Pharmacokinetics/Pharmacodynamics (Exam I) Flashcards
What does TTE mean in regards to pharmacodynamics/kinetics?
- Titrated to effect
Receptors are usually __________.
- Proteins
Almost all drugs are reversible except for drugs that are ________ ______.
- Covalently bonded
Regarding the graph below: What type of drug would you expect looking at the orange line? (agonist, antagonist, partial, inverse, etc.)
Orange = Full Agonist
Regarding the graph below: What type of drug would you expect looking at the blue line? (agonist, antagonist, partial, inverse, etc.)
Blue = Strong partial agonist
Regarding the graph below: What type of drug would you expect looking at the yellow line? (agonist, antagonist, partial, inverse, etc.)
Yellow = Weak partial agonist
Regarding the graph below: What type of drug would you expect looking at the black line? (agonist, antagonist, partial, inverse, etc.)
Black = Antagonist
Regarding the graph below: What type of drug would you expect looking at the green line? (agonist, antagonist, partial, inverse, etc.)
Green = Inverse agonist
What two mechanisms can occur with receptors that will increase or decrease their expressed quantity?
- Downregulation & Upregulation
What is tachyphylaxis and what drug was given as an example in lecture?
- Tachyphylaxis = rapid tolerance development
- Ex. Ephedrine
What sort of expression of β receptors would expect to see in a patient dealing with a chronic pheochromocytoma?
- Downregulation of β receptors in response to the increase in catecholamines
What three receptor locations were discussed in lecture?
- Lipid Bilayer
- Intracellular
- Circulating in plasma
What type of drugs interact with intracellular receptors?
- Insulin, steroids & milrinone
What type of drugs interact with circulating protein receptors?
- Anticoagulants
What type of drugs interact with membrane bound receptors?
- Opioids, benzos, β-blockers, NMBs
- Most common (especially for anesthetics)
Acidic drugs bind primarily to ________.
- Albumin
Basic/Alkalotic drugs bind primarily to _______.
- α1-acid glycoprotein
How much bound drug crosses protein membranes?
- 0% (only “free” unbound drugs cross membranes)
What degree of volume of distribution (VD) would be seen with drugs that are poorly protein bound and lipophilic?
What examples were given in lecture?
- ↑ ↑ ↑ VD
- Thiopental & Diazepam
What degree of volume of distribution (VD) would be seen with drugs that are highly protein bound and/or hydrophilic?
What example(s) were given in lecture?
- ↓ ↓ ↓ VD
- Warfarin
What drug examples were given in lecture as having active metabolites?
- Diazepam
- Propanolol (Inderal)
- Morphine (2 metabolites)
- Codeine (& other prodrugs)
What does metabolism convert active drugs into?
- H₂O soluble & inactive metabolite forms
What is the most common way that drugs are metabolized?
What other ways exist?
- Hepatic CYP450’s
- Hoffman Elimination, Ester hydrolysis, Kidneys, & Tissue Esterases (GI tract & placenta)
What is the purpose of Phase I reactions?
What chemical processes occur during these reactions?
- Increase polarity & prepare for phase II
- Oxidation/Reduction & Hydrolysis
What occurs during Phase II reactions?
By what chemical process does this occur?
- Covalent bond with polar molecule = H₂O-soluble
- Conjugation
What is the most common CYP450 enzyme?
How many drugs are estimated to be metabolized by this enzyme?
- CYP3A4
- > 50% (opioids, benzos, LA, antihistamines, etc)
What is CYP450 induction?
Give an example.
- Drug induces enzyme to increase enzyme activity.
- Phenobarbitol induces enzymes & metabolism of other drugs is increased.
What is CYP450 Inhibition?
Give an example.
- Drug inhibits enzyme & decreases enzyme activity.
- Ex. Grapefruit juice inhibits CYP activity and some drugs become more toxic.
What is the formula for Rate of Drug Metabolism?
- R = Q ( C-inflow - C-outflow)
or
- R = Q (ΔC)
What is flow-limited hepatic clearance?
- When Q limits metabolic rate
What is capacity-limited hepatic clearance?
- Liver CYP450’s ability to metabolize is the limiting factor
What are the three components of Renal Clearance discussed in lecture?
- Glomerular filtration
- Active tubular secretion
- Passive tubular reabsorption
What two factors determine glomerular filtration of drugs?
- GFR
- Amount of drug that is protein-bound
What drug example was given in lecture that is subject to active tubular secretion?
- Penicillins
What increases the tubular reabsorption of certain drugs?
What decreases the tubular reabsorption of drugs?
- Lipophillic = reabsorbed
- Hydrophillic = no reabsorption; excreted in urine.
Differentiate Elimination Half-Time & Elimination Half-Life.
- Half-Time = time to elimination of 50% of drug from the plasma.
- Half-Life = time to elimination of 50% of drug from all tissues.
80mg of a drug is given with the E 1/2 time known to be 5 minutes. What will the plasma concentration of the drug be in 20 minutes immediately after giving a second 80mg dose?
- 85mg
(5mg from original dose, 80mg from second dose)
What is the context-sensitive half-time?
Give an example of a drug with a low context-sensitive half-time vs a high context-sensitive half-time.
- Time to a 50% decrease after an infusion is discontinued. (essentially measures increasing tissue accumulation affecting how long it takes for a drug to leave the body)
- Fentanyl = higher context half-time
- Propofol = lower context half-time
What drug class is comprised of weak acids?
- Barbiturates
What drug class is comprised of weak bases?
- Local Anesthetics & Opioids
Ionization numbers that are ________ cross lipid bilayers very well.
- negative
If the drug is a weak acid then PK ______ pH.
After
If the drug is a weak base then PK ______ pH
Before
Aspirin (weak acid; PK = 7.7) travels to blood with a pH of 7.4. Will this aspirin work well?
- 7.4 - 7.7 = -0.3
- Yes; ionization is negative therefore non-ionized & crosses barriers.
Morphine (PK = 8.0) is injected into blood with a pH of 7.2. What will occur with this morphine?
- 8.0 - 7.2 = +0.8
- Ionization is + so drug will not cross membranes well and thus not work well.
What is the process of ion trapping?
- When a drug is ionized and thus accumulates somewhere without being “used up” (mother-fetus example).
What factors affect pharmacodynamics in elderly patients?
- ↓CO (affects brain & liver)
- ↓ protein binding
- ↑ body fat
Differentiate acute vs chronic alcohol ingestion effects on pharmacodynamics.
- Acute: EtOH using all CYPs (drugs will “stick around” longer)
- Chronic: less of an effect, body has usually compensated.
What is an example of a genetic phenotype correlating with increased anesthetic needs?
- Redheads
In the graph below, which line would in indicate the most efficacious drug?
- Red
In the graph below, which line would in indicate the most potent drug?
- Blue
What is relative potency (time to drug effect)?
- Lag time between administration & effects (fent vs alifentanil)
How is Therapeutic Index calculated?
What would a narrow TI indicate?
- LD50/ED50
- Narrow TI = more “dangerous” drug requiring careful monitoring.
Differentiate LD50 and ED50.
- LD50 = dose at which 50% of patients die.
- ED50 = dose at which 50% of patients experience drug effect.
What are chiral compounds?
- Molecules with asymmetric centers
What are the characteristics of enantiomers?
- Chemically identical
- Mirror images
- Non-superimposable
What term(s) would indicate a rightward rotation light in an optical isomer?
- Dextrorotary (D) or Rectus
What term(s) would indicate a leftward rotation light in an optical isomer?
- Levoorotary (L) or Sinister
What is a 50/50 mixture of optical isomers called?
Why does it matter?
- Racemic
- These compounds will have differing characteristics, effects, & ADME
Which isomer of Ketamine is more potent and results in less delirium?
- S-Ketamine
Which isomer of bupivicaine exhibits less cardiotoxicity?
- L-Bupivicaine
Why would one want Cisatracurium over atracurium?
- Atracurium causes massive histamine release. Cisatracurium does not.
