Exam1/ Lecture 2: Pharmacodynamics and Pharmacokinetics Flashcards by Jasmine Nowels

Lecture 1/22/23

What are the 5 reason why we need to know about pharmacodynamics and pharmacokinetics ?

Produce onset of drug effect quickly
Produce offset of drug effect quickly
Severe consequences to “under” or “over” dosing
Need to frequently adjust levels
Low therapeutic index

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Lecture 1/22/24

What is a receptor made of?

Usually a protein

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Lecture 1/22/24

What is a agonist

Activates receptor by binding to receptor

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Lecture 1/22/24

What are the 3 bonds in agonist that is reversable

Ion (or electrocovalent…oppositely charged ions)
Hydrogen (to a very electronegative atom)
Van der Waals interaction (the sum of attractive or repulsive forces; creates orbital shift)

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Lecture 1/22/24

What are the 2 things that happen to the receptors once it is activated?

Conformational shape changes (Bound vs unbound)
Thermodynamically more/less active

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Lecture 1/22/24

True or False: Drug effects is not effected by the number of bounds receptors.

False: Drug effect relates to number of bound receptors
Greatest effect….all receptors bound
Example: paralytics

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Lecture 1/22/24

What is a antagonist

binds to a receptor but does not activate the receptor

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Lecture 1/22/24

What are the reversible bond forces for an antagonist ?

3 reversible bond

Ion
Hydrogen
Van der waals

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Lecture 1/22/24

What type of antagonism, in large amounts progressively inhibits the agonist and shifts dose respone curve to the right?

Competitive antagonism

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Lecture 1/22/24

What type of antagonism does not allow the agonist effects to happen regardless of how much agonist is given?

Non-competitive antagonism

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Lectue 1/22/24

What type of agonist binds to a receptor casusing less response than the agoinst even at supramaximal dose?

Partial agonist

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Lecture 1/22/24

What type of agonist compete for the same site as the agonist but produce the oppose effects?

Inverse agonist

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Lecture 1/22/24

True or False: The number of receptors cannot increase or decrease depending on the comorbidity and drug therapy?

False, can increase or decrease depending on comorbidity, and drug therapy

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Lecture 1/22/24

What are the 3 types of receptors?

Lipid bilayer
Intracellular proteins
Circulating proteins

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Lecture 1/ 22/24

What are 7 examples of lipid bilaryer receptors?

Common for anesthesia drugs
Membrane bound
Opioids
bzd
b-blockers
catecholamines
nMbd

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Lecture 1/22/24

What are 3 examples of Intracellular proteins receptors?

Insulin
steroids
milrinone

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Lecture 1/22/24

What is an example of a circuating protein receptor?

anticoagulants

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Lecture 1/22/24

Please label the graph:
* partial agonist
* inverse agonist
* full agoinist
* weak partial agonist

partial agonist - B.
inverse agonist - D.
full agoinist - A.
weak partial agonist- C.

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Lecture 1/22/24

What does Renal Clearance involve?

Glomerular Filtration - GFR and amount of protein bound drug controls amount of drug entering tubule
Active Tubular Secretion - from peritubular capillaries, active transport process, penicillins
Passive Tubular Reabsorption - increased if drug is lipid soluble, ie thiopental, almost zero for water soluble drugs… excreted in urine

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1/22/24

What is Elimination 1/2 Time

time necessary to eliminate 50% of drug from PLASMA after bolus dose

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1/22/24

Time to a 50% decrease after infusion discontinued
(assumes a constant concentration, roughly relates to 1/2 life, increases the longer the infusion increases - accumulation in peripheral tissues)

Context Sensitive Half-Time

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1/22/24

what is Ionization

When the pk (dissociation constant) and ph are identical,
-50% of drug ionized, 50% of drug non-ionized

Most drugs are weak acids (Barbs) or weak bases (La and opioids)
-Acids are ionized in an alkaline ph/bases are ionized in an acid ph

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1/22/24

Characteristics of drug molecules

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1/22/24

how to figure out ionization vs non-ionization

Weak acids (barbiturates)
Pk after ph
Weak bases. (LA or opioids)
Pk before ph

So if a weak acid (pk 7.6) is put in a basic ph (blood 7.8)
7.8 – 7.6 = +0.2 acid drugs are ionized at basic ph

If weak base (pk 8.0) is put in an acid ph (Blood 7.2)
8.0 – 7.2= +0.8 weak bases are ionized at acid ph

“nicely negative numbers are nonionized”

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# 1/22/24 what is an Ion Trapping example

A pregnant lady gets a spinal anesthetic with LA and opioid (weak base, pk 7.3) But fetal ph is lower than maternal ph (baby is in distress) 7.3 – 7.4 = -0.1 a bit non- ionized for mom 7.3 – 6.8 = +0.5 ionized for fetus and is trapped…. ”ion trapping” In addition, the concentration gradient of non ionized drug to ionized drug for opioid is still higher in mom…. ## Footnote slide 31

# 1/22/24 what is: “The sensitivity of the body to the drug” “what the drug does to the body” How do we figure this out? Measure plasma concentrations at different pharmacologic responses…. Dopamine Ie. Clinically, what are the drugs effects…

Pharmacodynamics ## Footnote slide 33

# 1/22/24 What are causes for Individual Variability?

**Elderly** -Decreased cardiac output…. To brain and liver…. -Decreased protein binding -Increased body fat **Enzyme activity** -Acute vs chronic alcohol ingestion **Genetic disorders** -Atypical cholinesterase activity -Malignant hyperthermia ## Footnote slide 34

# 1/22/24 what is the difference between Potency vs Efficacy

*Potency*: concentration vs response….less drug with more effect = more potent *Efficacy*: the ability of a drug to produce a clinical effect ## Footnote slide 35

What is Relative Potency?

* Time to drug effect * Plasma *not* the site of effect for anesthetic drugs * Lag time between administration (*plasma concentration*) and effect ## Footnote slide 36

What is Effective Dose (ED50) ?

Dose required to produce effect in 50% of patients ## Footnote slide 37

What is Lethal Dose (LD50) ?

Dose required to produce death in 50% of patients ## Footnote slide 37

What is Therapeutic Index?

* ratio between (LD50/ED50 ) * the wider/bigger it is, the safer the drug is and the the narrower it is, the more dangerous the drug is ## Footnote slide 37

What is a Stereochemistry?

How drug molecules are structured In 3 dimensions ## Footnote slide 38

What are Chiral Compounds?

* Molecules with asymmetric centers usually related to way Carbon molecules are bonded. * the structure of an anti tumors and several of our popular drugs ## Footnote slide 38

What are structural basis of Enantiomers?

* Chemically identical * Mirror images * Can’t be superimposed - not overlapping but like having but when my thumbs and my pinkies are on same sides. ## Footnote slide 38

What is Dextrorotatory of an Enantiomer?

**RIGHT rotation** of light in a solution ## Footnote slide 39

What is Levorotatory of an Enantiomer?

**LEFT rotation** of light in a solution ## Footnote slide 39

What are the 2 drug sequences of Enantiomers?

* R: Rectus * S: Sinister ## Footnote slide 39

What is a Racemic?

* 50/50 mixture * Optical activity equal * Can exhibit different ADME * One enantiomer is active; other inactive or side effects * 1/3 of drugs ## Footnote slide 39

What are examples of different Enantiomers?

* S-Ketamine = more potent with less delirium vs. R-Ketamine = like head injury effects of delirium * L-Bupivicaine = less cardiac toxicity * Cisatracurium = isomer of Atracurium that lacks Histamine effects * Albuterol and Xopenex ## Footnote slide 40

What is Pharmacogenetics/Pharmacogenomics?

How a single gene or all genes (genome) influences responses to drugs ## Footnote slide 41

What is Pharmacogenetic Testing?

Look for variants in genes that code for: * Drug-metabolizing enzymes * Drug targets * Immune proteins ## Footnote slide 41

What does the acronym ADME stand for?

Absorption, Distribution, Metabolism, Excretion

Pharmacokinetics is the ________ study that details what the _______ does to the _____

Quantitative; Body; Drug

Pharmacokinetics determines the measurable concentration of the drug in the ______

Plasma

In a ONE compartment model, if a patient is hemorrhaging and a drug is administered, does the Volume of Distribution Increase or Decrease?

DEACREASE

What organs are considered part of a “Vessel Rich Group?”

Brain, Liver, Kidney

Is a one compartment volume distribution model accurate?

What are 4 common drugs that are taken up in 1st pass metabolism?

* Lidocaine * Propranolol * Meperidine * Fentanyl (Includes SUfentanil and ALfentanil)

A HIGH Volume of Distribution of 5,000L indicates that a drug is ____ Soluble

Fat/Lipid

How does LOW plasma protein affect drug distribution?

Allows for more free, unbound drug to be available to cross cell membranes (Distribute through the body)

Acidic drugs primarily bind to what protein?

Albumin

Alkalotic drugs primarily bind to what protein?

A1- Acid Glycoprotein

Low plasma protein is commonly found in what patient demographics?

* ICU Patients * Geriatrics * Patients with Extended NPO time * patients with Liver Cirrhosis Alcoholics * Patients in Renal Failure * Burn Patients

If a drug has a normal free fraction of 2%, what percentage is bound?

98% (2% is available to go off and elicit desired clinical/physiological response

What drug (include its classification) is used as the gold standard to measure other drugs against?

Thiopental It is a Barbiturate

If a drug is HIGHLY bound to plasma proteins, does it have a Large or Small volume of distribution? Give an example of one medication

Small Vd Rx: Warfarin

The process of metabolism converts active, lipid soluble drugs to ____ soluble

Water

Why are many anesthetics lipid soluble?

The effector sites of the anesthetics are not in the plasma, they are in other parts of the body

Active Metabolites can have as high as ___% effect of the parent drug

50%

What process do Prodrugs require to become active?

PO Drugs must first be ingested but all Prodrugs require some form of early Metabolism

How are most drugs metabolized?

Hepatic Microsomal Enzymes ( the greatest) Hoffman Elimination Ester Hydrolysis Kidneys Tissue Esterase’s (GI Tract and Placenta)

Hofmann Elimination depends on what two physiological properties being within normal limits?

Temperature and pH

Hofmann Elimination is important in what types of drugs?

Neuromuscular Drugs

What 2 phases occur in Metabolism?

Phase 1: Increase polarity and prepare for Phase 2 reactions Phase 2: Covalently link with highly polar molecule to become water soluble

What processes take place in Phase 1 metabolism?

Oxidation, Reduction, Hydrolysis

What process takes place in Phase 2 metabolism?

Conjugation

What gives the liver its red color?

A Heme cofactor

Where are the P450 enzymes located?

Attached to the Smooth Endoplasmic Reticulum of the hepatocytes

CYP450 absorbs what wavelength of UV light when exposed to Carbon Monoxide?

Wavelength 450nm

What is the most common enzyme in the CYP 450 family

CYP3a4, responsible for up to 60% of the CYP450 activity

Enzymatic INDUCTION leads to a(n) _______ in the amount of enzymes.

Increase

An induction of enzymes, _______ metabolism of a drug and requires _______ frequent dosing of a drug to reach desired clinical effect.

Increase; more

Enzymatic INHIBITION leads to a(n) _______ in the amount of enzymes

Decrease

Inhibition of enzymes, _______ metabolism of a drug and _______ the effects of the drug

Decreases; Prolongs

For most anesthetic drugs is constant so the Rate of clearance is proportional to ______

Concentration

What effects can be caused by the limited capacity of the liver to metabolize a drug

- Can lead to a buildup of a drug in the body, if the drug amount given exceeds the liver’s ability to metabolize

Exam1/ Lecture 2: Pharmacodynamics and Pharmacokinetics Flashcards

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