Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FM 1 > Drug Absorption and Metabolism > Flashcards

Drug Absorption and Metabolism Flashcards

1
Q

Factors affecting absorption

A
  • dissolution time
  • solubility
  • concentration at site of absorption
  • perfusion rate vs diffusion rate
  • area of absorbing surface
  • membrane permeability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

perfusion

A

volume of blood per gram of tissue per time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

diffusion

A

amount of drug that can penetrate membrane per time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

perfusion rate limited

A

absorption is limited by rate of blood flow in tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

diffusion rate limited

A

absorption limited by rate of diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Ion trapping

A

if pH is extremely different from the pka in the direction that the molecule becomes charged, very little of it will be able to cross the membrane
eg weak base in stomach

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

First pass effect

A

refers to metabolism of drugs in GI tract before reaching systemic circulation (stomach->liver)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Advantages oral drug administration (PO)

A
  • safest (time before absorption, gets metabolized->harder to get toxic levels)
  • easiest
  • most acceptable to pts
  • economical (don’t have to be sterile)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Disadvantages oral drug administration (PO)

A
  • slower onset (45-90 mins)
  • Variable absorption (food, stomach pH, gastric emptying time)
  • First pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Sublingual drug admin (SL)

A
  • lipophilic substances
  • onset w/in minutes
  • avoids 1st pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Rectal drug admin (PR)

A
  • suppositories, enemas
  • about 50% of absorbed drug will bypass liver -> decreased 1st pass effect
  • useful if pt unconscious or vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Parenteral drug admin advantages

A
  • more rapid onset
  • more predictable action
  • bypass gut enzymes, flora, liver
  • useful if pt unconscious or vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Parenteral drug admin disadvantages

A
  • drugs must be sterile for injection-$$
  • pain from injection
  • self-admin difficult
  • injection into vessels can produce too great an effect
  • possibility of thrombus or embolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

SubQ drug admin (SC)

A
  • just under skin
  • slow absorption can provide sustained effect
  • can create drug depots in oil or pellet form for long duration of action
  • not suitable for large volumes or irritating substances
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Intramuscular drug admin (IM)

A
  • rapid absorption of drugs in aqueous solution; can also give poorly soluble drugs via IM
  • higher blood flow->faster absorption
  • can inject more irritating substances than subQ
  • epinephrine for anaphylaxis and most vaccines are given IM
  • soreness is common and muscle tension makes injection more painful
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Intravenous drug admin (IV)

A
  • directly into vein
  • highly accurate; absorption dependent only on rate of infusion
  • suitable for large volumes and irritating substances
  • not suitable for oily solutions or insoluble drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Topical drug admin

A
  • skin, eyes, mucous membranes
  • used to deliver drug at or immediately beneath the point of application or for transdermal delivery of membrane- permeant drugs for systemic effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

intraarterial drug admin

A

chemotherapeutic agents, diagnostic agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

intrathecal drug admin

A
  • spinal anesthesia

- CNS infection or brain cancer chemotherapy; bypass blood brain barrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

pulmonary drug admin

A
  • gaseous and volatile drugs, aerosols
  • rapid absorption, large surface area
  • particles must be
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

factors affecting drug distribution

A
  • blood flow
  • affinity of cells for drug
  • ability of drug to cross biomembranes
  • liver-enterohepatic cycling of drugs excreted into bile (liver->bile->small intestine->hepatic portal vein->liver)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

ATP-binding cassette transporter

A
  • transmembrane proteins that can actively extrude a wide variety of endogenous and exogenous compounds from cells
  • broad and overlapping substrate specificities
  • expressed in liver, kidney, intestine, testes, placenta
  • These transporters can pump their substances into bile, feces, and urine, thus affecting the uptake, distribution, and elimination of many clinically impt drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

ABCB-1

A

P-glycoprotein

amphipathic anions, nonconjugated neutral or weakly basic lipophilic substrates

24
Q

ABCC-1, -2, -3

A

organic anions, glucuronides, sulfates, glutathione adducts, LTC4

25
Q

ABCG-2

A

substantial overlap in substrate specificity w/ ABCB-1

26
Q

blood-organ barriers

A

Brain (lipophilic substances pass)
Thymus (cortex not medulla)
Testis
Ocular (aqueous and retinal)

27
Q

drug metabolism

A
  • changes to chemical structure resulting in altered pharmacology and solubility
  • usually increases polarity of drugs, making them more water soluble and hence more excretable
  • usually renders drugs therapeutically inactive
  • sometimes produces toxic products
  • major sites-liver, kidney, lung, intestine
28
Q

Active drug metabolites

A

imipramine (antidepressant)->desipramine (NE transporter)
diazepam (sedative hypnotic)->nodiazepam
acyclovir (antiviral; inactive)->acyclovie triphosphate (activated by enzyme from virally infected cells)

29
Q

Phase I (functionalization) reactions

A
  • redox reactions that alter or create new chemical functional groups
  • hydrolytic rxns that cleave esters, amides, and epoxides to reveal latent carboxylic acids, alcohols, and amines
30
Q

Cytochrome P450 monooxygenases (CYPs)

A
  • Phase I enzyme
  • family (71 gene products) of closely related hemoproteins
  • only 5 isoforms participate in metabolism of most drugs (1A2, 2C9, 2C19, 2D6, 3A4 [half of currently prescribed drugs])
  • Ferrous form binds CO, req NADPH and O2
31
Q

CYP catalyzed reactions

A
  • aliphatic and aromatic hydroxylation
  • alkene and aromatic epoxidation
  • N, O, and S dealkylation
  • N oxidation and hydroxylation
  • oxidative deamination and desulfuration
  • S oxidation
  • oxidative dehalogenation
32
Q

Other Phase I oxidative enzymes

A
  • flavin adenine dinucleotide monooxygenase (FAD)
  • monoamine (serotonin, NE) and diamine (histamine) oxidase
  • alcohol dehydrogenase
  • aldehyde dehydrogenase (antabuse-blocks this)
  • xanthine oxidase
33
Q

Phase II (conjugation) reactions

A
  • reactions that usually couple polar groups to functionalized substrates
  • Typically product is bigger, less active, and more water soluble
  • glucuronidation, sulfation, mercapturic acid formation, N,O,S-methylation, acetylation
34
Q

Glucuronidation

A
  • Phase II
  • Uridine diphosphate glucuronyl transferase (UGT)
  • 19 isoforms, mainly in liver but also intestine, kidney, skin
  • adds glucuronic acid to acceptor molecules (hydroxyls, carboxylic acids, thiol, amines)
  • endogenous substrates include bilirubin, bile acids, steroid hormones
35
Q

Sulfation

A
  • Phase II
  • sulfotransterases
  • 11 isoforms; liver, intestine, lung, adrenals
  • attach sulfate groups to hydroxyl groups
  • 3’-phosphoadenosine-5’-phosphosulfate (PAPS) is donor
36
Q

Mercapturic acid formation

A
  • Phase II
  • Glutathione S transferase (GST)
  • found in liver, kidney, lung, intestine
  • adds glutathione (Gly-Cys-Glu) to acceptor molecule
  • followed by hydrolysis of glutamate and glycine, then acetylation of cysteine
37
Q

N, O, S methylation

A
  • Phase II
  • Methyl transferases (phenylethanolamine [PMNT], histamine, indolethylamine, catechol, thiol)
  • liver, kidney, lung, brain
  • adds methyl group from S-adenosyl methionine to acceptor molecules
38
Q

Arylamine-N-acetyl transferase

A
  • Phase II
  • 2 isoforms important in xenobiotic metabolism
  • catalyzes transfer of acetyl group from acetyl CoA to various amine and hydrazine acceptor molecules
39
Q

Enzyme Induction

A

Increased enzyme expression resulting from increased gene transcription
(if genes increased, metabolism increases->may not reach therapeutic drug levels [as quickly])

40
Q

CYP induction

A
  • polycyclic aromatic hydrocarbons (combustion products-smoke, BBQ meats, tobacco-1A2 isoform)
  • anticonvulsants (carbamazepine, phenobarbitol, phenytoin)
  • glucocorticoids (dexamethasone, prednisone, triamcinolone)
  • Peroxisome proliferator activated receptor a agonists (PPAR) (decrease triglycerides) (clofibrate, fenofibrate)
  • rifampin
  • St. Johns Wort (3A4)
  • HIV drugs (efavirenz, nevirapine, ritonavir)
41
Q

GST induction

A
  • phenobarbital
  • 3-methylcholanthrene
  • allyl isothiocyanate (horseradish, wasabi)
  • carvone (in some spices)
42
Q

UGT induction

A
  • phenobarbitol
  • 3-methylcholanthrene
  • carbamazepine (anti-seizure drug)
  • Nicotine
43
Q

Enzyme inhibition

A
  • inhibiting enzymes for metabolism-drugs last longers
  • cofactor depletion
  • reversible competitive inhibition
  • covalent inhibition
  • pseudo-irreversible inhibition
44
Q

Reversible competitive inhibitors

A
  • substrates for metabolic enzymes can compete w/ drugs for binding sites and inhibit their metabolism
  • antibiotics (clarithromycin, erythromycin)
  • gemfibrozil
  • azole-class antifungals (itraconazole, ketoconazole, posaconazole, voriconazole)
  • HIV protease inhibitors (indinavir, ritonavir, saquinivir) (coformulated so that one drug ties up CYP, and other can last longer)
  • 1st gen H2 (histamine) antagonists (cimetidine)
  • grapefruit juice (inhibition can last 3 days w/ regular consumption)
45
Q

Covalent inhibition

A
  • reactive intermediates covalently modify and inactivate enzymes
  • disulfiram inhibits aldehyde dehydrogenase
  • polyhalogenated compounds become reactive during metabolism
  • olefinic (double) and acetylenic (triple bond) drugs-in active site-kill enzyme
46
Q

Pseudo irreversible inhibition

A

metabolism results in intermediates that slowly dissociate

47
Q

MAO inhibitors

A
  • phase I enzyme
  • pargyline forms covalent bond with MAO, increases [ ] of biogenic monoamines (serotonin, NE, dopamine)-early antidepressant
48
Q

Aromatic L-amino acid decarboxylase inhibitor

A

carbidopa -> longer half life of levodopa -> increased plasma [ ] and CNS availability -> decrease dose of levodopa req’d to treat Parkinsons
(w/o carbidopa, levodopa get metabolized in periphery and doesn’t get to brain->no efficacy)

49
Q

Xanthine oxidase inhibitor

A

allopurinol-> decrease uric acid biosynthesis -> decrease gouty deposits

50
Q

Peptidase inhibitor

A

cilastatin -> inhibits renal dehydropeptidase-1 (responsible for B-lactam inactivation) -> increase therapeutic activity of B-lactam antibiotics

51
Q

CYP polymorphisms

A
  • 2C9, 2C19, 2D6
  • drugs affected: warfarin, omeprazole, codeine, dextromethorphan, most SSRIs, many anti-psychotic drugs, B-blockers
  • 2D6 mutations most common
  • -ultra rapid metabolizers (Ethiopians/Saudi Arabians highest)
  • -poor metabolizers (Blacks highest)
52
Q

N-acetyl transferase polymorphisms

A
  • isoniazid and procainamide inactivation
  • Fast acetylators (Asians, Eskimos)
  • Slow acetylators (Blacks, Egyptians, Scandinavians, Caucasians)
53
Q

COMT deficiency

A

catechol-o-methyltransferase

decreased isoproterenol metabolism (nonselective B agonist)

54
Q

Thiopurine S-methyl transferase deficiency

A

-azathioprine, 6-mercaptopurine toxicity

55
Q

Butyrylcholinesterase activity

A
  • aka pseudocholnesterase
  • succinylcholine sensitivity
  • succinylcholine resistance
56
Q

Other factors affecting drug metabolism

A
  • Age (infants and elderly lower hepatic metabolism)
  • Nutritional status (protein and iron deficiencies -> decreased CYP metabolism)
  • Pathological state

FM 1 (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions