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Clinical Pharmacology > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Describe the normal profile of plasma insulin throughout the day

A

Peaks at mealtimes with basal levels inbetween

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2
Q

In a normal person, what triggers an increase in insulin?

A
  • increased glucose
  • incretins (GLP-1, GIP)
  • glucagon
  • parasympathetic activity (M3)
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3
Q

In a normal person, what triggers a decrease in insulin?

A
  • decreased glucose
  • cortisol
  • sympathetic activity (alpha 2)
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4
Q

What is the role of insulin?

A
  • Decreased hepatic glucose output by inhibiting gluconeogenesis
  • Inhibits glycogenolysis
  • Promotes uptake of fats
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5
Q

What level of glucose in a random plasma glucose test would suggest diabetes?

A

plasma glucose _>_11 mmol/L

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6
Q

What are some of the symptoms of diabetes?

A
  • polyuria
  • polydipsia
  • weight loss
  • fatigue/ lethargy
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7
Q

What are some risk factors for developing type 2 diabetes?

A
  • Obesity - 80/85% risk
  • Family history
  • Ethnicity
  • Poor diet
  • Drugs - thiazide/ thiazide like diuretics, glucocorticoids, Beta blockers
  • Low birth weight (some evidence)
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8
Q

What 2 blood measurements are usually taken when monitoring diabetics?

A
  • Blood glucose - immediate measure of glucose
  • HbA1c- glycated Hb, reflets the average blood sugar over last 10-12 weeks
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9
Q

Why must insulin be given parenterally?

A

Insulin is a protein so would be digested in the gut if given orally

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10
Q

What form of insulin is given to patients in the UK today?

A

Recombinant form of human insulin (bacteria/ yeast)

or, enzymatic modification of porcine

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11
Q

What is the usual formulation of insulin given?

A

100 U/ mL

(although 300 and 500 U/mL are available)

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12
Q

How do you administer insulin?

A
  • Routinely delivered by subcutaneus injection
  • To; upper arms, thighs, buttocks, abdomen
  • Can be given intravenously for emergency treatment
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13
Q

When is concentration of insulin in plasma highest after meals?

When would you administer insulin around meal times?

A

Greatest 2-3 hours post meals

Administer 15-30 mins prior to meals

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14
Q

Why must you change the site of administration of insulin injections?

A

Repeated injection at the same site can cause lipdystrophy

(atrophy/ hypertrophy of lipid profile around the site changes absorption)

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15
Q

What are the different preparations of insulin?

(onset of action, peak of action, duration, class)

A
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16
Q

In which patients would you avoid giving insulin to?

A
  • Hypoglycaemic patients
  • Lipohypertrophic patients
  • Lipoatrophic patients
  • Patients with renal impairment

All have a risk of hypoglycaemia

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17
Q

In which patients do you have to use insulin with caution?

A
  • increased doses on patients with steroids
  • use with caution if on other hypoglycaemic agents
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18
Q

What is the benefit of delivering insulin via a pump?

A
  • reduces long term cost
  • less errors in dosing
  • less change of hypoglycaemia
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19
Q

What is basal bolus dosing for insulin?

A

A bolus dose is given around mealtimes- rapid acting e.g. aspart

A long acting (basal) dose is given to maintain basal levels - long acting e.g. glargine

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20
Q

When would you suspect diabetic ketoacidosis?

A

Blood glucose >11 mmol/L AND

  • infection
  • stress/ trauma
  • poor insulin adherance
  • adverse drug reaction
  • ketosis
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21
Q

What is the primary treatment for treating diabetic ketoacidosis?

A

Fluids are the priority, followed by insulin

22
Q

What is the secondary treatment for DKA

A

After fluids and insulin give…

Glucose and potassium

23
Q

Why do you need to give potassium in DKA?

A

Due to acidosis there is reciprocal movement of H+(into cells) and K+ (out of cells)

K+ movement out of cells causes eventual loss that will need to be replaced

Always monitor with an ECG due to changes in potassium

24
Q

What pathological changes happen in type 2 diabetes?

A
  • A reduction in sensitivity to insulin into cells
  • Insulin resistance initally overcome by an increase in pancreatic insulin secretion
  • Eventual decrease in insulin receptors and decrease in GLP-1 secretion
  • Glucotoxicity from fatty acids and ROS can cause Beta cell dysfunction
25
Q

How can you treat type II diabetes non-pharmacologically?

A
  • Lifestyle (can be reversed!)
  • Surgery (bariatric)
  • Education
26
Q

What is the first line pharmacological of treatment for type II diabetics?

A

Metformin (Biguanide)

27
Q

How does metformin work?

A
  • Decreases hepatic glucose output but reducing gluconeogenesis and glycogenolysis
  • Increase glucose utilisation in skeletal muscle
  • Suppresses appetite to limit weight gain
28
Q

What are the side effects of metformin.

When would you not prescribe metformin?

A

Side effects:

  • GI upset
    • Nausea
    • Vomiting
    • Diarrhoea
  • Lactic acidosis (rare)
  • Excreted unchanged by kidneys so stop if eGFR <30mL/min
29
Q

When would you be careful about prescribing metformin due to drug-drug interactions?

A

Patients on:

  • ACEi
  • Diuretics
  • NSAIDs
  • Any drug that may impair renal function e.g. thiazide like diuretics
  • Drugs that increase glucose may limit effectiveness
30
Q

What is the mechanism of action of sulfonylureas? (SU)

A

Stimulates Beta cell pancreas insulin secretion by blocking ATP K+ channels

  • blocking K+ channel causes membrane depolarisation
  • VOCC open → Ca2+ influx into cell causes insulin vesicle secretion

(needs some residual pancreatic function)

31
Q

What is the name of the most commonly used sulfonylurea?

A

Gliclazide

32
Q

What are the side effects of sulfonylureas?

A
  • Weight gain due to anabolic effect of insulin (not suitable for all patients)
  • GI upset
    • Nausea and vomiting
    • diarrhoea
  • Hypoglycaemia if given with other agents
  • Hypersensitivity reactions (rare)
33
Q

When should you prescribe sulfonylureas with caution?

A
  • Other hypoglycaemic agents
  • Hepatic impairment
  • Renal impairment
  • Thiazide like diuretics increase glucose so can reduce SU action
34
Q

What is the mechanism of action of thiazolinediones (glitazones) in treating type II diabetes?

A
  • Insulin sensitisation in muscle and adipose decreases hepatic glucose output
  • Activate PPAR-y causing changes in gene transcription
  • Turns glucose to triacylglyceride
  • Causes weight gain

Used less frequently than other agents

35
Q

Name the most common glitazones?

A
  • Pioglitazone
  • Rosiglitazone
36
Q

When are some of the risks of glitazones and when should they be used with caution?

A

Risks:

  • GI upset
  • fluid retention
  • fracture risk
  • CVD concerns
  • Bladder cancer

Use with caution: other hypoglycaemics

37
Q

What is the mechanism of action of SGLT-2 inhibitors (gliflozins)

A
  • Inhibit SGLT2 in PCT causing decreased glucose absorption from tubular filtrate
  • Increases glucose excretion in urine
  • Causes modest weight loss
  • Risk of hypoglycaemia is low
38
Q

Name the 2 most common SGLT2 inhibitors?

A

Dapagliflozin

Canagliflozin

39
Q

Which patients do you use SGLT2 inhibitors in?

When should you prescribe with caution?

A

Used in Type 1 diabetics at risk of DKA

Used in Type 2 diabetics as an add on therapy

Prescribe with caution in:

  • prescribed other antihypertensives
  • other hypoglycaemic agents
40
Q

What are some of the side effects of SGLT2 inhibitors?

A
  • UTI and genital infection
  • Thirst and polyuria (due to diuretic effect)
41
Q

What are some of the physiological effects of GLP-1 (Glucagon like peptide)

A
42
Q

What is the mechanism of action of DPP-4 inhibitors (gliptins)?

A
  • Prevent incretin degredation → increases plasma incretin
  • Incretins are glucose dependent so only act post-prandially (don’t stimulate insulin at normal blood glucose levels) therefore have low hypoglycaemic risk
  • Suppress appetite - good for weight control
43
Q

What are some of the side effects/ risks of DDP-4 inhibitors?

A
  • GI upset
  • Small risk of pancreatitis
  • Avoid use in pregnancy
44
Q

When should you prescribe DDP-4 inhibitors ( gliptins) with caution?

A
  • other hypoglycaemic agents
  • drugs that increase glucose (thiazides, loop diuretics) can oppose effects of gliptins
45
Q

Name 2 commonly used DDP-4 inhibitors (gliptins)

A
  • Sitagliptin
  • Saxagliptin
46
Q

Explain how GLP-1 receptor agonists work

A
  • Mimick effects of incretins (GLP-1)
  • Activates GLP-1 receptors (not degraded by DPP-4)
  • Promotes satiety and weight loss
47
Q

Name two GLP-1 receptor agonists

A
  • Exenatide
  • Liraglutide
48
Q

What are some side effects of GLP-1 agonists, when would you use with caution?

A

Side effects:

  • GI upset
  • GORD
  • Stop if eGFR <30mL/min

Use with caution with other hypoglycaemics

49
Q

What is diabulimia?

A

A problem with diabetics not using insulin to control their weight

Eating disorder

50
Q

Why swallow tablets whole when giving modified release preparations?

A

Coating of tablets causes modified release

Chewing tablet will stop modified release effect

Clinical Pharmacology (25 decks)

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