Week 1- hepatic treatment+ Hepatotoxicity

Question 1

what depends on the liver disease treatment?

Answer 1

type of liver disease

Question 2

what is the first advice given to ppl with liver disease for treatment and to help treatment?

Answer 2

lifestyle modifications is important to lose weight and stop alcohol help early stage fatty liver

Question 3

most liver diseases are …. but not ….

Answer 3

managed
cured
-except for gallstones and some viral infections

Question 4

what do patients with cirrhosis and end stage liver disease need to be on?

Answer 4

 Low protein diet
 Low sodium and diuretics to minimise water retention
 Draining of ascites fluid by paracentesis
 Surgery to treat portal hypertension and minimise risk of bleeding
 Medicines depend on disease and complications
 Diuretics, antibiotics for ascites
 Beta blockers and vasconstrictor medicines for varices
 Lactulose in hepatic encephalopathy to prevent build up of ammonia
 Transplant

Question 5

what are symptoms of acute alcohol withdrawal?

Answer 5

Minor – CNS hyperactivity resulting in insomnia,
tremulousness, mild anxiety, GI upset, headache,
diaphoresis, palpitations – resolve within 24-48h
more serious Seizures – convulsions usually occurring with 12-48h of
last drink ,chronic alcoholics. If untreated can lead to
delirium tremens
 Alcoholic hallucinosis – hallucinations that resolve within
24-48h
 Delirium tremens – 48-96h after last drink – results in
hallucinations, disorientation, tachycardia, hypertension,
hyperthermia, agitation, diaphoresis – can be fatal
 Fluid and electrolyte abnormalities

Question 6

what is the treatment for acute alcohol withdrawal?

Answer 6

 Symptom control and supportive care
 Benzodiazepines, control psychomotor agitation and prevent more severity
eg chlordiazepoxide, oxazepam - reducing regimen high to low dose over <9
days
 Lowest possible dose given to suppress symptoms without
sedation
 Seizures: IV lorazepam
 IV fluids
 Nutritional supplementation
 Frequent clinical assessment including vital signs
 Ideally do not send home with supply

Question 7

how is cholestatic pruritis caused?

Answer 7

-caused by deposition of excess bile salts under the skin

Question 8

what is the first line treatment for cholestatic pruritis?

Answer 8

-cholestyramine, they bind to bile salts and prevent them being absorbed

Question 9

what are some other treatment for cholestatic pruritis ?

Answer 9

Anti-histamines – non-sedating to avoid
encephalopathy eg cetirizine
 Calamine lotion/menthol in aqueous cream

Question 10

what is encephalopathy?

Answer 10

damage or disease to the brain

Question 11

what is ascites? cause?

Answer 11

• a condition in which fluid collects in spaces within your abdomen.
• occurs due to activation of the renin angiotensin system due to reduction in renal blood flow due to the disorder anatomy of the liver

Question 12

what is the treatment for ascites?

Answer 12

 Spironolactone – 1
st line (aldosterone
antagonist)
 Furosemide – add on if no weight
loss/peripheral oedema
 Bed rest
 Na+ & fluid restrict
 Paracentesis
 AIM: 0.5-0.75kg reduction per day
(up to 1-1.5kg/day if also peripheral
oedema)

Question 13

what is Wernicke-Korsakoff

syndrome?

Answer 13

-neurological abnormality due to thymine difference vitamin B

Question 14

what is the treatment for Wernicke-Korsakoff

syndrome?

Answer 14

-iv Pabrinex® (IV Vitamin B/C preparation)
 infusion over 30 min
 2 pairs amps tds for 3-5 days
 facilities for treating anaphylaxis as potential serious
allergic reaction
-Oral thiamine for treatment or prophylaxis
 100mg tds (regimes can vary)
 Administered at same time as IV then continue for 3-
6months after abstinence/indefinitely

Question 15

what is the treatment for Hepatic encephalopathy?

Answer 15

- Lactulose 30-50ml 3 times a day
 Adjust to aim for 2-3 soft stools daily
 avoid diarrhoea causing dehydration &
hypovolaemia
-Rifaximin
 Semi-synthetic derivative of rifamycin
 Decrease production/absorption of gut
ammonia
- Phosphate enemas
- Avoid precipitating factors – dehydration,
hypokalemia, g.i. hemorrhage, CNS drugs,
high dietary protein, constipation

Question 16

what is portal hypertension?

Answer 16

disordered anatomy in severe liver disease so not normal blood flow through liver cells it is reduced

Question 17

what is the treatment for portal hypertension?

Answer 17

Aim to decrease portal bp & resting heart rate by 25%

PROPRANOLOL low dose & increase cautiously

other vasodilators eg Nitrates

Question 18

what is bleeding oesophageal varices? treatment

Answer 18

-occur when swollen veins (varices) in your lower esophagus rupture and bleed.
-high mortality
-resuscitation & correct hypovolaemia
-Vasoactive therapy [eg vasopressin, terlipressin,
octreotide]

- Endoscope leads to
 Sclerotherapy [eg ethanolamine]
 ligation/’banding’
 balloon tamponade
 TIPS

Question 19

what clotting abnormalities in liver disease and the management?

Answer 19

-due to reduction in clotting factors in the blood
very common
Prothrombin time >(elevated to more than) 18 secs leading to
 Phytomenadione iv (vitamin K)
 Avoid aspirin/ NSAIDs/ warfarin

Question 20

is drug induced hepatoxicity common?

Answer 20

yes around 900 drugs, toxins and herbs an cause liver injury

Question 21

what are some of the risk factors that can cause the likelihood for drug-induced hepatoxicity?

Answer 21

 Age elderly, more drugs, aspirin CI in anyone under 16yrs
 Sex, females more liekly
 Alcohol ingestion
 Pre-existing liver disease
 Genetic factors
 Other co-morbidities
 Drug formulation

Question 22

what are some of the pathophysiological mechanism that can cause drug-induced hepatoxicity?

Answer 22

 Disruption of the hepatocyte
 Disruption of the transport proteins
 Cytolytic T-cell activation
 Apoptosis of hepatocytes
 Mitochondrial disruption
 Bile duct injury

Question 23

what are the different types of hepatic drug toxicity mechanisms?

Answer 23

theres two
-ADR Type A - Intrinsic or predictable
 Reproducible injury in animals
 Injury is dose related
 Due to drug or metabolite
 80% of all ADR
 Eg paracetamol or carbon tetrachloride

-ADR Type B – Idiosyncratic or unpredictable
 Hypersensitivity or immunoallergenic eg phenytoin with
fever, rash, eosinophilia
 Eg Chlorpromazine, Halothane
OR
 Metabolic-idiosyncratic – indirect metabolite of offending
drug

Question 24

what are the signs of drug-induced hepatoxicity?

Answer 24

Many drugs can cause inconsequential rises in LFTs
- up to 2x upper reference range

 Liver damage has occurred:
 rise ALT to > 2x upper limit
 increase conjugated bilirubin to > 2x upper limit
 combined increase ALP & total bilirubin with one > 2x
upper limit
 other symptoms of liver disease

Question 25

what is the management of Drug-induced hepatotoxicity?

Answer 25

```  Drug withdrawal  Antidote if appropriate  Corticosteroids??  Supportive therapy  Yellow card report ```

Question 26

what is some of the preventions that can be done to prevent drug-induced hepatoxicity?

Answer 26

``` -LFT monitoring  Patient education  Signs of liver disease  OTC – paracetamol, health food products, herbal remedies ```

Question 27

what is paracetamol hepatoxocity?

Answer 27

-Most common analgesic/antipyretic  Excellent safety profile when administered in proper therapeutic doses  Hepatotoxicity occurs:  Overdose  Mis-used in at-risk populations (alcohol and enzyme inducers increase toxicity)  Accounts for >50% acute liver failure  >15g leads to fatal hepatic necrosis  > 7.5g – risk of severe liver damage  >5g requires hospital admission and observation  Diagnosis – serum paracetamol concentration

Question 28

what are the 4 phases of paracetamol hepatoxicity?

Answer 28

 Phase 1 - 0.5-24 h after ingestion  Asymptomatic or anorexia, nausea, vomiting, malaise  Phase 2 – 18-72h after  Right upper quadrat abdominal pain and tenderness, anorexia, nausea, vomiting, possibly oliguria  Phase 3 – Hepatic phase 72-96 h after  Continued symptoms, hepatic necrosis may be seen as jaundice, coagulopathy, hypoglycemia, hepatic encephalopathy, possible acute renal failure, death from multiorgan failure  Phase 4 – Recovery 4d- 3wk after  Complete resolution if survive phase 3 and complete resolution of organ failure

Question 29

what is the mechanism whereby paracetamol cause a hepatoxicity problem? normal and toxic

Answer 29

the normal metabolic pathway: -95% of paracetamol conjugates with glucuronide and then excreted in the urine toxic: - 5% of paracetamol undergoes metabolism to the product NAPQI WHICH IS TOXIC - at normal doses its detoxicated by conjugation with glutathione then excreted through urine - but if its in overdose it leads to accumulation of NABQI due to glutathione stores being depleted and leading to cell damage DUE TO BIDNING TO HEPATOCYTES

Question 30

what is the treatment for paracetamol overdose?

Answer 30

-if its in the first hour of digestion then use activated charcoal  Acetylcysteine and methionine replenish glutathione stores  N acetyl cysteine  Give during first 8 h of overdose  Possibly effective up to and beyond 24h