Biotransformation + excretion Flashcards

(32 cards)

1
Q

What aa supplies the liver

A

hepatic aa

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2
Q

What is the portal triad of the liver

A

hepatic aa
bile duct
portal vein

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3
Q

What is the flow of blood thru functional units of liver

A

portal triad-> sinusoids-> central vein

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4
Q

What is the site of biotransformation in the liver and what is the function it

A

hypatocyte is site of major biotrasformation

-Creates molecules more water soluble so it can be excreted by kidney

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5
Q

What are the 3 zones blood must move thru to get to the central vein

A
  1. Periportal
  2. Midzonal
  3. Centrilobular
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6
Q

How does drug move thru hepatocyte

A

hepatocyte allows free drug to move thru endothelial wall into the sinusoids

-some of parent drug will go thru biotransformation and some will get thru without be be biotransformed on subsequent passes

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7
Q

How does bile flow thru the functional units of the liver

A

hypatocyte-> bile ductules-> portal triad

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8
Q

What are the following phases drugs that enter our system can go thru (4)

A
  1. Phase 1 -> excreted
  2. Phase 1->2->exreted
  3. Phase2->excreted
  4. Phase 2->1->excreted
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9
Q

What is the general steps and goal of phase 1 rxn

A

P450 enzyme system will change parent molecule -> intermediate-> hydroxylated compound

(aliphatic oxidation)
-substance more water soluble

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10
Q

What are the enzymes required for phase 1 rxns (3)

A

Microsomal mixed function oxidase
Monooxygenase system
P450 system

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11
Q

Requirements for p450 system to work (4)

A
  1. Endoplasmic reticulm
  2. P450
  3. Flavoprotein-NADPH0 cytochrome p450 recuctase
  4. Molecular oxygen
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12
Q

What kind of rxn is a phase II rxn and what is it doing different than phase I rxn

A

Glucuronidation rxn

-Adds to molecules while phase I took things off but also makes things water soluble

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13
Q

Steps of phase II rxn

A

Generation of glucuronide (UDPGA) from glucose via UDP glucose intermediate

-UDPGA then transferred to molecule undergoing biotransformation

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14
Q

What do you need to transfer UDPGA to molecules

A

UDP glucuronosyltransferate found in liver, gut, kidney, lung, adrenal gland, spleen etc

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15
Q

How can carbon tetrachloride be biotransformed in phase I rxn

A

can be biotrandsformed into phosogene, chloroform, lipid peroxidation or binds molecules causing irreversible binding

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16
Q

How can phase 1 rxn be induced to be more toxic

A

Some indv who chronically take meds/drugs may have induced p450 system resulting in even more free radical formation

17
Q

What is an example of an inhibitor of CYP isoenzymes (p450) and what do they do

A

reduces enzyomatic activity impacting half life

Grapefruit juice

18
Q

What is the main pathway for acetaminophen

A

Will go thru phase II pathway where UDPGA is added to make glycuronide

19
Q

If acetaminophen is overwhelming system what happens

A

Will go thu phase 1 where p450 will act on it and create a carbonium ion (can lead to cellular necrosis)

20
Q

What can covert carbonium reactive intermediate to non toxic molecule

A

Glutathione transferase

21
Q

What is used in ppl with acetaminophen who injested high amounts

A

N-acytl cystein can be used to promote gluitathione and possible stim biotransformation of intermediate

22
Q

What is found in zone 1 (periportal) of hepatocyte

A

more aerobic and have more GSH + alc dehydrogenase

23
Q

What is found in zone 3 (centrilobilar) of hepatocyte

A

higher level of chytochrome p450 (why this area is more damaged)

24
Q

What is a probe drug for CYP2D6

A

Dextromethorphan

25
What do kupffer cells do and where are they found
line sinusoids and are involved in the removal of foreign substances from blood by phago
26
Why is the liver targeted for toxic substances
- able to biotransform many substances but can form free rads in process - can interfere w endogenous metabolic pathways - billiary excretion of xenobiotics may lead to high conc of these substances in bile - blood supply of liver ensures high expose to toxic substances absorbed - enzyme induction can lead to faster generation of toxins
27
How is methanol biotransformed
biotransformed into formaldehyde and then to formic acid which causes metabolic acidosis + optic n damage
28
What is the antiddote to methanol poisoning
fomepizole is a competative inhibutor of alc dehydrogenase
29
What is steatosis and mc cause
Accululation of triglyeries in hepatocytes Ethanol mc cause
30
What is cirrhosis and mc cause
Chronic lesion resulting from repeated injury and subsequent repair Ethanol Mc cause
31
What is Cholestasis what substancce indicates damage
Bile stasis or dmage to the bile ducts, ductules or canaliculi Alkaline phosphatase
32
What two substances indicate hepatocellular damage
Alanine anino transferase Aspartate amino transferase