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MET3a > Prescribing in Hepatology > Flashcards

Prescribing in Hepatology Flashcards

1
Q

Functions of the liver?

A 
Immunological
Metabolic Homeostasis
Storage
Bile production
Biosynthesis - albumin, clotting factors
Metabolism of drugs, ammonia
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2
Q

Phase 1 metabolism in the liver

A

By cytochrome p450 enzyme family

  • prodrugs are activated by the enzyme
  • enzyme can reduce the bioavailability of some drugs= first pass metabolism
  • can deactivate drugs
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3
Q

Phase 2 metabolism in the liver

A

CONJUGATION

- makes metabolite water soluble so it can be excreted

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4
Q

Symptoms of acute alcohol withdrawal

A 
Anxiety
Nausea
Vomiting
Confusion
Anorexia
Delirium tremens if severe
Seizures
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5
Q

CIWA-Ar Chart

A

Used to manage alcohol withdrawal
List of different symptoms with scores to determine severity
Score determines Tx
If >10 = give benzodiazepine

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6
Q

What is the first line benzodiazepine?

A

Chlordiazepoxide

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7
Q

When is lorazepam used?

A

In alcohol withdrawal if patient has cirrhosis

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8
Q

Benzodiazepines metabolism

A
  • metabolised via p450 enzyme in liver
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9
Q

MOA of benzodiazepines

A
  • sedative by enhancing GARA (gamma aminobutyric acid) which is an inhibitory neurotransmitter
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10
Q

Side effects of benzodiazepines

A 
Addiction in LT use
Suicide ideation
Falls/fracturs in elderly
Confusion
Drowsiness
Respiratory Depression
Hallucinations
Rare = agitation
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11
Q

Chlordiazepoxide properties

A

Long acting

Half life 6-30 hours

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12
Q

How to prescribe chlordiazepoxide?

A

First 24 hours - PRN, 25-50mg depending on CIWA-Ar chart, 2 hourly, maximum dose in 24 hours is 250mg

Day 2 = stop PRN basis, calculate total administered in first 24 hours and prescribe in 4 divided doses reducing by 20% or 10mg QDS daily until reaches 0

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13
Q

Lorazepam

A

Short acting
12 hour half life
Minimal risk of excess which is needed if liver failure
If cirrhosis

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14
Q

How to prescribe lorazepam?

A

PRN 1-2mg 2 hourly as per CIWA-Ar

If >10mg/24 hours reviews as this is maximum

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15
Q

What dose of chlordiazepoxide is equivalent to 1mg of lorazepam?

A

25mg

10mg of diazepam

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16
Q

Dangerous side effect of benzodiazepines to look out for?

A

Respiratory depression if in excess (either overdose or accumulated in body) - ITU!

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17
Q

Treatment for seizures from acute alcohol withdrawal

A

Lorazepam 2-4mg slow IV up to 8mg in 24 hours max

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18
Q

Treatment for psychotic symptoms from acute alcohol withdrawal

A

haloperidol
0.5-1.5mg IM or 1-2mg PO 2-3 times daily
Only in combination with chlordiazepoxide

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19
Q

Pabrinex

A

High strength vitamin B and C

To prevent Wernicke’s and Korsakoff’s

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20
Q

Dose of pabrinex

A

2 pairs IV TDS for 3-5 days

Prophylactic dose = 1 pair TDS

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21
Q

Side effects/cautions with pabrinex

A

Anaphylaxis/allergic reaction
Need to be careful if giving a glucose infusion at the same time as pabrinex or thiamine (e.g. if diabetic patient) as can deplete thiamine reserves = Wernicke’s

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22
Q

What to give after Pabrinex course?

A

Need to continue supplementation

  • thiamine 100mg TDS PO
  • dietician review and nutritional supplements
  • Vitamin B co-strong needed if poor nutritional intake but risk of refeeding
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23
Q

Signs of decompensated liver cirrhosis

A 
Spider naevi
Jaundice
Palmar Erythema
Splenomegaly
Gynaecomastia
Encephalopathy
Ascites
Bleeding varices
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24
Q

How to go about treating encephalopathy?

A

Build up of toxins/ammonia in the body

  • treat triggers of it
  • eliminate ammonia through gut
  • target for 2 soft stools a day
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25
Q

Lactulose MOA

A

Osmotic laxative
Local osmotic effect in colon = increased faecal bulk & peristalsis
High doses = reduction in colon pH reducing absorption and increasing excretion of ammonia

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26
Q

How to prescribe lactulose?

A

Prophylaxis vs treatment different
Need to ensure patient is producing 2 loose bowel motions per day
- can take 48-72 hours to work
- 15-50ml TDS varied dose

27
Q

Compliance issues with lactulose?

A

Bloating
Abdominal Pain
Nausea
Bad taste

28
Q

Phosphate enemas

A

Alongside lactulose as a STAT if patient in encephalopathic
Means lactulose is fast acting
When patient passes stools - PRN BD

29
Q

Rifaxmin MOA

A

Antibiotic
Inhibits bacterial DNA dependent RNA polymerase
Poorly absorbed from GI tract so not much systemic effect
Resistance high risk
Metabolism by liver
Used alongside lactulose or recurrent encephalopathy only

30
Q

Dose of rifaximin

A

550mg BD

31
Q

Side effects of rifaximin

A 
Constipation
Abdominal pain
Ascites
Hyperkalaemia
Neutropenia
Depression
Dizziness
32
Q

Issues with rifaximin

A

Withhold if patient is on systemic ABs

- interacts with ciclosporin

33
Q

Drugs for ascites

A

Diuretic combination = furosemide and spironolactone

Also = fluid and sodium restriction, improve nutrition, manage liver disease

34
Q

Furosemide MOA

A

Loop diuretic
Bind to chloride site of Na-K-2Cl co-transporter in ascending LOH
Inhibits sodium reabsorption increasing diuresis

35
Q

Furosemide dose

A

40mg OM
Up to 80mg BD if possible
Give second dose at lunch not night as will keep needing to go toilet

36
Q

Risk of furosemide

A

Tend to avoid IV usage as risk of AKI

Hypokalaemia

37
Q

Spironolactone MOA

A

Aldosterone Antagonist

Inhibits aldosterone dependent Na-K exchange site in DCT

38
Q

Dose of spironolactone

A

100mg
Up to 400mg if possible
Much higher doses than HF dose

39
Q

Side effects of spironolactone

A

Painful gynaecomastia
Consider switch to amiloride but less effective in cirrhosis patients
Hyperkalaemia

40
Q

Monitoring need for diuretics

A
  • monitor BP as can reduce it =consider falls risk

- when use spiro + furosemide K+ problems cancel out but good to monitor

41
Q

Treatment for gastro-oesophageal varices

A

Endoscopy

Then vasoconstrictor start = terlepressin

42
Q

MOA of terlepressin

A 
Vasopressin analogue
4-6 hour half life
Reduced effect on kidneys and diuresis
Contraction of smooth oesophageal muscle = compression of varices
Increase in blood pressure
43
Q

What patients to be cautious with when on terlepressin?

A 
Those with:
HTN - especially if renal HTN or vessel sclerosis
Atherosclerosis
Cardiac dysrhythmias
Coronary insufficiency!
44
Q

What to monitor with terlepressin?

A

ECG
BP
Serum sodium and potassium
Fluid balance

45
Q

Dose of terlepressin

A

2mg IV bolus
Then 1-2mg every 4-6 hours until bleeding controlled
Continue until haemostasis achiever or up to 5 days
Can taper dose down

46
Q

Beta blockers

A

Prophylaxis post variceal bleed

Non cardioselective preferred as increased effect on portal pressures

47
Q

MOA of beta blockers

A

Competitive antagonists of beta adrenergic beta receptor sites

48
Q

What beta blocker is used for variceal bleed proophylaxis?

A

Carvediol

- complementary mild anti-alpha 1 adrenergic activity

49
Q

Types of injury drugs can cause to the liver?

A

Cholestatic
Hepatic
Acute liver failure

50
Q

Paracetamol overdose

A

7.5g = acute liver toxicity
3 weeks of 4g/day = ALP rise in 1/3 patients
24-72 hours marked elevations in ALT and AST
48-96 hours symptoms appear

51
Q

Symptoms of paracetamol overdose

A

Jaundice
Confusion
Hepatic failure
Potentially death

52
Q

What is the mechanism of hepatocellular injury?

A

Forms a toxin = N-acetyl-p-benzoquinoneimine

  • conjugated with glutathione, detoxified and secreted
  • high doses = acculumation of toxin
53
Q

RF of drug induced hepatocellular injury

A

Increase p450 metabolism - due to chronic alcohol or certain drugs
Decreased glutathione = fasting, malnutrition, alcoholism

54
Q

Treatment for paracetamol overdose

A

N-acetylcysteine IV infusion

  • restores glutathione levels or acts as alternative conjugation substrate
  • antioxidant properties
55
Q

Dose of IV NAC

A
  • within 8 hours of overdose effective
  • glucose 5% as diluent or NaCl 0.9%
  • first infusion = add 150mg/kg to 200mL over 1 hour
  • second = 50mg/kg to 500mL over 4 hours
  • third = 100mg/kg to 1000mL over 16 hours
  • may need continuation at third dose and rate
56
Q

Hep B treatment target

A

HBV DNA to undetectable levels and ALT to normalise

57
Q

Hep B treatment drugs

A

Tenofovir or entercavir to suppress virus
Then PEG-IFN but no longer used

To suppress not cure so need lifelong Tx

58
Q

Tenofovir

A

Nucleotide monophosphate analogue
Competitive inhibition
Replaces deoxyribonucleotide substrate in HBV DNA and acts as a chain terminator
Eliminated through kidney
Safe in pregnancy
Faster than entecavir at reducing viral DNA initially but after 1 year similar

59
Q

Entecavir

A

Competes with dexoyguanosine triphosphate inhibiting reverse transcription of HBV DNA
Eliminated through kidney
Toxic in pregnancy
Women of childbearing age should not be started on it

60
Q

Side effects/cautions with antivirals

A
  • LT = nephrotoxicity with lactic acidosis, Fanconi syndrome, reduction in bone mineral density
  • tenofovir = higher nephrotoxicity
  • monitor creatinine and phosphate levels
61
Q

Hep C Treatment

A

Short course oral anti-viral - very effective!
Tx based on genotype as multiple agents available and 6 possible genotypes
Also based on if patient has cirrhosis
In combination with ribavarin?
Frequent monitoring

62
Q

NS5A inhibitors

A

End in svir

Inhibit RNA polymerase

63
Q

NS5B inhibitors

A

End in buvir

Inhibit RNA polymerase

64
Q

NS3/4A protease inhibitors

A

End in previr

MET3a (38 decks)

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