain.

Answer 48

leptin

Question 49

humans missing leptin or the leptin receptor are ____ and ____

Answer 49

obese, diabetic

Question 50

with obesity: | ____ is elevated and may contribute to prolfieration of white adipose tissue and to ____

Answer 50

angiotensiongen; | HTN;

Question 51

with obesity: | _____ is elevated and increases the risk of emboli

Answer 51

plasminogen activator inhibitor (PAI 1)

Question 52

more glitazone side effects: increased risk of fractures due to _____; peripheral _____ due to ____ retention

Answer 52

decreased differentiation of stem cells into osteoblasts; | edema, Na