Lecture 2 - Pharmacodynamics and Pharmacokinetics (Test 1) Flashcards
What does TTE stand for?
Can we use this in our charting in the OR?
Titrate to Effect
YES! If you have a gtt on a roller-clamp, you can chart “TTE” and you’re covered :)
Slide 2
What does the Quantitative study component refer to Pharmacokinetics?
Quantitative - what we can measure (ADME) ADME is what the body does to the drug
(slide 12)
what does ADME stand for
Absorption, Distribution, Metabolism, Excretion
(slide 12)
Which four factors/disease processes would lead to decreased plasma proteins?
Renal Failure
Hepatic Disease
Age (Elderly)
Pregnancy
Burns (verbal)
Slide 17
If normal free fraction of a drug is 2% and the patient has lost 50% of plasma proteins, the free fraction of the drug would now be…
4% - It doubles bc the patient lost 50% of their ability to bind to the drug to protein (inactive form)
Slide 17
What is ED50?
The dose required to produce effect in 50% of patients
(Slide 37)
What does quantitative study refer to in the context of Pharmacokinetics?
Quantitative study refers to the study of Injected and inhaled drugs and their metabolites
(slide 12)
What is LD50?
The dose required to produce death in 50% of patients
(Slide 37)
Pharmacokinetics determines the concentration of the drug to what 3 factors?
- Amount in the plasma
- At the effector site on the receptor
- The variety of significant effects from person to person
(slide 12)
Therapeutic index is?
The ratio between (LD50/ED50 )
(Slide 37)
Which disease processes/factors would result in a large volume of distribution?
Burns
Sepsis
Pregnancy
Age
Malnourished
Liver/renal
Slide 18
Would you rather have a wide or narrow therapeutic index?
A wide therapeutic index because it makes the medication safer compared to a narrow one.
(Slide 37)
If a drug is lipophilic and has poor protein binding, the volume of distribution is…
Large
Slide 18
If a drug is highly protein bound to plasma proteins, the volume of distribution is…
Small
Slide 18
Which two drugs discussed in class have a high volume of distribution?
Thiopental (Barbiturate used to induce general anesthesia)
Diazepam/Valium
Slide 18
What is stereochemistry?
How drug molecules are structured in 3 dimensions.
(Slide 38)
What are chiral compounds?
Molecules with asymmetric centers
Usually related to way carbon molecules are bonded
(Slide 38)
Which drug, discussed in class, is highly bound to plasma proteins and therefore has a small volume of distribution?
Warfarin
Slide 18
What does 1 Compartment Model of distribution theorize?
After immediate injection of a drug into the blood, it mixes with 5L of cardiac output then leaves the blood stream. (does not take CO % to tissues into consideration)
[Ka –> Vd –> Ke]
(slide 13)
What process converts active, lipid-soluble drugs into in-active water soluble drugs?
Metabolism
Slide 19
What is the structural basis of enantiomers?
Chemically identical
Mirror images
Can’t be superimposed
(Slide 38)
The rotation of light to the right is called?
Dextrorotatory
(Slide 39)
What are some examples of active metabolites?
Diazepam
Propranolol
Morphine
Codeine (pro-drug)
Slide 19
What is another name for propranolol?
Inderal
Slide 19
Define Central Compartment distribution:
What dilutes (Venous blood in arm, then vena cavae, right heart, pulmonary vessels, left heart, aorta) the drug in the first minute following injection into the blood (vascular system) then mix with vessel rich group
(slide 13)
How are most drugs metabolized?
Hepatic Microsomal Enzymes
(Slide 20)
The rotation of light to the left is called?
Levorotatory
(Slide 39)
Besides hepatic microsomal enzymes, what are three other ways drugs are metabolized?
- Plasma - Hoffman Elimination(an elimination reaction of an amine to form alkenes) and Ester Hydrolysis
- Kidneys
- Tissue Esterases (GI Tract, Placenta)
Slide 20
Drug rotation to the right is rectus or sinister?
Rectus
(Slide 39)
Drug rotation to the left is rectus or sinister?
Sinister
(Slide 39)
Phase I metabolism consists of…
Increased polarity to prepare for phase II reactions
Oxidation
Reduction
Hydrolysis
Slide 20
A 50/50 enantiomer mixture is called a what?
Racemic mixture!
(Slide 39)
What are the characteristic of a racemic mixture?
Equal Optical activity
Can exhibit different ADME
One enantiomer is active; other inactive or side effects
(Slide 39)
In phase II metabolism, this happens when drugs are covalently linked with a highly polar molecule to become water-soluble…
COVALENTLY LINK WITH A HIGHLY POLAR MOLECULE TO BECOME WATER SOLUBLE
Conjugation
Slide 20
Define what a vessel rich group is when talking about Central Compartment.
It’s the low body mass % tissues that get the most cardiac output perfusion % than other tissues in the body.
(slide 13)
T/F: Are 1/3 of drugs racemic?
True
Slide 39
Large family, 10-isoforms
Membrane bound and contains a heme cofactor
Involves oxidation and reduction
CYP450 enzymes
Slide 21
What is the most common CYP450 enzyme for the metabolism of anesthetics, with up to 60% of CYP450 activity?
CYP3A4
Slide 21
In this CYP family, things are 40% homologous.
(Ex. All the guys in our class)
CYP3
SLIDE 21
In this CYP family, the group is 55% homologous.
(Ex. The guys in our class from Texas)
CYP3A
Slide 21
The individual enzyme from a group.
(Ex. Just Andrew :) )
CYP3A4
SLIDE 21
What does 2 Compartment Model theorize?
That SOME of the drug that is immediately injected into the blood stream and the central compartment will distribute to peripheral compartments (like the muscle bone tendons etc) but will then return back to the central compartment of the blood to get eliminated.
(Does NOT take into account different levels and rate of distribution with CO% and metabolism to these peripheral compartments)
(slide 15)
S-enantiomer of ketamine is more potent with less delirium?
T/F?
True
(Slide 40)
Why do people like L-bupivicaine?
Because of less cardiac toxicity
(Slide 40)
Why do people like Cisatracurium, the isomer of atracurium?
Lacks the histamine effects
(Slide 40)
Why is Xopenex preferred over Albuterol?
Because Xopenex causes less cardiac side effects (tachycardia)
(Slide 40)
What is Pharmacogenetics?
How a single gene or all genes (genome) influences responses to drugs!
*Why do some patients respond to the 1st antidepressant and some trial/error?
*Why does a dose of chemotherapy work or kill?
(Slide 41)
Acid drugs primarily like to bind to what type of protein in the blood?
Albumin
(slide 16)