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CP1 Therapeutics > Metabolic disorders > Flashcards

Metabolic disorders Flashcards

1
Q

Insulin: MoA, indications, contraindications, side effects

A

Insulin is secreted by pancreatic beta cells in response to elevated blood glucose. It acts to modulate glucose absorption from the blood, therefore lowering blood glucose levels.

Generally, it increases anabolic activity (e.g. glycogen/protein/lipid synthesis) and decreases catabolic acitivity (e.g. glycogenolysis, lipolysis) - as energy stores are plentiful.

Indications: T1DM and T2DM which is resistant to other antidiabetic medications

Side effects: Weight gain, hypoglycaemia, lipodystrophy at the injection site

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2
Q

Sulphonylureas: MoA, indications, contraindications, side effects

A

MoA: Increase insulin secretion from pancreatic beta cells

Indications:

  • 2nd line for T2DM who cannot tolerate metformin or can be used in addition to metformin when needs esculate
  • Short acting formulations have decreased risk of hypoglycaemia

Contraindications:

  • Cause weight gain → not best choice for overweight patients
  • Caution in mild-moderate renal impairment as can cause hypoglycaemia
  • Severe CV comorbidity

Side effects:

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3
Q

Metformin: MoA, indications, contraindications, side effects

A

MoA: Enhance the effect of insulin. Activate AMP kinase

Indications:

  • Obese patients (as do not cause weight gain)
  • Do not cause hypoglycaemia

Contraindications:

  • Renal impairment - increased risk of lactic acidosis

Side effects:

  • GI effects: Diarrhoea, nausea, vomiting
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4
Q

Meglitinide analogues: MoA, indications, contraindications, side effects

A

MoA: Enhance insulin secretion from pancreatic beta cells

Indications:

Contraindications:

  • Severe renal or hepatic impairment

Side effects:

  • Risk of hypoglycaemia
  • Weight gain
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5
Q

Thiazolindiediones: MoA, indications, contraindications, side effects

e.g. pioglitazone

A

MoA: Activate PPAR-gamma, changing gene expression, and causing insulin like effects

  • Enhances glucose ultilsation
  • Reduces hepatic glucose output
  • Increases skeletal muscle glucose transporters

Indications:

  • 2nd line option when metformin cannot be used
  • Can be used in combination with other drugs if esculating treatment is required

Contraindications:

  • Heart failure
  • Liver failure

Side effects: !RISKS!

  • Increases CV risk
  • Increased risk of bladder cancer
  • Weight gain
  • Risk of bone fractures (osteoporosis)
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6
Q

Dipeptidylpeptidase-4 inhibitors (DPP-4i or Gliptins): MoA, indications, contraindications, side effects

A

MoA: Inhibit GLP-1 degradation which leads to increased glucose-dependent insulin secretion

Indications:

  • 2nd line treatment, for when metformin cannot be tolerated
  • Should be used in place of thiazolindiediones (pioglitazone) when further weight cause would cause/exacerbate problems associated with high body weight

Contraindications:

  • Liver failure
  • Moderate/severe renal failure

Side effects:

  • GI complaints
  • Pancreatitis
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7
Q

Glucagon-like peptide-1 agonists (GLP-1 or incretins): MoA, indications, contraindications, side effects

A

MoA: Stimulate the GLP-1 receptor, stimulating insulin release

*Given SC

Indications:

  • 3rd line option - when metformin and 2 other oral drugs are not tolerated/effective/contraindicated

Contraindications:

  • GI mobility disorders

Side effects:

  • Nausea
  • Pancreatitis
  • Increased risk pancreatic cancer
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8
Q

Sodium-glucose co-transporter-2 inhibitors (SGLT-2): MoA, indications, contraindications, side effects

A

MoA: Cause glycosuria through inhibition of the renal SGLT-2 transporter in the PCT

Indications:

  • Can be used as monotherapy is metformin is inappropriate/not tolerate
  • Can be used in combination if treatment needs esculating - preferred use
  • Does NOT cause weight gain

Contraindications:

  • Age restrictions apply
  • If used in combination with insulin/other diabetic drugs then can stimulate insulin secretion. Insulin dose may need adjustment

Side effects:

  • Increased risk of DKA
  • Increased risk of UTI and yeast infections (more sugar for bacterial growth)
  • Polyuria and dehydration
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9
Q

DDP-4, GLP-1, insulin and glucagon relationship diagram

*AIDS UNDERSTANDING OF MECHANISMS*

A
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10
Q

Outline the guidance for treatment of T2DM

(flow chart)

A
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11
Q

Describe how blood pressure might be controlled in a diabetic patient

A
  • Target BP = < or equal to 140/80 mmHg if there are no additional complications
    • < or equal to 130/80 mmHg if kidney/eye/cerebrovascular complications are present
  • Monitor BP at least annually and provide diet/lifestyle advice
  • ACEi first line for most - usual NICE hypertension guidelines
  • Calcium channel blockers are first line for women of child bearing potential
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12
Q

Describe the pharmocological strategies for the prevention of diabetic nephropathy

A
  • Annual testing for microalbuminuria, urinary protein and serum creatinine
  • ACEi (or ARB) given to diabetic patients with nephropathy that is causing proteinuria/microalbuminuria
    • NOTE: ACEis can potentiate the hypoglycaemic effects of insulin and oral antidiabetic drugs
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13
Q

Describe lipid management in diabetic patients

A

Patients with diabetes are at higher risk of developing cardiovascular disease

CV risk can be assessed using:

  • Weight
  • BP
  • Lipids
  • Smoking
  • Hx of CV disease
  • Microalbuminuria

Atorvastatin 20mg is offered for the primary prevention of CVD with a QRISK score > 10 %

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14
Q

HMG CoA reductase inhibitors: MoA, indications, contraindications, side effects

A

MoA: Inhibit hepatic cholesterol synthesis through inhibition of HMG-CoA reductase. Induce LDL receptor expression leading to decreased LDL levels and elevated HDL levels

Indications:

  • First line for hypercholesterolemia
  • Patients with atherosclerotic CVD (coronary heart disease, stroke, peripheral vascular disease)

Contraindications:

  • Pregnancy and breast feeding
  • Active liver disease
  • Muscular disease

Side effects:

  • GI effects
  • Headache
  • Hepatic toxicity (CytP450 mediated degradation)
  • Muscle toxicity - check CK levels for elevation if muscle pain is experienced
    • Rhabdomyolysis may occur, increasing the risk of AKI
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15
Q

Fibrates: MoA, interactions, contrainteractions, side effects

A

MoA: Activates PPAR-alpha increasing lipoprotein lipase activity. ↓ LDL and TGs, ↑ HDL

Indications:

  • Second line for hyperlipidaemia

Contraindications:

  • Hepatic impairment
  • Renal insufficiency
  • Gall bladder disease

Side effects:

  • Dyspepsia
  • Cholelithiasis
  • Myopathy
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16
Q

Binding agents/resins (colesystyramine): MoA, indications, contraindications, side effects

A

MoA: Bind bile acids in the small intestine, interrupting enterohepatic circulation (increased excretion of bile acids). ↓ LDL, ↑ HDL, ↑ TGs (slightly)

Indications:

  • In addition to statins
  • Cholestasis induces pruritis
  • Digitoxin toxicity

Contraindications:

  • GI obstruction
  • HyperTG
  • Interacts with digoxin, warfarin and fat soluble vitamins

Side effects:

  • Nausea, abdominal bloating and cramping
  • Myalgia
  • Increased LFTs
17
Q

Cholesterol absorption inhibitors (ezitimbe): MoA, indications, contraindications, side effects

A

MoA: Selective inhibition of cholesterol absorption at the enterocyte brush border. ↓ LDL

Indications:

  • Dual therapy with statins if LDL reduction is insufficient
  • Monotherapy when statins are contraindicated

Contraindications:

  • Co-administration with statins in active liver disease

Side effects:

  • ↑ LFTs
  • Myalgia
  • Angioedema
  • Diarrhoea
18
Q

Thioamides: MoA, indications, contraindications, side effects

Examples: Carbimazole, propylthiouracil

A

MoA: Inhibit TPO (thyroperoxidase), leading to decreased iodination and ultimately decreased production of thyroid hormone

*Due to the long half lives of thyroid hormones the inhibitory effects of the medications will not be seen for several weeks (6-8 weeks) - ‘bridging therapy’ required*

Indications:

  • Hyperthyroidism

Contraindications:

Side effects:

  • Carbimazole: Agranulocytosis, leading to leucopenia
    • If sore throat, mouth ulcers, bruising or non-specific illness is reported then a FBC should be ordered to check for leucopenia
  • Mild side effects: Nausea, headache, taste disturbance, mild skin rashes
  • Liver side effects
19
Q

Beta-blockers for symptomatic relief: MoA, indications, contraindications, side effects

A

MoA: Reduce the action of catecholamines at beta-adrenoreceptors (which are augmented by the condition, as the thyroid hormone stimulates sympathetic activity)

Indications:

  • Co-prescribed with thioamides for the reduction of tremor, anxiety and palpitations
  • Non-selective beta blockers are required for relief of tremor
  • Propranolol is safe for use in pregnancy

Contraindications:

  • Do not use in uncontrolled heart failure
  • Caution in asthma and COPD
  • Diltiazem (Ca2+ channel blocker) may be used to control tachycardia in patients who cannot take a beta blocker

Side effects:

20
Q

Levothyroxine: MoA, indications, contraindications, side effects

A

Hypothyroidism:

↑ TSH ↓ T3/T4

↓ TSH ↓ T3/T4

MoA: Converted to active metabolite T3 in the liver and kidneys. Acts to replace endogenous thyroid hormone

☆ No effects seen for 6-8 weeks ☆

Indications:

  • Hypothyroidism - titrated and then used life long
  • Dose is dependent on age, weight and gender
    • Elderly + ischaemic heart disease → 25 micrograms
  • Dose required is that which allows TSH levels to be correct
    • TSH levels correct = correct dose

Contraindications:

  • Dose decreased in elderly and patients with ischaemic heart disease

Side effects:

  • May worsen or cause diagnosis of angina

Counselling:

  • Take on an empty stomach (30 minutes before food)
  • Must not take with other medications (particularly AdCal)
21
Q

In the context of hyperthyroidism, describe the principles of ‘block and replace’ regimens

A

Block and replace regimen: Thyroid activity is blocked using high dose carbimazole. Once thyroid activity is inhibited, levothyroxine is used to replace the hormone.

Contraindications:

  • Pregnancy - high levels of carbimazole cross the placenta
22
Q

Describe the clinical uses of corticosteroids

A
  • Allergic/septic emergency: IV (empirical steroids increased mortality in septic shock)
  • Asthma, COPD: Inhaled or oral
  • Topically: Inflammatory skin conditions
  • Topically or systemically: UC and Crohn’s disease
  • Rheumatoid arthritis: Oral, SC
  • Organ transplantation (to prevent rejection)
  • Pre-term labour to induce surfactant production
  • Mineralocorticoid activities may be exploited: Postural hypotension in autonomic neuropathy
  • Improve the prognosis: SLE, temporal arteritis, polyarteritis nodosa
    *
23
Q

Describe the problems associated with the use of corticosteroids

A

Maintenance dose should be kept as low as possible, to minimise side effects.

Oral long term courses (> 3 weeks) may lead to:

  • Diabetes
    • CAUTION: Must increase insulin dose for diabetic patients on steroids
  • Osteoporosis
  • Mental disturbances
  • Peptic ulceration (especially if given in combination with NSAIDS)
  • Cataracts and glaucoma
  • Cushing’s syndrome
  • Suppression of growth in children
  • Adrenal suppression
    • CAUTION: Sudden withdrawal can cause acute adrenal insufficiency, hypotension and death
    • The exogenous corticosteroids suppress the adrenal gland. Time must be allowed for endogenous synthesis to recommence
  • Infections
    • Increased susceptibilty/severity, particularly to chickenpox

ADVICE FOR PATIENTS:

  1. Take in the morning (induce insomnia if taken at night)
  2. Carry steroid card
  3. Do not suddenly stop taking the steroids - taper the dose
  • Gradual withdrawal should be considered for the followin patients:
    • > 40 mg of prednisolone for more than 1 week
    • OR > 3 weeks of low dose treatment
    • Repeated courses
    • Repeated evening doses
    • Have taken a short course within 1 year of stopping long term therapy
    • Other causes of adrenal suppression
24
Q

Thyrotoxic crisis: Treatment

A

Thyrotoxic crisis: Can occur in patients with untreated/poorly treated hyperthyroidism. An acute hypermetabolic state, resulting from excessive thyroid hormone release, arises.

Symptoms:

  • Severe tachycardia, AF, heart failure
  • Hyperpyrexia
  • Dehydration, diarrhoea, vomiting
  • Jaundice
  • Agitation, delrium, psychosis and coma

Treatment:

  • IV fluids (for CV support)
  • Paracetamol (for hyperhtermia)
  • Propranolol
  • Thioamine - propylthiouracil: Preferred to carbimazole as it also inhibits T4 → T3
  • Iodine solution (can paradoxically reduce T4/3 secretion)
  • Hydrocortisone (inhibits T4 → T3)
25
Q

Addison’s disease: Treatment

A

Addison’s: A deficiency of corticosteroid (cortisol) and mineralocorticoid (aldosterone) production by the adrenal gland.

Treatment

Life-long replacement of:

  • Glucocorticoid: Hydrocortisone, 20 mg AM, 10 mg 6 PM
  • Mineralocorticoid: Fludrocortisone, 50 - 100 micrograms daily

CP1 Therapeutics (7 decks)

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