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Flashcards in Liver 2 Deck (35):
1

How does the liver handle and affect drugs

Main elimination route for many drugs
Can alter response to drugs in several ways

Drugs can affect metabolism of other drugs by induction and inhibition of cytochrome P450 (CYP450) enzymes in liver:
- Inhibitors of erythromycin, amiodarone, ketoconazole, ciprofloxacin
- Increased effect and toxicity of affect drug unless it is prodrug- warfarin

Inducers:
Barbiturates, carbamazepine, ethanol, phenytoin, rifampicin, St John Wort
- Increased hepatotoxic metabolites of other drugs
- Decreased pharmacological effect of affected drug

2

What are the prescribing tips for someone with liver diease?

1. Most drugs are safe in
stable liver disease

2. Use older and more established drugs

3. Consider patient factors

4. Avoid drugs in severe disease esp if hepatotoxic

5. Consider renally excreted (caution HRS)

6. Start with small dose & increase slowly or give prn

7. Choose best option & monitor clinical response

3

What is the analgesia of choice in chronic liver disease?

Kept to minimum, smallest effective dose at greatest interval

Paracetamol- 500mg- 1g TDS
Overdose- severe liver damage
Common reason for liver transplant

Avoid NSAIDS and COX-2 inhibitors
Bleed, altered platelet function, GI irritation, ascites

Caution opioids
Sedation, hepatic encephalopathy
Tramadol then sevredol
Oramorph

Caution- soluble 10% ethanol

TCAs- low dose fine, nortriptyline

Gabapentin okay- neuropathic pain

4

What is the anti-depressant of choice in chronic liver disease

TCAS- avoid- sedating- risk of hepatic encephalopathy

SSRI- confer to bleeding risk, hyponatraemia, use low dose or increased interval
Sertraline 25-50mg OM
Citalopram max 20mg
Mirtazepine 15mg ON- lowest bleeding risk but sedating

5

Describe the use of statins in liver disease, is it okay to use?

All can cause elevations in transaminases (transient or persistent)

Monitor LFTs in all patents

No link between elevation in LFTs and developing toxicity

IF ALT > 3 x upper limit normal, asymptomatic repeat test

Avoid in acute liver and decompensated chronic liver disease

Can be used safely if no or mild synthetic dysfunction

Statins may be beneficial in NAFLD by improving transaminases

6

What are signs of cirrhosis

Increased bilirubin, AST, ALP, GGT, PT

Decreased albumin and Hb

Jaundiced, weakness in legs, palmar erythema, haematoma, spider naevi

Ascites, muscle wasting

7

What are the stages of alcoholic liver disease

Normal

Fatty liver or steatosis- reversible with abstinence, rarely symptomatic, occur after a few days

Steatohepatitis/ acute alcoholic hepatitis:
Accumulation of fat + hepatocellular injury, may or may not improve with abstinence, can occur several weeks after stopping drinking

Fibrosis or cirrhosis

8

What are the short term effects of alcohol on the body (8)

1. Anxiety

2. Decrease respiratory rate

3. GI disturbance

4. Impaired judgement

5. Loss of consciousness

6. Impotence

7. Acute poisoning

8.Unintentional injury

9

What are the long term effects of alcohol on the body

Liver disease
Cancer
Pancreatitis
GI ulceration
Osteoporosis
Infertility
Heart disease
Stroke
Hypertension
Obesity
Dementia

10

What are the withdrawal signs and symptoms from alcohol

Minor withdrawals:
Sweating
Shaking
Depression
Anxiety
Irritability
Nausea and vomiting
Restlessness
Poor concentration

Delirium tremens:
Severe agitation
Delirium
Course tremor
Large increases in pulse, blood pressure, respiratory rate
Auditory and visual hallucinations
Disorientation and reduced consciousness
Excessive sweating (diaphresis)

11

What drug treatments should be started

Chlordiazepoxide PRN
Pabrinex IV HP 1 pair OD (3 days)
Then multivitamin 1 OD, thiamine 100mg BD

Spironolactone 100mg OD

Furosemide 40mg OD

Lactulose 30mL TDS

Chlorphenamine and aqueous cream and menthol

Dalteparin 5000 units OD

12

What should the acute alcohol withdrawal policy include

Benzodiazepine
- Chlordiazepoxide, lorazepam, diazepam

Thiamine (IV pabrinex and/or oral)

Multi-vitamins

Nutrition

Fluid and electrolyte replacement

Document history of alcohol intake- AUDIT or CAGE questionnaire

Referral to community support where possible

13

Describe the fixed dose regimen of chlordiazepoxide

Day 1:
30mg QDS, 10mg (max 200mg/24 hours) PRN
Day 2:
20mg QDS, 10mg (max 200mg/24 hours) PRN
Day 3:
20mg TDS
Day 4:
20mg BD
Day 5:
10mg BD
Day 6: STOP

- Appropriate if previous delirium tremens, seizures or moderate alcohol withdrawal syndrome (AWS)

- Anxiolytic and anticonvulsant

- Review daily

- Individual titration

- Monitor for over sedation, respiratory depression, hypotension

- Can fit as dose is tailed off

- Risk of chest infection

- Reassess reducing dose if >3 prn doses are needed in 24 hours

- Maximum 10mg BD for 24 hours on discharge

14

Describe the "symptom triggered flexible regimen"

Tailored to individual requirements based on severity of withdrawal

Benzodiazepine dosed and administered via validated assessment tool: clinical institute withdrawal assessment scale for alcohol (CIWA-Ar)
- calculate every 2-4 hours- severity linked to frequency of assessment
- 10 item assessment to quantify severity and monitor and medicate appropriately
- Score 8+ an accepted trigger for PRN dosing

Several studies show lower total dose and shorter hospitalisation periods vs fixed dose regimen

15

Describe what you should do when oral route is unavailable or inadequate for instance delirium tremens (DT) occurs?

IV diazepam 5-10mg into large vein every 15-30 minutes until patient is calm

Parenteral diazepam repeated after 5 minutes

Lorazepam IV 1-4mg 15-60 minutes

Patients may need high doses

16

Describe seizures in complications of withdrawal of benzodiazepine

Complication of withdrawal, can occur if is tailed off too quickly

Options:
IV lorazepam or PR diazepam

Status epilepticus:
IV diazepam
Pabrinex
Chlordiazepoxide

Increase dose of oral benzodiazepine (BDZ) to reduce further seizure risk

Phenytoin not appropriate
43

17

What antipsychotics be used in Delirium tremens

Unlicensed in UK

Adjunctive to benzodiazepine

Not as mono therapy- do not treat alcohol withdrawal since can lower seizure threshold

Exclude Wernike's encephalopathy and hepatic encephalopathy before starting

Use of haloperidol or olanzepine

18

What other considerations do you consider in patients with liver disease

Nutrition:
Poor intake, chronic pancreatitis, chronic liver disease, poor absorption
Consider NG feeding (caution varicose)
Risk of re-feeding syndrome- electrolytes

Thiamine:
Prevent polyneuritis and wernike's encephalopathy (confusion, ataxia, memory loss, opthlmoplegia and subsequent Korsakoffs psychosis)
IVI pabrinex
PO thiamine
Other multivitamins

19

What do you give a patient when they are discharged

Maximum 24 hour benzodiazepines

Oral B vitamins

Referral to drug and alcohol support services

Needle exchange

20

How do you encourage abstinence from alcohol in a patient

Psychological support- local drug and alcohol services

Drugs given:
Disulfiram
Acamprosate
Naltrexone
Nalamefene

Be aware of alcohol containing drugs, toiletries, mouthwashes

21

Describe acute alcoholic hepatitis: markings and characterisation

Presented with marked inflammation of the liver presented with jaundice

Occur on background of a normal liver or complicate cirrhosis

Occur several weeks after stopping drinking

Reversible with abstinence but often underlying cirrhosis

Characterised by fever, hepatomegaly, leucocytosis, signs of liver failure e.g. ascites, raised ALT

Short term mortality among patients

22

What does the glasgow alcoholic hepatitis score look at (5)

1. Age
2. White cell count
3. Urea
4. Prothrombin ratio
5. Bilirubin

23

What can spironolactone and furosemide be used for in liver disease patients

Ascites and peripheral oedema

Causes:
low albumin, impaired aldosterone metabolism, reduced renal blood flow, portal hypertension, increased hepatic lymph production

Avoid drugs that can exacerbate:
NSAIDs, saline, high salt, fluid restriction

Natural history in chronic liver disease
- Diuretic sensitive than resistant, associate with HRS and hyponatraemia
50% mortality over 2 years

24

How do you treat and monitor ascites

Treatment:
Fluid and salt restriction- bed rest
Spironolactone- Aldosterone antagonist
Furosemide- add cautiously for peripheral oedema
Paracentesis (+ albumin)
TIPSS
Peritonea-Venous shunt

Monitoring:
Weight loss
Urine output/renal function
Yes (Na, K, Cr)
BP and encephalopathy
Diagnostic ascitic tap
SBP- temp and WCC

25

What is lactulose used for (in liver)

Hepatic encephalopathy

26

Define encephalopathy and what are the neuropsychiatric changes

Reversible changes in mental state secondary to failure of liver to metabolise digestive products or toxins; toxins bypass liver to brain

Neuropsychiatric changes- four reversible stages:
Stage 1: forgetfulness, confusion, agitation (day night muddle)
Stage 4: coma, unresponsive to painful stimulus

27

How do you treat encephalopathy

Remove and avoid precipitants
Reduce protein intake
Decrease bacterial ammonia product and enhance elimination

Lactulose:
Prevents constipation and inhibits colonic bacteria to convert NH3 to NH4

Phosphate enemas

Rifaximin- poorly absorbed antibiotic that eliminates colonic bacteria

28

Describe what chlorphenamine and aqueous cream with menthol is used for

Pruritus: due to bile acids within skin, up regulation of endogenous opioids, serotonergic pathways

Generally less severe than with pure chloestasis

Other options:
Colestyramine
Ursodeoxycholic acid
Rifampicin
Sertraline
Ondansertron
Naltrexone

29

Describe what dalteparin is used for and in terms of liver disease too

VTE prophylaxis

Liver- synthesis of clotting factors

Used as an indicator for prothrombin time

Acute and chronic liver disease elevated

Increase prolongation of clotting time if clotting factor deficient

Avoid intramuscular injections- haematoma

Usually used in more advanced cirrhosis with low albumin levels

30

What is the aetiology of a Variceal haemorrhage

Decreased blood flow through liver
Portal hypertension >12mmHg
Collateral vessels
Varices (stomach, oesophagus, rectum)

31

What is the acute treatment of bleeding varicies that include oesophageal varies and gastric varices

Resuscitate
Terlipressin- until haemostasis for five days
Prophylactic antibiotics

Oesophageal varices
Banding
Consider transjugular intrahepatic portosystemic shunts (TIPSS) if bleeding not controlled by banding

Gastric varices
Endoscopic injection of N-butyl-2-cyanoacrylate
Uses TIPS if not controlled by injection

32

In prophylactic treatment, what are the complications post bleeding

Bacterial sepsis- must use ceftriaxone 2g for 2 days of the week

Ascites- tx once BP is stable

Ulceration around scope site- oral PPI

alcohol withdrawal syndrome- pabrinex + benzodiazepine

33

In prophylactic treatment, how do you prevent rebleed

Weekly endoscopies until varicies are eradicated then every 2 years

Carvedilol or propranolol reduces portal pressure

Laxatives- POST TIPS

TIPS/Transplant

34

How do you help adherence

Keep medication to minimum and review regularly

Once daily timings

Stop drinking- support groups

Help with prescription costs

Counsel on indications and importance of medication prescribed

Medication charts (MDS)

District nurses support e.g. enemas for hepatic encephalopathy

Advise on OTC, herbals, illicit (no NSAIDS)

35

What is the role of the pharmacist in liver disease

Communicate with and offer evidence on based prescribing advice to multi-drug therapy

Check drug dosing in liver disease and potential induced liver disease

Drug history reviews

Check for cytochrome p450 interactions for hepatitis C

patient and carer medication education

Specifying drug regimens- adherence, pill burden

Contribute to production of guidelines- local and national

Monitor drug expenditure- HCV expensive

Audit- against local and national prescribing guidelines