Unit 9 - 4 Self Taught

Front 1

zinc finger

Back 1

involved with dimerization of pairing partners; binds DNA

Front 2

ligand hormone binding

Back 2

induces a conformational change in the ligand binding domain

Front 3

in the absence of presence of a ligand..

Back 3

corepressors might bind; might release the repressors and a whole complex of additional activates acetylate histones or other things that stimulate transcription

Front 4

structure of ligands

Back 4

small and hydrophobic (cortisol, aldosterone, T3 vit D, retinoids)

Front 5

point of beales lecture

Back 5

bind to dna as homodimers, heterodimers o rmonomers; effect transcriptors by inhibition or repression; important medical targets of actions of various drugs and hormones

Front 6

statins MOA

Back 6

HMG-CoA reductase inhibitors; inhibit de novo choloesterol synthesis and deplete the intracellular supply of cholesterol; liver upregulates LDL receptors which removes LDL from blood = decreased LDL in circulation

statins also stabilize atheromas

Front 7

rhabdomyloysis

Back 7

side effect of statins (atorvastatin/HMH-CoA reductase inhibitor)

risk increases when combined w other drugs or comorbidities like hypothyroidism

Front 8

atorvastatin

Back 8

HMG-CoA reductase inhbitor

Front 9

pt welevated creatinine kinase and transaminases

Back 9

statin toxicity; rhabdomyolysis and hepatocyte injury

Front 10

muscle aches and pain with dark urine

Back 10

rhabdomyolysis 2 to statin and fibrate use

Front 11

fibrates moa

Back 11

activate LPL to remove TG from CLDL and chylomicrons thus removing it from plasma

(PPAR-alpha agonist; downregulates apoCIII to disinhibit lipoprotein lipase (which is only expressed in capillaries of skeletal muscle and adipse (Fat tissue)

increased HDL

Front 12

contraindications for fibrates

Back 12

pts with liver dz or gallbladder dz due to increased cholesterol in bile (gall stones)

Front 13

fibrates + statins

Back 13

myopathy/rhabdomyolysis (dark urine)

Front 14

bile acid sequestrants

Back 14

bind bile acid to form a complex that is excreted in the feces instead of recycled; liver upregulates LDLR to take up intracellular cholesterol to synthesize more bile acid and thus removes the cholesterol from the body

Front 15

initial plasma TG spike leading to pancreatitis

Back 15

bile binding resins (cholestyramine) side effect

Front 16

decreased absorption of fat soluble vitamins

Back 16

cholestyramine (decreased absorption of all acidic drugs)

Front 17

bloating, constipation, flatulence side effects

Back 17

cholesytramine

Front 18

drug that inhibits cholesterol absorption in gut

Back 18

ezetimibe (NPC1L1 transporter inhibition)

Front 19

ezetimibe

Back 19

NPC1L1 transporter inhibition in gut

combined with statin there is a 30% reduction in LDL

increased hepatic expression of LDL receptors due to increasd demand for bile acid synthesis

Front 20

niacin (vitamin B3)

Back 20

decreases catabolism of triacylglycerol; inhibits lipolysis in adipose tissue (primary producer of circulating free fatty acids)

decreases plasma TG -> decreased VLDL -> decreased LDL

Front 21

flushing and itching with GI upset, hyperacidity, hyperuricemia and glucose intolerance

Back 21

flushing and itching (prostaglandin mediated) with GI upset, hyperacidity, hyperuricemia and glucose intolerance = niacin side effects

if you start at very low doses with food and slowly increase the dose you can develop tolerance to the side effects while the lipid lowering effects persist

Front 22

drug in which you can develop tolerance to the side effects while lipid lowein g benefits persist

Back 22

niacin

Front 23

why might high levels of CETP be bad

Back 23

transfers cholesterol from HDL to VLDL and LDL (normally you want HDL taking cholesterol to the liver for metabolism/excretion)

prototypes; anacetrapib, dalcetrapib, evacetrapib

Front 24

exercise for management of DM

Back 24

mild to moderate exercise increases insulin sensitivity and lowers blood glucose during and after activity
intense exercise leads to stress response (glycogenolysis and gluconeogenesis can cause progressive hyperglycemia)

Front 25

C peptide

Back 25

only found in endogenous insulin

can differentiate between low sugar levels due to endogenous vs exogenous insulin

Front 26

insulin:C peptide ratio

Back 26

1:1

if blood insulin >> blood C peptide then the insulin did not come from the patients pancreas

Front 27

blood insulin > blood C peptide

Back 27

the insulin did not come from the pts pancreas

Front 28

short acting insulin

Back 28

Short-acting: onset in 45 min; peak effect in 2-4 hrs; duration of action 4-6 hrs.
a bit too slow; ideal would be about 5-15 minutes
although inconvenient, it is best administered 45-60 min before meals so that its action follows the postprandial glycemic curve. Failure to eat on time will result in an acute hypoglycemic episode
a bit too long; ideal would be ~3 hrs)
Unfortunately, it peaks later than we would like it to (outlasts the postprandial glycemic phase), so the patient must schedule between meal snacks to avoid hypoglycemia

Front 29

The higher the dose, the later the peak and longer duration

Back 29

Injected in concentrations that favor hexameric aggregates (>10-3M), which distribute slowly until the concentration in fat is <10-8M, at which regular insulin disaggregates into monomers that are readily absorbed into the capillary circulation

Front 30

intermediate insulin duration of ation

Back 30

neutral protamine hagedorn aka isophane; should only be given subcutaneously

Front 31

Analogue (Lys-Pro) insulin

Back 31

An analog of human insulin in which B28Pro - B29Lys are switched to B28Lys - B29Pro
The switch has no effect on its antigenicity, its binding, its intrinsic activity at insulin receptors, or its circulating half-life
The advantage in contrast to regular insulin, is that lyspro readily dissociates into monomers:
Onset in 15 min; peak effect in 1-2 hrs; duration of action 2-4 hrs (corresponding closely to postprandial glucose)
Can inject with meals, less risk of severe hypoglycemic episodes, better glycemic control
Peak and duration do not increase with dose

Front 32

glyburide

Back 32

insulin secretogogues (drug which stimulates the release o fendogenous insulin from pancreatic beta cells); inhibits potassium channels in b islet cells; releases insulin

Front 33

1st line tx for DM-2 pts

Back 33

metformin; oral hypoglyemic; decreases hepatic glucose output

Front 34

contraindication for metformin

Back 34

pt with renal insufficiency; metaformin is not metabolized and has a high renal clearance; GI side effects common

Front 35

acarbose

Back 35

alpha glucosidase inhibitor; delays breakdown of complex starches and sugars into monosaccharides such as glucose for transport across the brush border

Front 36

what to advise pts on acarbose in case of hypoglycemic event

Back 36

keep glucose (not sucrose) on hand bc acarbose delays absorption of sucrose, whic his found in most sweets

Front 37

pioglitazone

Back 37

activates PPAR-gamma which increases target tissue sensitivity to insulin and decrease liver glucose output; associated w weight gain and fluid retention (caution in CHF pts)

Front 38

exenatide

Back 38

glucagon like peptide-1; makes B cells more sensitive to hyperglycemia (increased insulin release)

DPP-4 inhibitors (sitagliptin) prevents catabolism of endogenous incretins

Front 39

sitagliptin

Back 39

DPP-4 inhibitors (sitagliptin, saxa-, vilda-, duto-, …) prevent catabolism of endogenous incretins

Front 40

exenatide and sitaglipitin;

Back 40

1st line tx for pts w hazardous jobs; does not cause hypoglycemia; regulation of glitzones due to potential hypoglyceimc events

Front 41

used in type 1 and 2 DM; also life threatening hyperkalemia and stress induced hyperglycemia

Back 41

insulin (lispro SA, regular, NPH intermediate, detemir LA)

Front 42

used in type 1 and 2 DM; also life threatening hyperkalemia and stress induced hyperglycemia

Back 42

insulin (lispro SA, regular, NPH intermediate, detemir LA)

Front 43

used in type 1 and 2 DM; also life threatening hyperkalemia and stress induced hyperglycemia

Back 43

insulin (lispro SA, regular, NPH intermediate, detemir LA)

Front 44

stimulates release of endogenous insulin in type 2 DM; requires islet cell function so uselss in type 1 DM

Back 44

sulfonylureas (glyburide, glimepiride, glipizide)

closes K channel in B membrane so cell depolarizes -> release of insulin via increased Ca influx

Front 45

stimulates release of endogenous insulin in type 2 DM; requires islet cell function so uselss in type 1 DM

Back 45

sulfonylureas (glyburide, glimepiride, glipizide)

closes K channel in B membrane so cell depolarizes -> release of insulin via increased Ca influx

Front 46

stimulates release of endogenous insulin in type 2 DM; requires islet cell function so uselss in type 1 DM

Back 46

sulfonylureas (glyburide, glimepiride, glipizide)

closes K channel in B membrane so cell depolarizes -> release of insulin via increased Ca influx

Front 47

used in type 1 and 2 DM; also life threatening hyperkalemia and stress induced hyperglycemia

Back 47

insulin (lispro SA, regular, NPH intermediate, detemir LA)

Front 48

Use as oral hypoglycemia; can be used in pts w/o islet function

Back 48

metformin

decreases hepatic gluconeogensis

Front 49

delayed sugar hydrolysis and glucos eabsorption lead to decreased postprandial hyperglycemia

Back 49

alpha-glucosidase (acarbose, miglitol)

Front 50

Use as oral hypoglycemia; can be used in pts w/o islet function

Back 50

metformin

decreases hepatic gluconeogensis

Front 51

used in type 1 and 2 DM; also life threatening hyperkalemia and stress induced hyperglycemia

Back 51

insulin (lispro SA, regular, NPH intermediate, detemir LA)

Front 52

stimulates release of endogenous insulin in type 2 DM; requires islet cell function so uselss in type 1 DM

Back 52

sulfonylureas (glyburide, glimepiride, glipizide)

closes K channel in B membrane so cell depolarizes -> release of insulin via increased Ca influx

Front 53

Use as oral hypoglycemia; can be used in pts w/o islet function

Back 53

metformin

decreases hepatic gluconeogensis

Front 54

stimulates release of endogenous insulin in type 2 DM; requires islet cell function so uselss in type 1 DM

Back 54

sulfonylureas (glyburide, glimepiride, glipizide)

closes K channel in B membrane so cell depolarizes -> release of insulin via increased Ca influx

Front 55

delayed sugar hydrolysis and glucos eabsorption lead to decreased postprandial hyperglycemia

Back 55

alpha-glucosidase (acarbose, miglitol)

Front 56

delayed sugar hydrolysis and glucos eabsorption lead to decreased postprandial hyperglycemia

Back 56

alpha-glucosidase (acarbose, miglitol)

Front 57

Use as oral hypoglycemia; can be used in pts w/o islet function

Back 57

metformin

decreases hepatic gluconeogensis

Front 58

Use as oral hypoglycemia; can be used in pts w/o islet function

Back 58

metformin

decreases hepatic gluconeogensis

Front 59

delayed sugar hydrolysis and glucos eabsorption lead to decreased postprandial hyperglycemia

Back 59

alpha-glucosidase (acarbose, miglitol)

Front 60

delayed sugar hydrolysis and glucos eabsorption lead to decreased postprandial hyperglycemia

Back 60

alpha-glucosidase (acarbose, miglitol)