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Diabetes P2 Flashcards

(85 cards)

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1
Q

What does intake of carbohydrates tell the liver?

A

-inh glycogenolysis
-inh gluconeogenesis
-stim glycogen synth
-stim GLC uptake
-stim glycolysis

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2
Q

What does protein intake tell the liver?

A

-stim AA transport in liver and muscles
-stim protein synth
-inhibit release of AA from muscles

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3
Q

What ion is affected by insulin?

A

-potassium
-favors movements of K into cells
-lots of insulin treatment causes hypokalemia (K+ leaves blood for cells)
-also promotes growth and development

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4
Q

What is IGF?

A

-insulin-growth factor
-backup system for insulin
-IGF1 and IGF2
-secreted by liver, cartilage and tissue in response to growth hormone
-its receptor is very similar to insulin receptor

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5
Q

What is another name for IGFs?

A

-somatomedins

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6
Q

What are glucose transporters?

A

-helps glucose enter cell
-1-7
-GLUT1 in brain = insulin insensitive
-GLUT2 in beta cells
-GLUT4 in muscle and adipose

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7
Q

How are insulin secretions regulated?

A

-direct feedback of plasma glucose levels on beta cells or alpha cells
-tells the pancreas to secrete either glucagon or insulin to raise or lower blood glucose

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8
Q

What are three major drug groups that regulate insulin secretions?

A

-sulfonylurea
-biguanides
-thiazolidinediones

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9
Q

how does the sympathetic and parasympathetic NS affect the pancreas?

A

-symp: inhibits insulin secretion
-parasymp: increases insulin secretion

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10
Q

What GI secretions regulate insulin secretions?

A

-glucagon
-glucagon derivatives
-secretin
-cholecystokinin
-gastric inhibitory peptide

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11
Q

What is the incretin effect?

A

-when glucose is given orally it better stimulates insulin production than IV

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12
Q

What are two important incretin hormones?

A

-Glucose-dependent insulinotropic polypeptide (GIP)
-glucagon-like peptide 1

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13
Q

What are some characteristics of glucagon-like polypeptide 1?

A

-synth in L cells in ileum and colon
-stimulates insulin, suppresses glucagon
-slows gastric emptying
-increase beta cell mass
-increases insulin sensitivity
-long-term effects not fully known
-for type 2 diabetes
-30-31aa, derived from proglucagon

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14
Q

What are some characteristics of glucose-dependent insulinotropic peptide?

A

-42aa
-derived from proGIP
-secreted by K cells in duodenum and jejunum

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15
Q

What is GLP-1 degraded by?

A

-dipeptidyl peptidase 4 (DPP-4)
-after parenteral admin

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16
Q

What are two drug types that avoid DPP4?

A

-GLP-1 receptor agonists
-DPP4 inhibitors

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17
Q

What is the mechanism of action of insulin?

A

-binds to tyrosine kinase receptors
-phosphorylation cascade = translocate GLUT4 to PM
-induces transcription of genes for catabolism
-promotes the uptake of K+ into cells

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18
Q

What does insulin tell the muscle?

A

increase:
-glc transport
-glycolysis
-glycogen
-protein synth

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19
Q

What does insulin tell the adipose tissue?

A

increase
-glc transport
-increase lipogenesis
-decrease intracellular lipolysis

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20
Q

How is insulin given to best mimic regular non-diabetic insulin?

A

-combinations of short-acting and long/intermediate-acting
-short-acting gives the peak
-intermediate-acting gives the basal level

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21
Q

Difference between lispro and regular insulin and glulisine?

A

-lispro given 15min before meal and peak effect at 30-90min after
-regular insulin peak effect 50-120 min later
-glulisine can be taken 15 min before to 20 min after meal

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22
Q

What is lente insulin?

A

-amorphous insulin
-zinc ion
-slow onset but better sustained
-cannot be given IV

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23
Q

What is isophane NHP insulin?

A

-neutral protamine Hagedorn insulin
-crystalline zinc
-protamine: delays onset and prolongs effectiveness

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24
Q

Where in the body is the insulin pump?

A

-the fatty layer under the skin

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25
What is ultralente insulin?
-zinc insulin suspension -large particles that dissolve -delayed onset
26
what is insulin glargine?
-precipitation at the injection site -prolonged action -no peak gives baseline insulin
27
What is detemir insulin?
-insulin with a FA complex -slow dissolution
28
What are the adverse effects of insulin?
-hypoglycemia (insulin overdose, alcohol) -hypokalemia -lipodystrophy -weight gain -injection complications
29
What are the signs and symptoms of hypoglycemia?
-tachycardia -confusion -sweating -drowsiness -coma -death
30
How is type 2 diabetes mellitus treated?
-lifestyle changes -oral hypoglycemic drugs (lower glucose levels, may cause hypoglycemia)
31
What are oral hypoglycemics?
-agents useful in type 2 diabetes treatment -newly diagnosed pt respond well -never indicated for T1D
32
What are the drug classes for T2D?
-sulfonylureas -biguanides -thiazolidinediones -alpha-glucosidase inhibitors -meglitinides
33
What are sulphonylureas?
-work on ppancreas -stimulates the release of insulin from islet cells -increase receptor sensitivity -adverse effect: hypoglycemia from not enough food or too much meds
34
What is a common issue of insulin?
hypoglycemia is the number one problem with drugs that promote insulin release
35
MOA of sulfonylureas
-release insulin from beta cells -binds to SUR1 subunit and block the ATP-sensitive K+ channel in b-cell -> depolarization causes Ca influx -> insulin secretion -also reduce glucagon
36
What is the pharmacokinetics of sulfonylureas?
-binds to plasma proteins -met and exc in liver
37
tolbutamide
-sulfonylureas -short-acting -associated with 2.5x increase in cardiovascular mortality -banned in canada
38
glyburide
-sulfonylureas -intermediate-acting
39
glipizide
-sulfonylureas -intermediate-acting
40
glimepiride
-sulfonylureas -long-acting
41
What are the adverse effects of sulfonylureas?
-weight gain -hyperinsulinemia -hypoglycemia -hepatic or renal insufficiency would make risks worse -may increase cardiovascular events
42
Which organelle is important in diabetes?
-mitochondria -we inherit only mothers mitochondria -if mother has type 2 diabetes, then you will probably have type 2 diabetes
43
**slide 60 drug interactions**
remember any two in each box
44
Which drugs reduce the effects of sulfonylureas?
-diuretics -corticosteroids -niacin
45
Which drugs increase the effects of sulfonylureas?
-beta-blockers -monoamine oxide inhibitors -salicylates
46
Metformin
-biguanide -insulin sensitizer
47
What are biguanides?
-works on the liver and occasionally muscle/adipose -decrease hepatic gluconeogen
48
What is the MOA of metformin?
-reduces plasma glucose -inh hepatic gluconeogen -slows abs of sugars -reduces hyperlipidemia -decreases appetite -reduces cardiovascular mortality
49
What are the adverse effects of metformin?
-hypoglycemia in combination medication -rarely lactic acidosis
50
Why can you not have hypoglycemia when on metformin?
-does not promote insulin secretion
51
What is AMP Kinase?
-regulator for metabolism
52
What is the inhibitory pathway of AMPK?
decreases in ATP:AMP -> activates AMP kinase -> inhibits ATP consuming pathways (protein, glycogen, FA synthesis) -> consumes less ATP -> brings ATP:AMP ratio back
53
What is the activating pathway from AMPK?
stimulates ATP producing pathways -glycolysis, beta-ox, glc uptake -produces more ATP -brings ATP:AMP back up
54
How does metformin work in a hepatocyte?
-enters cell via SLC22A1 transporter -> inhibits mito complex 1 -> less ATP -> high AMP -> gluconeogenesis suppressed -> reduced glucogenic enzymes -> reduced gene expression -also suppresses fat metabolism and improves insulin receptor function
55
What are a-glucosidase inhibitors?
-for type 2 diabetes -work on GI tract -oligosaccharide derivatives -inhibits an enzyme of the intestinal brush border
56
Acarbose
-a-glucosidase inhibitor -poorly absorbed -stays in intestinal lumen
57
miglitol
-a-glucosidase inhibitor -absorbed and excreted by kidney -effects intestinal lumen
58
MOA of a-glucosidase inhibitors
-taken beginning of a meal -inhibits a-glucosidase = membrane-bound enzyme in the intestine -hydrolyses oligosach to monosach -> absorbed -> blunts post-prandial glucose rise -> rises modestly and stays slightly elevated
59
What are thiazolidinediones?
-work on the liver and peripheral tissue -insulin sensitizers -increase insulin sensitivity of PPARy receptors in cell nucleus -does not promote insulin secretion -insulin required for function -decreases insulin resistance by inhibiting gluconeogen
60
What are the adverse effects of thiazolidinediones?
-fluid retention -headache -weight gain -NOT hypoglycemia
61
pioglitazone
-thiazolidinedione -can be taken with insulin
62
rosiglitazone
-thiazolidinedione
63
What is the MOA of thiazolidinediones?
-activate peroxisome proliferator-activated receptor-gamma -when ligand binds -> increases insulin sensitivity in adipocytes, hepatocytes and muscle -elevates HDL levels
64
What is PPAR-y?
-when ligand is bound, it regulates adipocyte production, FA secretion, and glucose met -liver: decreases FA and gluconeogen, increases insulin action -muscle: increases insulin action -liver: increases b-cell mass and insulin secretion -pancreas: increases FA uptake, decreases lipolysis
65
Which drug can you not take with rosiglitazone?
-insulin -causes severe edema
66
What are meglitinides?
-work on pancreas -new class of oral hypoglycemics -work similar to sulfonylureas -stimulate release of insulin from islet cells -short-acting
67
What does secretagogue mean?
-a substance that causes another substance to be secreted
68
repaglinide
-meglitinide analog -secretagogue
69
nateglinide
-meglitinide analogs -secretagogue
70
MOA of meglitinide analogs?
-bind to ATP sensitive K channels -> mimick prandial and post-prandial insulin release -> very short acting
71
What are the adverse effects of meglitinide analogs?
-hyopglycemia (but less than sulfonylureas -drugs that inhibit CYP3A4 prolong effects -interactions with other drugs
72
What is incretin therapy?
-naturally occurring hormones secreted by the gut -increases when food is digested
73
what two drugs block cyp3a4?
-fluconazole -erythromycin
74
What does DPP-4 enzymes do?
rapidly degrades active incretins when released
75
How does januvia (sitagliptin) work?
-food ingested -> incretins released -> januvia inhibits DPP-4 -> less incretins degraded -> increases insulin and reduces glucagon
76
What is SGLT 1 and 2?
-both: responsible for renal glucose reabsorption -1: minor; in intestinal mucosa and proximal straight tubule in nephron -2: major; in proximal convoluted tubule in nephron
77
How do sodium-glucose cotransporters work?
-let in sodium and glucose into cell
78
What is the difference between the three types of SGLTs?
-SGLT1:in GI and kidney; high affinity cotransporter -SGLT2: in kidney; low affinity cotransporter -SGLT3: throughout body; not glucose transporter
79
What are some SGLT2 inhibitors?
-dapagliflozin -canagliflozin -empagliflozin -ipragliflozin
80
dapagliflozin
-SLGT2 inhibitor
81
canagliflozin
-SLGT2 inhibitor
82
empagliflozin
-SLGT2 inhibitor
83
What are the adverse effects of SLGT2 inhibitors?
-increase in genital infections (high glucose environment = bacteria grow) -decrease in BP and weight -increase in cancer: but not rly anymore?
84
What is the difference between standard and intensive treatment of diabetes?
more frequent hypoglycemic events
85
What is HbA1c used for?
-hemoglobin A1c -good measure of glucose control

Pharm 2 (11 decks)

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