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PATHO > Lecture 5: Hepatic Elimination > Flashcards

Lecture 5: Hepatic Elimination Flashcards

1
Q

Hepatic elimination consists of

A

-metabolism
-bilary excretion

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2
Q

Enterohepatic cycle

A

-small intestine to portal vein to liver to bile duct to small intestine

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3
Q

portal vein

A

-blood flow INTO liver

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4
Q

First-pass effect / presystemic elimination

A

-100% of oral drug goes to liver
-if 90% eliminated by liver, only 10% of drug gets to systemic circulation

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5
Q

Drug passage through liver

A

-drug enters liver lobule from portal vein through sinusoids
-blood flow from outside to inside
-drug enter space of disse
-diffusion or active transport to hepatocytes

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6
Q

lobule

A

functional unit of live

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7
Q

endothelium of sinusoid

A

-very porous
-drug diffuses into space of disse into hepatocytes
-then excreted in bile or goes to blood

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8
Q

Collection of bile

A

-hepatocytes secrete bile into canaliculi
-canaliculi converge to form small bile ductules and ducts
-bile moves from INside to OUTside of lobule

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9
Q

Passage from liver to intestine

A

-bile moves via hepatic ducts to gall bladder
-bile stored in gall bladder
-bile released in intervals into intestine (after meals)

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10
Q

No gall bladder

A

-bile always flowing into intestine instead of stored
-have to eat less fat

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11
Q

transporter proteins

A

-important for uptake and efflux form blood and transfer to bile
-pgp
-active transport

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12
Q

Greatest effect on billary excretion

A

-molecular weight
-optimal is 500-600 but >300
-low molecular wight can be passively absorbed before entering bile duct
-conjugated drugs more easily excreted

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13
Q

Conjugated drugs

A

-larger
-more readily excreted by bile

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14
Q

Classification of agents

A

-compounds that enter bile can be classified into 3 groups dependent on bile to plasma concentration

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15
Q

Class A compounds

A

-bile:plasma = 1
-Na+, K+, glucose

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16
Q

Class B compounds

A

-bile:plasma > 1
-bile salts, bilirubin, xenobiotics
-REQUIRE ACTIVE TRANSPORT INTO BILE

17
Q

Class C compounds

A

-bile:plasma < 1
-insulin, phospholipids, sucrose, proteins

18
Q

Enterohepatic circulation

A
  1. Systemic circulation -> liver
  2. Liver -> back to circulation or bile duct
  3. Bile duct –> GI tract
  4. GI tract –> portal vein to liver if it can be reabsorbed
19
Q

Enterohepatic circulation

A

-can reduce elimination of xenobiotics
-drug can keep getting reabsorbed and stay in body longer

20
Q

Interuption of enterohepatic cycling

A

-reduces half-life
-drug interactions can occur in GI tract

21
Q

Dapsone

A

-20 hour half life
-add charcoal = drug coming from bile duct binds to charcoal in GI tract
-cant be reabsorbed
-shorter half-life

22
Q

Bile binding agent

A

-increases elimination
-prevents enterhepatic recycling

23
Q

drug storage in gallbladder

A

-periodic dose dumping into intestines
-can cause a spike in plasma concentration from reabsorption

24
Q

Metabolite of drug in enterohepatic circulation

A

-drug broken down to metabolite in liver
-metabolite go back to GI tract through bile
-metabolite can be metabolized BACK into drug and go back to liver

25
Q

Glucuronosyltransferase

A

-adds sugar to drug in LIVER
= glucuronide

26
Q

glucuronidase

A

-removes sugar from glucuronide in GI TRACT
= back to drug

27
Q

CPT-11 metabolism

A

-metabolized to SN-38G
-goes to GI tract
-cleaves G in intestine
=toxicity to bowels

28
Q

neomycin

A

-decreases diarrhea from neomycin
-sterilize gut of microflora that produce glucuronidase

29
Q

Pulmonary excretion

A

-only passive diffusion
-anesthetics or alcohol

30
Q

blood:alveolar air ethanol

A

-constant ratio of 2100:1
-allows calculation of blood alcohol concentration

31
Q

Hair excretion

A

-trace amounts of drug from circulation
-can estimate drug and metal exposure but NOT concentration

32
Q

Detection time of drug tests (shortest to longest)

A

-saliva
-urine
-sweat
-meconium
-hair

33
Q

Sweat and saliva excretion

A

-may cause skin reactions

34
Q

milk excretion

A

-milk more acidic than plasma
-basic compounds may accumulate
-may pass agricultural compounds/antibiotics

35
Q

Tear excretion

A

-rifampin stains contacts

36
Q

Variability of drug response

A

-concentration that’s affected by elimination that’s affected by metabolism

37
Q

variability in drug concentration

A

-ELIMINATION
-distribution and absorption

38
Q

Variability in elimination

A

-METABOLISM
-bilary and renal excretion

39
Q

Variability in metabolism

A

-genetics
-environmental exposure
-physiological variations
-disease

PATHO (31 decks)

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