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PA 2306- MOD 7 > Biotransformation + excretion > Flashcards

Biotransformation + excretion Flashcards

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
Q

What do kupffer cells do and where are they found

A

line sinusoids and are involved in the removal of foreign substances from blood by phago

26
Q

Why is the liver targeted for toxic substances

A
  • 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
Q

How is methanol biotransformed

A

biotransformed into formaldehyde and then to formic acid which causes metabolic acidosis + optic n damage

28
Q

What is the antiddote to methanol poisoning

A

fomepizole is a competative inhibutor of alc dehydrogenase

29
Q

What is steatosis and mc cause

A

Accululation of triglyeries in hepatocytes

Ethanol mc cause

30
Q

What is cirrhosis and mc cause

A

Chronic lesion resulting from repeated injury and subsequent repair

Ethanol Mc cause

31
Q

What is Cholestasis what substancce indicates damage

A

Bile stasis or dmage to the bile ducts, ductules or canaliculi

Alkaline phosphatase

32
Q

What two substances indicate hepatocellular damage

A

Alanine anino transferase

Aspartate amino transferase

PA 2306- MOD 7 (8 decks)

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