Pharmacology of Drug Treatment in Liver disease

Question 1

Functions of the liver (7)

Answer 1

• Immunity
• relates blood clotting
• clears blood
• converts glucose to glycogen for storying
• excretes wasta via bile
• excretes bile fo fat digestion
• factory for proteins and cholesterol

Question 2

What are LFTs and how is liver function measured

Answer 2

• liver function tests measure serum levels of liver enzymes
• levels of ALP, GGT , AST , ALT and Bilirubin
• to test liver function will measure Prothrombin time and albumin level

Question 3

Describe the bioavailability of drugs process

Answer 3

• oral drugs have to pass through gut wall then pass through portal system into liver
• get phase one and two metabolism in liver , some drugs then make it to systemic system and some is removed
• the part that makes it is bioavailability of drug

Question 4

Explain phase 1 reactions in liver ( type of system , substrates used, type of reaction , purpose )

Answer 4

• CYP450 monooxygenase system
• preparation reaction carried out by isoenzymes
• isoenzymes : 2D6 AND 3A4
• isoenzymes have overlapping substrate specifies, drugs have many receptors they can bind to
• Redox hydrolytic reactions
• breaks up drug molecules making it more reactive to be ready for phase 2 and more water soluble

Question 5

List Enzyme inducers (PC BRAGS) , and level they work at

Answer 5

• Phenytoin
• Carbamazepine
• Barbituates
• Rifampicin
• Alcohol
• Glucocorticoids
• St John’s Wort
  Induce enzymes at a genetic level , happens slowly and takes time to stop

Question 6

What are Enzyme Inhibitors , give examples

Answer 6

• inhibit isoenzymes, acts quickly and stops quickly

- Amiodarone for warfarin

Question 7

What is the difference between enzyme inhibition and enzyme inducers

Answer 7

• inducers work slowly while inhibitors work fast

Question 8

Explain Phase 2 reactions in liver

Answer 8

• Conjugation of molecules
• water soluble substitute added to drug molecule
• changes molecule shape and structure , usually making drug less active
• conjugation is done by transferase enzymes
• makes molecule more water soluble

Question 9

How do hepatotoxic drugs effect liver

Answer 9

• damage transaminases ( AST & ALT ) in liver

- can lead to liver failure if not stopped

Question 10

Give examples of hepatotoxic drugs (8)

Answer 10

• alcohol
• excess paracetamol
• isoniazid
• statins
• methotrexate
• amidarone
• chlorpromazine : cause obstructive jaundice
• halothane

Question 11

Effect of paracetamol on liver

Answer 11

• excess doses overwhelm conjugation pathways

- remaining paracetamol will be oxidized to toxic metabolite NAPBQI

Question 12

How many paracetamol tablets does it take to overdose

Answer 12

• 20 tablets or 10 grams in healthy adult

Question 13

What counteracts NAPBQI

Answer 13

• glutathione can usually mop up the oxidative metabolites unless there is too much NAPBQI and not enough glutathione

Question 14

List manifestations of cirrhosis and explain them (5)

Answer 14

• ascites : build up of fluid
• encephalopathy : brain chemistry is changes and patient is confused
• coagulopathy :
• hepatorenal syndrome : reduced fluid in systemic system and reduces blood flow in kidneys
• varices / portal hypertension : dilated veins

Question 15

What point system is used to class cirrhosis in child patients

Answer 15

Child - Turcotte-pugh scoring system

Question 16

Ascites treatment

Answer 16

• non-pharmacological methods : fluid is removed

- pharmacological measures: diuretics to cause dehydration to reduce movement of water to stop it from recurring

Question 17

What is a TIPS procedure

Answer 17

• procedure that redirects blood flow from liver by connecting hepatic portal vein to central vein ( hepatic )
• only used in serious conditions

Question 18

Which diuretics are used for Ascites

Answer 18

• Spironolactone : blocks aldosterone receptors in distal tubule
• Furosemide
• loop diuretic : inhibit NA K CL carriers in loop of Henley , stop salt loss so a lot of fluid is lost in urine

Question 19

What causes hepatic encephalopathy

Answer 19

• access ammonia in blood is toxic to brain

- excess GABA is neuroinhibitory

Question 20

Hepatic encephalopathy treatment

Answer 20

• protein meals are avoided
• avoid GI bleeding
• avoid constipation so time bacteria has to make ammonia is reduced, lactulose is used
• high thiamine vitamin b and C IV to treat malnutrition ( padrones thiamine )
• Rifaximin ( antibiotic ) if patient has pain in abdomen incase there’s bacteria : reduce spontaneous bacterial peritonitis
• Hepatic merz : provides substrates important for urea formation and reduce ammonia

Question 21

Coagulopathy treatment

Answer 21

• Phytomenadione ( vitamin K ) to increase prothrombin time

- activated clotting factors if patient is bleeding

Question 22

Hepatorenal syndrome treatment

Answer 22

• ADH selective vasopressin to reduce splanchnic vasodilation
• stop blood from going the wrong direction and stop reducing arterial blood volume
• also used for vatical bleeding due to portal hypertension

Question 23

Why is diazepam avoided in liver failure : a highly protein bound drug that has a long half life and promotes GABA in brain

Answer 23

• encephalopathy due to increase in GABA in brain
• diazepam binds to albumin and since there are low albumin levels there will be less diazepam binding
• normally this doesn’t matter since free drugs are eliminated by the liver but due to liver failure they won’t be metabolized so there will be more free dug