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Endocrinology > T2DM Drugs > Flashcards

T2DM Drugs Flashcards

1
Q

Describe insulin release.

A

Glucose enters ß-cells through GLUT2

Glucose phosphorlyates to glucose-6-phosphate in cytoplasm by glucokinase increasing ATP:ADP ratio

ATP closes KATP channel by acting on Kir6 suninits
(ADP opens channel by acting on SUR1 subunit)

Closure of KATP channel depolarises the cell membrane which opens voltage-gates-Ca channels increasing intracellular Ca

Intracellular Ca releses insulin from secretory vesicles

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2
Q

Is more insulin produced in response to oral glucose of IV glucose.

Why?

A

Oral glucose produces more insulin

Oral glucose stimulates release of GLP-1 from stomach which amplifies insulin and delays gastric emptying

GLP-1 is quickly inactivated by DPP-4 enzyme

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3
Q

What is the mechanism of action of metformin?

A

Insulin sensitiser

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4
Q

What is the first line medication in T2DM?

A

Metformin

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5
Q

What is metformin’s effect on weight?

A

Can reduce weight

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6
Q

Which T2DM drugs carry a risk of hypoglycamia?

A

Sulphonylureas

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7
Q

What are some side effects of metformin?

A

GI upset

Lactic acidosis

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8
Q

What doses of metformin are used?

A

Start at 500mg

Titrate up to maximal 1000mg BD as needed

If eGFR

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9
Q

What are some contraindications to metformin?

A

eGFR<30 (CKD G4)

Creatinine>150

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10
Q

Name a sulphonylurea.

A

Gliclazide

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11
Q

How do sulphonylureas work?

A

Block ADP binding on KATP channel (SUR1 subunit) which prevents opening of the channel, depolarising the membrane and releasing insulin

(this works independently of glucose and so hypoglycaemia is a risk)

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12
Q

What are some side effects of sulphonylureas?

A

Weight gain

Headache

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13
Q

What are the indications of sulphonylureas?

A

Second line add on to metformin

First line if metformin intolerant or contraindicated (poor renal function)

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14
Q

What is pioglitazone?

A

Thiazolidinedione (TZD) / PPAR-y agonist

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15
Q

How do PPAR-y agonists work?

A

Bind to transcription factor PPAR-y which alters gene transcription and up regulates insulin action

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16
Q

What are some side effects of PPAR-y agonist?

A

Fluid retention

Reduced bone density

17
Q

What are the contraindications to PPAR-y use?

A

Heart failure

Renal failure

Over 65s (reduced bone density)

18
Q

What do SGLT-2 inhibitors do?

A

Inhibit glucose reabsorption resulting in glucose excretion

19
Q

What are some side effects on SGLT-2 inhibitors?

A

Thrush

UTI

20
Q

What are contraindications to SGLT-2 inhibitor use?

A

Renal failure

21
Q

Name an SGLT-2 inhibitor.

A

Dapagliflozin

22
Q

What are gliptins? How are they administered?

A

DDP-4 inhibitor

Oral

23
Q

Name a DDP-4 inhibitor.

A

Vildagliptin

24
Q

How do DDP-4 inhibitors work?

A

Inhibit DDP-4 preventing GLP inactivation which amplifies insulin release

25
Q

Which of DDP-4 inhibitors and GLP agonists are

  1. injected and PO?
  2. more potent and why?
A
  1. DDP-4 inhibitors oral and GLP agonists injected

2. DDP-4 inhibitors are less potent as they require endogenous GLP production which is low in T2DM

26
Q

What drugs are associated with an increased risk of pancreatitis and pancreatic cancer?

A

GLP agonists

DDP-4 inhibitors

27
Q

What class of drug is exenatide?

A

GLP-1 receptor agonist

28
Q

Name a GLP-1 receptor agonist.

A

Exenatide

29
Q

How do GLP-1 receptor agonists work?

A

Amplify insulin release by acting on GLP-1 receptor

30
Q

What are GLP-1 receptor agonists effect on weight?

A

Weight loss via reduced appetite and delayed gastric emptying

31
Q

Name the injected therapies available to T2DM patients.

A

GLP-1 receptor agonists

Insulin

32
Q

Name the 7 drug classes used in T2DM, give an example and its administration route.

A

Metformin, oral

Sulphonylurea, gliclazide, oral

PPAR-y agonist, pioglitazine, oral

SGLT-2 inhibitor, dapraflozin, oral

DDP-4 inhibitor, vildagliptin, oral

GLP-1 receptor agonist, exenaide, injected

Insulin, injected

Endocrinology (10 decks)

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