1. Pharmacokinetics (Random stuff that is tough to memorize) Flashcards
Which drug did they give as the example of a drug that has it’s permeability increased as extracellular pH rises? Why?
Lidocaine
Basic, as increased pH pull of Hs –> becomes unionized –> able to diffuse better
Which drug did they give as the example of a drug that has a much higher concentration in gastric acid? Why is this important?
Cocaine, gets ionized in low pH & trapped in stomach
Have to test gastric secretions if suspect overdose cuz plasma level may be undetectable
Phase 1 metab includes?
oxidation, epoxidation, deakylation, dehalogenation, reduction, hydrolysis
Phase 2 metab includes?
Acetylation, sulfanation, glucaronidation, glutathionation
How does renal extraction work for polar drugs?
Most drugs filtered at glomerulus if not protein bound
Secreted at proximal tubule
Passively reabsorbed at distal tubule (due to being concentrated)
What drugs were given as examples of drugs that are secreted? What is it’s estimated clearance?
Penicilin & p-aminohippurate
600 mL/minute
What drug was given as the example of a drug that is filtered, but not secreted or reabsorbed? What is its estimated clearance?
Inulin
130 mL/minute
Generally speaking what processes involve first order kinetics? Zero order?
Small [substrate] relative to enzyme (enzyme is not saturated), filtration, renal secretion, diffusion & ion trapping
Only when have high [substrate] relative to enzyme (enzymes are saturated) –> as substrate levels get low 0 turns into 1st order
Why are most drugs eliminated by 1st order elimination?
Our enzymes have a high capacity
Which type of elimination is related to the concentration of the drug present?
1st Order
Which type of drug elimination is independent of drug concentration?
AKA constant no matter what
0 order
Which type of elimination has a half life independent of drug concentration?
1st order
Which type of elimination occurs at a constant fraction?
1st order
Which type of elimination occurs at a constant rate?
0 order
The elimination time is directly proportional to amount consumed in what type of elimination?
0 order
Drugs with zero order elimination?
Phenytoin
Ethanol
Salicylate
What is the plateau principle?
Says it will take 3-5 half lives for drug with first order elimination to get to steady state & that once at steady state it would take 3-5 half lives to be eliminated if doses were stopped
Does NOT state what the SS is, just how long to get there
How would the maintenance dose/IV infusion rate change for somebody that has 50% of normal renal function?
Maintenance/infusion would be 50% of what you would use for a normal person
Example given of a drug that has biphasic elimination? Why? Why is this important?
Gentamycin
multi-compartment
Stays in system longer than would expect of normal 1st order elim
What is the example given for a drug which stops being effective as it is moved to other compartments (rather than elimination)?
Thiopentin anesthesia
What is efficacy? Efficacy is dependent on what?
Max response (only dependent on # functioning receptors)
What is potency? What is it dependent on?
effect at a given dose (independent of # receptors, affinity intrinsic to receptor & drug)
• EC50 = [drug] for ½ of efficacy
• ED50 = dose for ½ of efficacy
How is the response vs. log[drug] curve changed if you theoretically make a drug more potent? What does this represent in a practical sense?
Shift sigmoidal curve to the L
Need a smaller dose to achieve the same effect
What is the example given of a drug that has rebound sensitivity (supersensitivity) if therapy is stopped?
Propranalol
If stop, worse than when started cuz have made more receptors
What is the difference between a dose response curve & a quantal dose response curve/histogram?
Individual vs. population
Difference between quantal dose response curve & histogram?
Histogram includes only the individuals that responded to that dose
Curve includes everyone who responded to that dose + all the doses smaller than that
How is the response vs. log[drug] curve changed if you theoretically make a G protein receptor undergo amplification (1 receptor activates multiple G proteins)? What does this mean?
Shifts curve to the L (more potent)
Not all receptors need to be occupied to get max effect (exception to rule)
Why do some organs get more drug than others? Which get most & which get least?
Different levels of blood flow per g tissue
Most = Kidney & lung Medium = heart, liver & brain Least = skin, muscle & adipose
Which drug is 99% bound to proteins in plasma? Why is this important?
valium
Higher chance of drug itneractions
What is the name of the membrane transporter responsible for active efflux of drug?
P-glycoprotein
Example(s) of Tyrosine Kinase Receptor(s)?
EGF receptor
Example(s) of Cytokine Receptors?
Jak-Stat
GH
Leptin
What does it mean if all of a radiolabeled oral drug is eventually found in urine?
[Practice problem from hand out]
Drug & metabolites are all absorbed (can’t assume 100% bioavailabilty because drug may have been broekn down into metabolites & then absorbed & excreted)
For an oral drug, what are the steps to get from GI into systemic circulation?
- Drug has to get absorbed into intestine (otherwise just get excreted)
- During travel some drug gets metabilized by small amount of cytochrome p450 in the intestine wall = Pre-first pass
3 . 1st pass effect - Into systemic
What does parenteral mean?
“not via GI”
IV, injections …
Charged vs neutral for acid & base?
Acid is H donor –> goes from uncharged to - charged if in basic environment
Weak bases are H acceptors –> go from nuetral to + charged if in acidic enviroment
Vd for different drugs & molecules?
See p18 of lecture 18
How will iver or kidney disease effect Vd of a drug?
Less binding proteins –> increase Vd as moves into periphery
Lower yield. Memorize the reactions for various forms of metabolism?
See lecture 3
What type of metab is performed by flavine protein?
reduction
What type of metab is performed by soluble enzymes?
hydrolysis of esters & amines
What drugs are given as examples of drugs that can be affected by a person being a rapid or slow acetylator?
Isoniazid
Hydralazine
Examples of ligand gated ion channels?
Ach
GABA
Serotonin
Glutamate
Phosphoinositide pathway (a type of g protein)?
activation of phospholipase c (PLC) –> Phosphoinositide –> DAG & IP3
Prostaglandin pathway (a type of G protein)?
Angiotensin –> activation of PLA2 –> membrane phospholipase –> arachadonic acid –> COX –> prostaglandin –> becomes extracellualr signal for another receptor –> Camp, Ca or PKC
What is the main mechanism for receptor uncoupling & desensitization?
Phosphorylation of receptor
What were the examples given as situations where desensitization can be present?
High beta adrenergic in heart failure (better to treat with beta antagonist than agonist, this is not intuitive)
Intentional desensitization for treatment with Lueprolide (–> lower testerone effects)
desensitization of leptin receptor –> obesity
How does hyperthyroidism effect individuality of response to drugs?
thyroid hormone stimulates creation of beta receptor –> supersensitive to beta agonists
Why do infants/newborns have different drug responses?
Different distribution due to body fat
Lower GFR
Less p450
Less plasma proteins
Why do the elderly have different drug responses?
Lower GFR (like peds) Lower p450 (like peds) Changes in PD
How do ant-acids effect drugs?
Decreased absorption
How does grape fruit juice or tropical fruits alter drug effects? Charbroiled meat, broccoli or sprouts?
Inhibit p450
Induce p450
What habit induces p450? Effect of this?
Smoking, drugs & alcohol
Need higher doses cuz metab
What drugs are given as examples of drugs that can inhibit drug transport?
Verapamil & digoxin
What drug inhibits p450?
Warfarin
