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Clinical Pharmacology And Therapeutics > Endocrine > Flashcards

Endocrine Flashcards

1
Q

What is T1 diabetes

A

A progressive destruction of islet B cells

Onset usually <40 years

Autoantibodies may be detected

Tendency to ketosis

Treated with exogenous insulin combined with a healthy diet and exercise

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2
Q

What are the different types of insulin preparations

A

Short acting:
- soluble
- analogues (rapid-acting: lispro, aspart)

Intermediate acting:
- isophane (complexed with protamine)

Long acting:
- insulin zinc suspension
- analogues (glargine, detemir)

Biphasic:
- mix of short and intermediate acting insulins

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3
Q

What is DAFNE

A

Dose adjustment for normal eating
- adjusting insulin regimens to suit the individual lifestyle

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4
Q

What can increase insulin requirements

A

Stress
Infection
Puberty (GH)
Accidental or surgical trauma
Pregnancy post 1st trimester

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5
Q

Why does insulin injection site need to be rotated

A

To limit Lipodystrophy

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6
Q

What is T2 diabetes

A

Relative insulin deficiency (impaired B cell function) and / or insulin resistance

  • impaired insulin signalling pathways
  • nutrient oversupply, cellular stress and inflammation
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7
Q

How is T2DM managed

A

Diet and lifestyle changes

Agree on a glycaemic target (HbA1c)

Cardiovascular risk management

Management of CKD

Pharmacotherapy

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8
Q

How should people with T2DM adjust their lifestyle

A

Exercise
Smoking cessation

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9
Q

When should metformin be cautioned

A

Patients with renal impairment

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10
Q

What should be given first line if metformin is inappropriate in T2DM

A

DPP-4 inhibitor
Pioglitazone
Sylphonlyurea
SGLT2 inhibitor

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11
Q

When is an SGLT2 inhibitor given with metformin

A

If the CVD/ CHF/ QRISK2 is >10%

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12
Q

When is insulin given in T2DM

A

After triple therapy has not been effective

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13
Q

What is metformin

A

MoA not clear, described as an insulin sensitiser
May activate AMP kinase

  • reduces hepatic glucose production, reduces lipid stores, increases liver sensitivity to insulin
  • increases peripheral glucose uptake and utilisation
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14
Q

What are sulphonylureas

A

Inhibit islet B cell ATP sensitive potassium channels - increase insulin secretion

Cause weight gain as a side effect, hypoglycaemia especially with long acting

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15
Q

What is pioglitazone

A

Activates nuclear peroxisome proliferator activated receptors

An insulin sensitiser - enhances glucose utilisation in tissues and reduces insulin resistance

Reduces hepatic glucose output
Increases glucose uptake and utilisation in skeletal muscle
Increases fatty acid uptake into adipose cells

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16
Q

Adverse effects of pioglitazone

A

Liver toxicity (monitor)
Avoid in heart failure
Increased risk of bladder cancer and bone fractures

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17
Q

What do incretins (GLP-1) do

A

Stimulate glucose induced insulin release
And inhibit glucagon release

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18
Q

What are some benefits of incretin based therapies

A

Reduce gastric emptying
Promote satiety
Reduce hepatic glucose production

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19
Q

What do SGLT2 inhibitors do

A

Inhibit renal glucose reabsorption and increase urinary glucose excretion which reduces blood glucose

Cardiovascular and renal benefits

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20
Q

Side effects of SGLT2 inhibitors (flozins)

A

Genitourinary infections
Increased urination, thirst
Hypovolaemia, hypotension
DKA

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21
Q

What are complications of diabetes treatment

A

Hypoglycaemia (insulin SUs)

Diabetic ketoacidosis: lack of insulin; SGLT2 inhibitors

Hyperosmolar hyperglycaemic state (HHS, T2DM)

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22
Q

What are Microvascular complications

A

Damage of the small vessels
1. Retinopathy (eye)
2. Nephropathy (kidney disease)
3. Neuropathy (nerve damage)

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23
Q

What are Macrovascular complications

A
  1. CVD
  2. Stroke
  3. Peripheral vascular disease
24
Q

What are the individual HbA1c targets

A

T1DM: 40mmol/mol (adults)

T2DM: 40mmol/mol when using diet/lifestyle and 1 drug and not hypoglycaemic
T2DM: 53mmol/mol when using drugs that can cause hypoglycaemia

25
Q

Ways of reducing CV risk in T2DM

A

Glycaemic control (HbA1c)
Lifestyle: diet, exercise, weight management, alcohol, smoking cessation
BP control
Use of statins for primary prevention (atorvastatin 20mg with QRISK>10%)

26
Q

What are the target BP for T1DM

A

135/85
But 130/80 is presenting with albuminuria or 2 more more features of metabolic syndrome
Use a first line ACEi or an angiotensin receptor blocker

27
Q

What is the target BP for T2DM

A

140/90
130/80 if CKD is present
Use a first line ACEi or angiotensin receptor blocker

28
Q

How to prevent Microvascular complications

A

Good glycaemic control
Control of hypertension (ACEi, ARB, CCB)

29
Q

How to manage macrovascular risk factors

A

Good glycaemic control
Control hypertension
Control dyslipidaemia
Use of anti platelet drugs in CVD

30
Q

Metabolic Signs and symptoms of hypothyroidism

A

Cold intolerance
Weight gain
Constipation
Reduced appetite
Reduced BMR
Reduced sweating
Reduced body core temp

31
Q

CNS signs and symptoms of hypothyroidism

A

Depression
Confusion
Poor memory
Difficulty concentrating
Cretinism (perinatal) - mental retardation and dwarfism

32
Q

Resting CVS signs and symptoms of hypothyroidism

A

Decreased heart rate
Decreased arterial BP

33
Q

Why are newborns tested for TSH and T4

A

To test for congenital hypothyroidism as can cause dwarfism and mental retardation

34
Q

How is hypothyroidism diagnosed

A

Thyroid function test
Primary: reduced T3 and T4; increased TSH
Secondary: reduced T3, T4 and TSH

35
Q

Management of hypothyroidism

A

Synthetic thyroid hormones

Levothyroxine - first line
Liothyronine

36
Q

What is Graves’ disease

A

Most common cause of hyperthyroidism
90% of cases
Autoimmune condition in which body makes thyroid stimulating immunoglobulins which activate the thyroid gland to produce and release thyroid hormones

37
Q

Symptoms of Graves’ disease

A

Nervousness
Palpitations
Weight loss
Tremor
Sweating
Heat intolerance
Goitre

38
Q

Diagnosis of hyperthyroidism with thyroid function test

A

Elevated T3 and T4 and decreased TSH (tumour / Graves’ disease)

Radioactive isotope scan - increased uptake in Graves’ disease

Presence of thyroid autoantibodies

39
Q

Management of hyperthyroidism

A

Anti thyroid drugs
Radioiodine
Surgery (thyroidectomy)

40
Q

What are anti thyroid drugs

A

Carbimazole and propylthiouracil
- decrease production of thyroid hormones by inhibiting iodination and coupling processes

Takes several weeks for a clinical response

41
Q

How is levothyroxine prescribed (replacement for T4)

A

Adults aged 18-49 are given a loading dose of 50-100ug/d
Increased by 25-50 ug every 4 weeks until plasma TSH has normalised
Maintenance dose is 100-200ug/d

Adults 50+ or with cardiac disease are given a loading dose of 25ug/d
This is increased by 25ug every 4 weeks until plasma TSH has normalised.
Maintenance dose is 50-200ug/d

42
Q

What are the cautions with levothyroxine

A

May worsen or uncover angina.
If angina, a B blocker may be prescribed

43
Q

How is liothyronine prescribed (replacement for T3)

A

Maximum effect is 24h, disappears at 24-48h
Not used routinely, rapid onset can induce heart failure

Used in severe hypothyroid states when rapid response is desired

44
Q

What are some counselling points for levothyroxine

A

Life long condition therefore life long treatment

Take daily dose at least 30min before breakfast, caffeine containing drinks or other medications

Consult GP if experiencing angina or pre existing angina gets worse

Report symptoms such as diarrhoea, nervousness, tremors or insomnia as can indicate overdose

Requirements may change during pregnancy

TSH levels need measuring every 3 months until stabilised, then yearly thereafter

45
Q

Why are non selective B blockers given alongside anti thyroid drugs

A

Propranolol, nadolol, metoprolol

These reduce the actions of catecholamines and provide rapid symptomatic relief of tremor, palpitations and anxiety and have no effect on thyroid hormone release

CCI can be used is B blockers are contraindicated

46
Q

Explain the dose titration approach that is used with anti thyroid drugs

A
  • only anti thyroid drugs are used
  • doses are adjusted to achieve normalisation of thyroid hormone production
47
Q

Explain the block and replace approach used with anti thyroid drugs

A

Where anti thyroid drugs are given with thyroxine replacement

48
Q

How is carbimazole prescribed in a dose titration approach

A

Initial dose - 15-40mg daily until euthyroid - 4-8 weeks
Gradually reduce to maintenance dose 5-15mg daily

49
Q

How is carbimazole prescribed in a block and replace approach

A

40-60mg daily
Plus levothyroxine 50-150ug daily

50
Q

Side effects of carbimazole

A

Rashes and pruritus are common
Rare complication - neutropenia and agranulocytosis (bone marrow suppression)

Patients are counselled to report signs and symptoms suggestive of infections eg sore throat
WBC count performed if clinical evidence of infection

Increased risk of congenital malformations - effective contraception

Risk of acute pancreatitis

51
Q

Who should not be prescribed carbimazole

A

Patients with a history of acute pancreatitis

52
Q

What is the second line choice if carbimazole is inappropriate

A

Propylthiouracil

  • initial dose 200-400mg daily until euthyroid roughly 4-8 weeks
  • gradually reduce to maintenance dose 50-150mg daily
53
Q

When switching from carbimazole to propylthiouracil what is the equivalent dose

A

Carbimazole 1mg is considered equivalent to propylthiouracil 10mg but the dose may need adjusting according to the response

54
Q

What is the recommendation for use of anti thyroid drugs in pregnancy

A

Can be used but at lowest dose to control hyperthyroid state

High doses can cause foetal goitre and hypothyroidism

55
Q

Pros and cons of radioactive iodine as a treatment

A

Pros:
- Safe, effective and cost effective treatment for Graves’ disease
Reduced rate of recurrence of hyperthyroidism

Cons:
- not for use in a patient trying for a family in the next 4-6 months
- not for use in patients with a suspected malignancy

56
Q

When is surgery used to treat hyperthyroidism

A

If radioactive iodine and anti thyroid drugs are unsuitable
Indicated if malignancy is suspected or there are obstructive symptoms

Clinical Pharmacology And Therapeutics (7 decks)

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