Midterm - Pharmacodynamics & Pharmacokinetics Flashcards

1
Q

NAPRA I drugs

A
  • Prescription needed for sale by Pharmacist
  • Includes prescription drugs (Pr), narcotics (N), controlled substances (C1, C2, C3), and targeted substances (TS)
  • eg. Fentanyl patch
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2
Q

NAPRA II drugs

A
  • Prescription not required
  • Must be dispensed by pharmacist (ie. behind the counter)
  • eg. insulin
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3
Q

NAPRA III drugs

A
  • Client may obtain at pharmacy without need of pharmacist
  • eg. ranitidine (Zantac)
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4
Q

Unscheduled drugs

A
  • Client may obtain at retail stores as well as pharmacy
  • eg. naproxen (Aleve)
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5
Q

Pharmacodynamics vs pharmacokinetics

A

Dynamics = drug’s actions on body
Kinetics = body’s actions on drug

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6
Q

Signal transduction pathway

A
  • aka receptor-effector coupling mechanism
  • consists of the receptor, its cellular target, and any intermediary molecules
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7
Q

Drug affinity

A
  • Favourability of a drug-receptor binding interaction
  • Sum total of forces imparts high affinity of the drug for receptor
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8
Q

What drugs are MORE selective for their receptors?

A

Drugs that bind through multiple weak bonds to their receptors (if a drug has a super strong bond, it can likely bond to lots of things and will be less selective)

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9
Q

Strength of bonds from greatest to least

A

Covalent (uncommon, irreversible) > ionic > hydrogen > Van Der Waals (common, reversible)

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10
Q

Enantiomer

A
  • Same atomic structure but arranged spatially different (optical isomer)
  • produce different effects
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11
Q

Racemic mixture

A

50:50 mix of both enantiomers

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12
Q

Cell-type distribution

A

The more restricted the cell-type distribution of the receptor targeted by a drug, the more selective the drug is likely to be
eg. restriction of H2 receptors in the
stomach means Ranitidine has limited effects on body beyond the stomach

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13
Q

Effector domain purpose

A

Message propagation = conformational change in receptor that is transduced intracellularly to effect downstream molecules to cause a response (activate, enhance, diminish, terminate)

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14
Q

Ligand activated (gated) channels

A
  • found in the CNS
  • binding of molecules induces a conformational change that opens the pore
  • eg. nicotinic acetylcholine receptor
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15
Q

Types of ligand activated (gated) channels

A
  • Excitatory (ACh or glutamate)
  • Inhibitory (glycine or GABA)
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16
Q

Voltage-activated channels

A
  • Initiate action potentials in the
    axons of nerves and muscle cells
  • activated channel depolarizes the membrane to attract positive ions through open pore
  • refractory period = “reset”
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17
Q

Sulfonylurea receptor

A
  • aka SUR1
  • Regulates ATP-dependent K+ channel in pancreatic β-cells
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18
Q

G-protein coupled receptors

A
  • aka GPCRs
  • sensory perception, nerve activity, etc.
  • target of over half of all non-antibiotic
    drugs
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19
Q

G-protein activation

A

1) Agonist binding
2) GTP-GDP exchange
3) G-protein activation
(terminated by GTP hydrolysis)

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20
Q

β-adrenergic receptor group

A
  • group of G-proteins
  • eg. epinephrine and norepinephrine (both are catecholamines that increase second messenger cAMP)
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21
Q

Transmembrane receptors with an intracellular linked enzymatic domain

A
  • single membrane spanning
  • add/remove phosphate groups from specific aa’s
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22
Q

Types of transmembrane receptors with an intracellular linked enzymatic domain

A
  • Receptor Tyrosine Kinases
  • Tyrosine Kinase-Associated Receptors (receptors have no intrinsic enzymatic activity, but dimerization allows for binding of an intracellular tyrosine kinase)
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23
Q

Nuclear hormone receptors

A

“lag on, lag off”

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24
Q

Nitric oxide (NO)

A
  • binds N-terminal of soluble GC and enhances activation of cGMP (vasodilation)
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25
Q

Dissociation constant

A
  • aka Kd
  • most important for impacting the chance of binding (drives affinity)
  • ligand concentration where 50% of receptors are bound by ligand (lower Kd = higher affinity)
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26
Q

[LR]/Ro

A

Fraction of all available receptors that are ligand bound

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27
Q

Types of D-R relationships:

A
  • Graded = D-R of individual
  • Quantal = D-R of population
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28
Q

Efficacy

A

Maximal response produced by the drug at that receptor

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29
Q

Potency

A
  • drug concentration which elicits 50% of the maximal response
  • considers both affinity and efficacy
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30
Q

Therapeutic Index

A
  • Gives an estimate of relative safety margin of drug
  • considers both toxic and effective doses
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31
Q

Effect of competitive ANTagonists

A
  • increase Kd for agonist = decrease affinity = decreases potency
  • no effect on efficacy since they can be outcompeted with higher doses
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32
Q

Non-competitive ANTagonists

A

irreversible binding can not be “washed out” or outcompeted by the agonist
- decrease efficacy (sometimes potency too)

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33
Q

Types of non-receptor ANTagonists

A
  • Chemical = renders agonist inactive
  • Physiologic = binds different receptor and produces opposite effect
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34
Q

Allosteric modulators

A

Indirectly influence the effects of an agonist at its receptor (alters Kd or conformational change)

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35
Q

Types of passive transport

A
  • passive diffusion = unbound drug carried through cell membrane by bulk flow of water
  • paracellular transport = passage of molecules through intercellular gaps
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36
Q

Passive flux formula

A

Flux = [concentration gradient (aka C1 - C2) x area x partition coefficient] / membrane thickness

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37
Q

Partition coefficient

A
  • solubility of drug
  • greater coefficient = faster diffusion
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38
Q

Un-ionized species vs ionized species

A
  • Unionized = more lipid soluble, more readily diffuse cell membranes
  • Ionized = less lipid soluble, less able to diffuse through cell membranes
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39
Q

pKa

A

pH at which 50% of drug is ionized and 50% is unionized

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40
Q

Ionized form of an acid

A

Deprotonated (negatively charged)

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41
Q

Ionized form of a base

A

Protonated (positively charged)

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42
Q

Henderson-Hasselbalch equation

A

log([protonated]/[deprotonated]) = pKa - pH

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43
Q

Ion trapping

A
  • Drug accumulates on side of cell membrane where ionization is highest
  • Basic drugs accumulate in acid fluids
  • Acidic drugs accumulate in basic fluids
44
Q

What determines the degree of ionization of a drug?

A

pH on either side of the cell membrane

45
Q

Weak acid formula

A

HA = A- + H+

46
Q

Weak base formula

A

BH+ = B + H+

47
Q

Carrier-mediated transport

A

Large, insoluble molecules (can’t passively diffuse)

48
Q

Types of carrier-mediated transport

A
  • Active transporters (requires ATP to move molecules against concentration or electrical gradient)
  • Facilitated transporters (no energy required, moves large/lipid insoluble molecules DOWN the electrical gradient)
49
Q

Pharmacokinetic processes

A
  • Absorption
  • Distribution
  • Metabolism
  • Excretion
50
Q

Absorption

A
  • into systemic circulation from site of administration (to get to target site)
  • slower rate of absorption = drug sticks around in body longer
51
Q

What administration methods do not require absorption?

A

Intravenous, intrathecal (into spine), topical

52
Q

Dissolution

A
  • liberation of active pharmaceutical ingredient
  • required for absorption to occur
53
Q

What keeps the concentration gradient in favour of drug absorption?

A

regional or local blood flow (continuously takes drug away)

54
Q

Enteric coated formulations

A
  • protect against destruction by gastric juices
  • eg. Acetylsalicyclic acid (aspirin)
55
Q

Long-acting insulins

A
  • addition of proteins or changes in formulation pH (slows dissolution)
  • eg. adding protamine or zinc
56
Q

Controlled release formulations

A

eg. Paroxetine

57
Q

Bioavailability

A

Fraction (%) of administered dose that reaches the systemic circulation unchanged

58
Q

Precipitation of drug

A
  • local reaction at site of injection
  • drug is now unavailable and not absorbed in the time frame you want
59
Q

Reverse transport protein

A
  • P-glycoprotein throws drug back out across epithelial barrier (can’t be absorbed by GI tract now)
60
Q

First pass

A

Liver metabolizing enzymes can inactivate/destroy drug before it gets out into systemic circulation

61
Q

Oral administration

A
  • aka per os (PO)
  • risk of first pass elimination
62
Q

Types of oral transmucosal administration

A
  • Sublingual (under tongue)
  • Buccal (between gum and cheek)
63
Q

Rectal administration

A

Used for patients with GI issues (motility, nausea)

64
Q

Bypassing the first pass effect

A
  • sublingual methods = venous
    drainage to superior vena cava
  • rectal methods = ~50% of drug will bypass
  • parenteral methods (SC, IM, IV, topical, transdermal)
65
Q

Subcutaneous injection

A
  • Into tissues lying below the skin (not into muscle or vein)
  • easier to administer than IV, but absorbs slower than IM and can be erratic
66
Q

Intramuscular injection

A
  • Into muscle
  • Absorption is typically rapid for drugs in aqueous solution; oily suspensions will form depot
67
Q

Intravenous injection

A
  • Into vein
  • good for rapid emergency administration of large volumes, full bioavailability
68
Q

Topical administration

A
  • drug is locally administered, but may end up systemic
69
Q

Transdermal administration

A
  • applied to skin (absorbed into systemic circulation)
  • can control release and prolong action, but takes a long time to reach levels
70
Q

Distribution

A
  • drug must reach target site in adequate concentrations to be effective
  • achieved by systemic circulation and lymphatics
71
Q

Why might a drug remain in the vascular space (blood)?

A

If it is highly protein bound

72
Q

Why does the first pass effect occur?

A

Vessel-rich (aka perfuse) tissues receive the greatest cardiac output and thus distribution of drug
- eg. liver, kidney, brain, heart

73
Q

Tissue perfusion

A

Vessel-rich tissues are more perfuse but have lower capacities than other areas like muscle

74
Q

Non-target binding of a drug

A
  • Plasma protein binding = drugs bound to plasma protein (eg. albumin) cannot diffuse from the vascular space into tissues
  • Tissue binding = accumulate in tissues by binding cellular proteins or phospholipids
75
Q

Volume of distribution

A
  • aka Vd
  • extent to which a drug partitions between blood and tissue compartments
76
Q

Volume of distribution formula

A

Vd = amount of drug in body / plasma drug concentration

77
Q

Total body water

A
  • 66% intracellular
  • 33% extracellular (25% interstitial, 7-8% intravascular)
78
Q

Drug elimination methods

A
  • Excretion (cleared from body unchanged)
  • Biotransformation (aka metabolism, converted to metabolites)
79
Q

First-order elimination

A

A constant fraction (%) of drug is eliminated per unit time

80
Q

Clearance

A

The apparent complete removal of drug from a certain volume of plasma per unit time per unit body weight

81
Q

Extraction ratio

A

Extent to which an organ contributes to drug clearance

82
Q

Enteroheptic recirculation

A

Reabsorption of excreted drug into small intestine to re-enter systemic circulation

83
Q

Active drug secretion

A

From proximal convoluted tubule into urine

84
Q

Reabsorption of drug

A
  • from urine back into blood (in distal convoluted tubule OR passive reabsorption of unionized drug)
85
Q

Inactive “prodrugs”

A
  • activated by metabolism
  • eg. Ramipril (Altace) = converted to active metabolite by hepatic metabolism
86
Q

Catalysis of biotransformation reactions

A
  • performed by cellular enzymes that are located in hepatocytes
  • in cytoplasm and smooth ER
87
Q

Phases of drug metabolism

A

1) Phase I reactions (oxidation/reduction/hydrolysis reactions) = drug converted to polar metabolite, then excreted or enters:
2) Phase II reactions (conjugation reactions) = dietary component binds to product to become a more polar, excretable product

88
Q

Cytochrome P-450

A
  • aka CYP
  • group of enzymes used for Phase I reactions
  • found in smooth ER
89
Q

Goal of Phase I reactions

A

Introduce or unmask functional groups

90
Q

What does Phase II require?

A

Metabolite must have an acceptor for the hydrophilic conjugate moiety

91
Q

Types of Phase II reactions

A
  • Glucuronic acid conjugation
  • Sulphate conjugation
  • Acetylation
  • Glutathione conjugation
92
Q

Sulphate conjugation

A

Phenols and alcohols conjugated to sulphate (SO4)

93
Q

Acetylation

A

Occurs in drugs with -NH2 group conjugated to COCH3

94
Q

Glucuronic acid conjugation

A

Conjugation to glucuronic acid

95
Q

Glutathione conjugation

A

Epoxides & arene oxides conjugated to glutathione (GSH)

96
Q

Key parameters of drug disposition (PK) and dosage regimens

A
  • Bioavailability (%F)
  • Volume of distribution (Vd)
  • Clearance
  • Elimination half-life
97
Q

Amount of drug eliminated after 4 half-lives

A

93.75%

(4-5 half-lives is when a drug is clinically eliminated)

98
Q

Minimum effective concentration

A
  • point where adverse effects begin OR where desired effects begin
  • maximum dose you would want to administer OR minimum
  • multiple small doses above MEC for desired can help avoid MEC for adverse
99
Q

Elimination half life

A

Is a hybrid constant = depends on volume distribution and clearance

100
Q

Loading dose

A

Initial higher dose of drug to reach therapeutic levels faster

101
Q

Factors affecting drug elimination half-life

A
  • aging = decreases (less distribution)
  • obesity = increases (more distribution)
  • pathologic fluid = increases (drug can distribute farther through this fluid)
  • cytochrome P-450 = decreases (more metabolism)
  • organ failure = increases (less clearance)
102
Q

Pharmaceutical interactions: in vitro

A
  • Before the drug is absorbed by the patient
  • Affects total dose available for absorption
103
Q

Pharmacokinetic interactions

A
  • causes most drug interactions of clinical significance
  • interactions during absorption, distribution, metabolism, excretion
104
Q

Induction of P450 enzymes

A
  • increased gene transcription = increased expression of enzyme
  • increased metabolism of the inducing drug means reduced half-life
105
Q

Inhibition of P450 enzymes

A
  • enzyme directly inhibited by affecting drug
  • inhibition effects on other co-administered drugs means decreased dose is required