Week 205 - Hepatitis Flashcards
What are the routes of hepatitis transmission?
Oral Faecal
Parenteral
Blood
Which hepatitis viruses are transmitted via the oral faecal route?
A & E
Which hepatitis viruses are transmitted via the parenteral route?
B & C, E (and D in the presence of B)
What are prodrome symptoms of hepatitis?
Flu like (anorexia, nausea, vomiting, fatigue, malaise, low-grade fever)
What viruses other than the hepatitis viruses, cause hepatitis?
Adenovirus, EBV, CMV, Herpes simplex
What is the incubation period of Hep E virus?
15-60 days (avg. 40)
What is the treatment available for HBV?
Peg interferon Entecavir Tenofovir Lamivudine Adebovir Telbivudine
What are the hotspots of HBV?
Central + South Africa, China
What are the hotspots for HBC?
Egypt, Ukraine, Brazil
What are side-effects of Interferon?
Flu like symptoms (+ bone marrow suppression, thyroid dysfunction, exacerbation of autoimmune diseases)
What are side-effects of Ribavirin?
Teratogenic, haemolytic anaemia, skin rash, cough, insomnia
What are side-effects of Telaprevir?
Rash
DRESS (drug reaction with eosinophilia and systemic symptoms)
Bleeding PR
What are side-effects of Boceprevir?
Anaemia
Rash
Who’s at risk of HBC?
Recepients of clotting factors before 1987
IV drug users
Long term haemodyalisis pts
What is the natural history of HCV?
15% Resolve
85% ⇒ Chronic Infection (20% of these ⇒ cirrhosis)
What is the treatment available for HCV?
Peg interferon
Ribavirin
+/- telaprevir or boceprevir
Describe the route of a drug from the sinusoid to the hepatocytes
Sinusoids ⇒ drug passes through fenestrae in the endothelium
Through the space of Disse
In the hepatocytes the enzymes may convert them into more polar compounds
What is the phase I reaction (Drug Metabolism)?
Processing that creates/exposes functional groups (done my P450)
What is the phase II reaction (Drug Metabolism)?
Products are coupled with endogenous substrates such as glycine, acetic acid and sulphuric acid (conjugation)
Describe the first pass metabolism of Ethanol?
Ethanol ⇒ Acetaldehyde (Alcohol dehydrogenase)
Acetaldehyde ⇒ Acetyl CoA (acetylaladehyde dehydrogenase + NAD+)
What are the actions of alcohol?
Depressant
Inhibits NMDA receptors
Inhibition of neurotransmitter release
Enhancement of GABA transmission
What auto-antibodies would you look for in primary biliary cirrhosis?
anti-mitochondrial antibodies
What auto-antibodies would you look for in autoimmune hepatitis?
Smooth muscle antibodies
What auto-antibodies would you look for in primary sclerosing cholangitis?
Anti-nuclear cytoplasmic antibodies
What are the characteristic features of Wilson’s Disease?
Kayser Fleischer rings
↑Copper
↓Ceruloplasmin
How can you diagnose haemochromatosis?
↑Ferritin
Gene test for HFE gene
What are the symptoms of haemochromatosis?
30-50 yrs Weak, tired Pain in joints, tummy Hepatomegaly, liver cirrhosis Bronzing of skin Cardiomyopathy
What comprises the portal triad?
Bile Duct
Portal Vein
Hepatic Artery
What is the function of stellate cells in the liver?
Store fat + vit A
Produce collagen IV
Role in liver regeneration
Control blood flow through sinusoid
List the causes of splenomegaly
Infection Congestion (portal hypertension) Haemolytic anaemia Autoimmune (RA, SLE) Haematological malignancy Amyloid Rare storage disorders
What does prophylaxis for splenectomy consists of?
Pneumococcus, Meningococcus, Haemophilus
Prophylactic Penicillin V
What is the definition of TOLERANCE?
Decreased response to the effects of a set drug concentration after continued use (compensatory homeostatic mechanisms)
What is the definition of DEPENDENCE?
Need to take a drug to avoid withdrawal symptoms produced by compensatory homeostatic mechanisms
What is the definition of ADDICTION?
Continued drug use despite known despite know adverse consequences
What are treatments available for alcoholism?
Naltrexone + Nalmefene (opiod receptor antagonists)
Acamprosate (NMDA receptor antagonist)
Behavioural Therapy
What is the basis of replacement therapy?
Replacing a fast acting drug with a slow one
Name some psychostimulant drugs
amphetamines, methamphetamine, cocaine
Put dopamine transporter into reverse
MDMA (ecstasy), MMC (mephedrone)
What is the neurobiology behind addiction?
VTA releases dopamine which goes to Nucleus Accumbens (via the mesolimbic dopamine system)
What is the benzodiazepine used in alcohol withdrawal?
Chlordiazepoxide or Diazepam (Valium)
What receptor does caffeine work on?
Adenosine (receptor antagonist)
Adenosine triggers sleep
Theophylline (tea) & theobromine (cocoa) have similar effects
How does ketamine act?
NMDA receptor antagonism
Dissociative narcotic
Name some Hallucinogens?
LSD, Psilocybin (magic mushrooms)
How does acute intoxication with cannabis present?
Confusion Depersonalization Paranoid delusions Hallucinations Anxiety, Agitation
Where is the CB1 receptor found?
In the brain - binds cannabis and endocannaobinoids
Where is the CB2 receptor found?
Immune system (esp. B cells) Also brain stem & cerebellum
What is the net effect of CB1 receptor?
Local hyperpolarisation
To what state in the mesolimbic system are schizophrenic symptoms attributed to?
Hyperdopaminergic state in the mesolimbic system
What are Type A drug reactions?
Predictable, more common,mostly dose related
What are Type B drug reactions?
Not predictable, less common + tend to be more severe
What substances will go up in liver damage (relating only to what is stored in the liver)
↑CRP
↑α-1-antitrypsin
↑B12
Which Hepatitis antigen is elevated in Acute HBV infection?
HBcAg
Which Hepatitis antigen is elevated in Chronic HBV infection?
HBsAg
Which Hepatitis antigen indicates replicative form of HBV infection?
HBeAg
