Pharmacokinetics/Pharmacodynamics Flashcards by Grace Prinsell

“the drug’s effect on the body”

therapeutic and/or toxic doses

Sensitivity and responsiveness of receptors

Variability from person to person

Mechanism of action

effective dose (ED)

Pharmacodynamics

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When is a drug considered eliminated?

when 95% has been eliminated – usually 4-5 elimination ½ lives

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The time for the drug in the plasma to decrease by 50%; affected by volume of distribution and changes in clearance.

Elimination ½ life

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The time for the plasma drug concentration to decrease by 50% after discontinuing a continuous infusion of a specific duration

Context-Sensitive Half-Time (infusion duration)

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Which drug has a short context-sensitive half-time?

remifentanyl

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The half-time of equilibration between drug concentration in the blood and the drug effect*

Accounts for the delay between IV injection into the plasma and the delivery of the drug to its site of action

Important for redosing intervals!

Effect-Site Equilibration Time

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Number to describe the apparent volumes of compartments that constitute the compartmental model.

Describes the distribution characteristic of a drug in the body.

Calculated – dose of drug given divided by the resulting plasma concentration prior to elimination (at maximal concentration)

Volume of Distribution

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What is Volume of Distribution effected by?

1) Lipid solubility
2) Binding to plasma proteins
3) Molecular size

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Large Vd Drug

propofol

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small Vd drug (MOSTLY IN PLASMA)

NMB

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Which drug has more effect, bound or unbound?

unbound (in the plasma, can cross cell membrane, not bound to the protein)

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What is an ionized drug?

WATER-soluble

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What is a nonionized drug?

LIPID-soluble

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What 4 areas are lipid soluble?

blood-brain barrier
renal tubules
GI endothelium
placental barrier

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high vD

low protein binding

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low vD

high protein binding

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One effective dose plus another effective dose

1 + 1 = 2

Sebo and nitrous

Additive

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Given together to create a bigger effect

1 + 1 = 3

fentanyl and midazolam

Synergistic

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Enhancement of one drug action by second drug with no action of its own

1 + 0 = 3

Potentiation

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Working against each other

1 + 1 = 0

Fentanyl and nalaxone

Antagonistic

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Having or showing abnormally high sensitivity to stimuli

such as bronchial response to an irritant

Hyperreactive

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Abnormally susceptible physiologically to a specific agent

can be an immune-mediated response

Hypersensitive

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Having or showing abnormally low sensitivity to stimuli

Hyporeactive

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What type of response can occur with a person on an antihypertensive drug given vasodilation?

Hypersensitive

hypersensitive to vasodilation, super responsive, extremes of BP lows and highs

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What type of response can occur with a person who chronically uses oxy for back pain?

Hyporeactive developed a tolerance, may have low sensitivity to narcotics

The difference between the usual effective/therapeutic dose and the dose that causes severe or life-threatening side effects (toxic)

Safety margin

the capacity of the body to endure or become less responsive to a substance (as a drug) or a physiological insult especially with repeated use or exposure

tolerance

diminished response to later increments in a sequence of applications of a physiologically active substance less of a response the next times you give it (second dose often needs to be larger)

Tachyphylaxis

Example of tachyphylaxis?

ephidrine

what is ED50?

effective dose in 50% of patients

A substance that binds to a specific receptor and triggers a response in the cell. Mimics the action of an endogenous ligand that binds to the same receptor

Agonist

Can some drugs be partial agonists and antagonists?

Yes Activates a receptor, but cannot produce a maximum response May partially block effect of full agonists Lower efficacy than a full agonist

A drug that has affinity/potency for the receptor, but no efficacy does NOT activate the receptor to produce a physiologic action.

Antagonist

Does an antagonist produce a physiologic action?

no, it produces a CONSEQUENCE (block of the response)

What type of antagonist is reversible?

Competitive

What type of antagonist is irreversible?

non-competitive

Two agonist drugs that bind to different receptors – causing opposing responses

Physiologic antagonism

NO receptor activity is involved – one drug binds with the second drug to inactivate it

Chemical antagonism

example of chemical antagonism?

protamine and heparin

example of physiologic antagonism?

vasodilation v. vasoconstriction

the component of a cell that interacts with a drug and initiates the chain of events leading to the drug’s effect

Receptor

What is responsible for the selectivity of drug action?

receptor

the degree of drug receptor interaction for a given drug

affinity/potency

drug’s ability to produce desired response (maximum effect)

efficacy/intrinsic activity

Maximal or nearly maximal response can often be produced by activation of only a fraction of the receptors present

Spare receptor concept

Is the relationship between the number of receptors stimulated and the response usually: linear OR nonlinear?

NONlinear Example: muscle receptors and antagonists – takes 70% of receptors blocked before reduction in muscle response – only 30% of receptors activated by ACh produces maximal response

occurs with continued stimulation of cells with agonists – the effect is diminished

Down-regulation/Desensitization Example: beta agonist bronchodilators – tolerance develops from repeated use – increased dose required for same effect

chronic exposure to antagonists cause receptor number and sensitivity to increase

Up-regulation Example: Beta-blockers cause up regulation of receptors if taking beta blocker on regular basis, have them continue on morning of surgery if level is too low, there will be increase of beta 1 receptors, so there is going to be exaggerated response (greater tachycardia, etc.)

what type of drug binds to circulating protein receptors?

drugs affecting components of the coagulation cascade

AGE Variability of Pharmacologic Response

neonates (not ready yet, not good enzymes, large water content, there response to water soluble vs lipid soluble) 80s age (dehydrated, malnourished, things are starting to fail)

SEX Variability of Pharmacologic Response

NMBs (guys have a higher muscle content than men, could possibly impact duration)

Pathological State (PS) Variability of Pharmacologic Response

muscular dystrophy, myasthenia gravis

Variability of Pharmacologic Response

Age Sex Body weight Body surface area Basal metabolic rate Pathologic state Genetic profile

the actions of the body on the drug Absorption Distribution Metabolism Elimination of drugs and metabolites

Pharmacokinetics

What is another word for absorption?

bioavailability

What types of routes are effected by first-pass effect?

PO, rectal

circulation through the liver

first-pass effect

where does sublingual go?

superior vena cava

where does fentanyl and sufentanyl go first?

lungs

What are the components of the Two Compartment Model

distribution (alpha) elimination (beta)

what is elimination phase?

metabolism and excretion

what is distribution phase?

central (vessel rich group, then muscle, then fat, than redistributed) to peripheral

% for Fat Group

”im fat and 26" 6% CO and 20% body mass

% for Muscle Group

"People are more muscley at 19 than 50" 19% CO, 50% body mass

% for VRG

"wise with the brain at age 75" 75% CO, body mass 10%

what is the VRG (5 places)

brain heart liver kidney endocrine

does metabolism always create inactive metabolites?

no Morphine-6-glucuronide is more potent than morphine itself Prodrug – metabolized to an active drug – codeine to morphine

what are 5 sites for metabolism?

MOSTLY Hepatic microsomal enzymes Plasma – Hofmann elimination Lungs Kidneys Gastrointestinal tract

what effects Hoffman elimination?

temperature and pH

Does enzyme induction impact inner patient variability?

yes taking certain medications can increase metabolism of drugs

Hepatic microsomal enzymes mostly Oxidative metabolism of most drugs

Cytochrome P-450 Enzymes

The ability of drugs or chemicals to stimulate activity of the cytochrome P450 system.

Enzyme induction

Non-microsomal enzymes Metabolism by conjugation, hydrolysis, and some oxidation and reduction Present largely in the liver, but also found in the plasma and GI tract

NON-cytochrome P-450 Enzymes (Esters) plasma cholinESTERase, plasma ESTERases

Are NON-cytochrome P-450 Enzymes (Esters) inducible?

Can NON-cytochrome P-450 Enzymes (Esters) be altered by genetics?

YES

what are phase I enzymes?

Cytochrome P-450 Enzymes NON-cytochrome P-450 Enzymes (Esters)

are FAST or SLOW acetylators are at greater risk for side-effects?

SLOW

What are the 2 major sites of elimination?

kidneys and the liver

ED50 is an example of what*

pharmacodynamics (drug effecting the body)

CSHT is effected by what 3 things*

distribution, metabolism, duration