Week 1- hepatic treatment+ Hepatotoxicity Flashcards
what depends on the liver disease treatment?
type of liver disease
what is the first advice given to ppl with liver disease for treatment and to help treatment?
lifestyle modifications is important to lose weight and stop alcohol help early stage fatty liver
most liver diseases are …. but not ….
managed
cured
-except for gallstones and some viral infections
what do patients with cirrhosis and end stage liver disease need to be on?
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
what are symptoms of acute alcohol withdrawal?
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
what is the treatment for acute alcohol withdrawal?
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
how is cholestatic pruritis caused?
-caused by deposition of excess bile salts under the skin
what is the first line treatment for cholestatic pruritis?
-cholestyramine, they bind to bile salts and prevent them being absorbed
what are some other treatment for cholestatic pruritis ?
Anti-histamines – non-sedating to avoid
encephalopathy eg cetirizine
Calamine lotion/menthol in aqueous cream
what is encephalopathy?
damage or disease to the brain
what is ascites? cause?
- 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
what is the treatment for ascites?
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)
what is Wernicke-Korsakoff
syndrome?
-neurological abnormality due to thymine difference vitamin B
what is the treatment for Wernicke-Korsakoff
syndrome?
-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
what is the treatment for Hepatic encephalopathy?
- 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
what is portal hypertension?
disordered anatomy in severe liver disease so not normal blood flow through liver cells it is reduced
what is the treatment for portal hypertension?
Aim to decrease portal bp & resting heart rate by 25%
PROPRANOLOL low dose & increase cautiously
other vasodilators eg Nitrates
what is bleeding oesophageal varices? treatment
-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
what clotting abnormalities in liver disease and the management?
-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
is drug induced hepatoxicity common?
yes around 900 drugs, toxins and herbs an cause liver injury
what are some of the risk factors that can cause the likelihood for drug-induced hepatoxicity?
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
what are some of the pathophysiological mechanism that can cause drug-induced hepatoxicity?
Disruption of the hepatocyte Disruption of the transport proteins Cytolytic T-cell activation Apoptosis of hepatocytes Mitochondrial disruption Bile duct injury
what are the different types of hepatic drug toxicity mechanisms?
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
what are the signs of drug-induced hepatoxicity?
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
what is the management of Drug-induced hepatotoxicity?
Drug withdrawal Antidote if appropriate Corticosteroids?? Supportive therapy Yellow card report
what is some of the preventions that can be done to prevent drug-induced hepatoxicity?
-LFT monitoring Patient education Signs of liver disease OTC – paracetamol, health food products, herbal remedies
what is paracetamol hepatoxocity?
-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
what are the 4 phases of paracetamol hepatoxicity?
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
what is the mechanism whereby paracetamol cause a hepatoxicity problem? normal and toxic
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
what is the treatment for paracetamol overdose?
-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
