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(Hepatic Disease)
5. Vascular abnormalities
Example: Budd-Chiary syndrome • Obstruction of Hepatic venous
outflow
Cirrhosis
↓
↑ resistance to blood flow from portal system – Portal HTN
↓ Gradually
Liver cells death
↓
↓ Functioning Liver cells
↓
Chronic Liver Failure [Figure 1]
Pathophysiology [Figure 1]
Clinical Manifestations
Symptoms Characteristic to LD
• Weakness, Fatigue, Malaise
• Jaundice (Striking symptom)
• Bleeding complications • Common in all LD
• Loss of muscle bulk • (ALD/CLD)
• Abdominal discomfort
B. Antihistaminics
Ex: Cetirizine, Loratidine
Chlorpheniramine, Hydroxyzine
C. Opioid antagonists
Ex: Naloxone, Naltrexone, Nalmefene
Choice of Drugs:
Colestyramine > antihistaminics > UDCA > Rifampicin > Others
Therapeutic M/A:
Colestyramine + Bile Salts → C-BS complex → Inhibit bile salts reabsorption →
Antipruritic effect
Dose/RoA/DOA/Preparation:
4-16g (Tablet/Granules) in 2-3 divided doses by PO
2. Clotting abnormalities
Choice of Drugs:
Vitamin K (Phytomenadione)
Therapeutic M/A:
Vitamin K is a co-factor for the synthesis of majority of clotting factors in liver .
Caution:
NSAIDS & anticoagulants should be avoided in LD due to risk of bleeding.
Dose/RoA/DOA/Preparation:
10mg/day injected iv for 3 days. Repeated when required.
3. Ascites
Choice of drugs/methods:
1 Line: (a) Low salt diet (Low volume ascites)
(b) Diuretics (Moderate-Large volume ascites)
(c) Paracentesis (Moderate-Large volume ascites)
2 Line: TIPS
Therapeutic M/A:
Spironolactone → ↓ Na+ reabsorption → Diuresis (↑ Na+ Excretion)
@ distal renal tubule
Efficacy and Safety:
Produce slow diuresis
Tolerable side effects (Hyperkalemia, Gynaecomastia)
Administered with furosemide if diuresis by Spironolactone is unacceptable
Caution is required as excessive diuresis can produce renal failure. Monitoring
of urea, Na+ & K+ is required during the diuretic therapy.
Dose/RoA/DOA/Preparation:
Spiron: 50-400mg/day by PO (Tab). With Furosemide: 40-160mg/day by PO (Tab)
Ascites Contd…
Therapeutic M/A:
Ascite is perforated with hollow needle to remove the fluid in large amount.
Dose/RoA/DOA/Preparation:
Paracentesis is done once in 2-4 weeks. Additionally, 6-8g albumin is administered
iv/1L of ascite fluid removed
OR
100ml of human albumin solution (20%) administered iv/2.5L Ascite fluid removed
4. Spontaneous Bacterial Peritonitis (SBP)
B. Penicillins
Ex: Amoxycillin + Clavulanic acid
C. Quinolones
Ex: Norfloxacin
Spontaneous Bacterial Peritonitis (SBP) Contd…
Choice of drugs:
Cefotaxime > Penicillins & Quinolones
Therapeutic M/A:
Cefotaxime → Inhibit bacterial cell wall synthesis → Antibacterial effect
Dose/RoA/DOA/Preparation:
2gms injected tid by iv route.
5. Hepatic encephalopathy
Choice of drugs:
Lactulose > Antibacterial drugs > Other drugs
Therapeutic M/A:
Gut Flora
Lactulose -------→ Lactic acid + Acetic acid + Formic acid --→ Acidity colonic content
↓
↓ Absorption of nitrogenous products ←----- Ionization of nitrogenous products
(@GIT)
Dose/RoA/DOA/Preparation:
30-40ml/day titrated PO till 2-3 bowel motions/day is maintained
6. Oesophageal varices
Choice of drugs:
Terlipressin > Somatostatin, Octreotide
Propranolol is used prevent re-bleeding as 1 Line treatment
Therapeutic M/A:
Dose/RoA/DOA/Preparation:
1-2mgs administered as iv bolus 4-6 times/day for 48hrs.
Oesophageal varices Contd…
Invasive, non-invasive and drugs are used to treat oesophageal varices as alone
or combined therapy in step wise manner. Meaning of some non-drug techniques
is mentioned below [Figure 2]:
Sclerotherapy: Salt solution is injected directly into varicose vein. Solution irritates
lining of blood vessels & causes it to collapse & stick together & blood to clot.
Surgical decompression shunt: Shunt is placed between hepatic vein and inferior
venacava. It can decompress portal vein system side to side to create a channel.
Therapeutic M/A:
Tenofovir --------- → Competes with natural nucleotide ----- → HBV polymerase
(Nucleotide analogue) & binds to active site of HBV polymerase (Inhibited)
Dose/RoA/DOA/Preparation of Tenovir:
8mg/kg by PO (Tablet/Powder). Maximum dose: 300mg/day.
2. Hepatitis C
Therapeutic M/A:
Peg Interferon inhibits replication of HCV & stimulates apoptosis in the infected cells.
+
Ribavirin is converted to Ribavirin triphosphate. R. triphosphate binds to nucleotide
binding site at RNA polymerase by competing with correct nucleotide. RNA synthesis
in inhibited.
Dose/RoA/DOA/Preparation:
Peg. Interferon: 180micrograms/week for 6-12months by transfusion
Ribavirin: 400-800mg/day for 6-12months by transfusion
3. Autoimmune hepatitis
Therapeutic M/A:
Inhibits antigen-antibody induced consequences in the liver.
Dose/RoA/DOA/Preparation:
Prednisone: 40-60mg/d PO for 6 weeks. Later, dose is to be reduced to 7.5mg/day
up to 3 months + Azathioprene: 1-1.5mg/kg/day
4. Primary Biliary Cirrhosis (PBC) & 5. Primary Sclerosing Cholangitis (PSC)
Choice of Drugs:
Ursodeoxycholic acid (UDCA)
Therapeutic M/A:
Protects against cytotoxic effects of hydroxy bile acids.
Dose/RoA/DOA/Preparation :
PBC: 10 mg/kg/day in two divided doses. PSC: 15mg/kg/day.
6. Wilson’s disease
Choice of Drugs:
Penicillamine > Trientine >> ZInc
Therapeutic M/A:
Prevents copper accumulation & promotes its excretion in urine by forming chelate
complex.
Dose/RoA/DOA/Preparation :
1.5-2gms/day by PO in divided doses with Pyridoxine, 25mg/day
References
A. Kennady P, O’Grady JG. In: Roger Walker, Cate Whittelesea, editors. Clinical
Pharmacy and Therapeutics. 5th ed. London, Elsevier Publishing; 2012.
B. Research articles