Drug Therapy In Patients With Hepatic Disease

Front 1

Flow dependent drugs

Back 1

clearance so rapid that it's effectively dependent only on the rate of hepatic blood flow

high first pass clearance - low oral bioavailability

this group most affected by chronic liver disease (as fibrosis leads to obstructed vessels and shunting)
all - bioavailability increases and clearance decreases

Front 2

Enzyme dependent drugs

Back 2

clearance is limited by the amount of enzyme (generally P450) available

clearance subject to change by enzyme induction or inhibition

can't make the same generalisations about it in liver disease (may/may not have impaired clearance of enz dep drugs)
Just conserve dosing for really old people

Front 3

Flow dependent drugs (examples)

Back 3

"5 critical flow-dep drugs"
1. Nitrates
2. Opiates
3. b-blockers (not atenolol)
4. Ca channel blockers
5. Lignocaine

Front 4

Enzyme dependent drugs (examples)

Back 4

most anti convulsnts
warfarin
benzodiazepines (except oxazepam)
theophylline
most NSAIDs
amiodarone

Front 5

Altered Volume of Distribution

Back 5

Liver failure = Oedema (less Albumin & less protein bound to albumin)

More ECW volume = more Vd for H20 soluble drugs - drawing these drugs away from the organs responsible for their elimination

incr Vd = incr t1/2 (if clearance unchanged)

Prolongs toxic effects (this only matters in drugs with high toxicity)

Front 6

Pharmacodynamics:
Increased sensitivity of drugs

Back 6

In liver disease - these are more sensitive:

Anticoagulants (incr. bleeding)
Sedatives (risk of oversedation)
Diuretics (avoid K+ wasting)
-in liver disease, less albumin, less plasma vol, less RBF, more aldosterone, more sodium retention and potassium excretion, hence those with liver disease generally hypokalaemic)