The Liver Pharmacology Flashcards
Alcohol effects the GABA system. what does GABA stand for?
Gamma- Aminobutyric Acid
bilirubin is usually excreted via
excretion via bile ducts as a water-soluble conjugate
fibrosis and cirrhosis are characterised by
Inflammation + Fibrogenesis + Collagen deposition
high levels of ALT can be indicative of:
viral hepatitis, drugs, sepsis
How are Radicals produced in the liver?
When there’s higher alcohol intake, CYP450 2EI metabolises alcohol to unstable free radicals
list 5 signs of liver disease
Varices, Fatty Stools, Spider Naevi, Ascites and Jaundice
liver fibrosis can lead to
cirrhosis
name 3 other investigations done with LFTs
CT scan, liver Ultrasound, MRI
Name and explain an invasive treatment of Ascites
Paracentesis. is extracted from peritoneal cavity and colloids, albumin and terlipressin is exchanged
what is Steatohepatitis
Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes
normal albumin range?
35-50 g/dl
role of kupffer cells?
release macrophages to kill off bacteria and viruses in the liver
Treatment of SBP
3rd generation Cephalosporin, Co-Amoxiclav
Norfloxacin/Ciprofloxacin as prophylaxis
what are Ascites patients at risk of in terms of infection? where does it infect?
SBP - Spontaneous Bacterial Peritonitis. infects the peritoneal fluid
Long and short term consequences of alcohol
Short term:
- Loss of consciousness
- impotence
- anxiety
- acute poisoning
- GI disturbances
Long term:
- GI ulcer
- Stroke
- Increased BP
- Obesity
- Insomnia
(additionally generate free radicals, and affects GABA system)
what are the three main theories of Ascites
- underfill - reduction of circulating plasma volume
- overfill - increased plasma volume
- peripheral artery vasodilation
What are the two patterns of liver damage?
Cholestasis or Hepatocellular damage
what condition is Terlipressin used in? what is it?
Ascites and Variceal bleeding. It is a vasoactive drug used to raise blood pressure when norepinephrine doesn’t help.
what does ‘compensated liver disease’ mean
the small amount of viable liver you have left, works well.
what does ‘deompensated liver disease’ mean
the small amount of viable liver cells you have left doesn’t work well
normal range of bilirubin?
5-20 micromol/L
What is Varices, and what drug is used to treat it
Collateral vessels formed that enables blood to bypass the liver. Treat with Terlipressin
what is acute liver failure
history of onset does not exceed 6 months
what is cholestasis
Disruption of bile flow. Can be intra out extra hepatic
what is chronic liver failure
persists for more than 6 months, with permanent structural changes following standing cell damage
what is elevated bilirubin a clinical sign of
Haemolysis
Hepatocellular damage
Cholestasis
what is first line in alcohol withdrawal management plan and why?
How to administer?
If the patient has cirrhosis what do we give?
A Benzodiazepine: Chlordiazepoxide long half life sedative + anticonvulsant properties slower onset of action.
Shorter acting than Oxazepam.
Front loading - loading dose followed by repeat dose every 90 minutes
In cirrhosis, give lorazepam or oxazepam
what is Hepatitis
Inflammation of the liver. can be caused by viruses
what is Hepatocellular disease caused by
- inflammation (Hepatitis) - Fatty infiltration (steatosis) - Injury to hepatocytes - necrosis
what is liver fibrosis.
in injury to liver, collagen develops haphazardly and scars replace liver cells. the hard tissue formed is non functioning
what is Sepsis
the body’s own response to infection injures it’s tissues and organs
what is Steatohepatitis
accumulation of fat plus hepatocellular injury
what is Steatosis?
“Liver Enlargement”.
There’s a disruption of metabolic pathways (redox imbalance) in liver which cause accumulation large droplets lipid within hepatocyte.
what is the most important metabolite leading to liver disease?
Accumulation of Acetylaldehyde which is produced by oxidising ethanol (with alcohol dehydrogenase)
what unfortunate condition can occur several weeks after quitting alcohol? what can we give as first line?
Acute Alcoholic Hepatitis. Prednisone 40m OD to switch off the inflammatory process
what vitamin supplement do you recommend for alcohol management, and why do we need vitamins?
Panrinex. Patient is vitamin deficient due to poor diet.
Pabinex contains a mixture of vitamins for supplementation e.g Thiamine and Ascorbic acid
What is this and what is the treatment for it?
Asterexis (a sign of liver diease)
Lactulose, Phosphate enema - Metronidazole, Neomycin, Sodium benzoate - Rifaximin
what is jaundice? and what causes it?
Yellowing of the skin and whites of eyes.
- It’s caused by a build-up of bilirubin in the blood and tissues of the body.
- Common signs of jaundice are: -yellowing of the skin, eyes and mucus membrane (the lining of the body’s passageways and cavities, such as the mouth and nose
- pale-coloured stools (faeces) -dark-coloured urine
What is Ascites?
Accumulation of fluid in the peritoneal cavity leading to swollen abdomen
Main theory of Ascites?
Most common cause overflow which begins from cirrhosis of the liver. There is a decreased effective intravascular volume which leads to renal sodium retention. This now causes increased blood volume resulting in acites as water moves out into peritonieal cavity
Treatment of Ascites
Diuretics: • Spironolactone • Amiloride • Furosemide •
*Fluid/Sodium restriction*
• Paracentesis for large volume. Need to maintain adequate circulating volume – colloids, albumin, Terlipressin • TIPS for more refractory ascites (along with paracentesis)
what does TIPS stand for?
Transjugular intrahepatic portosystemic shunting
Monitoring points in Ascites
Monitor: Daily U&Es – esp Na, K, Cr
- Daily wt – aim for 0.5-1kg/day wt loss
- Fluid chart – note fluid restriction, urine output
- Avoid high Na contents preparation
- Complications – dilutional hypoNa, HE, HRS, gynaecomastia, hyperK, muscle cramps, SBP
Terlipressin Indication, action and monitoring points. How to administer dose.
Indicated for vasiceal bleed.
Has a Biphasic action: • Intact molecule has an immediate vasoconstricting effect
- Followed by delayed effect caused by slow transformation of terlipressin in-vivo to lysine vasopressin
- Administer in bolus doses 1-2mg every 4-6hours (continue until haemostasis achieved)
Monitor - Blood pressure, sodium, potassium, fluid balance
Side-effects include headaches, abdominal cramps, ischaemia
Secondary prophylaxis in variceal bleeds
- Non-selective beta-blocker e.g Propranolol
- Splanchnic vasoconstriction (beta2 blockade)
- reduced Cardiac output results in reduced portal pressures (beta1 blockade)
- Beta-blockers: Prevent re-bleeding and Increase survival
What is this and what causes it?
Spider Naevi. Caused by raised oestrogen level imbalance
- pregnant women. Hormone replacement therapy, Oral Contraceptive Pill. (raised oestrogen)
- Hepatic Disease – failure to metabolise oestrogen
What do Albumin and INR tell us about Drug Handling?
Generally: • Decreased Albumin and/or increased INR indicate reduced synthetic function • Significance will depend on the drug and is difficult to predict • Lower doses with close monitoring may be required
Albumin
- Decreased Albumin = decreased protein binding
- Highly protein bound drugs - increase in “free” drug available to act and hence an increased clinical effect e.g. Phenytoin
- Dose adjustment if PT > 130% normal
Explain the Key liver function tests
-
Albumin
- Hypoalbuminaemia = feature of advanced chronic liver disease (LD)
-
Bilirubin
- An increase means a blockage in bile flow
-
Aminotransferase (AST and ALT)
- An increase means hepatocellular damage
-
Gamma-glutamyltransferase (γGT)
- Sensitive to drugs and alcohol
-
Alkaline phosphatase (ALP)
- An increase means blockage of bile flow
- yGT and ALP together indicate cholestatis -> Partial or full blockage of bile ducts
- If bile duct is inflamed/damaged, yGT and ALP spill out of liver into blood stream due to pressure.
what conditions cause a rise in yGT and ALP levels?
Scarring of the bile ducts
Fatty liver (steatosis)
Liver tumors
Gall stones
Alcoholic liver disease
what causes AST and ALT to rise
Viral hepatitis
excess alcohol intake
liver inflammation from medicines
fatty liver
autoimmune
normal range of:
- AST
- ALT
- ALP
- yGT
- Albumin
And what do they stand for?
AST (0-40 iu/L) Aspartate aminotransferase
ALT (5-30 iu/L) Alanine aminotransferase
ALP (30-120 iu/L) Alkaline Phospatase
yGT-(5-55 iu/L) y-Glutamyltransferase
Albumin (35-50 g/dL)
How do I interpret a LFT?
- LFTs are fairly non-specific
- Generally if 2 x ULN considered abnormal
- If Liver dysfunction – usually at least 2 will be deranged
- Trends not isolation
- Check reference ranges and units
- Child’s Pugh Scoring System takes into acount EABAI - Encephalopathy, Ascites, Bilirubin, Albumin and INR
what is hepatic encephalopathy
- Several theories including accumulation of toxins esp. ammonia, increased permeability of BBB, increased levels of neurotransmitters
- Precipitating factors – increased protein load, reduced ammonia excretion, electrolyte disturbance, dehydration, drugs, infection
- Occurs in 4 stages
what are the four stages of hepatic encephalopathy
mental status
- Impaired attention, irritability, depression
- Drowsiness and memory impairment
- Confusion and amnesia
- Stupor and coma
corresponding neuromuscular function
at stage 1: Tremor and incoordination
at stage 2: Asterexis and slurred speech
at stage 3: Hypoactive refleces
at stage 4: dilated pupils
state invasive techniques to manage variceal bleeds
- sclerotherapy (glue)
- balloon taponade
- band ligation
state 5 causes of liver disease
- Alcohol
- viral infections
- drugs
- toxins
- cancer
- autoimmune
Outline the management plan for Alcoholic hepatitis
- Manage withdrawal symptoms
- Manage Vitamin deficiency
- Treate acute alcoholic hepatits with anti-inflammatory agent
- Manage any complications associated with liver disease e.g cirrhosis, coagulopathy, ascites
what are the presenting signs of alcohol withdrawal? What first line
delerium
fever
seizures
rapid pulse
tremor
First line is to manage the symptom. Give Chlordiazepoxide + Pabrinex
If a patient is getting additional seizures from alcohol withdrawal, what do you reccommend?
Lorazepam or Haloperidol in sever psychosis
what markers are elevated in Acute Alcoholic Hepatits?
White Cell Count
Neutrophil count
Bilirubin
INR
Raised AST
How to treat alcoholic cirrhosis?
How to manage Alcoholic Cirrhosis?
Treatments
- anti-TNF agents - Infliximab
- Antioxidants
- Vitamin E
Management
- Diuretics for Ascites
- Propanolol for Portal Hypertension
- Vitamin K for
- Coagulopathy
- Antibiotics for SBP
- Lactulose for HE
what causes alcohol dependence to begin with?
The release of β-endorphins, coupled with the release of dopamine, is thought to result in the pleasurable feelings associated with alcohol dependence.
When alcohol is withdrawn the result is CNS Hyperactivity. This explains the seizures
what agents can we give to help abstincence of alcholol
Disulfiram! - inhibits acetaldehyde degydeogenase. 800mg OD then reduce by 200mg each day.
maintain at 100-200mg OD
