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
Glucuronosyltransferase
-adds sugar to drug in LIVER = glucuronide
26
glucuronidase
-removes sugar from glucuronide in GI TRACT = back to drug
27
CPT-11 metabolism
-metabolized to SN-38G -goes to GI tract -cleaves G in intestine =toxicity to bowels
28
neomycin
-decreases diarrhea from neomycin -sterilize gut of microflora that produce glucuronidase
29
Pulmonary excretion
-only passive diffusion -anesthetics or alcohol
30
blood:alveolar air ethanol
-constant ratio of 2100:1 -allows calculation of blood alcohol concentration
31
Hair excretion
-trace amounts of drug from circulation -can estimate drug and metal exposure but NOT concentration
32
Detection time of drug tests (shortest to longest)
-saliva -urine -sweat -meconium -hair
33
Sweat and saliva excretion
-may cause skin reactions
34
milk excretion
-milk more acidic than plasma -basic compounds may accumulate -may pass agricultural compounds/antibiotics
35
Tear excretion
-rifampin stains contacts
36
Variability of drug response
-concentration that's affected by elimination that's affected by metabolism
37
variability in drug concentration
-ELIMINATION -distribution and absorption
38
Variability in elimination
-METABOLISM -bilary and renal excretion
39
Variability in metabolism
-genetics -environmental exposure -physiological variations -disease