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Cology Final thank god > Oral hypoglycemics 3 - slides 48 to 66 > Flashcards

Oral hypoglycemics 3 - slides 48 to 66 Flashcards

1
Q

What are DPP4 inhibitors?

A

Dipeptidyl peptidase 4 inhibitors
Peptidase is involved in the breakdown of GLP-1 and GIP as well as several peptides including peptide YY, neuropeptide Y, and growth hormone releasing hormone
Also involved in T-cell activation (CD26)
Serine protrease cleaves two N-terminal amino acids from peptides with proline or alanine in second position

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2
Q

What is Sitagliptin?

A

Competitive DPP4 inhibitor

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3
Q

What is Saxagliptin?

A

DPP4 inhibitor that binds covalently

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4
Q

What is Linagliptin?

A

DPP4 inhibitor that is combined with metformin

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5
Q

What is Alogliptin?

A

DPP4 inhibitor combined with metformin and pioglitazone

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6
Q

What is Vildagliptin?

A

DPP4 inhibitor that binds covalently; requires further studies on renal insufficiency

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7
Q

How well do DPP4 inhibitors inhibit DPP4?

A

They all inhibit DPP4 by > 95%

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8
Q

How are DPP4 inhibitors administered?

A

Oral

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9
Q

What can DPP4 inhibitors be combined with?

A

Can be combined with merformin, pioglitazone, sulfonylureas, and insulin

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10
Q

Metabolism of DPP4 inhibitors?

A

Excreted unchanged in the urine

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11
Q

Adverse effects of DPP4 inhibitors?

A

Few consistent adverse effects
Can see diarrhea, headaches
Angioedema, anaphylaxis, skin rash
Pancreatitis (related to GLP-1)

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12
Q

Which combination of drugs was able to reduce A1C by 2.1%?

A

Sitagliptin 50 mg and Metformin 1000 mg BID

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13
Q

Differences between GLP-1 and DPP-4 inhibition:

Enhancing insulin secretion

A

Same (+++)

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14
Q

Differences between GLP-1 and DPP-4 inhibition:

Reducing glucagon

A

GLP-1 +++

DPP4 Inhibitors ++

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15
Q

Differences between GLP-1 and DPP-4 inhibition:

Postprandial hyperglycemia

A

Same (Reduced in both)

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16
Q

Differences between GLP-1 and DPP-4 inhibition:

Gastric emptying

A

GLP-1 agonist +++

DPP4 Inhib +

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17
Q

Differences between GLP-1 and DPP-4 inhibition:

Satiety

A

GLP-1 agonist +++

DPP4 inhib None

18
Q

Differences between GLP-1 and DPP-4 inhibition:

N/V

A

GLP-1 agonist +++

DPP4 inhib None

19
Q

Differences between GLP-1 and DPP-4 inhibition:

Appetite suppressed

A

GLP-1 agonist +++

DPP4 inhib None

20
Q

Differences between GLP-1 and DPP-4 inhibition:

Weight loss

A

GLP-1 agonist ++

DPP4 inhib: None

21
Q

Differences between GLP-1 and DPP-4 inhibition:

Administration

A

GLP-1 Injectable

DPP4 Inhib Oral

22
Q

Differences between GLP-1 and DPP-4 inhibition:

Antibody formation

A

GLP-1 Yes

DPP4 No

23
Q

Differences between GLP-1 and DPP-4 inhibition:

Safety

A

GLP-1 Worry about pancreatitis

DPP4 Inhib worry about pancreatitis and allergic rxns (SJS)

24
Q

What are alpha-glucosidase inhibitors? What are some examples?

A

Competitive inhibitors of alpha-amylase and alpha-glucosidase enzymes in intestinal brush border
They decrease postprandial glucose absorption

Examples: Acarbose, Miglitol

25
Q

Comparing Acarbose and Miglitol: Metabolism/excretion?

A

Acarbose is not absorbed, metabolized by intestinal bacteria

Miglitol has saturable absorption, excreted unhanged in kidney

26
Q

Comparing Acarbose and Miglitol: Dosing

A

Both take with first bite of each meal

27
Q

Comparing Acarbose and Miglitol: Monitoring?

A

Monitor liver function with Acarbose (can cause elevated liver enzymes)

28
Q

Adverse effects of Acarbose, Miglitol?

A

Abdominal pain (21%)
Diarrhea (33%) - glucose is food for bacteria, bacteria grow
Flatulance (77%) - undigested carbohydrates in colon

29
Q

Contraindications for Acarbose, Miglitol?

A

Inflammatory bowel disease
GI obstruction or ulceration
Chronic intestinal disease

30
Q

What is Pramlintide?

A

Islet amyloid polypeptide, secreted by Islet B cells
It binds to the amylin receptor in the CNS to decrease stomach emptying, decrease glucagon release, and increase satiety
Also lowers insulin requirement (can lower dose of insulin given), can lead to weight loss

31
Q

Pramlintide dosing

A

SubQ before meals, can be given with insulin but not mixed with insulin (?????)

32
Q

Indications for Pramlintide?

A

Type 1 and Type 2 diabetes

33
Q

Adverse effects of pramlintide?

A

Nausea and hypoglycemia

34
Q

Pramlintide excretion?

A

Kidney

35
Q

What are SGLT2 inhibitors? Example?

A

Sodium-glucose transporter in the proximal tubule responsible for glucose reabsorption
SGLT1 is responsible for glucose uptake in the GI
Decreasing serum glucose, increasing weight loss

Canagliflozin, dapagliflozin, empagliflozin

36
Q

Cautions with Canagliflozin?

A

Approval requires post marketing CV outcomes trial, monitoring for pancreatitis, malignancy, hypersensitivity reactions, adverse pregnancy outcomes, and a bone safety study and 2 pediatric studies

37
Q

Adverse effects with Canagliflozin?

A 
UTI's
Vaginal yeast infections
Headache, diarrhea
Diuresis
Hypoglycemia
Decreased intravascular volume leading to orthostatic hypotension
38
Q

Cautions with Dapagliflozin?

A

FDA denied approval in 2012 citing problems with increased bladder and breast cancer risks, UTI and liver damage. Then approved in 2014.

39
Q

Adverse effects of Dapagliflozin?

A

Contraction of vascular volume
Use caution in renal impairment, if you’re on loop diuretics, and in elderly
Urinary tract infections

40
Q

Adverse effects of Empagliflozin?

A

Contraction of vascular volume
Use caution in renal impairment, if you’re on loop diuretics, and in elderly
Hypoglycemia can occur with insulin and sulfonylureas
UTI’s
Vaginal yeast infections
Increased LDL

41
Q

What is Degludec?

A

Extended form of insulin
B29 I-glutamyl spacer to hexadecanedioic acid, B30 Thr missing

42 hour duration of action

Indicated for type 1 and type 2 diabetes

Limits nocturnal hypoglycemia

Available as injector pen

Cology Final thank god (10 decks)

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