Diabetes Drugs DSA

Question 1

which pathway has direct effect on increased glut-4 expression

Answer 1

CBL

PI3K/AKT

Question 2

insulin effects on MEK/ERK–> increased ___ and effects

Answer 2

ELK1

cell growth and differentiation
cell proliferation and increased survival

Question 3

insulin and increased AP-1

Answer 3

cell growth and differntiation

cell proliferation and apoptosis

Question 4

insulin and FOX01

Answer 4

decreased FOX1–> increased PPAR-y =lipogenesis

decreased glycogenolysis

decreased gluconeogenesis

Question 5

inhibition of gluconeogenesis

Answer 5

PI3K/AKT—-> ^PDE —>decrease cAMP which
reduced expression glucose-6 phosphatase
decreased fructose 1,6 bisphosphatse
reduced PEPCK

Question 6

clinical use of aspart, lispro, glulisine

duration

Answer 6

postprandial hyperglycemia
-take before meal
1-3 hrs

Question 7

clinical use of regular insulin

duration

Answer 7

basal insulin maintenance
overnight coverage
if for postprandial hyperglycemia, inject 45 min before the meal
10 hrs

Question 8

NPH, protamine has to what before what

Answer 8

be digested by tissue proteolytic enzymes before insulin can be absorbed

Question 9

clinical use of NPH

Answer 9

basal insulin maintenance and or overnight coverage

duration is 10-12 hrs

Question 10

loop diuretics on K+

Answer 10

K+ wasting

Question 11

AE of insulin

Answer 11

hypoglycemia

lipodistrophy (hypertroph/atrophy of subcut fat at site of injection, change site to prevent)

resistance: IgG Abs can develop to neutralize exogenous insulin

allergic reactions

hypokalemia

Question 12

common causes of hypoglycemia

Answer 12

delay of meal or missed meal
exercise
overdose of insulin

Question 13

treatment for hypoglycemia

Answer 13

glucose: juice, candy, IV glucose

diazoxide-> K+ channel opener, inhibits insulin release

glucagon

Question 14

MOA of glucagon

Answer 14

Gs coupled GPCR
activates AC–>PKA–>glycogen phosphorylase = glycogenolysis

increased PEPCK and Glu-6-phosphatase = gluconeogenesis

Question 15

glucagon effects

Answer 15

hepatocytes: increased glucose output, glycogen depletion (no depletion in skeletel muscle)

potent inotropic and chronotropic effect on heart

GI smooth muslce relaxation

increase insulin release by beta cells

increase release of catecholamines by chromaffin cells

Question 16

what pts is glucagon contraindicated in

Answer 16

pts with pheochromocytomas

Question 17

clinical uses of glucagon

Answer 17

mod to severe hypoglycemia
beta blocker overdose
radiology of the bowel

Question 18

clinical use of pramlintide

Answer 18

type 1 diabetes

type 2 diabetes as adjunt to insulin therapy before meal

Question 19

onset
duration
pramlintide

Answer 19

rapid

3 hr

Question 20

AE pramlintide

Answer 20

nausea, vomiting, diarrhea, anorexia

severe hypoglycemia

Question 21

drug interactions of pramlintide

Answer 21

enhances effects of anticholinergic drugs in GI tract (constipation)

Question 22

long acting GLP-1 receptor agonists and half life

Answer 22

exenatide =2.4hrs

liraglutide = 11-15 hrs

Question 23

clinical use of long acting GLP-1 receptor agonists

Answer 23

GLP-1 inhibits glucagon secretion and excesive hepatic glucose output postprandially

• this is diminished in type 2 diabetic pts
• approved for these pts who can’t control diabetes with metformin/sulfonylureas/thiazolidineodiones

Question 24

GLP receptor against and weight

Answer 24

can induce some weight loss

Question 25

AE long actinv GLP-1 receptor agonists

Answer 25

GI disturbance acute pancreatitis and pancreatic cancer possible link to thyroid cancer

Question 26

DDP-4 inhibitor clinical use alone or in combo?

Answer 26

approved as adjunctive therapy in DM2 | monotherapy and in combo with metformin/sulfonylureas/TZDs

Question 27

AE of DDP-4 inhibitor

Answer 27

URI nasopharyngitis acute pancreatitis hypoglycemia

Question 28

adverse effects of sulfonylureas

Answer 28

hypoglycemia weight gain secondary failure- respond initially then later cease to respond = hyperglycemia again disulfiram-like effect of alcohol induced flushing dermatological and gen hypersens rxns

Question 29

clinical use of sulfonylureas

Answer 29

type 2 diabetes as monotherapy or in combo with insulin or other anti-diabetic drugs

Question 30

drug interactions of sulfonylureas | enhancing hypoglycemic effect

Answer 30

displace from binding with plasma proteins: sulfonamides, clofibrate, salicylates enhance effect on KATP channel: ethanol inhibiting CYP enzymes: azoles, gemfibrozil, cimetidine

Question 31

drug interactions of sulfonylureas decreaseing glucose lowering effect

Answer 31

inhibiting insulin secretion: beta blocker, CCB antagonizing effect on Katp channel: diazoxide inducing hepatic CYP enzymes: phenyotoin, griseofulvin, rifampin

Question 32

side effects of meglitinides

Answer 32

hypoglycemia secdonary failure weight gain

Question 33

clinical use of meglitinides take how combo or alone?

Answer 33

control postprandial hyperglycemia in pts with DM2 take orally before meal use alone or in combo with other antidiabetic drugs

Question 34

MOA biguanides (metformin)

Answer 34

activation of AMP-dep protein kinase | inhibit respiratory complex I in mitochondria

Question 35

clinical use of metformin -advantages

Answer 35

most common oral agent for DM2, first line advantages: -taken orally, no hypoglycemia, no weight gain, decreased risk of micro and macro vascular complications, superior glucose lowering efficacy

Question 36

AE and contraindications of metformin

Answer 36

GI complications decreased B12 absorption lactic acidosis, especailly with hypoxia, renal and hepatic insufficiency contraindicatied in pts with HF and copd, renal fialure, alcholism and cirrhosis

Question 37

MOA thiazolidinediones effects of MOA

Answer 37

ligand of PPAR-y nuclear receptor which dimerizes with RXR binds to PPRE effects of PPARy activation increased GLUT4 in skeletal muscle and adipocytes increased IRS1,2, PI3K = increased insulin sensitivity increased adiponectin = increased insulin sensitivity decreased: NFK-B, AP-1, PEPCK (RL step gluconeogensis)

Question 38

pk of thiazolidinediones -taken how effects when and persist how long

Answer 38

orally takes 1-3 months for full effect effects persist after drugs elminated for weeks-months

Question 39

metabolization of thiazolidinediones - pioglitazone - rosiglitazone

Answer 39

metabolized by liver pioglitazone by CYP2C8 and CYP34A rosiglitazone by CYP2C8 and CYP2C9 (rosie from lake was a 2 from neck up and 8-9 from neck down)

Question 40

clincial use TZDs

Answer 40

``` type 2 diabetes alone or in combo delay progression of prediabetes to DM2 euglycemi drugs (no hypoglycemia when used alone) ```

Question 41

AE TZDs

Answer 41

exacerbation heart failure link to increased risk bladder cancer osteoporisis increased TC and LDL-C

Question 42

other effects of SGLT2 inhibitors

Answer 42

``` osmotic diuresis weight loss reduced BP reduced plasma uric acid no hypoglycemia when used alone ```

Question 43

how should flozins (SGLT2 inhibitors) be taken | and clinical use

Answer 43

orally before first meal once a day | adjunct to diet and exerceise in adults with DM2

Question 44

AE SGLT2 inhibitors

Answer 44

hypotension hypoveolemia (orthostatic HTN, dizziness, syncope) UTI (can lead to urosepsis and pyelonephritis) increased LDL-C renal function impairment ketoacidosis hyperkalemia

Question 45

hyperkalemia can form in which pts taking SGLT2 inhibitors

Answer 45

pts with impaired renal fnct | htose taking ACEIs, ARBs, and K+ sparing diuretics

Question 46

MOA of miglitol and acarbose

Answer 46

competivie inhibtion of a-glycosidases

Question 47

clinical use of miglitol and acarbose does not cause

Answer 47

DM2 monotherapy or in combo take orally at mealtime no hypoglycemia or weight gain

Question 48

AE of miglitol and acarbose

Answer 48

malabsorption, flautulence, diarrhea, abdominal bloating

Question 49

drug interactions of miglitol

Answer 49

decrease absorption of propranolol and ranitidine Miggy ran the game proper

Question 50

drug interaction of acarbose

Answer 50

decrease absorption of digoxin dont dial phone digits in ACAR(bose)