LIVER Flashcards
LIVER (76 cards)
1
Q
Hepatitis means inflammation of the liver and it’s cause by?
A
Hepatitis Virus but also
Alcohol
Drugs
Autoimmune Disease
Herpesvirus
CMV Epstein Virus
Adenovirus
2
Q
Describe Hepatitis A?
A
Acute (self limiting illness)
Fecal-Oral Transmission (through improper hand washing or via contaminated food/water)
Vaccine Available
First Line Treatment: SUPPORTIVE CARE
3
Q
Describe Hepatitis B?
A
Acute and Chronic (acute can lead to chronic infection, cirrhosis, cancer, liver failure and death)
Blood and Body Fluids Transmission (sex, needle, perinatal)
Vaccine Available
First Line Treatment: PEG-INF (Pegylated Interferon or NRTI (Tenofovir or Entecavir)
4
Q
Describe Hepatitis C?
A
Acute and Chronic (acute can lead to chronic infection, cirrhosis, cancer, liver failure and death)
Blood and Body Fluids Transmission (sex, needle, perinatal)
NO Vaccine Available
First Line Treatment:
-NAIVE PT:
DAA ( Direct Acting Antiviral) Combination
-SELECTED PT:
DAA ( Direct Acting Antiviral) Combination + RBV (Ribavirin)
DAA ( Direct Acting Antiviral) Combination +RBV (Ribavirin) +PEG-INF (Pegylated Interferon)
5
Q
How many types of Genotype does the Hepatitis C have?
A
6 genotype ( 1–6)
Various Subtypes ( 1a or 1b)
Treatment and Duration depends on genotype, presence of Cirrhosis and pt treatment history.
6
Q
What’s the PREFFERED Hepatitis C (HCV) Treatment REGIMEN of treatment NAIVE patient WITHOUT Cirrhosis ?
A
- 2 to 3 Direct Acting Antiviral (DAAs) with DIFFERENT MECHANISMS of ACTION usually for 12 WEEKS ( some 8 Weeks in appropriate pt).
- Some combination includes: RITONAVIR which is NOT ACTIVE for HCV but USED to BOOST LEVELS of HCV protease inhibitors used with it.
RITONAVIR can be ADDED to DAA as an alternative treatment option.
INTERFERON are NOT RECOMMENDED but could be USED if DAA are CONTRAINDICATED or TOO Expensive.
7
Q
PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?
A
MOA : NS3/4A Protease Inhibitor
PREVIR : P for PI
DRUGS:
Grazo-PREVIR
Parita-PREVIR
Sime-PREVIR
Voxila-PREVIR
8
Q
PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?
A
MOA: NS5A Replication Complex Inhibitor
ASVIR: A for NS5A
DRUGS:
Daclat-ASVIR
Ledip-ASVIR
Ombit-ASVIR
Pibrent-ASVIR
Velpat-ASVIR
9
Q
PREFFERED Hepatitis C (HCV) DAA Treatment REGIMEN and Mechanisms?
A
MOA: NS5B Polymerase Inhibitor
BUVIR: B for NS5B
DRUGS:
Dasa-BUVIR
Sofos-BUVIR
10
Q
Why are Direct Acting Antiviral (DAA) TREATMENT IMPORTANCE IN HCV?
A
DAA have revolutionized HCV treatment and replace older treatment( lnterferon and Ribavirin) and offer CURE for MOST patients.
Consist of DRUG COMBO that TARGET DIFFERENT PHASES of the HCV LIFE CYCLE.
11
Q
Direct Acting Antiviral (DAA) Treatment Regimen should consist of 2 DIFFERENT MECHANISMS of ACTION?
A
Preffered: Daclat-ASVIR + Sofos-BUVIR
Not Preffered: Dasa-BUVIR + Sofos-BUVIR
12
Q
What IMPORTANT to REMEMBER about PROTEASE Inhibitors used for HCV and HIV?
A
Take with food (Almost All)
PI(G) : PIG and FOOD
Except:
Elb-ASVIR/Grazo-PREVIR (Zepatier) : Without Regard to Food
Fosamprenavir Oral Suspension: Without Food in Adult
13
Q
What’s the Box Warning for ALL class of DAA (Direct Acting Antiviral) Drugs?
A
*Risk of REACTIVATING HBV; test all patients for HBV before starting a DAA.
14
Q
What’s the Warning for SOFOS-BUVIR Containing Regimen?
A
- Serious Symptomatic BRADYCARDIA reported when taken with AMIO-DARONE.
- DO NOT use Amiodarone with SOFOS-BUVIR or SOFOS-BUVIR Containing Regimen.
15
Q
What’s are the SIDE EFFECTS of ALL class of DAA (Direct Acting Antiviral) Drugs??
A
*Well Tolerated;
Head ache
Fatigue
Diarrhea
Nausea
16
Q
What’s the MONITORING of ALL class of DAA (Direct Acting Antiviral) Drugs?
A
LFT ( Including Bilirubin)
HCV-RNA
17
Q
What’s are the Drug INTERACTION of ALL class of DAA (Direct Acting Antiviral) Drugs?
A
*SIGNIFICANT Drug INTERACTION Potential.
See package insert of each agent for more details.
18
Q
What’s are the CONTRAINDICATIONS of ALL class of DAA (Direct Acting Antiviral) Drugs?
A
*CONTRAINDICATIONS with strong INDUCERS of CPY3A4 example:
Car-bama-zepine
Ox-carba-zepine
Phe-no-barbital
Phe-ny-toin
Ri-fam-pin
Rifa-butin
St. John’s Worth
*Most DAA’s INCREASE concentration of STATINS and INCREASE risk of Myopathy.
19
Q
Sofos-BUVIR
So-Val-Di
A
SOVALDI
Serious Drug INTERACTION
- Monotherapy Not Recommended
- Dispense in ORIGINAL Container: ( Applies to all Sofos-BUVIR containing COMBINATION)
- AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametime , PPI) during treatment.
Use Less Than or Equal to 40 mg Famotidine BID or Equivalent
APPROVED FOR:
Children greater than 12 Years Old with CERTAIN Genotypes
20
Q
*Sofos-BUVIR/ Ledip-ASVIR
Har-Vo-Ni
A
- HARVONI
- Dispense in ORIGINAL Container
- AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at the sametime , PPI) during treatment.
Use Less Than or Equal to 40 mg Famotidine BID or Equivalent
APPROVED FOR:
HCV/HIV Co-Infection
Children greater than 12 Years Old with CERTAIN Genotypes
21
Q
*Sofos-BUVIR/ Velpat-ASVIR
Ep-Clu-Sa
A
- EPCLUSA
- Dispense in ORIGINAL Container
- AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametime , PPI) during treatment.
Use Less Than or Equal to 40 mg Famotidine BID or Equivalent
*DO NOT Use PPI with EPCLUSA
APPROVED FOR:
Pan-Genotypic (ALL 6 HCV genotype) in treatment NAIVE Pt
HCV/HIV Co-Infection
22
Q
Sofos-BUVIR/ Velpat-ASVIR/ Voxila-PREVIR
Vo-Se-Vi
A
*VOSEVI
Take with FOOD
- Dispense in ORIGINAL Container
- AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametimrle , PPI) during treatment.
Use Less Than or Equal to 40 mg Famotidine BID or Equivalent
APPROVED FOR:
Salvage Therapy ( FAILED previous therapy)
23
Q
Sofos-BUVIR/ Velpat-ASVIR/ Voxila-PREVIR
Vo-Se-Vi
A
*VOSEVI
Take with FOOD
- Dispense in ORIGINAL Container
- AVOID or MINIMIZED ( Separate by 4 HRs) Acid Suppressive therapy ( ANTACIDS, H2RAs ; separate 12 HRS or take at sametimrle , PPI) during treatment.
Use Less Than or Equal to 40 mg Famotidine BID or Equivalent
24
Q
Gleca-PREVIR/ Pibrent-ASVIR
Ma-Vy-Ret
A
*MAVYRET
Take with FOOD
APPROVED FOR:
Pan-Genotypic (ALL 6 HCV genotype) in treatment NAIVE Pt.
Salvage Therapy ( FAILED previous therapy)
8 Week Course ( SELECTED PT)
HCV/HIV Co-Infection
CONTRAINDICATIONED with Efavirenz , Cyclosporine, Ethinyl Estradiol products, and HIV Protease Inhibitor s ( ataza-NAVIR, Daru-NAVIR, Lopi-NAVIR, Rito-NAVIR)
25
Which DAA DRUGs are APPROVED FOR:
PAN- GENOTYPIC (ALL 6 HCV genotype) in treatment NAIVE Patients.
Epclusa
Mavyret
26
Which DAA Drugs are APPROVED FOR:
SALVAGE THERAPY ( FAILED previous therapy)
Vosevi
Mavyret (selected pts)
27
Which DAA DRUGS is APPROVED FOR:
8 WEEKs Course of Therapy ( SELECTED PT)
Mavyret
28
Which DAA DRUGS are APPROVED FOR:
HCV/HIV Co-Infection
Epclusa
Harvoni
Mavyret
29
Which DAA DRUGS are APPROVED FOR:
Children GREATER THAN 12 Years Old with CERTAIN Genotypes
Sovaldi
Harvoni
30
Acid Suppressive Therapy (ANTACIDs, H2RAs, PPI) should be AVOIDED OR MINIMIZED in these DAA DRUGS:
SOVALDI (Sofos-BUVIR )
HARVONI (Sofos-BUVIR/Ledip-ASVIR): Decrease concentration of Ledip-ASVIR)
EPCLUSA (Sofos-BUVIR/Velpat-ASVIR) : Decrease concentration of Velpat-ASVIR
VOSEVI (Sofos-BUVIR/Velpat-ASVIR/ Voxila-PREVIR) : Decrease concentration of Velpat-ASVIR
31
Daclat-ASVIR
| Dak-Lin-Za
* DAKLINZA
* Combined with Sofos-BUVIR
* Monotherapy NOT Recommended
CONTRAINDICATIONS: CYP450 3A4 Inducers
Consider screening for NS5A polymorphism if patient has HCV genotype 1A with CIRRHOSIS
32
Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR
| Tech-Ni-Vie
* TECHNIVIE
* Take with FOOD
*CONTRAINDICATIONS:
Moderate Severe Hepatic Impairment (Child Pugh B or C)
DO NOT use with drugs HIGHLY DEPENDENT ON CYP3A4 for Elimination ( INCREASE Level can cause Adverse Event)
DO NOT use with MODERATE to STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.
DO NOT use with RIBAVIRIN in COMBINATION REGIMENS
* WARNING: Hepatic Decomposition and Hepatic Failure in patients with CIRRHOSIS; risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED Risk.
* SIGNIFICANT DRUG INTERACTION POTENTIAL
* Risk of HIV PROTEASE INHIBITOR RESISTANCE
Side Effect:
Insomnia
Pruritus
33
Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR + Dasa-BUVIR
| Vie-Ki-Ra XR/Pak
* VIEKIRA
* Take with FOOD
* Parita-PREVIR/ Rito-NAVIR/ Ombit-ASVIR ; take ONCE daily in am
* Dasa-BUVIR:take TWICE daily with FOOD
* VIEKIRA XR: Take ONCE daily with meal
*CONTRAINDICATIONS:
Moderate Severe Hepatic Impairment (Child Pugh B or C)
DO NOT use with drugs HIGHLY DEPENDENT ON CYP3A4 for Elimination ( INCREASE Level can cause Adverse Event)
DO NOT use with MODERATE to STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.
DO NOT use with STRONG INDUCERS or INHIBITORS of CYP2C8 (Ex. Gemfibrozil); Dasa-BUVIR is a major. CYP2C8 substrate
DO NOT use with RIBAVIRIN in COMBINATION REGIMENS
* WARNING: Hepatic Decomposition and Hepatic Failure in patients with CIRRHOSIS; risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED Risk.
* SIGNIFICANT DRUG INTERACTION POTENTIAL
* Risk of HIV PROTEASE INHIBITOR RESISTANCE
* Side Effect:
Insomnia
Pruritus
34
TECKNIVIE and VIEKIRA are CONTRAINDICATED with STRONG CYP3A4 INDUCERs along with
* Ethinyl Estradiol Products ( Lo Loestrin FE, Norinyl, Ortho Tri Cyclen Lo, Xulane, NuvaRing, Femhr: hormone replacement therapy)
* Lovastatin
* Simvastatin
Alfuzosin, Colchicine, Ranolazine, Dronedarone, Lurasidone, pimozide, Ergotamine Derivative s, Efavirenz, Sildenafil, Triazolam, and Oral Midazolam
35
Elb-ASVIR/ Grazo-PREVIR
| Ze-Pa-Tier
*ZEPATIER
*CONTRAINDICATIONS:
Moderate to Severe Hepatic Impairment (Child Pugh B or C)
DO NOT use with STRONG CYP3A4 INDUCERs due to DECREASE EFFICACY of HCV Therapy.
DO NOT use with EFAVIRENZ, HIV Inhibitors and OATP1B1/3
DO NOT use with RIBAVIRIN in COMBINATION REGIMENS
* WARNING: Risk of increased LFTs ( Greater Than 5 x ULN) within 4 weeks of treatment. Patient taking ETHINYL ESTRADIOL product are at INCREASED
* SIGNIFICANT DRUG INTERACTION POTENTIAL
Screening for NS5A polymorphism is RECOMMENDED when treating patient with HCV genotype 1A.
36
Ribavirin
| Ri-Bas-Phere or Rebetol
MOA: INHIBIT of REPLICATION of RNA and DNA viruses
INDICATION: HCV in COMBINATION with other agents (DAAs/ INTERFERON ALFA); Toxicity within 4 WEEks
NEVER use as a MONOTHERAPY
Aerosolized form Use for RSV (Respiratory Syncytial Virus); Toxicity in ventilated pt
* BOX WARNING: Significant TERATOGENIC EFFECTS; not effective as MONOTHERAPY; HEMOLYTIC ANEMIA
* CONTRAINDICATIONS:
Pregnancy
Women of Childbearing age not on CONTRACEPTIVE
Male Partner of PEGNANT Women
Hemoglobinopathies
CrCl less than 50 mL/min
Autoimmune Hepatitis
DO NOT use with DIDANOSINE
SIDE EFFECTS:
HEMOLYTIC ANEMIA ( especially in Cardiac Disease)
Fatigue, Insomnia, Anorexia, N/V/D, Myalgia, Hypothyroidism, HA
MONITORING: CBC with diff, PLTs, Electrolyte, LFTs/bili, HCV-RNA, TSH, monthly preg test
NOTES: AVOID in PREGNANCY in FEMALE and FEMALE PARTNERS of MALE PATIENTS during therapy DURING THERAPY and 6 MONTHS AFTER COMPLETION.
USE 2 Reliable CONTRACEPTIVE form DURING THERAPY and 6 MONTHS AFTER COMPLETION.
37
INTERFERON ALFA Basic Information
* MOA: Natural produce CYTOKINES that have ANTIVIRAL, ANTIPROLIFERATIVE, and IMMUNOMUDULATORY Effects
* INDICATION: approved for HBV and HCV
* PEG-INF-Alfa have POLYETHYLENE GLYCOL added to PROLONG the HALF-LIFE (Wrekly Dosing)
No Longer RECOMMENDED in HCV except if other treatments are CONTRAINDICATED or COSTLY
COMBINATIONS FORMERLY USE :
INF +RBV
INF +RBV + DAA/s
*INTERFERON have TOXICITIES and LAB ABNORMALITIES that limit their use
38
INTERFERON ALFA Basic Information
Alfa Treats: HBV, HCV, and Some CANCERS
Beta Treat: MULTIPLE SCLEROSIS (MS)
DO NOT provide a CURE and are HARD to TAKE
FLU-LIKE Syndrome after Injection is Common
39
INTERFERON ALFA DRUGS :
Interferon - Alfa- 2b (Intron A): for HBV and HCV, many CANCERS
Pegylated -Interferon-Alfa- 2b (Pegasys): for HBV and HCV
Pegylated -Interferon-Alfa- 2b (Pegintron, Sylatron): for HCV
*SC dosing (Intron x 3; Pegasys and PegIntron x WEEKLY)
*BOX WARNING: can CAUSE or EXACERBATE
Neuropsychiatric, Autoimmune, Ischemic,or Infectious Disorders
If used with RIBAVIRIN,TERATOGENIC/ ANEMIA Risk
CONTRAINDICATIONS: Autoimmune Hepatitis, Decompensated Liver Disease in Cirrhotic patients , Infant/Neonates (Pegasys)
WARNING: Neuropsychiatric, Cardiovascular Events, Endocrine Disorder (hypo/hyper thydroidism/ glycemia), Visual Disorder (Retinopathy, Decreased in Vision), Panncreatis, Myelosuppression, Skin Reaction
*SIDE EFFECTS:
CNS Effect( Fatigue, Depression,Anxiety, Weakness)
GI Upset
INCREASED LFTs( 5-10 x ULN during Treatment)
Myelosupression
Mild Alopecia
*Flu-Like-Syndrome ( Fever, Chills, HA, Malaise); pretreat with APAP and ANTAHISTAMINE
MONITORING: CBC with differential and platelets, LFTs, Uric Acid, SCr, Electrolyte, TGs, Thyroid Function Test, Serum HBV-DNA or HCV-RNA levels
40
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV Basic Information:
* MOA: Inhibit HBV Replication by Inhibiting HBV Polymerase resulting in DNA Chain Termination.
* APPROVED as MONOTHERAPY for HBV
* TEST ALL Patients for HIV prior to Starting HBV Therapy
* Antiviral used for HBV can have activity against HIV and if a pt is CO- INFECTED with BOTH HBV and HIV chose therapy appropriate for both to MINIMIZED RISK of HIV ANTIVIRAL RESISTANCE.
41
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV Basic Information:
* CrCl less than 50 mL/min DECREASED Dose and Frequency (Except VEMLIDY)
* BOXED WARNING:
Lactic Acidosis
Severe Hepatomegaly with Steatosis (Fatal)
Exacerbation of HBV can occur upon D/C
Can CAUSE HIV Resistance in HBV Patient with Unrecognized or Untreated HIV Infection
42
*NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV
(TDF) Tenofovir Disoproxil Fumarate (Vi-Read)
(TAF) Tenofovir Alafenamide ( Ve-Mil-Dy)
* VIREAD and VEMILDY
* VEMILDY not RECOMMENDED in CrCl less than 15 mL/min
* WARNING:
Renal Toxicity including acute renal failure
Faconi Syndrome
Osteomalacia
DECREASED Bone Density
*SIDE EFFECT:
TDF: *Renal Impairment, *Decreased Bone Mineral Density, N/V/D, HA, Depression, Increased LFTs and CPK
TAF: *Nausea, Decreased Bone Mineral Density, Abdominal Pain, Fatigue, Cough, HA, Increased LFTs
NOTES:
* VIREAD ( TAF) and VEMILDY (TDF): Protect from moisture; DISPENSE only in ORORIGINAL CONTAINER
* TAF is associated with Decrease RENAL and BONE TOXICITY Compared to TDF
VEMILDY (TDF) Approved only for HBV
43
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV
Entecavir ( Bara-Clude)
* BARACLUDE
* Take on Empty Stomach
SIDE EFFECTS:
Peripheral Edema
Pyrexia
Ascites
Increase LFTs
Hematuria
Nephrotoxicity
Increase SCr
NOTES:
Food reduce AUC by 18 to 20% ; take on an empty stomach 2hrs before or after a meal
44
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV
Adefovir (Hep-Sera)
* HEPSERA
* BOXED WARNING:
Caution in patients with RENAL IMPAIRMENT or those at RISK of RENAL TOXICITY ( including concurrent NEPHROTOXIC agents or NSAIDs)
SIDE EFFECTS:
HA, Weakness, Abdominal Pain, Hematuria, Rash, Nephrotoxicity
45
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV
Lamivudine ( Epi-Vir HBV)
*BOXED WARNING:
DO NOT used Epivir for Treatment of HIV ( Contains lower dose of Lamviduvine) can result in HIV Resistance.
SIDE EFFECTS:
*HA, N/V/D, Fatigue, Insomnia, Myalgias, Increase LFTs
46
NucleoSide/Tide Reverse Transcriptase Inhibitors(NRTIs) Used for HBV
Lamivudine ( Epi-Vir HBV)
*BOXED WARNING:
DO NOT used Epivir for Treatment of HIV ( Contains lower dose of Lamviduvine) can result in HIV Resistance.
SIDE EFFECTS:
*HA, N/V/D, Fatigue, Insomnia, Myalgias, Increase LFTs
47
NRTI Counseling
Epivir HBV Tabs and Oral Solutions are not INTERCHANGEABLE with Epivir( higer dose)
48
What is CIRRHOSIS and it's COMMON CAUSE?
Advanced FIBROSIS Scarring) of the liver that is usually IRREVERSIBLE.
COMMON CAUSE:
Hepatitis C
Alcohol Consumption
49
In CIRRHOSIS, as scar tissue replaces the healthy liver tissue blood flow through the liver is impaired cause complications.
What ate these COMPLICATIONS ?
Portal Hypertension
Varices
Ascites
Hepatic Encephalopathy
50
What are the SYMPTOMS of CIRRHOSIS?
*Yellow skin and yellow white of the eyes (JAUNDICE)
N/V/D
Loss of Appetite
Malaise
Pain in upper right quadrant of abdomen
Darkened Urine and/or lightened color (white or clay-colored) due to low bile production
51
LAB TESTS for LIVER disease: what is
Aspartate Aminotransferase (AST)
Alanine Aminotransferase (ALT)
AST and ALT are LIVER Enzymes
Normal Range for BOTH : 10-40 units/L (vary)
HIGHER Values= MORE ACTIVE (acute) the LIVER Disease
52
What is the CLINICAL SIGNS of LIVER Disease?
```
*INCREASE:
ALT
AST
ALP or Alk Phos ( Alkaline Phosphate)
Tbili ( Total Bilirubin)
LDH ( Lactate Dehydrogenase)
PT ( Prothrombin Time)
```
*DECREASE:
Albumin ( PROTEIN produced by the liver; normal range 3.5 - 5.5 g/dL)
Note: Albumin and PT/INR are markers of synthetic ( PRODUCTION ABILITY) liver function and likely alter in chronic liver disease ( cirrhosis).
53
LIVER Disease can be CLASSIFIED as:
Hepatocellular ( Increase ALT and AST)
Cholestatic (Increase Alk Phos and Tbili)
Mixed (Increase ALT, AST, Alk Phos and Tbili)
54
Lab ABNORMALITIES to distinguished between TYPES of LIVER Disease:
* Acute Liver Toxicity (Drugs):
- Increase ALT/AST
*Chronic Liver Disease (Cirrhosis):
-Increase ALT/AST, Alk Phos, Tbili
LDH ,PT/INR
-Decrease Albumin
*Alcoholic Liver Disease:
-Increase AST greater than increase ALT
( AST will be about double the ALT)
- Increase GGT (Gamma-Glutamyl Transpeptidase)
* Hepatic Encephalopathy:
- Increase Ammonia
54
Lab ABNORMALITIES to distinguished between TYPES of LIVER Disease:
*Acute Liver Toxicity ( Including Drugs)
55
Assessing severity of LIVER Disease:
Child-Turcotte- Pugh (CPT) or
Child Pugh Classification System
( Online Calculatoion System)
Model End-Stage Liver Disease (MELD)
CPT Score Range: 0 to 15
Class A (Mild Disease): < 7
Class B (Moderate Disease) : 7 - 9
Class C (Severe Disease): 10 - 15
MELD another scoring system ranges from 0-40; HIGHER number = GREATER RISK of death within 3 MONTHs.
56
Information to GUIDE Hepatically Cleared Agent in LIVER FAILURES
Information NOT widely AVAILABLE.
In PACKAGE INSERT, caution is ADVISED when using hepatically cleared agent in SEVERE LIVER DISEASE
Generally is best to START at LOWER DOSE and TITRATE
57
NATURAL Products and LIVER Disease
* Milk Thistle : use by patients with liver disease, not harmful but limited data on efficacy.
* SE of Milk thistle: Diarrhea
Drug INTERACTION : Milk thistle and Antiviral HCV Meds
Kava, Comfrey and Flavocoxid (Limbrel) are known Hepatotoxins.
58
SELECTED Key DRUGs that has BOXED WARNING for Liver Damage.
Acetaminophen ( High Doses, Acute or Chronic)
Isoniazid
Ketoconazole
Methotrexate
Nefazodone
Nevirapine
NTRIs
Propylthiouracil
Tipranavir
Valproic Acid
59
Other DRUGs that has BOXED WARNING for Liver Damage.
Amiodarone
Bosentan
Felbamate
Flutamide
Leflunomide and Teriflunomide
Lomitapide
Maravirioc
Mipomersen
Tolcapone
60
Drug Induced Liver Injury:
Many Drugs can cause Liver Damage
Primary Treament : STOP DRUG
DISCONTINUE: when LFT are > 3 times the UPPER LIMIT of NORMAL ( > 150 units/L of ALT or AST)
Agent can be rechallenge if clinically necessary.
DILI( Drug Induced Liver Injury) website:
http://livertox.nih.gov
61
What KNOWN Hepatoxic Agent can cause SEVERE INJURY?
Acetaminophen (APAP); can be use at low dose for limited period in Cirrhosis pt
NSAIDS should be AVOIDED in patients with CIRRHOSIS due to Deocompensation and Bleeding
ACTIVE ALCOHOLIC = Futher Liver Damage
62
ALCOHOL Induce Liver Disease
Most Common DILI ( Drug Induced Liver Disease)
Includes: Fatty Live, Alcoholic Hepatitis, and Chronic Hepatitis with hepatic fibrosis or cirrhosis.
Chronic Alcohol ingestion over long period of time can causes STEATOSIS or Fatty liver.
Risk increase with drink amounts; WOMEN more than MEN
63
ALCOHOL Induce Liver Disease PATHOPHYSIOLOGY
Chronic alcohol consumption result in secretion of pro Inflammatory (TNF-alpha, IL-6, and IL-8) cytokines, stress and toxic these factors causes inflammation, apoptosis and eventually fibrosis of liver cell.
64
ALCOHOL Induce Liver Disease TREATMENT
*ALCOHOL CESSATION
DRUGS:
*Benzodiazepines: WITHDRAWAL in INPATIENT
Anticonvulsants: WITHDRAWAL in OUTPATIENT
*Naltrexone (Revia) , Acamprosate (Campral), and Disulfiram( Antabuse): use to PREVENT RELAPSES
Vitamins and Trace mineral ; Vit A,D, thiamine(Vit B1), folate, pyridoxine (Vit B6)
and Zinc to help REVERSE MALNUTRITION
* THIAMINE is use to PREVENT and TREAT Wernicke-Korsakoff Syndrome ( BRAIN DAMAGE cause by LACK of VITAMIN B1)
* Supportive Group
Avoid Hepatotoxic Drugs
65
Complications of Liver Disease and Cirrhosis:
PORTAL HYPERTENSION
VARICEAL BLEEDING
PORTAL HYPERTENSION: Increase BLOOD PRESSURE in the PORTAL VEIN
This cause COMPLICATIONS including development and BLEEDING of ESOPHAGEAL VARICES (englarged veins in the lower part of the esophagus)
VARICEAL BLEEDING (FATAL) : cause by BLOCKAGE of blood flow through the Liver by scar tissue , it backs up and flow into smaller vessels causing a balloon effect and bleed of break open.
66
VARICEAL BLEEDING TREAMENT
FIRST LINE TREATMENT:
Band Ligation: putting a BAND AROUND the VESSEL
Sclerotherapy: INJECTING a SOLUTION into the VESSEL to make it COLLAPSE and CLOSE
Note: Band Ligation and Sclerotherapy are procedures performed by a physician using endoacopy.
SUPPORTIVE THERAPY: Blood Volume Resuscitation/ Blood Product, Mechanical Ventilation, Correction of Coagulapathy, Attempts to Stop Bleeding and Prevent Rebleeding
DRUGs:
* Ocreotide (Sandostatin): Selective
* Vasopressin (Vasostrict): Non-Selective
SURGICAL PROCEDURE:
Ballon Tamponade
Tranajugular Intrahepatic Portosystemic Shunt (TIPS)
NOTE: Consider surgery if patients is not responding to treatment and for future prevention
SECONDARY PREVENTION:
Non-Selective Beta Blocker( Nadolol and Propranolol) after resolution and Endoscopic Variceal Ligation
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Complications of Liver Disease and Cirrhosis:
PORTAL HYPERTENSION TREAMENT
BETA Blocker REDUCE portal pressure by reducing portal venous in flow via 2 mechanism::
1. DECREASE Cardiac Output( Via BETA-2 blockade)
2. DECREASE Splanchnic Blood Flow by Vasoconstriction (Via BETA-2 blockade and unopposed Alpha Activity)
Titrated to MAXIMAL tolerated dose (Target HR 55 - 60 BPM)
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Complications of Liver Disease and Cirrhosis:
Medications that VASOCONTRICT the SPLANCHNIC (GI) Circulation to stop and minimize the bleeding.
Octreo-Tide (San-Do-Statin)
Vaso-pressin (Vasostrict)
*Octreo-Tide (San-Do-Statin): Analog of Somatostatin with greater potency and longer duration of action
SIDE EFFECTS: *Bradycardia, *Cholelithiasis, *Biliary Sludge, Chest Pain, Fatigue, HA, Pruritus, Constipation, NVD, Myalgias, Hyper/Hypoglycemia, URTIs, Arthropathy, Abdominal Pain, Malaise, Fever, Hypothyroidism
MONITORING:BG, HR, ECG
*Vaso-pressin (Vasostrict): Antidiuretic Hormone Analog; use with NITROGLYCERIN to PREVENT MYOCARDIAL ISCHEMIA
SIDE EFFECTS: Arrhythmias, Chest Pain, MI, Decreased Cardiac Output, Increase BP, N/V
MONITORING: BP, HR, ECG, Fluid Balance
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Non-Selective Beta-Blockers USED in PORTAL HYPERTENSION and VARICEAL BLEEDING
*Nadolol (Corgard)
Propanolol (Inderal)
BOXED WARNING:
Do Not WITHDRAW ABRUPTLY taper gradually to Avoid acute Tachy, HTN, Ischemia
CONTRAINDICATIONS:
Sinus Bradycardia
Asthma Exacerbate
WARNING:
Use for PORTAL HYPERTENSION
Extreme CAUTION in Asthma and COPD, Peripheral Vascular Disease, Raynaud's Disease, DIABETES, PSYCH
MONITOR:
HR and BP
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Complications of Liver Disease and Cirrhosis:
Hepatic Encephalopathy (HF)
Caused by ACUTE or CHRONIC Hepatic Insufficiency
SYMPTOMS: *Due to Accumulation of Gut-derived Nitrogenous Substance in the Blood ( Ammonia, Glutamate)
*Musty Odor of the Breath and/or Urine,
* Changes in thinking,
*Confusion,
*Forgetfulness,
*Hand Tremor (Asterixis) ,
Mood Changes, Poor Concentration, Drowsiness, Disorientation, Worsening Handwriting, Sluggish Movements, and Risk of Coma.
*Daily PROTEIN intake: 1-1.5g/Kg Vegetables and Diary Protein PREFFERED due to lower calories yto Nitrogen Ratio.
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TREATMENT of Hepatic Encephalopathy (HF)
Goal: Identifying and treating precipitating factors and REDUCING Blood AMMONIA levels through diet (LIMIT ANIMAL PROTEIN) abd drug therapy
DRUGs:
NON-ABSORBALABLE DISSACHARIDES (FIRST LINE):
Lactulose ( Enulose, Constulose, Kristalose)
ANTIBIOTICS:
Rifaximin ( Xifaxan): (SECOND LINE)
Neomycin
Metronidazole (Flagyl, Metro)
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TREATMENT of Hepatic Encephalopathy (HF) DRUGs:
NON-ABSORBALABLE DISSACHARIDES (FIRST LINE TREATMENT):
Lactulose ( Enulose, Constulose, Kristalose)
Lactulose (* Enulose, Constulose, Kristalose)
MOA: *Convert AMMONIA to AMMONIUM( polar cannot diffuse into the blood); ALSO diffuse Ammonia into colon for excretion
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SIDE EFFECTS:
*Flatulence
*Diarrhea
*Dyspepsia
*Abdominal Discomfort
Dehydration, Hypernatremia, and Hypokalemia
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MONITOR: Mental Status, Bowel Movements, Ammonia, Fluid Status, Electrolyte
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TREATMENT of Hepatic Encephalopathy (HF) Drugs:
ANTIBIOTICs:
Rifaximin ( Xifaxan): (SECOND LINE)
Neomycin
Metronidazole (Flagyl, Metro)
MOA: INHIBIT the activity of UREASE-Producing BACTERIA, decreasing the AMMONIA Production
DRUGS:
RIFAXIMIN( Xifaxan): (SECOND LINE)
SE: Peripheral Edema, Dizziness, Fatigue, Fatigue, HA, Nausea, Ascites
MONITORING:Mental Status, Ammonia
NEOMYCIN
SE: *GI Upset, Ototoxicity, Nephrotoxicity, Irritation/Soreness of Mouth/rectal area
MONITORING: Mental Status, Ammonia, Renal Function and Hearing
BOXED WARNING:* Neurotoxicity, Nephrotoxicity, Neuromuscular Blockade and Respiratory Paralysis
METRONIDAZOLE (Flagyl, Metro)
WARNING: DO NOT used LONGTERM due to PERIPHERAL NEUROPATHIES
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Complications of Liver Disease and Cirrhosis:
Ascites
FLUID ACCUMULATION within the PERITONEAL SPACE that can lead to SBP and HRS
*Spontaneous Bacteria Peritonitis (SBP) : ACUTE Infection of the ASCITIC FLUID
TREATMENT: Targets Streptococci and Enteric Gram Negative Pathogens
CEFTRIAXONE
*Hepatorenal Syndrome (HRS): RENAL FAILURE in patients with ADVANCED CIRRHOSIS.
CAUSE: renal constriction mediated by activation of RAAS and SNS through HEPATORENAL reflex feedback mechanism.
PREVENTION: Treat CIRRHOSIS; AVOID Nephrotoxin and Renal Hyperfusion
DRUGS: Albumin, Octreo-Tide, Midodrine
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ASCITES TREATMENT S
Portal Hypertension:* RESTRICT Dietary Sodium intake to < 2g/day; AVOID sodium retaining drugs (NSAIDS) ; DIURETIC to increase fluid loss Except in SEVERE HYPONATREMIA(Na <120 mEq/L).
DRUGs for ASCITES: Diuretics:
Monotherapy: Spironolactone
Combination: Spironolactone + Furosemide (not effective alone)
Spironolactone ( initiate at 50-100 then 400/d)
Furosemide ( Ratio: 40mg to 100mg Spironolactone to maintain K balance)
*ALL PATIENTS with Cirrhosis and Ascites: should consider LIVER TRANSPLANT
