Lec 3.5 - Diabetes drugs Flashcards

1
Q

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

A

cDNA;

E. coli

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2
Q

Insulin:

name the 3 rapid acting/short action drugs:

A

lispro, aspart, glulisine;

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

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3
Q

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

which has a cloudy appearance?

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

NPH

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4
Q

insulin:

name the 3 slow onset, long acting insulins

A

glargine, detemir; decludec

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

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5
Q

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

A

NPH

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6
Q

why are the rapid onset insulins so rapid?

what are they used for?

A

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

for post-prandial spike (ie administer immediately before meal

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7
Q

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

A

albumin

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8
Q

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

A

fast-onset, long acting

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9
Q

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

A

all forms;

buffered regular

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10
Q

____ insulin may be administed via IV for ____ or ____

A

regular; hyperglycemia, ketoacidosis

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11
Q

_____ 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

A

afrezza; shorter;

asthma, COPD

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12
Q

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?

A

hypoglycemia;
Glucagon, glucose;

alcohol

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13
Q

other insulin side effects:

____ or _____ at an injection site

A

lipodystrophy, lipoatrophy

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14
Q

replacement insulin is necessary in treatment of type _____ DM;

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

A

1 (used in severe type 2);

beta, 2

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15
Q

mechanism of action of sulfonylureas

A

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

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16
Q

what transporter does glucose use to enter a beta cell?

A

GLUT2

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17
Q

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

A

“-amide”;

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

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18
Q

2nd gen sulfonylureas (3):

A

glimepiride, glipizide, glyburide;

all have 24 hour duration

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19
Q

name the 2 meglitinides: (end in ____)

mechanism of action?

A

glinide = nateglinide, repaglinide;

bind K+ channels (similar to sulfonylureas)

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20
Q

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?

A

meglitinides;
sulfonylureas;
both

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21
Q

sulfonylurea side effects
risk of _____;
weight ____

A

hypoglycemia (can be severe);
weight gain

also disulfiram-like effects

22
Q

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

_____ has its own hypoglycemic effects = increased risk hypoglycemia

A

displace, protein;

alcohol

23
Q

name 2 GLP1 analogs: end in “___”

these are used for type __ DM

A

tide = exenatide, liraglutide
2;

coadministered with metformin, sulfonylureas, or glitazones

24
Q

side effects of GLP1 analogs:

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

A

pancreatitis; liraglutide

25
Q

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

A

albiglutde (tanzeum);

albumin

26
Q

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

A

dulaglutide;

C cell

27
Q

name the 3 gliptins:

what do these molecules do?

A

lina, saxa, sitagliptan;

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

28
Q

gliptin side effects:

increased ____ or ____ infections due to reduced WBC. severe ____ reactions, increased risk of ____

A

UTI, respiratory;

skin; cancers

29
Q

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

A

amylin analog; postprandial rise;p

type 1 and 2

30
Q

pamlinitde slows ____ ____ and inhibits ___ release;

A

gastric emptying, glucagon

31
Q

mechanism of action of acarbose and miglitol:

A

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

32
Q

side effects of the alpha glucosidase inhibitors:

____ ferment carbs, leading to ____ disturbances

A

bacteria;

GI

33
Q

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

A

cana-, dapa-, empagliflozin; SGLT2

ie block reabsorption in PCT = decrease threshold for glucose excretion

34
Q

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

A

loss; UTI, vaginal;

renal

35
Q

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

A

depletion;
orthostatic;
dapagliflozin (farxiga)

36
Q

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

A

biguanide, anti-hyperglycemic;

weight gain, hypoglycemia

37
Q

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

A

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

38
Q

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

A

TG’s, LDL;

Type 2

39
Q

metformin side effets:

_____ ____, decreased _____ absorption, GI upset

A

lactic acidosis, vit b12

40
Q

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

A

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

41
Q

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

A

sensitivity;
adipocytes;
sub Q fat

42
Q

glitazones:

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

A

liver, skeletal muscle

43
Q

glitazone side effects:
weight ____;
contraindicated in patients with ____.
some _____ toxicity.

pioglitazone is associated with increased risk of ____

A

gain;
CHF;
liver;

bladder cancer

44
Q

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

A

adipokines;

white

45
Q

Adipokines in diabetes:

resistin is _____ in type 2 DM. it stimulates insulin ____

A

elevated, resistance

decreased in response to glitazones

46
Q

adipokines:

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

A

decreased;
resistance;

increased with glitazones

47
Q

adipokines:

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

A

TNF alpha;

resistance

48
Q

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

A

leptin

49
Q

humans missing leptin or the leptin receptor are ____ and ____

A

obese, diabetic

50
Q

with obesity:

____ is elevated and may contribute to prolfieration of white adipose tissue and to ____

A

angiotensiongen;

HTN;

51
Q

with obesity:

_____ is elevated and increases the risk of emboli

A

plasminogen activator inhibitor (PAI 1)

52
Q

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

A

decreased differentiation of stem cells into osteoblasts;

edema, Na