PK/PD/etc! Flashcards

1
Q

Hydrogen Bond

A

H atoms bound to Nitrogen or O2 become more + polarized, allowing them to bond to more (-) polarized atoms such as O2, Nitrogen or Sulfer. Strength: Second Weakest

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2
Q

Covalent Bond

A

Two bonding atoms share electrons - Strongest bond - often irreversible
Example: ASA

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3
Q

Ionic Bond

A

Atoms with an excess of electrons (imparting overall (-) charge on the atom) are attracted to atoms with a deficiency of electrons (imparting an overall (+) charge on the atom. Third strongest bond.

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4
Q

Van der wals

A

Shifting electron density in areas of a molecule, or in a molecule as a whole, results in the generation of transient (+) or (-) charges - these areas interact with transient areas of opposite charge on another molecules

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5
Q

Define PD

A

what the drug does to the body

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6
Q

Define PK

A

What the body does to the drug

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7
Q

Efficacy vs. potency

A

Potency: Strength (amt of drug needed to achieve intended effect.
Efficacy: ability of drug to produce same response:
NOTE: Drugs can have the same efficacy but different potency (i.e. statins).

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8
Q

Characteristics of HYDOPHILIC

A

Water loving
Polar, usually ionized
Renal excretion
Requires transport mech to x cell membranes and BBB
Forms H= bonds (ionized = (-) charge somewhere)
Can penetrate CNS via active transport, facilitated transport, intrathecal admin.

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9
Q

Characteristics of HYDOPHOBIC

A
Think Oil/Vinegar
LIPOphilic 
Fat Loving/water insoluble
Passively diffuses across cell membranes and BBB (d/t lipid bilayer so fat soluble will go through)
Non-polar, usually NOT-ionized
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10
Q

Core of a cell is what: hydrophilic or phobic?

A

Hydrophobic lipid core

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11
Q

Membrane of a cell is what: hydrophilic or phobic?

A

Hydrophilic

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12
Q

“D+R DR DR* “ means what?

A

Empty drug + empty rc (does nothing)
DR = drug bound to rc
DR* activated drug/rc (activity taking place).

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13
Q

Agonists : Full

A

Elicit max. result
Stabilize DR*
Think “Full faucet”
i.e. ACH binds to nicotinic rc and induces conformational change from nonconducting to fully conducting state.

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14
Q

Partial Agonist

A

Activates rc w/o max efficacy
Stabilizes DR and DR*
i.e. Beta Blockers
Typically this is an intended design ie. CNS meds when you do not want full firing or full activity.

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15
Q

Inverse agonists

A

Inactivates free active rc’s (which is active at BSL)
Stabilizes DR in the case of R* (which is the natural state of the enzyme).
Example: inactivate an overactive enzyme in CA pt.
Example: Diphenhydramine: inverse agonist when need histamine to be turned OFF.

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16
Q

Competitive Antagonists

A

Reversible binding blocks agonist at ACTIVE SITE
Stabilizes DR, PREVENTS DR*
Agonist can bump antagonist off which would lead to DR* therefore, need more agonist on board to out compete the antagonist.

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17
Q

Noncompetitive Antagonist

A

Irreversible binding
Blocks agonist at Active or Allosteric site
Can reach plateau b/c agonist is taken out of play or antag prevents it from doing anything.

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18
Q

TI: What and how calculated

A

TI = TD50/ED50
Want higher TI for low toxicity and high efficacy; high TD and low ED
High TI: wide therapeutic window with TD much > ED

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19
Q

pKa and why do we care?

A

pH at which 50% of drug is ionized, ph at which 50% of a drug can passively diffuse across membranes. Want to know if a drug can cross membrane or not and NOT GET TRAPPED as it needs to be WITHOUT a charge to passively diffuse.

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20
Q

What is the MOST desirable PD for a medication:

a. Low LD50
b. Low TI
c. High TI
d. Low TD50

A

C: high efficacy and low toxicity

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21
Q

Absorption: where

A

GI tract, parenteral, Skin/Membranes

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22
Q

Absorption and drug tx affected by:

A

Absorption: concentration, circulation at the site, drug solubility, surface area.
Transfer: concentration, circulation, drug solubility, surface area

23
Q

Distribution: where

A

Blood, target tissue

24
Q

By what is volume of distribution affected?

A

Age (body composition changes); Volume status; protein binding, high tissue binding

25
Q

Metabolism: where?

A

Liver, tissue, blood, CYP450 enzymes

26
Q

By what is metabolism affected?

A

Inhibition, induction, race/ethnicity, age, gender, diet, disease.

27
Q

Excretion: where?

A

Kidney, lungs, fecal

28
Q

Low Vd vs. High Vd?

A

Vd: volume of fluid required to contain the total amt of drug absorbed in the body at uniform concentrations = to that in plasma steady state.
Low: distribution retained in the plasma and not distributed well.
High: high distributed into non-vascular component.
**SLOW in, SLOW out and vice versa*

29
Q

T/F: nonionized lipophilic drugs favored for oral absorption.

A

True (small and passive)

30
Q

T/F: Weak acids are best absorbed in the stomach

A

T

31
Q

T/F: Rectal administration of drug provides for inconsistent and unregulated absorption

A

T

32
Q

T/F: weak bases are best absorbed in the small intesting

A

T (will get absorbed from mucosa there)

33
Q

T/F: Drugs with a low Vd may be highly protein bound and more likely to remain the plasma compartment

A

True.

34
Q

CYP450 enzymes: Induction: what does that mean?

A
  • Inc. transcription or translation
  • Dec. degradation
  • Induction by another drug or autoinduction
    (note: a drug that is an inducer increases metabolism of a drug that is ALSO metabolized by that same enzyme)
35
Q

CYP450 enzymes: Inhibition: what does that mean?

A

Incidental or deliberate
Competitive inhibition
Irreversible inhibition

36
Q

Drug toxicities: On-target A/E

A

Intended tissue, intended rc OR

Unintended tissue, intended rc

37
Q

Drug toxicities: Off-target A/E

A

Intended tissue, unintended rc OR
Unintended tissue, unintended rc
EXAMPLE from async: metoprolol given for HR control, causes bronchoconstriction in respiratory tract. Unintended rc (B2) in unintended tissue (lungs, not heart).

38
Q

What are the 3 types of transmembrane channels:

A
  1. Ion channel
  2. G coupled protein (indirect)
  3. Enzyme within cytosolic domain (direct_
    Drug will either open and allow influx OR close channel and PREVENT influx into the cell.
39
Q

How does intracellular interaction work?

A

Drug x’s membrane and works inside the cell itself. Drug NEEDS to be hydrophobic (where in transmembrane that is irrelevant).

40
Q

What is the difference b/w allosteric and irreversible NONCOMPETITIVE antagonists:

A

Irreversible; compete in a way that is irreversible (covalent). When bind to same site, agonist being added will NOT reverse no matter how much you give).
Allosteric: binds to alternate side which prevents the agonist from binding OR prevents DR* when it does bind.

41
Q

Distribution: Initial phase

A

initial phase reflects regional blood flow.

Delivery of drug is slower to muscle, most viscera, skin, and fat

42
Q

Distribution: Second phase

A

Distribution to tissues
Rapid distribution to interstitial compartment d/t highly permeable nature of capillary endothelial membranes
Restricted distribution: a) lipid insoluble that permeate membranes poorly; b) drug binding plasma proteins

43
Q

Drug metabolism: 5 things metabolism does

A
active drug -> inactive drug
active drug -> active metabolite
active drug -> toxic metabolite
prodrug -> active drug 
Unexcretable drug -> excretable metabolite
44
Q

what is a prodrug?

A

in parent form it has no activity; needs metabolite in order to do its job

45
Q

why is first pass significant?

A

determines bioavailability of a drug

46
Q

Can a drug that is protein bound be metabolized?

A

No

47
Q

Phase 1 metabolism: CYP450 3A4, 2D6, 2C9, 2E1, 1A2

A

enzyme family-subfamily-specific enzyme
substrate specificity
MAO: oxidizes amines

48
Q

Phase II Metab

A

substrates include drugs or drug metabolites
Results in large polar conjugates (allow urine and fecal excretion)
Active metabolite possible (i.e. active conjugate of morphine is a more potent analgesic with phase II making it more active).

49
Q

What is a substrate?

A

breaks something down

50
Q

what is an inducer?

A

increases activity from the enzyme to break down

51
Q

what is the inhibition?

A

slow down activity

52
Q

What are some factors affecting metabolism?

A
  1. genetics: slow-acetylator phenotype
  2. race and ethnicity (cyp450 2D6 is nonfunctional in 8% of caucasians
  3. Age and Gender (lack of UDPGT in neonates)
  4. Diet (grapefruit juice)
  5. Disease States (liver disease, cardiac disease)
53
Q

Three most important parameters to clinical PK:

A
  1. Clearance
  2. Volume of distribution
  3. Bioavailability
54
Q

Therapeutic doses goals

A

Maintain Cmax below toxic concentration
Maintain Cmax above minimum effective concentration
Maintain Cxx w/in therapeutic window
Want to steady state concentration
Dose timing based upon half life (dose does not change based on half life)