Module 3 Flashcards
When discussing inhalational agents, what is the relationship between a higher blood/gas partition coefficient and its’ lipid solubility?
Higher lipophilicity
Involves both pharmacodynamic and kinetic factors.
Other factors such as co-morbidities play a role in dosing.
In GENERAL dosing should be reduced by 50-60%
Elderly Dosing
Administered via lungs
Kinetics are the same as for any drug
Other factors may come into play
Inhalation agents
Factors determining partial pressure gradiant necessary for establishment of anesthesia: Transfer of inhaled anesthetics from Anesthetic Machine to Alveoli
- Inspired partial pressure
- Alveolar ventilation
- Characteristics of anesthetic breathing system
Factors determining partial pressure gradiant necessary for establishment of anesthesia: Transfer of inhaled anesthetics from Alveoli to Arterial Blood
- Blood-gas partition coefficient
- Cardiac output
- Alveolar-to–venous partial pressure difference
Factors determining partial pressure gradiant necessary for establishment of anesthesia: Transfer of inhaled anesthetic from Arterial Blood to Brain
- Brain-blood partition coefficient
- Cerebral blood flow
- Arterial-to-venous partial pressure difference
When a gradient is established between your machine and the patient via the lungs, the lungs in turn…..
Equilibrates with the blood, which in turn will equilibrate with brain causing the desired effect
Most important factor in determining potency of inhalation agents
Blood-gas partition coefficient
Function of solubility of the agent in blood and is a measure of how quickly the inhalation anesthetic equilibrates between the lungs and blood and ultimately the target site in the brain
Blood-gas partition coefficient
Blood-gas partition coefficient is _________ proportional to induction rate, the higher the number the longer the induction and thus the longer the emergence
INVERSELY
In the case of inhalational agents, what is the relationship between a higher lipophilicity and agent potency?
Higher potency
With inhalational agents, the higher the blood/gas partition coefficient in the agent the _________ the solubility.
Higher
Inhalational agents with high solubility have _________ uptake/onset of anesthetic effect
Slower onset/uptake
A high blood/gas partition coefficient generally would mean a ________ MAC (Mean Alveolar Concentration).
Low MAC.
When considering the effects of inhalational agents on induction it is helpful to consider that what is happening in the lungs is likely happening in the _________.
Brain
A mnemonic that identifies inhaled anesthetics in order of highest blood/gas partition-lipophilicity-solubility- and therefore slowest uptake.
“HI-SE” (H-alothane, I-soflurane, Se-voflurane) Not included are Desflurane and N20, in that order.
Name inhaled anesthetics in order of fastest uptake.
N20, Desflurane, Sevoflurane, Isoflurane, Halothane (“HI-SE” in reverse)
In reference to the elimination rate with inhaled anesthetic agents, the higher the plasma drug concentration the _________ the rate of elimination is.
Faster
Inhaled anesthetic agents follow what type of pharmacokinetics?
First-order
Order of recovery times from inhaled anesthetics from fastest to slowest.
Desflurane-Sevoflurane-Isoflurane-Halothane. “HI-SE” in reverse. (inverse relationship between partition coefficient and uptake and recovery)
Increased cardiac output does what to the speed of induction?
Slows it down with all inhaled anesthetics.
How does hypothermia affect inudction with inhaled anesthetics?
Slows induction.
How does a high minute ventilation affect inhaled anesthesia induction?
Makes for a faster induction
What is the MAC and blood:gas coefficient for N20?
104%, 0.47
What is the MAC and blood:gas coefficient for Desflurane?
6%, 0.45
What is the MAC and blood:gas coefficient for Sevoflurane?
2%, 0.65
What is the MAC and blood:gas coefficient for Enflurane?
1.7%, 1.8
What is the MAC and blood:gas coefficient for Isoflurane?
1.4%, 1.4
What is the MAC and blood:gas coefficient for Halothane?
0.75%, 2.3
What is Pharmacodynamics?
the branch of pharmacology that studies the relationship between drug concentration at the site of action (receptor) and the resulting physiologic effect as well as any adverse effects
Defined as the biological and physiologic effect of a drug (what the drug does to the body).
Pharmacodynamics
A macromolecular complex which acts as the site of action for a drug. It is also a protein located on the cell surface that interacts with the cellular environment.
Receptor
The effective dose in 50% of the population.
ED50
The concentration (blood) at which an individual experiences 50% of the drug’s effect
EC50
An index for estimation of drug dosage which can treat disease effectively while staying within the safety range.
Therapeutic window (or pharmaceutical window)
What is the expression for Therapeutic Window
LD50/ED50
The relationship between therapeutic dose and lethal dose. The higher the number the safer the drug.
Therapeutic Index (TI)
What is the expression for Therapeutic Index
TI=TD50/ED50
A drug that produces an effect when it binds to its receptor
Agonist
A drug that binds to the active conformation of receptor until all receptors are occupied producing maximum effect
Full Agonist
What is a Full Agonist?
Full agonist the drug binds to the active conformation of receptor until all receptors are occupied producing maximum effect.
A drug that has an equal affinity for the active and inactive receptor. It is therefore unable to activate all the receptors and only a partial effect is observed
Partial Agonist
What is a Partial Agonist?
A drug that has an equal affinity for the active and inactive receptor. It is therefore unable to activate all the receptors and only a partial effect is observed
A drug that has negative efficacy by diminishing the intrinsic activity of receptors, very hard to distinguish from antagonist.
Inverse agonist
A drug or endogenous chemical that binds to a receptor, resulting in the opposite action of an agonist. Using the two-state model, they appear to bind preferentially to the inactivated receptor.
Inverse Agonist
A drug that may partially block the effects of full agonists and has a lower efficacy than a full agonist.
Partial Agonist
These drugs possibly possess both agonist and antagonist properties.
Agonist-Antagonist
Do antagonist bind or activate the receptors?
Bind receptors
What do competitive antagonist drugs compete for?
Compete for binding sites on receptors
Do competitive antagonist drugs elicit activation of receptors?
Do not elicit activation of receptors
Where do non-competitive antagonist drugs bind to?
Non-competitive antagonist drugs bind to receptors at non-active site
What happens to enzymes/receptors when non-competitive antagonist drugs bind to receptors?
The enzymes/receptors are not able to be activated by the agonist.
What is the purpose of Allosteric sites on receptors?
Allosteric sites on receptors affect the manner in which the receptor behaves by enhancing or diminishing the effect of other drugs.
When does antagonism occurs?
When the combined effect of two drugs is less than the sum of their individual effects.
What is Physiological or functional antagonism?
Two drugs that act on different receptors and antagonize the actions of each other.
When does a Pharmacodynamic interaction occur?
When two or more drugs are given concomitantly.
What is an Additive interaction?
When the combined effect of two drugs equals the sum of their individual effects.
When does Synergy occurs?
When two drugs are combined in therapy and produce a pharmacologic effect greater than the sum of their individual effects.
Mention 4 examples of basic drug actions divided into broad categories.
Stimulation (epinephrine), Depression (benzodiazepines), Replacement (insulin), Cytotoxic (antibiotics/chemo agents)
Mention a few drugs that do not act on receptors to exert their effects.
Antacids, laxatives, and mannitol.
PK-PD principle?
links pharmacokinetics and pharmacodynamics in order to establish and evaluate dose-concentration-response relationships and subsequently describe and predict the effect-time courses resulting from a drug dose.
Differences between anesthesia and other specialties?
?
Ideal anesthetic drug would?
would induce anesthesia smoothly and rap
idly while allowing for prompt recovery after its administration is discontinued. The drug would also possess a wide margin of safety and be devoid of adverse effects.
what is graded response?
Response to a drug dose is gradual and constant. It depends on the amount of drug, as the Concentration increases so does the effect (it also includes adverse effects).
what is the Law of mass action?
when a drug combines with a receptor, it does so at a rate which is dependent on the concentration of the drug and of the receptor
what is tolerance?
the ability of the body to metabolize drugs faster after prolonged exposure
what is desensitization?
Desensitization refers to a change in the responsiveness of the receptor after prolonged exposure. The receptors are still present but do not respond to the drug. The reason for this is varied but in some cases may be due to secondary messenger exhaustion
what is tachyphillaxis?
rapidly diminishing response to successive doses of a drug, rendering it less effective.(acute response)
Dosing for obesity
Drug dependent. For example propofol dosing for bolus is based on ideal body weight but for infusions it should be based on total body weight
how do you dose midazolam and ketamine on obese patients?
Bolus doses should be based on total body weight, infusions should be dosed on IBW
A drug with a left-shifted concentration versus responsive curve is said to be
More potent
A drug with a right shifted dose versus response curve is said to be
Less potent
Concentration versus response relationship is known as
Potency
The measure of the intrinsic ability of a drug to produce a given physiological or clinical effect.
Efficacy
The window between the drug response and adverse effects
Therapeutic window
Study of three dimensional molecule structure
Stereochemistry
Compounds that have the same chemical structure but are non-superimposable.
Enantiomers
Enantiomers are compounds which are classified as d or l because of their ability to:
Rotate polarized light
Two enantiomers present in equal proportions (50:50)
Racemic Mixture
The strength of the interaction between the drug and the receptor
Affinity
Effect of the drug when the drug reaches the site of action at the target tissue.
The Biophase
Compliance, dosing and medication errors, absorption, tissue and body fluid, mass and volume, drug interactions, elimination, and drug metabolism are what branch of pharmacology?
Pharmacokinetics
Drug receptor status, genetic factors, drug interactions, tolerance are what branch of pharmacology?
Pharmodynamics
How do you measure drug concentration in the target tissue?
Plasma concentration is used together with other measurements to estimate concentration at the site of action.
Apparent volume into which the drug is dissolved
Volume of distribution
What is the relationship between the volume of distribution and half life?
The larger the Vd the longer the half-life. This does not equate with clinical effect
Defined as the amount of drug needed to produce a clinical effect.
Potency
The measure used to compare 2 drugs
EC50- Effective concentration
The ability of a drug to bind with its receptor and produce a physiologic response.
Efficacy
The ability of the drug to elicit a response when it binds to the receptor
Efficacy
As the amount of substrate increase, does the enzyme increase or decrease its rate of reaction?
Increase
True/False- Once Vmax is reached, adding more substrate will increase the rate of reaction?
False- adding more substrate WILL NOT increase the rate of reaction
