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Gwen - Diabetes > Clinical Pharmacology > Flashcards

Clinical Pharmacology Flashcards

1
Q

What is the mechanism of action of metformin?

A
  • Lowers blood glucose by increasing the response (sensitivity) to insulin
  • Suppresses hepatic glucose production (glycogenolysis and gluconeogenesis),
  • Increases glucose uptake and utilisation by skeletal muscle
  • Suppresses intestinal glucose absorption.
  • It reduces weight gain and can induce weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes mellitus.

DECREASES GLUCOSE PRODUCTION AND ABSORPTION

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2
Q

Why does metformin cause lactic acidosis?

A

Inhibits lactic acid uptake by liver

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3
Q

What are contraindications to metformin use?

A
  • General anaesthesia - should be withheld on the day of surgery
  • Intra-venous contrast x-rays - should be withheld for at least 2 days
  • AKI/eGFR < 36
  • Illness
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4
Q

What are adverse effects of metformin use?

A
  • GI upset - diarrhoea, vomiting, abdo pain
  • Lactic acidosis
  • B12 malabsorption
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5
Q

When would you consider not giving someone metformin?

A

eGFR < 36 ml/min - risk of lactic acidosis

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6
Q

What is the mechanism of action of sulphonylureas?

A

Sulfonylureas act by increasing insulin secretion from pancreatic islet cells. In order for them to be effective, there must be some residual insulin secretion.

PROMOTES INSULIN SECRETION

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7
Q

What are the contraindications (absolute and relative) for sulphonyurea use?

A
  • Acute porphyria
  • Renal impairment
  • Hepatic impairment
  • Pregnancy and breast feeding
  • Elderly (avoid long acting sulfonylureas)
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8
Q

What are the main side effects of sulphonylureas?

A
  • Hypoglycaemia
  • Weight gain
  • Gastro-intestinal upset
  • Hepatic impairment
  • Hypersensitivity reaction (rash, liver disease)
  • Rarely haematological abnormalities - agranulocytosis
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9
Q

When (during the course of a day) should sulphonylureas be given?

A

Before meals - Absorption may be postponed by eating

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10
Q

What is the mechanism of action of DPP-4 inhibitors?

A

Inhibition of DPP-4 activity causes an increase in incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide). This increases glucose dependent insulin secretion and reduces glucagon secretion.

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11
Q

What are examples of sulphonylureas?

A
  • Gliclazide
  • Glimepiride
  • Glipizide
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12
Q

What are example of DPP-4 inhibitors?

A
  • Sitagliptin
  • Vildagliptin
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13
Q

What are contraindications (absolute and relative) to DPP-4 inhibitors?

A
  • Pregnancy / breast feeding
  • Elderly
  • Renal impairment
  • Hepatic impairment
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14
Q

What are adverse reactions to DPP-4 inhibitors?

A
  • Gastrointestinal upset
  • Oedema
  • Hepatic toxicity (vildagliptin)
  • Pancreatitis
  • Upper respiratory tract infection / nasopharyngitis
  • Stevens-Johnson syndrome

Can cause hypoglycaemia.

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15
Q

What is the mechanism of action of GLP-1 agonists?

A

GLP-1 agonists act by mimicking the action of GLP-1, which causes increased insulin secretion, reduced glucagon secretion and slows gastric emptying.

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16
Q

What are the contraindications (absolute and relative) to GLP-1 use?

A
  • Pregnancy / breast feeding
  • Gastrointestinal disease e.g. inflammatory bowel disease
  • Elderly
  • Hepatic impairment
  • Renal impairment
17
Q

What are examples of GLP-1 agonists?

A
  • Exenatide
  • Liraglutide
18
Q

What are adverse effects of GLP-1 agonists?

A
  • Gastrointestinal upset
  • Pancreatitis
  • Injection site reactions
  • Anaphylaxis

Can cause hypoglycaemia.

Tend to reduce weight, which may be beneficial, but may be problematic if too rapid.

19
Q

What is the mechanism of action of SGLT-2 antagonists?

A

SGLT-2 is primarily responsible for mediating glucose reabsorption in the kidneys, and is expressed in on the epithelial cells lining the first segment of the proximal convoluted tubule. It promotes approximately 90% of the kidney’s glucose reabsorption.

By inhibiting SGLT-2, the kidneys’ reuptake of glucose from the glomerular filtrate is reduced and subsequently lower the glucose level in the blood and promote the excretion of glucose in the urine (glucosuria)

WORKS AT KIDNEY

20
Q

What are the main side effects of SGLT-2 antagonists?

A
  • Genital mycotic infections
  • UTIs
  • Increased urinary frequency
21
Q

What is the mechnism of action of insulin?

A
  1. Increases glucose uptake by insulin-sensitive tissues (e.g. adipose, muscle)
  2. Increases glycogen synthesis in muscle and liver
  3. Increases amino acid uptake into muscle
  4. Increases protein synthesis
  5. Increases triacylglycerol synthesis in adipocytes and liver - stimulates lipogenesis and inhibits lipolysis
  6. Inhibits the enzymes of gluconeogenesis in the liver
  7. Promotes K+ ion entry into cells
22
Q

Whenis caution needed when using insulin?

A
  • Renal impairment - insulin requirements may be reduced
  • Hepatic impairment - insulin requirements may be reduced
  • Pregnancy and breast feeding - insulin requirements may change – specialist input required
23
Q

When putting someone on a sliding scale of insulin, what fluids would you use?

A

5% dextrose with 10 mmol/L potassium

24
Q

What can cause lactic acidosis in individuals taking metformin?

A
  • Intercurrent illness that causes metformin accumulation (e.g. worsening renal impairment)
  • Increased lactate production (e.g. sepsis, hypoxia, cardiac failure)
  • Reduced lactate metabolism (e.g. liver failure).
25
Q

What is the mechnism of action of Thiazolidinediones (glitazones)?

A

Thiazolidinediones are insulin sensitisers. They lower blood glucose by activating the gamma subclass of nuclear peroxisome proliferator-activated receptors (PPARγ). This induces genes which enhance insulin action in skeletal muscle, adipose tissue and the liver, with increased peripheral glucose uptake and utilisation and reduced hepatic gluconeogenesis.

Thiazolidinediones do not stimulate pancreatic insulin secretion, hence do not cause hypoglycaemia.

INCREASES INSULIN SENSITIVITY

26
Q

What are the main adverse reactions to thiazolidinediones?

A
  • GI upset
  • Anaemia
  • Neuro - dizziness, headache, disturbed vision
  • Oedema
  • Cardiac failure
  • Increased bladder cancer risk
  • Severe liver toxicity

Gwen - Diabetes (11 decks)

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