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Year 3 - Met3a > Prescribing in Hepatology > Flashcards

Prescribing in Hepatology Flashcards

1
Q

What are the functions of the liver

A
  • immunological
  • metabolic homeostasis
  • storage
  • bile production
  • biosynthesis such as albumin and clotting factors
  • metabolisms e.g. drugs, toxic products such as ammonia
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2
Q

what are the two main phases of drug metabolism in the liver

A
  • Phase 1 - metabolism by the cytochrome P450 enzyme family

- Phase 2 - conjugation

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3
Q

describe what happens in the phases of drug metabolism

A

Phase 1 - metabolism by the cytochrome P450 enzyme family

  • activates the drug/metabolites (prodrug)
  • reduces the bioavailability of the drug/metabolites (first pass metabolism)
  • deactivates the drug/metabolites

Phase 2 - conjugation
- normally makes the metabolite water soluble so that it can be excreted

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4
Q

What are the symptoms of alcohol withdrawal syndrome

A
  • anxiety
  • nausea
  • vomiting
  • confusion
  • anorexia
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5
Q

What chart is used to monitor symptoms and severity of alcohol withdrawal syndrome

A
  • CIWA-AR chart

- take the score and is used to determine the treatment that patients require

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6
Q

what happens if a patient is scoring greater than 10 on the CIWA-AR chart

A
  • given a benzodiazepine to help control the symptoms
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7
Q

What is the first line treatment for alcohol withdrawal

A
  • chlordiazepoxide is first line treatment

- lorazepam is used in patients with liver cirrhosis

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8
Q

What enzyme metabolise benzodiazepines

A
  • metabolised in the liver via CYP450
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9
Q

How do bezodiazepines work

A
  • produce a sedative effect through enhancing gama-aminobutyric acid (GABA) - an inhibitory neurotransmitter
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10
Q

What are the common side effects of bezodiazepines

A
  • confusion
  • drowsiness
  • respiratory depression
  • hallucinations
  • paradoxical effects
  • agitation
  • high risk of addiction with long term use
  • associated with suicide ideation
  • falls and fractures int he elderly
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11
Q

what is the 1st line choice on benzodiazepine that is used

A

Chlordiazepoxide - long acting

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12
Q

What is the half life of chlordiazepoxide

A
  • half life of 6-30 hours with active metabolites

- accumulation half lives of 10-18 hours and 21-78 hours

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13
Q

Describe how the drugs are managed in the first 24 hours and on day 2 of alcohol withdrawal

A 
chlordiazepoxide 
First 24 hours 
- prescribed on PRN section of chart 
- 25-50mg 
 - 2 hourly as per CIWA- AR 
- maximum dose in 24 hours - 250mg - R/V if greater doses required

Day 2

  • total dosing in first 24 hours is used to set detox regimen
  • after first 24 hours stop the chlordiazepoxide prescribed on a PRN basis
  • calculate the total benzodiazepines administered during the first 24 hours, prescribe in 4 divided doses and reduce by approx 20% or 10mg QDS daily
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14
Q

Why do you give lorazepam instead of chlordiazepoxide when the person has cirrhosis

A
  • liver function is impaired therefore you don’t want to give chlordiazepoxide as it has a long half life and therefore can accumulate and might cause respiratory depression
  • lorazepam has a short half life of 12 hours therefore there is a minimal risk of excessive accumulation
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15
Q

How do you prescribe lorazepam on the chart

A
  • Prescribed on PRN section of chart. 1-2 mg, 2 hourly, As per CIWA-Ar,
  • If doses greater than 10 mg/24 hrs – R/V patient
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16
Q

How much chlordiazepoxide equals 1mg of lorazepam

A

• Chlordiazepoxide 25mg (approximately) = Diazepam 10mg = Lorazepam 1mg

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17
Q

What is a severe form of alcohol withdrawal

A
  • delirium tremens
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18
Q

What can high doses of benzodiazepines cause

A
  • respiratory depression therefore transfer to the ITU
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19
Q

How do you treat seizures in alcohol withdrawal

A
  • Lorazepam 2-4mg slow IV up to a maximum dose of 8mg in 24 hours
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20
Q

How do you treat psychotic symptoms of 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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21
Q

what is also prescribed for alcohol withdrawal

A

Pabrinex

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22
Q

What is pabrinex

A
  • this is a high strength mixture of vitamin B and C
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23
Q

What is the treatment dose of pabrinex

A

Treatment dose: 2 pairs IV pabrinex TDS for 3-5 days

Prophylactic dose: 1 pair TDS

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24
Q

What are the side effects of pabrinex

A
  • risk of anaphylaxis/allergic reaction

Caution - glucose infusion before pabrinex/thiamine may deplete thiamine reserves and precipitate wernickes

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25
Q

What is pabrinex used to treat

A

Wernickes korakoff syndrome

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26
Q

What would you use after completing the pabrinex course

A
  • Thiamine 100mg TDS PO
  • A dietician review and nutritional supplements such as Fresubin may also be required
  • vitamin B co-strong in those with poor nutritional intake and risk of refeeding
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27
Q

Who do you give vitamin B co-strong in

A
  • poor nutritional intake

- risk of refeeding

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28
Q

what is encephalopathy

A

• Build up of toxins/ammonia in the body

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29
Q

What is the target of encephalopathy

A

2 soft stools a day

- need to eliminate ammonia through the gut

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30
Q

Name some symptoms of encephalopathy

A
  • marked confusion
  • stuporous
  • neuromuscular disturbances
  • asterxis
  • hyperreflexia
  • impaired thinking
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31
Q

What do you use to treat encephalopathy

A
  • Lactulose
  • phosphate enemas
  • rifaximin - only in recurrent encephalopathy
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32
Q

How does lactulose treat encephalopathy

A
  • Osmotic laxative
  • local osmotic effect in the colon - there is increased faecal bulk and peristalsis
  • high doses lead to a reduction in colonic pH, reducing absorption of and increasing excretion of ammonia
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33
Q

what is the downside of lactulose in treatment of encephalopathy

A
  • can take up to 48-72 hours to work
  • compliance issues - side effects include bloating, abdominal pain, nausea and taste
  • dose varies from 15ml-50ml TDS dependent on patient
34
Q

when are phosphate enemas given for treatment of encephalopathy

A

Given alongside lactulose as a STAT if patient is encephalopathic

35
Q

What does phosphate enemas function as

A
  • functions as a fast acting osmotic laxative
36
Q

What does rifaximin do

A

Antibiotic - inhibits bacterial DNA dependent RNA polymerase

37
Q

How is rifaximin used in encephalopathy

A
  • gets rid of any gut bacteria
  • poorly absorbed from the GI tract
  • metabolised by the liver
  • dose is 550mg BD
  • prescribed only in recurrent encephalopathy
38
Q

What are the side effects of rifaximin used in encephalopathy

A
  • constipation
  • abdominal pain
  • ascities
  • hyperkalaemia
  • neutropenia
  • depression
  • dizziness
  • withheld if patient is receiving systemic antibiotics
  • interacts with ciclosporin
39
Q

What drug does rifaximin interact with

A

interacts with ciclosporin

40
Q

What is ascites

A
  • Build up of fluid in the peritoneum
41
Q

How do you treat ascites

A
  • furosemide

- spironolactone

42
Q

What do patients also benefit from when treating ascities

A
  • Improvement in nutritional status
  • Fluid / dietary sodium restriction
  • Management of underlying liver disease
43
Q

How does furosemide work when treating ascites

A
  • Binds to the chloride site of the Na-K-2Cl co-transporter in the ascending Loop of Henle
  • Inhibits sodium reabsorption, increasing diuresis
44
Q

What dosage should furosemide be given in in ascites

A

• Started at 40 mg OM, increased up to 80 mg BD if

possible (second dose at lunchtime- so patient are not up all night going to the toilet )

45
Q

What do you have to be cautious of when treating ascites using furosemide

A
  • IV usage in ascitic patients due to the risk of AKI
46
Q

What is the mechanism of action of spironolactone

A

Aldosterone antagonist

• Inhibits aldosterone-dependent Na-K exchange site in the distal convoluted renal tubule

47
Q

What is the dosage of spironolactone used in ascites

A
  • Normally started at 100 mg OM, increased to 400 mg if possible
  • Much higher doses than those used in heart failure
48
Q

What do you have to be careful of in spironolactone use in ascites

A
  • can cause painful gynaecomastia
  • consider switch to amiloride
  • but this is less effective in cirrhosis patients so ideally want to keep them on spironolactone
49
Q

What are the side effects of furosemide

A
  • can reduce patients blood pressure
  • can cause hypokalemia
  • can cause hyponatremia
  • AKI
50
Q

What are the side effects of spironolactone

A
  • can red patients blood pressure
  • can cause hyperkaelima
  • can cause hypernatremia
  • AKI
51
Q

furosemide and spironolactone are …

A

• Complementary when used in combination

52
Q

what is the treatment for variceal bleed

A
  • Initial treatment is in endoscopy
  • patient is then started on a vasoconstrictor
  • first line use at Barts is terlipressin
53
Q

What is the half life of terlipressin

A
  • long half life of 4-6 hours and a reduced effect on the kidneys and diuresis
54
Q

how does terlipressin work

A
  • acts on oesophageal varices by contraction of smooth oesophageal muscle causing compression of the varices
55
Q

What are the side effects of terlipressin

A
  • hypertension
  • atherosclerosis
  • cardiac dysrhthmias or coronary insufficiency
56
Q

What can terlipressin do to blood pressure

A
  • can cause an increase in blood pressure which can increase more in those with renal hypertension or blood vessel sclerosis
57
Q

What do you need to monitor when using terlipressin

A
  • ECG
  • monitor blood pressure
  • serum sodium, potassiuma and fluid balance
58
Q

Describe the dosage of terlipressin

A

• Initially 2mg by intravenous bolus
• Then 1mg-2mg every four to six hours, until the bleeding
is controlled
• NICE and BSG recommend continuing treatment until haemostasis achieved or for up to 5 days
• Dose can be tapered down

59
Q

what are beta blockers used for in varices

A
  • they are prophylaxis
60
Q

how do beta blockers work

A

Beta blockers are competitive antagonists that block the
adrenergic beta receptor sites
• Non-cardio selective beta-blockers preferred due to increased effect on portal pressures

61
Q

What is the preferred beta blocker in varices

A

Carvedilol preferred due to complementary mild anti-alpha 1 adrenergic activity

62
Q

what should you ask in the history if you think it is drug induced liver injury

A

Drug handling by the liver
• Is the drug metabolised by the liver?
• Is the drug toxic to the liver in overdose?

The type of hepatic injury
• Cholestatic
• Hepatitic
• Acute liver failure

Drug interactions
• Side effects, pharmacodynamics, pharmacogenetics

Any pre-existing liver disease or complications?

63
Q

How much paracetamol can cause acute liver toxicity

A

Single 7.5 g dose can cause acute liver toxicity

64
Q

How much paracetamol is needed to cause an ALP rise

A

• Three weeks of 4g/day (licensed dose) can cause ALP

(3xULN) rise in one third of patients

65
Q

what markers rise in an overdose of paracetamol

A
  • there is marked elevations in serum ALT and AST
66
Q

what clinical symptoms can arise in an overdose of paracetamol

A
  • Jaundice
  • confusion
  • hepatic failure
  • potentially death
67
Q

How does paracetamol lead to acute liver failure

A
  • paracetamol is conjugated with glutathione, detoxified and secreted
  • this forms N-acetyl-p-benzoquinoneimine
  • this high dose leads to accumulation of the toxic metabolite
68
Q

What are the risk factors of a paracetamol overdose

A
  • increased metabolism of P450 system
  • certain drugs
  • chronic alcohol use
  • decrease glutathione
  • fasting
  • malnutrition
  • alcoholism
69
Q

What is the treatment of a paracetamol overdose and how does it work

A

N-acetylcysteine (NAC) IV infusion

  • mechanism not fully understood but;
    • Restores glutathione levels or acts as an alternate substrate for conjugation
    • Also antioxidant properties
70
Q

How do you give NAC in paracetamol overdose

A

Highly effective in preventing liver damage if given within 8 hours of overdose. After this efficacy falls substantially; potential for severe hepatotoxicity
• FIRST INFUSION: Add 150mg/kg acetylcysteine to 200mL and infuse overone hour.
• SECOND INFUSION: Add 50mg/kg acetylcysteine to 500mL and administer over 4 hours.
• THIRD INFUSION: Add 100mg/kg acetylcysteine to 1000mL and administer over 16 hours.

  • Continued treatment with acetylcysteine (given at the dose and rate as used in the third infusion) may be necessary depending on the clinical evaluation of the patient
71
Q

what is the target for hepatitis B treatment

A

HBV DNA to go to undetectable levels and ALT to normalise.

72
Q

what drugs do you use to suppress hepatitis B

A
  • Tenofovir disoproxil

- entecavir

73
Q

How does tenofovir work

A

Nucleotide monophosphate analogue;
• competitive inhibition, replaces the deoxyribonucleotide substrate in HBV DNA and acts as a chain terminator
• Eliminated through renal excretion
• Safe in pregnancy

74
Q

What is the difference between tenofovir and entecavir

A
  • Tenofovir is faster than entecavir at reducing viral DNA initially, but after 1 year has similar treatment effectiveness
  • women of child bearing potential should not be started on entecavir
75
Q

describe how entecavir works

A
  • Competes with deoxyguanosine triphosphate, inhibiting reverse transcription of HBV DNA
  • Eliminated through renal excretion
  • Toxicity in pregnancy
76
Q

What are the side effects for tenofovir and entecavir

A
  • Long-term therapy may cause nephrotoxicity associated with lactic acidosis, Fanconi syndrome or a reduction in bone mineral density
  • TDF believed to have higher nephrotoxicity in comparison to ETV
  • Monitor creatinine and phosphate levels
77
Q

How many genotypes does Hepatits C have

A

6 genotypes - with distinct subtypes within genotypes

78
Q

What agents are available for hepatitis C

A 
Multiple oral agents available;
• Epclusa (sofosbuvir / velpatasvir)
• Harvoni (sofosbuvir / ledipasvir)
• Maviret (glecaprevir / pibrentasvir)
• Zepatier (elbasvir / grazoprevir)
• Vosevi (sofosbuvir / velpatasvir / voxilaprevir)
  • may be used in combination with ribavirin
79
Q

What is treatment of hepatitis C dependent on

A

Treatment based on genotype, presence of cirrhosis and previous treatment exposure as per NHS England guidance

80
Q

Name 3 types of Hepatits C medications

A
  • NS5A inhibitors
  • NS5B inhibitors
  • NS3/4A protease inhibitors
81
Q

Give examples of hepatitis C medications

A 
NS5A inhibitors
• Velpatasvir
• Pibrentasvir 
• Elbasvir
• Ledipasvir

NS5B inhibitors
• Sofosbuvir

NS3/4A protease inhibitors
• Glecaprevir
• Grazoprevir
• Voxilaprevir

82
Q

Patients with ascites secondary to liver cirrhosis should be given..

A

an aldosterone antagonists e.g. spironolactone

Year 3 - Met3a (43 decks)

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