Pharmacodynamics/kinetics Flashcards
Test 1
What are the 4 ways a drug binds to a receptor? How do they work?
Ion: one atom transfers an electron
Hydrogen: attracted to nearby electronegative atoms
Van der Waals: weak fluctuating bonds
Covalent: shared electrons
What is another name for ion bonding?
Electrocovalent
Competitive antagonists shift the dose curve to the ______
Right
What is an inverse agonist? Give examples
A drug that competes for the same site as an agonist but produces the opposite effect.
Propranolol
Metoprolol
Cetirizine
Loratadine
Prazosin
Naloxone
“Pro met sneezing cat named Lora, who praised Nala”
Inverse agonist were once called _______
Antagonist
T/F: the amount of receptors that we have can increase or decrease depending on comorbidities and drug therapies
T
How are receptors classified?
By location
What are the three types of receptors? What do they consist of?
- Lipid bilayer: opioids benzos, beta blockers, catecholamines, NMBD
- Intracellular proteins: insulin, steroids, Milrinone
- Circulating proteins: anticoagulant (warfarin)
What are your vessel rich groups?
Parts of the body that have a high cardiac output; in a 1 compartment model, blood flows here after the aorta
Heart
lungs
liver
kidney
brain
What is the more realistic model?
2 compartmet model
What type of drugs are able to leave the central compartment and go to the peripheral compartment?
Fat soluble drugs (lipid solube)
Which drugs have a larger volume of distribution, fat/lipid soluble, or water soluble?
Fat soluble
Where do water soluble drugs normal stay?
Plasma
Can narcotics cross the bilayer?
Yes
What are the 2 things that affect volume of distribution?
- changes in blood volume
- # of carrier proteins
Almost all drugs we give are bound to ________
plasma proteins
What type of protein do acidic drugs primarily bind to? Alkalotic drugs?
Acidic drugs: albumin
Alkalotic drugs: A-1 acid glycoprotein
What are conditions that decrease albumin? Would affect does this have on anesthesia?
Malnutrition
Burns
Liver failure
Acidosis
This increases the free drug which can cross into membranes and increase concentration/potency.
What can cause decreased plasma proteins in general?
Pregnancy
Age
Hepatic disease
Renal failure
What does it mean when a drug has poor protein binding and is lipophilic? What are some examples?
This drug is free and can cross lipid bilayers
This drug will have a big volume of distribution
ex) Thiopental, Diazepam
Highly protein bound to plasma, protein drugs have a _________ volume of distribution. What are some examples?
Small
Ex) warfarin
What drugs have active metabolites?
Diazepam
Propranolol
Morphine (has 2)
Prodrugs like codeine
What happens during metabolism?
Convert active, lipid, soluble drugs to inactive drugs that are able to be excreted
What are the ways that drugs are metabolized?
- CYP450 enzyme in the liver (liver main way)
- Kidney
- Tissue esterase (GI, Placenta)
What is phase 1 of metabolism consist of?
Oxidation
Reduction
Hydrolysis
** all drugs and bonds are getting ready to be water soluble**
What is phase 2 of metabolism consist of?
Conjugation
** covalently links, a highly polar molecule to become water soluble**
Describe CYP450
-Large family with 10 isoforms
-Membrane bound
-contains a heme cofactor
-involves oxidation and reduction
What is the most common Phase 1 enzyme for anesthesia drugs?
CYP3A4
What is the difference between something that induces and inhibits the CYP450 enzyme? Give examples.
Induces: increases the amount of enzyme –> increases metabolism
ex) phenobarbital
Inhibits: decreases amount of enzyme –> increases concentration of drug
ex) grapefruit juice
T/F: Hepatic aesthetic drugs clearance is constant
T
Differentiate between flow llimited and capacity limited hepatic clearance
Flow limited: rate is proportional to concentration
Capacity limited: metabolism is exceeded since liver capability is not unlimited
What is Context Sensitive Half-Time?
Time to a 50% decrease after an infusion at a constant concentration is discontinued
What does it mean when the PK & the pH are identical?
50% of the drug is ionized and 50% of the drug is non-ionized
What’s the main difference between ionized drugs, and non-ionized drugs?
Drugs that are ionized are more likely to stay water soluble and not cross barriers
Most drugs are ______ acids & bases
weak
ex) acids: barbs
bases: LA; opioids
Elderly populations have _________ cardiac output and __________ protein binding
Decreased
Decreased
Define efficacy versus potency
Efficacy: the ability of a drug to produce a clinical effect
Potency: less drug with more affect. Concentration versus response.
T/F: plasma is a site of effect for anesthetic drugs
F
CNS
What is lag time?
Time between administration and effect in the CNS
The therapeutic index =
Lethal dose 50% / effective dose 50%
What are enantiomers?
Structures that are chemically identical & are mirror images
What are chiral compounds?
Molecules with asymmetric centers
What are optical isomers?
Enantiomers
Describe rotation of light in optical isomers
rotates light in solution
If right: Dextrorotatory
left: levorotatory
Describe molecule sequence in optical isomers
R: rectus
S: sinister
Describe Racemic mixtures
50/50 mixtures of 2 optical isomers/enantiomers
1 enantiomer is active
the other is inactive of has adverse side effects
The enantiomer for Albuterol is ______
Xopenex
_______ is the enantiomer for Atracurium. What does it do?
Nimbex
Lacks histamine effects
PCN is ________ the PT cap
secreted from
