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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
Lactulose MOA
Osmotic laxative Local osmotic effect in colon = increased faecal bulk & peristalsis High doses = reduction in colon pH reducing absorption and increasing excretion of ammonia
26
How to prescribe lactulose?
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
Compliance issues with lactulose?
Bloating Abdominal Pain Nausea Bad taste
28
Phosphate enemas
Alongside lactulose as a STAT if patient in encephalopathic Means lactulose is fast acting When patient passes stools - PRN BD
29
Rifaxmin MOA
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
Dose of rifaximin
550mg BD
31
Side effects of rifaximin
``` Constipation Abdominal pain Ascites Hyperkalaemia Neutropenia Depression Dizziness ```
32
Issues with rifaximin
Withhold if patient is on systemic ABs | - interacts with ciclosporin
33
Drugs for ascites
Diuretic combination = furosemide and spironolactone | Also = fluid and sodium restriction, improve nutrition, manage liver disease
34
Furosemide MOA
Loop diuretic Bind to chloride site of Na-K-2Cl co-transporter in ascending LOH Inhibits sodium reabsorption increasing diuresis
35
Furosemide dose
40mg OM Up to 80mg BD if possible Give second dose at lunch not night as will keep needing to go toilet
36
Risk of furosemide
Tend to avoid IV usage as risk of AKI | Hypokalaemia
37
Spironolactone MOA
Aldosterone Antagonist | Inhibits aldosterone dependent Na-K exchange site in DCT
38
Dose of spironolactone
100mg Up to 400mg if possible Much higher doses than HF dose
39
Side effects of spironolactone
Painful gynaecomastia Consider switch to amiloride but less effective in cirrhosis patients Hyperkalaemia
40
Monitoring need for diuretics
- monitor BP as can reduce it =consider falls risk | - when use spiro + furosemide K+ problems cancel out but good to monitor
41
Treatment for gastro-oesophageal varices
Endoscopy | Then vasoconstrictor start = terlepressin
42
MOA of terlepressin
``` 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
What patients to be cautious with when on terlepressin?
``` Those with: HTN - especially if renal HTN or vessel sclerosis Atherosclerosis Cardiac dysrhythmias Coronary insufficiency! ```
44
What to monitor with terlepressin?
ECG BP Serum sodium and potassium Fluid balance
45
Dose of terlepressin
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
Beta blockers
Prophylaxis post variceal bleed | Non cardioselective preferred as increased effect on portal pressures
47
MOA of beta blockers
Competitive antagonists of beta adrenergic beta receptor sites
48
What beta blocker is used for variceal bleed proophylaxis?
Carvediol | - complementary mild anti-alpha 1 adrenergic activity
49
Types of injury drugs can cause to the liver?
Cholestatic Hepatic Acute liver failure
50
Paracetamol overdose
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
Symptoms of paracetamol overdose
Jaundice Confusion Hepatic failure Potentially death
52
What is the mechanism of hepatocellular injury?
Forms a toxin = N-acetyl-p-benzoquinoneimine - conjugated with glutathione, detoxified and secreted - high doses = acculumation of toxin
53
RF of drug induced hepatocellular injury
Increase p450 metabolism - due to chronic alcohol or certain drugs Decreased glutathione = fasting, malnutrition, alcoholism
54
Treatment for paracetamol overdose
N-acetylcysteine IV infusion - restores glutathione levels or acts as alternative conjugation substrate - antioxidant properties
55
Dose of IV NAC
- 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
Hep B treatment target
HBV DNA to undetectable levels and ALT to normalise
57
Hep B treatment drugs
Tenofovir or entercavir to suppress virus Then PEG-IFN but no longer used To suppress not cure so need lifelong Tx
58
Tenofovir
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
Entecavir
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
Side effects/cautions with antivirals
- LT = nephrotoxicity with lactic acidosis, Fanconi syndrome, reduction in bone mineral density - tenofovir = higher nephrotoxicity - monitor creatinine and phosphate levels
61
Hep C Treatment
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
NS5A inhibitors
End in svir | Inhibit RNA polymerase
63
NS5B inhibitors
End in buvir | Inhibit RNA polymerase
64
NS3/4A protease inhibitors
End in previr

MET3a (38 decks)

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