Breakdown for ease of elimination May become active (prodrug) or inactive Metabolites may be more toxic than parent compound

Terminal oxidase in a multicomponent electron transfer chain Phase I type reactions

Inhibition: Will keep the enzyme from working properly Ability to increase amount of parent compound

Pharmacokinetics Flashcards by Jeff Welsted

Pharmacokinetics include

Absorption
Distribution
Metabolism
Excretion

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Bioavailability (F) is

% of medication that reaches systemic circulation

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Oral Administration: Considerations in GI Tract

Gastric pH and contents
Surface area
Blood flow
GI motility
Complete GI tract
Flora

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Sublingual/Buccal route drains to ________, Very rapid.

• Must be HIGHLY _______ and _________

vena cava

lipid soluble and potent

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90% of oral medication is metabolized and destroyed by the

liver

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Topical eye gtts may become systemic via the

nasolacrimal canal

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Topical administration includes

Skin, eye, inhalation

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Inhalation agents avoid

first pass metabolism

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Simple diffusions rates are limited by:

amount of capillaries, solubility, molecular size and composition

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Volume of Distribution is the

Size of compartment necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the plasma
• Average adult plasma Vd= 3 Liters
• Total body water = 0.65 L/kg

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Loading Dose =

Vd x Cd

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Two Compartment Model:

• Re-distribution before elimination
• Slow rate of administration for secondary re-
distribution
• Target organ may be in the initial or secondary “compartment”

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Due to Protein Binding, the Unbound/free drug =

active

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Tissue Binding examples:

Fat: Reservoir for lipid soluble drugs
• Bone: Tetracyclines
• Heart muscle: Digoxin

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In order to enter an organ, a drug must ___________ that separate the organ from the site of drug administration.

permeate all membranes

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Fetal plasma is more acidic, therefore ion trapping of _______ drugs occurs

basic

• P-glycoproteins limit transport

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P-glycoproteins are

• Family of transporter proteins
• Found all over, including the blood brain barrier
• Kidney, colon, jejunum, liver, pancreas
• Important for medication interactions and
drug resistance
• Requires ATP

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Passive diffusion, carrier? energy?
Facilitated diffusion, carrier? energy?
Aqueous channels. carrier? energy?
Active Transport. carrier? energy?

Passive Diffusion No, No
Facilitated Diffusion No, Yes
Aqueous Channels No, No
Active Transport Yes, Yes

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Metabolism is the

Breakdown for ease of elimination
May become active (prodrug) or inactive
Metabolites may be more toxic than parent compound

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Phase I Metabolism is

Induce or expose a functional group on the parent compound
Generally lose activity, rare instances of preserved.
Then often hydrolyzed or ester linked for rapid elimination thru the kidneys

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Phase II Metabolism

• Conjugation reactions
• Links parent compound OR phase I
metabolite with a functional group via
covalent linkage
• Functional groups: glucouronic acid, sulfate, glutatione, amino acid, acetate
• Example: Morphine: 6-glucouronide metabolite
• Becomes MORE active than parent compound

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Most reactions are ______ driven

enzyme

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Cytochrome P450 is

Terminal oxidase in a multicomponent electron transfer chain
Phase I type reactions

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Inhibition:

Inhibition: Will keep the enzyme from working properly

* Ability to increase amount of parent compound

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Induction:

* Induction: Will enhance the capability of the enzyme | * Ability to quickly metabolize the parent compound

Factors Affecting Metabolism

* Genetics * Environmental, diet * Disease Factors * Age and Sex

Easier to eliminate _________ compounds than ____________ compounds

Easier to eliminate polar/hydrophillic compounds than lipophillic compounds

Renal elimination includes 3 processes:

* Glomerular Filtration * Active tubular secretion * Passive tubular reabsorption

Besides renal elimination, other routes of elimination include:

* Biliary and Fecal * Sweat, saliva and Tears * Lungs

In first order kinetics, the length of the half life is

constant, curved downward slope

In zero order kinetics,

half life decreases with decreasing concentration | straight down slope (45 degree)

Elimination Rate (k): is the

fraction or % of the total amount of drug in the body removed per unit of time

Half Life and Elimination Rate are used to estimate the

estimate the time to steady state • Estimate the time to eliminate the medication from the body • Predict non-steady state plasma levels • Predict steady state from a non-steady state level • Determine dosing intervals

pharmacokinetics is

what the body does to the drug (ADME)

pharmacodynamics is

what the drug does to the body

Steady state is

Amount of drug administered over time = amount of drug eliminated during the same time period - rate in = rate out

A steady state is acheived after

4-5 half lives

Does a loading dose shorten the time to ready steady state?

Would you reach steady state faster if the dose was given at one half of the medication’s half life?

How to interpret drug levels:

- NEVER treat an isolated number n check dosing history | - Always treat the patient not the number

A trough is drawn to check

efficacy

A peak is drawn to check

toxicity

Drugs exert their primary action at the

cellular level

Most drugs bind to ____________ where they initiate biochemical reactions that alter the cell’s physiology

cellular receptors

There is a _____ number of receptors on a given cell.

finite

The strength of binding between a drug and its receptor.

Affinity

The measure of a drug’s affinity for a given receptor. The concentration of drug required in solution to achieve 50% occupancy of its receptors.

Dissociation Constant (Kp)

Drugs which alter the physiology of a cell by binding to plasma membrane or intracellular receptors.

Agonist

an agonist which causes maximal effects even though it may only occupy a small fraction of receptors on a cell.

Strong Agonist

an agonist which must be bound to many more receptors than a strong agonist to produce the same effect.

Weak Agonist

inhibit or block actions caused by agonists.

Antagonist

competes with agonist for | receptors.

Competitive antagonist

binds to a site other than the agonist-binding domain. Induces a conformational change in the receptor such that the agonist no longer “recognizes” the agonist-binding domain.

Noncompetitive antagonist

agents compete with agonists for the agonist-binding receptor .

Irreversible antagonism

The degree to which a drug is able to cause maximal effects.

Efficacy

the amount of drug required to produce 50% of the maximal response that the drug is capable of causing.

Potency

is frequently used to compare drugs within the same chemical class. Drugs within the same chemical class will usually have similar maximal efficacy if a high enough dose is given.

Potency

is used to compare drugs with different mechanisms. For example, toradol (NSAID) has equal efficacy to morphine (narcotic) in controlling post-op pain.

Efficacy

Before new drugs are approved for marketing, their _______and _________ must be tested in animal and human population studies.

efficacy and safety

EC50

(Effective Concentration 50%) The concentration of drug which induces a specified clinical effect in 50% of the subjects to which the drug is administered.

LD50

(Lethal Dose 50%) the concentration of drug which induces death in 50% of the subjects to which the drug is administered.

Therapeutic Index

a measure of the safety of a drug. Calculated by dividing the LD50 by the ED50.

Margin of Safety

the margin between therapeutic and lethal doses of a drug.

Drug interaction: addition

the response elicited by combined drugs is EQUAL TO the combined responses of the individual drugs. 1+1=2

Drug interaction: synergism

the response elicited by combined drugs is GREATER THAN the combined responses of the individual drugs. 1+1=3

Drug interaction: potentiation

A drug which has no effect enhances the effect of a second drug. 0+1=2

Drug interaction: antagonism

Drug inhibits the effect of another drug. Usually, the antagonist has no inherent activity. 1+1=0

Tolerance represents a

decreased response to a drug, dose of a drug must be increased to achieve the same effect.

Dependence occurs when a patient needs a drug to

“function normally” - Clinically this is noted when cessation of a drug produces withdrawal symptoms. - Dependence may be both physical and/or psychological.

Withdrawal occurs when a drug is

not administered to a person who has become dependent on it. | § Symptoms of withdrawal are often opposite the effects achieved by the drug.

CRRT provides an average of what creatinine clearance

30 mL/min

Pharmacokinetics Flashcards

(71 cards)