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Quarter 2 > Pharm Exam 1 > Flashcards

Pharm Exam 1 Flashcards

1
Q

Glucuronyl transferase

A

the only phase II enzyme that is microsomal and inducible

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2
Q

CYP450

A

microsymal enzymes in the liver, perform oxidation of multiple drugs and foreign molecules. form OH

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3
Q

subtypes of CYP450

A

3A4- metabolize >50% drugs
2D6- impairs codeine metabolism
2E1- metabolizes & is induced by alcohol (increases drug toxicity!!)

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4
Q

Why is CYP2E1 dangerous?

A

it increases the metabolism of acetaminophen and increases potential hepatotoxicity caused by the metabolites

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5
Q

Smoking/chargrilled foods are inducers of

A

CYP 1A2

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6
Q

Barbiturates/phenobarbital, St Johns Wort are inducers of

A

CYP 2A6, 2B6, 2C8, 2C9, 2C18, 3A4

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7
Q

Ethanol is an inducer of

A

2E1

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8
Q

Grapefruit juice is an inhibitor of

A

CYP 3A4

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9
Q

Fluoxetine (Prozac) is an inhibitor of

A

2D6

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10
Q

most common types of phase II rxns

A

functional groups (OH, SH, NH2) conjugated with glucuronic acid

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11
Q

Genetic polymorphisms

A

mutations lead to enzyme deficiency and altered response to drugs

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12
Q

How do you “free” the drug to make it re-absorbable?

A

remove the conjugate! undoes the phase II step basically. done by digestive enzymes in the GI tract

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13
Q

Excretion of drug is enhanced by:

A
  1. agents that bind drugs in the intestine (Charcoal) thus increasing peristalsis
  2. antibiotics that eliminate GI bacteria
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14
Q

Estrogen (birth control) is re-absorbed into the enterohepatic circulation. This is normal!

A

Problem: when abx are taken, this reduces the amount of GI bacteria and therefore the drug is not unconjugated or re-absorbed
Result: drug is excreted from body! you get pregnant.

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15
Q

Antibiotics effect on estrogen

A

they decrease birth control reabsorption consequently eliminating it from body

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16
Q

larger Vd

A

means harder to purify the blood through hemodialysis bc it does not bind to the plasma

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17
Q

At high and toxic concentrations, what happens to elimination orders

A

Drugs normally eliminated by first order kinetics are now eliminated by zero order kinetics

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18
Q

gastric lavage

A

not recommended after 4 hours

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19
Q

activated charcoal is a form of tx for acute poisoning

A

will absorb many toxins

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20
Q

Smaller the Vd

A

more effective dialysis

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21
Q

Activated charcoal used to treat poisoning

A

by absorbing chemicals

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22
Q

Ammonium Chloride used to treat poisoning

A

acidify urine (bases)

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23
Q

Sodium bicarbonate used to treat poisoning

A

alkalinizing the urine (acid)

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24
Q

Drugs that treat poisoning by chelating metals:

A

Dimercaprol, Penicillamine, Deferoxamine, Calcium disodium edetate

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25
Q

Dimercaprol

A

used to treat poisoning from: arsenic, gold, mercury, acute lead

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26
Q

Penicallamine

A

used to treat poisoning from: copper (wilson disease, resistant case of rheumatoid arthritis)

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27
Q

Deferoxamine

A

iron poisoning

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28
Q

Calcium disodium edetate

A

lead poisoning

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29
Q

Acetylcysteine (inactivates toxins)

A

acetaminophen poisoning

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30
Q

Atropine is an antidote for

A

Cholinesterase inhibitor poison

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31
Q

Cyanide poisoning

A

tx: sodium nitrite, Na thiosulfate, and amyl nitrite

32
Q

Ethanol is an antidote for

A

methanol or ethylene glycol poisoning

33
Q

Fomepizole is an antidote for

A

ethylene glycol poisoning

34
Q

Antibodies are antidotes for

A

various toxins

35
Q

Dimercaprol

A

Arsenic poisoning

36
Q

Penicillamine

A

Copper poisoning

37
Q

Deferoxamine

A

Iron poisoning

38
Q

Calcium disodium edetale

A

Lead poisoning

39
Q

G6PD deficieny

A

Pamaquine- induced Hemolytic Anemia d/t genetic variation of G6PD gene

G6PD supplies NADPH & glutathione in RBC

Sex linked mutation; X chromo

40
Q

NAT2

A

I.e. of Change in Protein Function mutation

txr of Acetyl group results in formation of an Amide on the drug

R allele= rapid acetylation –> Hepatotoxicity

r allele= slow acetylation –> Lupus

Test: Give Isoniazid and determined plasma conc @ specific time after administered

41
Q

CYP-2D6 Mutation

A

A deletion, duplication, or SNP

Can be Poor, Intermediate, Normal, or Ultrarapid Metabolizer

Ex: Nortriptyline, Codeine, Debrisoquin

42
Q

OATP1B1

A

Drug Transporter Polymorphism

Sinusoidal membrane of hepatocytes, affects uptake of statin drugs

Mutations= reduced response to HMG Coenzyme A Reductase Inhibitors AKA Statins

43
Q

HLA Human Leukocyte Antigen

A

Immune Gene Polymorphism

Response mediated by cytotoxic CD8 T cells

Involved in hypersensitivity rxns- SJS/TEN

Ex: Abacavir sensitivity, screen for HLA B*5701 variant

44
Q

Probe Drugs

A

used to evaluate ratio of metabolite to drug- measure the plasma concentration of metabolites

45
Q

Enantiomer

A

mirror image

46
Q

Example of a Lipid soluble, Hyrdophobically bonded drug

A

Anticonvulsant,

Local Anesthetic

47
Q

Covalent bond; often irreversible; very strong

A

Aspirin,
DNA-alkylating agent,
Cholinesterase inhibitors

48
Q

Potency

A

Dose required to produce a given effect

49
Q

Are potency and efficacy related?

A

NO

50
Q

Efficacy

A

Ability of a drug to initiate a response

51
Q

The lower the EC50

A

The more potent the drug

52
Q

Physiological antagonism

A

(functional) acts through a totally different mechanism to counteract the effects of agonist
generally not as specific or easy to control
I.e. reversing fall in BP produced by Histamine with Epinephrine

53
Q

Chemical antagonism

A

directly interact w/agonist to inactivate it

I.e. inactivating Heparin w/Protamine Sulfate, Neutralizing stomach acid w/antacids

54
Q

TKR Tyrosine Kinase Receptors

A 
Insulin
Epidermal & Nerve Growth Factor
Platelet Derived Growth Factor
CA relation to this
Imatinib/Gleevec- cancer drug, works by signal transduction inhibiton
55
Q

Cytokine Receptors

A

Growth hormone
Erythropoietin
Interferons
Interleukins

56
Q

Desensitization

A

Acute. Receptor keeps getting hit with something it doesn’t respond to it like normal. i.e. gun violence. Will not change number, just less sensitive to effects!

57
Q

Down-regulation

A

Chronic.Takes weeks-months. Receptors CHANGE IN NUMBER. Pharmacodynamic change.

58
Q

Ras/Raf pathway

A

associated with Receptor Tyrosine Kinase pathways

RTKs activate the Ras/Raf pathway

59
Q

Major targets for cAMP

A

Protein Kinases

PKA;PKC

60
Q

Tachyphylaxis

A

very rapid development of tolerance following repeated dose over a short period of time
i.e. smoking meth

61
Q

Physiologic tolerance

A

when two agents w/opposing effects are given together

Histamine (vasodilation) & Norepinephrine (vasoconstriction)

62
Q

Pharmacodynamic tolerance

A

classic “drug tolerance”

response decreases d/t change in receptor # or fx

63
Q

Pharmacokinetic tolerance

A

response decreases bc the enzyme that metabolizes the drug are induced
Barbiturates & alcohol; warfarin

64
Q

Overextension type of adverse effects

A

Drug does TOO much of what it’s supposed to do:

Sedative hypnotics: excessive CNS depression
Antiarrhythmic: Arrhythmia
Insulin & other anti-DM: Hypoglycemia
ASA, Warfarin, Heparin: Hemorrage

65
Q

Organ Directed Toxicity

A

Some drugs are toxic to organs/tissues with no connection to therapeutic effect

Aminoglycoside abx: Renal & Ototoxicity
Acetaminophen: Hepatotoxicity
Tetracycline (acne): Teeth discoloration, Bone growth retardation
Thalidomide, Methotrexate, Phenytoin, Warfarin: Teratogenic effects (birth defects)
Metabolite toxicity: Acetaminophen & Isoniazid toxicity

66
Q

To cross a membrane, a drug must be

A

LIPID SOLUBLE &

NON IONIZED

67
Q

What is the point of ion trapping?

A

to increase elimination of that drug

68
Q

If you make urine basic:

A

acidic drugs will be trapped and excreted from the body

i.e. Sodium Bicarb

69
Q

If you make urine acidic:

A

basic drugs will be trapped and excreted from the body

i.e. Ammonium Chloride

70
Q

Basic drugs that can accumulate in the BREAST MILK and become trapped (bc breast milk is acidic)

A

Tetracyclines

Phenobarbitol

71
Q

Rate limiting for First Order Elimination

A

plasma concentration

72
Q

Rate limiting for Zero Order Elimination

A

the biological system
if given repeatedly in high doses, will NOT develop a steady state bc it’s not dependent on plasma levels
when given at higher doses than the elimination rate, will accumulate in the body and produce excessive plasma levels and TOXICITY

73
Q

First order

A

certain % of drug is eliminated per time

can accumulate and reach steady state (Css)

74
Q

Zero order

A

certain fixed AMOUNT of drug is eliminated per time
Alcohol 10g/hour
If you drink this much each hour, it will not accumulate and you will not reach steady state.
HOWEVER, if you exceed levels, will build up in plasma and produce TOXICITY= drunk

75
Q

Cytokine receptor- JAK (kinase activity in a separate protein)

A

Growth hormone
Erythropoetin
Interferons
Interleukons

76
Q

Gq- activates PLC

A

alpha 1 receptors

PIP2 is cleaved into DAG and IP3
DAG activates PKC
IP3 releases intracellular Ca2+ stores

Quarter 2 (16 decks)

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