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104 Cards in this Set
- Front
- Back
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pharmacodynamics
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the effects of a drug on the body, relates the drug concentration to its effect
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pharmacokinetics
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relationship bet. drug dose and tissue concentration, involve ADME processes, how the drug get into tissue
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agonist
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a substance which interacts at a receptor to elicit a response
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antagonist
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a substance which blocks the response of an agonist at a receptor
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receptor locations
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cell memb, cell cytoplasm, nuclear envelope
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association constant
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kA, the affinity of drug binding, kA= kon/koff
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dissociation constant
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kD, the concentration at which 50% of the receptors are occupied, kD=1/kA=koff/kon
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clearance
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the removal of a drug in units of volume/time
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intensity of effect
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relate to drug concentration at receptor sites
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duration of action
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r/t how long drug concentration at receptor site remains high enough to provide response
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mathematical model
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encompassing known factors about drug, hypothesized first, them proven by real-life observation
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one-compartment model
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assumes a single compartment which is in equilibrium which accounts for drug in plasma and various tissues
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two-compartment model
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seen when drug moves into tissues and is handled at different rates than central plasma compartment
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kCp
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kCp=dCp/dt
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Cp
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Cp=C0*e-kt
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logCp
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logCp=logC0-kt/2.303
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Vd
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volume of distribution
Vd=D0/C0 |
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elimination half life
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t1/2=0.693/k
(0.693=ln2) |
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zero-order kinetics
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rate is independent of the concentration
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bioavailability
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% of a drug or drug product that enters the general systemic circulation
includes not only amount entering body but also rate of entry fructions of admi. drug that gains access to the syst. circulation in a chemically unchanged form |
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specific receptor
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act at receptor site inside on the ribosomes to change the way proteins are synthesized
ex. Neuroleptics, Aminoglycoside antibiotics |
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semispecific
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anesthetics
heavy metals |
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nonspecific
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mannitol
acidifying drugs |
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affinity
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strength to bind at site
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intrinsic activity
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response that elicited by the binding
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Atropine
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blocks muscarinic Ach receptors (on smooth muscle and glands)
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nicotinic receptors
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on skeletal muscle
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ionophore
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ion channels
receptor site coupled with proteins exclude/include only certain ions |
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metabophore
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causes metabolic process
ex. Adenylate cyclase & GTP |
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bioavailability
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F=AUC(oral)/AUC(IV)
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total body clearence
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Cltot=kVd
Cltot=D/AUC(IV) |
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Q
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Q=amount of drug supplied per unit time
Q=kVd*Cpss Q=Cltot*Cpss |
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loding dose
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L=Vd*Cpss
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average Cpss
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average Cpss=(Dm/Tm)/Cl
Dm=maintenance dose Tm=maintenance dose interval Cl=kVd |
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ideal doseing regimen
maintenance dose |
Dm=(Cptox-Cpther)Vd
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ideal dose regimen
maintenance dose interval |
Tm=(ln Cptox- ln Cpther)/k
=(2.3/k)log (Cptox/Cpther) =3.32t1/2 log (Cptox/Cpther) |
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high extraction ratio
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ClH controled by flood flow rate only
strong first-pass effect plasma protein binding may facilitate clearance |
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extraction ratio=1
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Cv=0
when the entire drug is removed during one pass through the organ |
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if hepatic blood flow increased
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ER hep is decreased since the transit time of the drug through the liver is shortened, and hepatic uptake is reduced
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low extraction ratio
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does not depend on hepatic perfusion, but rather dep. on plasma protein binding and intrinsic clearance
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renal clearance
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rate of renal excretion=rate of filtration + rate of secretion - rate of reabsorption
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ClR
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ClR=(excreted amount/time interval)/plasma concentration
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biliary excretion
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ClB=(D concentration in bile/ D concent. in plasma)*bile flow
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normal bile flow
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0.5-0.8ml/min.
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clearance
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is additive
Cltot=ClH + ClR + .... |
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extraction ratio
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E=(Ca-Cv)/Ca
Ca=D concent. in arterial inflow Cv=D concent. in venous outflow E=0-1 |
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therapeutic equivalence
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comparable clinical effectiveness and safety bet. similar drugs
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zero-order kinetics
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rate is independent of the concent.
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Cl tissue
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Cl tissue= Q tissue*E
Q tissue= tissue blood flow |
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first pass effect
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FH=1-E
FH= the bioavailability fraction due to first pass E=extraction ratio |
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bioequivalence
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comparable bioavailability bet. drugs
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enantiomers
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are pairs of molecules existing in forms that are mirror images of each other but that cannot be superimposed
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Henderson-Hasselbach equation
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pH=pKa+log[protonated]/[unprotonated]
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drug absorption
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depend on route, MW (size), solubility, and availability of carrier molecules
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tissue permeability
GI mucose, skin, cornea, lung, urinary bladder |
barrier: occluding zonulae
permeability: complete blockage of intercellular spaces; drugs must permeate cell memb. |
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CSF/plasma equilibrium
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more lipid-soluble drugs ex. thiopental, equilibrate more readily bet. CSF and plasma
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CSF to brain
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no barrier, very easy passage
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CSF barriers
Chorold plexus cells to CSF |
B: occluding zonulae
P: difficult passage |
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BBB
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B: occluding zonulae
P: drugs permeate memb. |
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Glomeruli, excretory and secretory organs
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B: Fenestrae
P: free passage of MW < 45,000 |
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placenta
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B: limited by blood flow
P: slow equilibrium |
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distribution
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phase following absorption
describes how a drug gets to it's target tissue for action incluenced by solubility, body water, protein binding, tissue binding, specific carriers |
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total body water
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intracelluler -40%
extracelluler -20% (interstitial 15%, vascular 5%) |
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peritoneum
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B: Maculae
P: free passage |
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prodrugs
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utilize metabolism to form active compounds
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phase 1 metabolism
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breakdown
involves oxidation, reduction, and/or hydrolysis large # of these reactions are catalyzed by cytochrome P450 dependent enzmes |
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CYP 3A4
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isoenzyme in liver and GI wall
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phase 2 metabolism
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synthetic
involves conjugation reaction ex. addition of glucuronic acid, sulfonic acid, or acetylation |
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morphine-6-glucuronide
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phase 2 metabolite of morphine
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competitive antagonist
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cause a shift of the agonist dose-response curve to the right
have no intrinsic activity both the antagonist and the agonist bind to the same site on the receptor |
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non compeitive antagonist
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"allosteric"
the antagonist binds to a site other than where the agonist binds |
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negative antagonist
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inverse agonist
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partial agonist/antagonist
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have efficacies (intrinsic activities)greater than zero but less than that of a full agonist
compounds act less get less effect |
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pharmacogenetics
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single gene differences among population groups and the effects on pharmacodynamics
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pharmacogenomics
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genome-wide varietions in DNA sequences responsible for pharmacodynamic differences
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human genome
comprised of ? |
approximately 30,000 genes from a total of 3 billion base pairs
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different base-pair combinations
result in? |
different proteins produced
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single base mutation
can alter? |
a produced protein (enzyme) significantly
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different population groups have?
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somewhat different proteins and enzymes
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Multidrug Resistance Gene
can cause differences in? |
absorption of some drugs (digoxin) by altering carrier proteins or barrier compounds in the GI tract
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5-hydroxytrypamine transporter polymorphisms
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can affect the neuronal reuptake of serotonin, an important neurotransmitter
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plasma cholinesterase
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breaks down succ, tetracaine, mivacurium
is seen in some individuals to have reduced activity, which can cause increased duration of these compounds |
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different CYP genes
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different metabolic rates of some drugs by individuals
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CYP 2D6
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shows widest known differences
responsible for appro. 25% of all drug metabolism |
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drugs meta. by CYP 2D6
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analgesics
neuroleptics antiarrhythmics amide-type LA's beta-blockers TCA's antiemetics |
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CYP 2C9 metabolises?
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warfarin
phenytoin NSAIDS |
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NAT metabolises?
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isoniazid (INH)
sulfonamides procainamide |
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NAT polymorphisms
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fast (Asian)
slow (European) |
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CYP 3A4
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female clear drugs oxidized by CYP3A4 40% faster than male
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conjugation metabolic reactions
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occur at a faster rate in males than females
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females
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lower pain tolerance
greater opioid sensitivity higher risk of Halothane toxicity than males |
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females with anesthesia
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awaken 50% faster from propofol, alfenta, N2O than men
require greater doses to reach proper anes. levels |
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why has pharmacogenetics not become more important in practice of anesthesia?
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require genetic testing, which concerns prople
costs and time of screening |
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physiochemical interaction
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=drug incompatiblilities
physical properties of different drugs are sometimes incompartible |
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pharmacokinetic interaction
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occurs when one drug alters the way another drug is handled by the body
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example of enzyme induction
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enhanced metabolism of neuromascular blockers by pts taking anticonvulsants chronically
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pharmacodynamic
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occurs when a drug increases or decreases the effect of another drug
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additive drug interaction
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involves two drugs that act by the same mecanism (sometimes different mecha.)
the effect is equal to what would be expected by direct summation of each effect |
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synergistic drug interaction
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involves effects of two drugs acting by different mechcanisms (sometimes the same mecha.)
the effect is greater than the simple sum of each drug effect |
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antagonistic drug interaction
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effect of two drugs where the observed effect is less than additive
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common causes of drug interactions
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1)additive, synergestic, antagonistic actions
2)enzyme induction 3)enzyme inhibition 4)displacement 5)absorption interference 6)water and ionic disturbances |
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giving two synergistic drugs
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allow decreased doses of each and minimize potential toxicity
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volatile anesthetics (or propofol) and opioid interactions
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giving together, a synergistic interaction occurs, allowing lower doses of each to be used and provide good overall anesthetic and pain blocker
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ultra-short acting opioids (Remifentanil) together with propofol
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provide excellent short acting synergistic anesthesia
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