Brainscape's Knowledge GenomeTM

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


See full index

Block 1 > W7: Pharmalcology > Flashcards

W7: Pharmalcology Flashcards

1
Q

Large/narrow therapeutic index (TI) is safe (what is TI?)

A

Large (big gap between effectiveness and toxicity)

TI is ratio: TD50/ED50

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

Define pharmacokinetics and name what ADME stands for.

A

what body does to drug;

ADME – absorption, distribution, metabolism, excretion

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

What is quantal dose-response (d-r) curve? Describe its components:

X and Y axis

ED50
TD50
LD50

A

graph used to quantify quantal response to a drug (quantal - all or none; yes or no)

X - dosage each person took
Y - % of people who responded to the drug

Median effective dose (ED50) - dosage at which 50% responded favorably

Median toxic dose (TD50) - toxic dosage for 50% of participants

Median lethal dose (LD50) - dosage at which 50% found lethal

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

What is graded dose-response (d-r) curve ?

X and Y axis?

What are 2 important information you can get?

A

D-R curve is a graphical representation between quantity of drug and a graded biological effect

X - drug concentration
Y - % maximal response

efficacy and potency

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

Magnitude of a response is called __.

A

Efficacy

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

EC50 is used to compare the potency/efficacy of two drugs.

A

Potency

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

Therapeutic window is utilized in quantal/graded dose-response to gauge the effective plasma drug concentration range.

A

graded

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

competitive/non-competitive antagonist reduces the EC50 (efficacy/potency) of the original drug.

A

competitive, potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Non-competitive antagonists reduces the efficacy/potency of the original drug which can/cannot be overcome with increased [original drug].

A

efficacy, cannot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Define concept of spare receptors. How was this discovered?

A

Idea that when maximal response is reached, not all receptors are activated

Experiment: When agonist + irreversible antagonist are added, maximal response was still achieved.

Conclusion: Max response can be achieved with less than 100% of receptors (because spare receptors are present)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

difference between EC50 and Kd?

A

EC50 describes potency of the drug action.

Kd describes the binding affinity of drug/ligand to receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between occupancy theory and the two state receptor model?

A

occupancy: one ligand, one receptor (receptor inactive if no ligand)

two state: presence of constitutively active receptor and inactive receptor that needs to be bound to a ligand (receptor can be spontaneously active in absence of ligand)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Draw a dose x drug activity graph indicating the terms below:

constitutive activity
full agonist
partial agonist
antagonist
inverse agonist
A

constitutive activity - activity (y axis) > 0 (all graphs start here)

full agonist - sigmoidal, max activity

partial agonist - sigmoidal, less than max activity

*antagonist = constitutive
(two state receptor model)

inverse agonist - decrease to zero from constitutive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

3 targets of drug

A
  1. receptor (potency, efficacy)
  2. enzyme (affinity, efficacy)
  3. transporters (blockers)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Two factors that influence absorption of drug into plasma are __ and __, which both determine the __ of drug.

A

route of administration, membrane penetration;

bioavailability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Differentiate therapeutic index and therapeutic window and their parameters (X vs. Y).

A

TI: range of safe dose for general population
(X - dose; Y - % of people who responded to the drug)

TW: - range of doses that produce a therapeutic response without unacceptable side effects
(X - time; Y - PLASMA drug concentration)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Calculation for oral bioavailability (%)

A

AUC (area under the curve)
iv does is 100% bioavailability (plasma absorption)

oral dose AUC/ iv dose AUC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Enteral/Parenteral administration of drug means via the GI tract.

A

Enteral

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

__ is the disadvantage of oral administration of drug, subjecting drug to degradation/alteration in __ and __ prior to reaching the systemic circulation (blood).

A

First Pass Effect;
liver and intestine

Trajectory: oral –> GI –> vasculature –> portal vein –> liver (metabolism) –> hepatic vein –> systemic circulation (absorption)

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

3 ways drug enters cell/tissue (distribution)

A
  1. Diffusion (partition coefficient)
  2. Carrier-mediated transport
  3. Endocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What determines the diffusion of drug into cell/tissue?

A

Jx = Px A (Co – Ci)

Px - partition coefficient
A - area of membrane
(Co – Ci) - concentration gradient

22
Q

__ is measure of solubility of drug in lipid.

A

Partition coefficient

[Drug] lipid phase / [Drug] aqueous phase

23
Q

Drug distribution to tissue is influenced by 3 factors (list them), determining the __.

A

ion trapping, protein binding, tissue barrier;

volume of distribution

24
Q

Drug-protein binding in the plasma functions as a

__ of drugs in the circulation. The fraction of bound (drug-protein complex) to total drugs in plasma remains constant.

A

reservoir

25
Q

Treatment for Aspirin toxicity is __ by administering __ intravenously.

A

basifying (alkalinization) of urine, bicarbonate

26
Q

Describe the mechanism of detoxification of aspirin in the context of ion trapping.

A

When urine is alkalinized, aspirin (weak acid) in urine (basic environment) becomes charged (cation). A significant amount of drug (cation) is now trapped in urine for excretion.

27
Q

Drug distribution to target tissue will be most ideal for a weak acid drug in an acidic/basic environment.

A

acidic (weak acid becomes more neutral)

basic environment for weak base drug (conjugate acid)

28
Q

Drugs first end up in location with highest/lowest blood flow (2 organs in the body)

A

highest; kidney and liver

29
Q

Functional outcome of metabolism (actions of phase I and II)

A

make metabolites more H2O soluble
Phase I - functionalization
Phase II - conjugation reaction

30
Q

Sites of metabolism (2)

A

GI tract (intestine) and liver

31
Q

What is CYP450 system and where does it occur?

A

CYP450 system facilitates (the most common) Phase I of drug metabolism. CYP450 proteins are mostly found in the liver.

32
Q

Components of CYP450 and how they work

A 
Flavoprotein (P450 reductase)
Heme protein (CYP450)

Oxidation of drug: flavoprotein takes e- from NADPH, transfers to CYP450, add -OH to H (oxidizes the drug)

33
Q

4 different mechanisms of phase I

A

Monooxygenase (oxidation by CYP450)
Monoamine Oxidase (non-P450 oxidation)
Alcohol Metabolism (CYP and non-CYP)
Esterase (hydrolysis)

34
Q

List 4 major P450 CYP enzymes.

A

CYP3A4/5
CYP2E1 (minor metabolism of ethanol)
CYP2D6
CYP2C19

35
Q

Major pathway for ethanol metabolism:

enzymes and their products

A

ADH (alcohold DH)
ALDH (aldehyde DH)

ethanol –ADH–> aldehyde –ALDH–> acetate

36
Q

Esterase is part of Phase __ activity, found in __.

A

I; plasma and other tissues

37
Q

Monoamine oxidase (located in __ of cell) is part of Phase __ activity, converting __ to __.

A

mitochondria; I; amine to aldehyde

38
Q

Describe the main types of end-products of phase 1 metabolism (3).

A

aliphatic hydroxylation
aromatic hydroxylation
N-dealkylation

39
Q

Describe the main types of end-products of phase 2 metabolism (5).

A 
glucuronidation (add sugar)
acylation (add R-C=O)
glycine conjugation
sulfate conjugation
glutathione conjugation
40
Q

Most phase II metabolites are active/inactive (except __)

A

inactive; morphine

41
Q

Prodrugs become active upon __.

A

metabolism

42
Q

What does induction of CYP450 mean and what is the result?

A

Enhancing synthesis and activity of CYP450 that results in reduced availability, hence reduced effect of drug

43
Q

What does inhibition of CYP450 result in?

A

Decreases ability of CYP450 to metabolize more drug, resulting enhanced effect of drug

44
Q

To increase drug effect, you __ (induction/inhibition of CYP450)

A

add drug that acts as a CYP450 inhibitor (inhibition)

45
Q

CYP450 inhibition leads to increased/decreased drug effect.

A

increased

46
Q

CYP450 induction leads to increased/decreased drug effect.

A

decreased

47
Q

To decrease drug effect, you __ (induction/inhibition of CYP450)

A

add inducing agent of CYP450 (increase expression) (induction)

48
Q

Phase I and II application:

Acetaminophen (Tylenol) toxicity can be reversed by administration of __ (mechanism?)

A

NAC (N-acetylcysteine)

mechanism: NAC + glutamine–> glutathione in liver (avoid toxic pathway)

49
Q

__ can result in difference in ability to metabolize xenobiotics in the body (extensive vs. poor metabolizers)

A

SNP (single nucleotide polymorphism)

50
Q

Enzyme polymorphism: give examples of how polymorphism of each enzyme can have adverse effect.

ADH -

ALDH -

A 
ADH - alcohol dehydrogenase
high activity (and relatively low activity of following ALDH) leads to build-up of acetaldehyde.

ALDH - aldehyde dehydrogenase
many Asians produce inactive ALDH, leading to acetaldehyde build-up

51
Q

Build-up of __ leads to histamine release from __ cells

A

acetaldehyde; mast cells

Block 1 (26 decks)

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