Transcript Liver Cirrhosis

Liver Cirrhosis
Lamya Alnaim, PharmD
1
Background
• Cirrhosis →the end stage of any
chronic liver disease.
• Hepatitis C and alcohol are the main
causes
• Two major syndromes result
– Portal hypertension
– Hepatic insufficiency.
• peripheral and splanchnic vasodilatation
with the resulting hyperdynamic
circulatory state
2
Background
• Cirrhosis can remain compensated for
many years before the development of a
decompensating event.
• Decompensated cirrhosis is marked by
the development of any of the following
complications:
–
–
–
–
Jaundice,
Hemorrhage
Ascites
Encephalopathy.
• Other than liver transplantation, there is
no specific therapy for this complication.
3
Background
• Other complications occur as a
consequence of PHTN and the
hyperdynamic circulation.
• Gastroesophageal varices result from
PHTN, although hyperdynamic
circulation contributes
• Ascites results from sinusoidal HTN
and sodium retention, which is 2ndry
to vasodilatation and activation of
neurohumoral systems.
4
Background
• The hepatorenal syndrome results
from severe peripheral
vasodilatation that leads to renal
vasoconstriction.
• Hepatic encephalopathy is a
consequence of shunting of blood
through portosystemic collaterals
(due to PHTN), brain edema
(cerebral vasodilatation), and
hepatic insufficiency.
5
Definition
• A chronic disease of the liver with
wide spread hepatic parenchymal
injury and hepatocyte destruction.
• It may lead to anatomic and
functional abnormalities of blood
vessels and bile ducts
6
Causes
• Alcohol
• Viral illness
• Biliary dysfunction
• Metabolic disorders
• Inherited disorders
• Drugs
• The most common causes are
alcoholism and viral hepatitis
7
Clinical Features
• Insidious development
• Often produces no clinical
manifestations
• Common symptoms
– Anorexia, nausea, abdominal discomfort,
weakness, weight loss, and malaise
8
Clinical Features
• Physical examination:
– Enlargement of the liver and spleen due to
PHTN
– ascities,
– peripheral edema,
– Jaundice
– Spider angiomas
– GI bleeding
– Palmer erythema
– Right upper quadrant pain
9
Portal Hypertension
• Portal vein collects blood from GI
tract, pancreas and spleen to the
liver
• Contains oxygen, nutrients and
bacterial waste
• A pathway for detoxification and
metabolism of absorbed substance.
• Fibrosis and nodular regeneration of
liver with distortion of hepatic veins
is the main cause of ↑ intrahepatic
resistance
10
Portal Hypertension
Persistent PHTN lead to
• Changes in blood and lymphatic
flow → hyperfiltration and ascites
• ↑ collateral circulation ↑ the risk for
esophageal and gastric varices
• Hepatic encephalopathy and
hepatorenal syndrome
11
Lab Findings
• Bilirubin> 2mg/dl to 40 mg/dl
• AST, ALT, alkaline phosphatase
– Aid in early diagnosis, prognosis, and
response to treatment
– ↑ ALkPo > 3 times normal indicate
billiray disease
12
Lab Findings
Albumin
• (non-specific protein) & Factor V and
VII (specific proteins) can provide
information on the functional
capacity of the liver
• Low albumin < 3 that does not
respond to therapy is bad prognosis
13
Lab Findings
•PT
– Prolongation due to impaired synthesis
of vitamin K dependant clotting factors
– No response to VIT K is poor prognosis
•BUN
– < 5 due to inadequate protein intake
and depressed hepatic capacity for
urea synthesis
•Biopsy
– Confirm the presence of cirrhosis
14
General Management
• Largely symptomatic
• Maintain fluid and electrolyte
balance
15
General Management
• Analgesics:
– NSAIDs may worsen gastritis and GI
bleeding
– Acetaminophen may lead to
hepatoxicity
– Narcotics may lead to CNS and
respiratory depression
– Sedatives and hypnotics should be
avoided if the patient is in danger of
hepatic coma
16
General Management
• Diet
–2000-3000 calorie diet with 1g
protein/kg
–In encepalopathy, dietary
supplentation of BCAAs
–Thiamine replacement 50-100mg/da
–Iron and folate if patient is anemic
–Vitamin K 10 mg sc if PT is elevated,
if PT is not improved in 3-5 days D/C
17
I-Ascities
Definition:
• Accumulation of protein rich fluid in
the peritoneal cavity.
• The most common clinical feature
Clinical features:
• Inability to fit into one's clothes
• Abdominal and back pain
• Gateroesophageal reflux
• SOB secondary to impaired
diaphragm movement Or pleural
effusions
18
Ascities
Pathophysiology: Underfill theory
1-↑ hydrostatic pressure in portal vein
and ↓ oncotic pressure.
– Exudation of fluid from the splanic
capillary bed and liver surface when
drainage capacity of the lymphatic
system is exceeded.
19
Ascities
Pathophysiology: Underfill theory
2-Portal hypertension & ↓ oncotic
pressure →↓ arterial blood flow to
vital organs → vasoconstriction.
– Reduced circulation to kidney activate
rennin angiotension sys → ↑
aldosterone & Na/ water retention.
– Renal K excretion > Na excretion &
urinary Na: K ratio abnormal.
20
Ascities
Goals of therapy
• Mobilize fluid
• Diminish abdominal discomfort, back
pain, and difficulty in ambulation
• Prevent complications such as
bacterial peritonitis, hernias, pleural
effusion, hepatorenal syndrome,
respiratory distress.
• Prevent complications of treatment
such as acid-base imbalance,
hypokalemia, and volume depletion
21
Ascities -Treatment
A- Sodium Restriction: (500mg2g/day)
–10-20 mEq/day plus bed rest (to
↓rennin)
• Degree of success depends on:
–Duration of restriction
–Extent of hepatic injury
–Patient with urine Na >10 mEq/l
likely respond
22
Ascities -Treatment
B-Water Restriction
–Effective in dilutional hyponatremia
(Na<130)
–Patients with low urine sodium <10
mEq/l
–Normal renal function
• Not effective in
–reduced 24-hour Na urinary
excretion
–Reduced GFR & free water clearance
–May lead ↓ renal blood flow and
azotemia
23
Ascities -Treatment
C.
•
•
•
Diuresis
The cornerstone of treatment
Must be slow
If urinary losses > reabsorption from
ascites→ volume depletion ,
hypotension and renal insufficiency
• Should be limited to 0.2-0.3 kg /day
in patients without edema
• 0.5-1kg /day for patients with edema
24
Ascities -Treatment
I- Spironolactone
• An aldosterone-inhibiting agent
• Patients have high levels of aldosterone
• Increased production
– Portal hypertension, ascities, ↓ intravascular
volume, ↓ renal blood flow activate rennin-ang
system
• Decreased excretion
– Hepatic impairment prolongs half-life due to
metabolism
↓
– ↓ albumin ↑ unbound hormone in the blood
• Dose: 100-200 mg/day, may be
every 2-4 days
↑ slowly
25
Ascities -Treatment
I- Spironolactone
Monitoring Parameters
• weight
• urine output
• changes in abdominal girth
• BUN
• Increase in K/Na ratio from
pretreatment baseline
• Table
26
Complication of Spironolactone
1-Hypokalemic hyperchloremic metabolic
alkalosis and hyponatermia
• May occur in untreated cirrhosis
• Initial deficiency of K due to diarrhea, vomiting,
hyperaldosterone
• May be corrected with KCl supplement
• Hyponatermia corrected by temporary withdrawal of
diuretic and free water restriction
2- Prerenal azotemia
• ARF due to overdiuresis with compromise in
intravascular volume and decreased renal perfusion
• gradual rise in Scr and Bun
• If large fluid volume must be removed quickly,
paracentesis should be preformed
3- Gynecomastia:
• can be related to cirrhosis independent of drug use
27
Ascities -Treatment
II-Other Diuretics
• If spironolactone fails to produce diuresis
or hyperkalmeia occurs additional diuretic
are needed
• The dose should be started low 50 mg/day
HCTZ or 20-40 mg furosemide and
gradually increased
• Loop and thiazide diuretics may affect the
value of monitoring urinary electrolyte
• The may cause excessive sodium loss in
the presence of continued
hyperaldosteronism
28
Ascities -Treatment
D- Paracentesis
Removal of large amount of ascetic fluid with
a needle or catheter
Uses
• Ascites unresponsive to diuretic therapy
• If respiratory and cardiac functions are
compromised
• Not definitive because fluid quickly
reaccumliated due to transudation of fluid
from the interstitial and plasma
29
D- Paracentesis
Major complications
• 15-100% of the fluid reaccumlates
with 24-48 hrs → transient
hypovolemia and possibility of shock,
encaphalopathy and ARF
• Hypotension
• Hemconcentration
30
D- Paracentesis
Major complications
• Shock
• Oliguria
• Hepatorenal syndrome
• Hemorrhage
• Perforation of abdominal vicra
• Infection, bacterial peritonitis
• Protein depletion
31
E- Albumin
• Combined with paracentesis
• Effective as the initial management
in tense ascites
Typical regimen:
Removal of 4-6 l/day with replacement
of 40-50g of albumin
32
E- Albumin
Benefits of combination:
• More ascetic fluid can be removed
• Shorter hospital stay
• Superior to diuretic therapy
• No worsening of hepatic, renal or CV
function
• Albumin alone can promote diuresis in
ascites & edema by increasing intravascualr
volume
• The effects are not long lasting
• Variceal hemorrhage may be precipitated
33
F- Dextran 70
• Can be combined with paracentesis
• Equally effective to albumin in
mobilizing ascities
• More cost-effective
• Does not correct the underlying
hemodynamic abnormalities, so
albumin is preferred
34
G-Surgical therapy
1- Peritoneovenous shunt
•An implanted valve in the abdominal
wall, with cannula that empties into
the vena cava
•Urine output as high as 15 L in 24
hrs
•Supplemental fruosamide may be
needed to prevent vascular overload
35
G-Surgical therapy
1- Peritoneovenous shunt
Contraindications:
–
–
–
–
–
Peritonitis,
Recurrent coma
Sever coagulopathy
Significant cardiac failure
Acute alcoholic hepatitis
36
G-Surgical therapy
1- Peritoneovenous shunt
Complication
– Pulmonary edema
– Coagualopahty
– Fever, Wound infection, Septicemia,
GI bleeding
•Reserved for patients with good renal
and hepatic function who fail standard
therapies
37
G-Surgical therapy
2-transjugular intrahepatic
portosystemic shunt (TIPS)
•a radiologic procedure in which a
stent is placed in the middle of the
liver to reroute the blood flow.
•it makes a tunnel through the liver
connecting the portal vein to one of
the hepatic veins.
•A metal stent is placed in this tunnel
to keep the track open.
38
SBP
• SBP is an infection of ascites that
occurs in the absence of a
contiguous source of infection.
• SBP occurs in 10 to 20 % of
hospitalized cirrhotic patients.
• Early diagnosis is a key issue in the
management of SBP.
• SBP pathogenesis in patients with
cirrhosis is considered
• to be the main consequence of
bacterial translocation.
39
SBP-Predisposing factors
• Severity of liver disease
• Total ascites protein <1 g/dL
• GI bleeding
• Bacteriuria
• Previous SBP
Recurrence rates: 43% by 6 mts,
69% by 1 yr and 74% by 2 yrs
40
SBP-Clinical features
• signs may be absent in up to 1/3
• fever/hypothermia
• abdominal pain and tenderness
• hepatic encephalopathy
• diarrhoea
• ileus
• shock
• Unexplained deterioration in a
patient with cirrhosis and ascites
should lead to diagnostic
paracentesis
41
SBP-diagnosis
A diagnostic paracentesis should be
performed in
• Any patient admitted to the
hospital with cirrhosis and ascites,
• Any cirrhotic patient who develops
compatible symptoms or signs
• Any cirrhotic patient with
worsening renal or liver function.
• Diagnosis is established with an
ascites PMN of > 250/mm3
42
SBP- Treatment
• Once an ascites PMN count of
>250/mm3 is detected, and before
obtaining the results of ascites or
blood cultures, antibiotic therapy
needs to be started.
• The antibiotic that has been most
widely used in the treatment of
SBP is IV cefotaxime (2g 8 hrly)
with which SBP resolves in around
90 90% of treated patients
43
SBP- Treatment
• The combination of amoxicillin and
clavulanic acid was shown to be as
effective and safe as cefotaxime
• Antibiotic treatment can be safely
discontinued after the ascites PMN
count decreases to below 250/mm3
• duration of antibiotic therapy
should be for a minimum of 8 days
44
The following interventions are recommended based on controlled trials or cohort studies
demonstrating infection cure rates of around 90 percent:
Intravenous cefotaxime or other third-generation cephalosporins (ceftriaxone) for a duration of 5
to 8 days
Intravenous ampicillin/sulbactam is an alternative
In patients with community-acquired SBP, no renal dysfunction, no encephalopathy, and a low
prevalence of quinolone-resistant organisms, an orally administered widely bioavailable
quinolone (ofloxacin, levofloxacin) is an alternative
In patients with renal dysfunction, intravenous albumin at a dose of 1.5 g/kg body weight on the
first day and 1 g/kg body weight on the third day
The following interventions are not recommended based on clinical trials, uncontrolled studies
demonstrating that other interventions are either more effective or safer, as well as theoretical
considerations:
Aminoglycoside-containing antibiotic combinations
Procedures and medications that will decrease intravascular effective volume (e.g., large volume
paracentesis, diuretics)
The following intervention is under evaluation and cannot be widely recommended until additional
information is available:
Intravenous albumin as an adjunct to antibiotic therapy
45
Prevention of recurrent SBP
• In patients who survive an episode
of SBP, the 1-year cumulative
recurrence rate is high, at about 70
%.
• It is essential that patients be
started on antibiotic prophylaxis to
prevent recurrence before they are
discharged from the hospital.
46
Prevention of recurrent SBP
• Long-term prophylaxis with oral
norfloxacin at a dose of 400 mg QD
• treatment should be initiated as
soon as the course of antibiotics for
the acute event is completed.
• oral ciprofloxacin at a dose of 250
mg QD could be used, although
levofloxacin may be a better
alternative given its added grampositive coverage.
47
Prevention of recurrent SBP
• Weekly administration of
quinolones is not recommended
given a lower efficacy and an
increase in the development of
fecal quinolone-resistant
organisms.
• Prophylaxis should be continuous
until disappearance of ascites (i.e.,
patients with alcoholic hepatitis
who stop drinking) or transplant
48
The following interventions are recommended based on randomized clinical trials or expert
opinion:
Oral norfloxacin at a dose of 400 mg QD (not on VA National Formulary)
Oral ciprofloxacin or levofloxacin at a dose of 250 mg QD
The following intervention is not recommended based on clinical trials or uncontrolled studies
demonstrating that other interventions are either more effective or safer:
Weekly administration of quinolones
The following intervention is under evaluation and cannot be recommended until additional
information is available:
Trimethoprim/sulfamethoxazole
49
50
Esophageal varices
Definition
• Compensatory hemodynamic mechanism due
to PHTN
• Shunting of blood supply through low-pressure
collateral veins in the esophageaus, rectum.
• ↑ pressure in the gastric fundus and
esophagus cause swelling and burst resulting
in life threatening upper GI bleeding
• Bleeding may be ↑ by impaired clotting system
caused by deficincies of vitamin K dependant
clotting factors
• It is the leading cause of death in cirrhosis
• Considered a medical emergency
51
Esophageal varices
Goals of therapy
• Volume resuscitation
• Acute treatment of bleeding
• Prevention of recurrence
52
EV-General Management
Resuscitation
• Gastric lavage with suction of gastric fluid to
prevent complication as aspiration & pneumonia
• Pharmacological treatment to stop bleeding
• If PT > 15 sec, INR. 1.7 give 10mg IV vitamin K
• Monitor electrolytes, blood gases, and urine output
Hypovolemia
• Signs: Pallor, cold clammy skin, rapid pulse, SBp <
80 mmHg
• Blood and blood products transfusion
• Keep HCT > 30%
• Whole blood is preferred due to homeostatic
properties
53
Therapy of Bleeding Varices
1-Vassopressin
• Powerful non-specific vasoconstrictor
that reduces blood flow in the
splanchnic bed
• Effective in 60% of patients
• short half-life and must be given as
CIV
• May be used before sclerotherpay to
slow bleeding and visualize varices
54
Therapy of Bleeding Varices
1-Vassopressin
• Dosing
• Use lowest effective dose because
ADRs dose related
• IV bolus 20U → IVI of 0.2-0.4 u/min
Max 0.9 u/min
• Taper dose over 24-48 hrs when
bleeding controlled
55
1-Vassopressin
SE:
• Intense vasoconstrictor action decreases
C.O. and may cause coronary ischemia
• Bradycardia due to stimulation of the vagus
nerve
• Abdominal cramping and Skin blanching
due to stimulation of smooth muscle
contraction
• Phlebitis
• Hematoma at the site of infusion
• Excess water retention and dilutioanl
hyponatremia
56
Therapy of Bleeding Varices
2-Terlipressin
• A synthetic analogue
• 80% effective
• Longer half-life and can be give
as bolus every 6 hrs
• Dose 2 mg
• Less cardiac side effects have
been reported
57
Therapy of Bleeding Varices
3-Somatosatin
• Natural peptide with shorter half life
• Dose: bolus 50-250 mcg, infusion 250500 mcg/hr
• Similar efficacy to vasopressin but les
side effects and higher cost
4- Octreotide
• Synthetic analogue of somatostatin
• Selective, potent vasoconstrictor that
reduces portal and collateral blood flow
• Comparable efficacy to vasopressin
• Dose: bolus 50-100 mcg followed by
infusion 25-50 mcg/hr
58
Sclerotherapy
• Insertion of a flexible fiberoptic
esophagoscope to directly visualize and
inject a sclerosing agent in varices to
induce immediate homeostasis →intense
inflammation → thrombus formation and
cessation of bleeding in 2-5 minutes
• Permanent destruction of the vessel over
several days
• Procedure may need to be repeated several
times
59
Sclerotherapy
• Treatment of choice
• 95% effective
• More effective that vasopressin and balloon
tamponade
• Following scleotherapy, prophylaxis with
antacids, histamine blockers, omeprazole or
suclafate
60
Sclerotherapy
Complications
• Esophageal ulceration
• Stricture formation
• Esophageal perforation
• Retrosternal chest pain
• Temporary dysphasia
Sclerosing agents
• Sodium tetradecyl sulfate
• Ethanolamine oleate
• 0.5-2 ml of the solution is injected
61
Therapy of Bleeding Varices
Alternative treatments: Balloon
tamponade
• After initial sclerotherapy fails before
trying a second sclerotherapy
• Used for acute treatment
• 90% effective
• Direct compression of the varices
• Temporary procedure limited to time
balloon is inflated
• An additional procedure required
within 24 hrs
62
Therapy of Bleeding Varices
Alternative treatments: Balloon
tamponade
Complication
• Aspiration
• Pneumonitis
• Esophageal ulceration
• And rupture
• Chest pain
• Asphyxia
63
EV-Long-Term Management
1- Propranolol
• Used for secondary prophylaxis
• To reduce hepatic flow and portal
pressure
• Beneficial in alcoholic cirrhosis and
less advanced disease
• Does not decrease mortality
• Abrupt discontinuation may lead to
rebreeding
64
EV-Long-Term Management
2- Endoscopic Band Legation
• An elastic band is placed around
the mucus a and submucosa of the
esophageal area containing the
varix
• Leading to strangulation and
fibrosis of the varix as effective as
sclerotherpay with less
complications
• Effective in preventing rebreeding
3-Surgery
65
EV-Long-Term Management
Primary prophylaxis
• Primary prevention of bleeding
episode
1-Beta-Blockers
• Studies shown beta blockers to
prevent bleeding
• Using 25% reduction in heart rate
or hepatic venous gradient
• Propranolol and nadolol have been
used
• They do not increase survival
66
EV-Long-Term Management
Primary prophylaxis
2-Isosorbide mononitrate
• Can reduce portal pressure
• Combination with propranolol has
greater reduction in pressure
• Similar efficacy to propranolol, with
regard to bleeding and survival
3-Sclerotherpay
• As a primary preventive measure
has a higher mortality rate and is
not recommended
67
3-Hepatic Encephalopathy
• a metabolic disorder of the CNS and
occurs in patients with advanced
cirrhosis or fulminate hepatitis.
Clinical Features
• Altered mental status
• Fetor heapticus : sweetish musty
pungent odor of the breath
• Asterixis: flapping tremor, non=specific
• Personality changes
• Drowsiness and confusion
• Deep coma, reversible
68
Pathogenesis-HE
1- Ammonia
• The byproduct of protein
metabolism
• Large portion is derived from diet
or blood in the GIT
• Ammonia is metabolized to urea,
which is renally eliminated
69
Pathogenesis-HE
1- Ammonia
• In cirrhosis serum and CNS
ammonia are increased
• In the CNS it combines with alphaketogluarate to form glutamine an
aromatic amino acid.
• High glutamine in CSF is
characteristic of encephalopathy ,
but it may not be the only cause
70
Pathogenesis
2-Amino acid balance
• normal ratio of branched to aromatic AA is
4-6:1
• Catabolic state → -ve nitrogen balance
and preferential use of BCAAs as a source
of energy
71
Pathogenesis
• As liver failure progress → liver no
longer produce glucose for energy →
BCAA used by skeletal muscle → ↓ their
level in the blood.
• Plasma clearance of AAAs is ↓
• The blood brain barrier become more
permeable to AAA via exchange for
glutamine in the CSF
73
Pathogenesis
• In the CSF the aromatic compounds are
metabolized into chemicals that disrupt
normal neurotransmitter balance
• E.g. tryptophan is converted to
serotonin, which can compete with
norephineprine for normal CNS function
74
Pathogenesis
3-Gamma-aminobuyteric acid (GABA)
• GABA is the primary inhibitory
neurotransmitter in the CNS
• Activation of GABA receptors results in
increased Chloride permeability, hyper
polarization of the neuronal membrane,
and inhibition of neurotransmission.
• GABA binds to postsynaptic receptors
sites in the brain, and causes the
neurological abnormalities associated
with hepatic encephalopathy.
75
Precipitating factors
• Increase the serum ammonia or
produce excessive somnolence in
patients with impending hepatic
coma
• Excess nitrogen load and metabolic
or electrolyte abnormalities may
increase ammonia levels
76
A- Excess nitrogen load
1- GI bleeding
Varices
Hemorrhoids
Peptic ulcer
Bacterial degradation
of blood proteins
result in absorption
of large amounts of
ammonia and toxins
2- Excess dietary proteins
3- Azotemia
Diuretic induced hypovolemia
Uremia of renal failure
Excessive introhepatic circulation of
BUN
Induce prerenal
azotemia, and
promote
hypokalemia, and
alkalosis,
77
4-Infection
5-Constipaiotn
Increased tissue
catabolism
↑ ammonia
generation due to ↓
gut transient time
78
Metabolic and electrolyte abnormalities
1-Hypokalemaia
Increases the
Diuretic induced
concentration of
Dietary deficiency
ammonia in renal
Excessive diarrhea
venous blood
Hyperaldosteroism
2-Alkalosis
Promotes diffusion of
Hypokalemia
nonionic ammonia
Excessive nausea and vomiting and other amines
into CNS
79
Drug-induced CNS depression
Sedatives
Tranquilizers
Narcotic analgesics
Increased CNS
sensitivity and
decreased hepatic
clearance which lead
to accumulation
Also bound drugs
increase their free
fraction.
80
Treatment
1-removal of precipitating factor
2-reducing the amount of ammonia or
nitrogenous products in the blood
3- Stop or limit protein intake at the onset
of encephalopathy
• May be increased at 10-20 g/day every
2-5 days depending on the clinical
condition.
• Vegetable protein may be better
tolerated because they contain fewer
methionine and aromatic amino acids
are less ammoniagenic
81
Drug Therapy
1-Lactulose
• A disaccharide broken down by GI bacteria to
lactic, acetic, and formic acid
• MOA:
– acidification of the colon to convert NH3 →
less absorbed NH 4+ → lower plasma NH3
– Induce osmotic diarrhea decreases intestinal
transient time available for NH3 production
and absorption.
• Dose
– Syrup 10g/15 ml
– Acute: 30-45 ml TID titrated to resolution of
symptoms & 3 soft stools /day.
– In coma : rectal retention enema 1:3
lactulose in tap water
– Effects appear in 24-48 hrs
82
Drug Therapy-Lactulose
• Precautions
–Avoid excessive diarrhea because
it could lead to dehydration and
hypokalemia which could
exacerbate encephalopathy
–20% may have gaseous
distention, flatulence, belching
83
Drug Therapy
2-Neomycin
•MOA:
– reduces plasma ammonia levels by
decreasing protein metabolizing
bacteria in the GI tract
•Dose:
–
1-2 g orally QID
– 1% retention solution as retention
enema foe 20-60 min QID
84
Drug Therapy -Neomycin
• Precautions
– 1-3% of the dose can be absorbed and may
cause ototoxicity or nephrotoxicity
especially with chronic use in patients with
renal failure.
– Monitor serum creatinine, protein in the
urine, CrCl when using high doses are used
for long periods
– May lead to reversible malabsorption
syndrome that may decrease absorption of
fat, iron, vit B digoxin, penicillin, and vit K
• Comparison
– Similar effectiveness
– Neomycin produces a faster response in
acute case
– A patient who does not respond to one may
respond to the other
85
Drug Therapy
• Combination
– May be more effective than either
drug alone
– Sterilization of gut bacteria by
neomycin may impair bacterial
degradation of lactulsoe and prevent
colonic acidification
– A stool PH < 6.0 reflects synergistic
effects
– Lactulose alone is preferred for long
term use
– Always try lactulose first if no
response try neomycin, then try
combination
86
Drug Therapy
3-Branched chain amino acids
•Diets high in BCAA and low in AAAs may
help restore normal AA balance and
reduce encepalopathy
•Heptamine is marketed as an 8% AA
solution and contains more BCAAs than
standard parental solutions
•Indications
–
Due to high cost and limited efficacy
information Patients with life threatening
encepalopathy refractory to conventional
therapy and with documented elevated
serum ammonia levels
•Hepatic-aid- Dietary supplement
87
Drug Therapy
4-Flumazenil
• A benzodiazepine antagonist
• Bases on GABAergic
neurotransmission in hepatic
encephalopathy
• Demonstrated clinical
improvement
• Dose: chronic: 25 mg BID
88