Pharmacokinetics and Pharmacology Review Flashcards
pharmacodynamics
the drug’s effect on the body, therapeutic and toxic
agonist
substance that binds to a specific receptor and triggers a response in the cell.
mimics the actin of an endogenous ligand that binds to the same receptor
Full agonist
maximal activation of all receptors
partial agonist
can block some receptors while effecting other receptors
agonist-antagonist - have both agonist and antagonist effects
activates a receptor but cant produce a maximum response
antagonist
- drug that has affinity for the receptor but no efficacy
- combination with receptor may block a response
- higher affinity for receptor
physiologic antagonism
two agonists drugs that bind to different receptors causing opposing responses
ex: phenylephrine vs cardene
chemical antagonism
no receptor activity is involved. One drug binds with the second drug to inactivate it
ex: protamine and heparin
receptor
the component of a cell that interacts with a drug and initiates the chain of events leading to the drug’s effect
-may be membrane bound, intracellular proteins (caffeine, insulin, steroids, theophylline, milrinone), or circulating proteins (coag cascade)
affinity
the degree of drug receptor interaction for a given drug - potency -
efficacy
-intrinsic activity- a drug’s ability to produce the desired response expected by stimulation of a given receptor, the max effect that can be achieved with the drug
spare receptor concept
not all receptors have to be covered to work
-maximal or nearly maximal response can often be produced by activations of only a fraction of the receptors present
down regulation
desensitization - occurs with continued stimulation of cells with agonists - the effect is diminished
ex: beta agonist bronchodilators - tolerance develops from repeated use, increased dose will be required
up regulation
chronic exposure to antagonists cause receptor number and sensitivity to increase
ex: beta blockers
drugs that don’t act on proteins
sodium citrate
chelating drugs
iodine
sodium bicarb
What causes variability of pharmacologic response
age sex body weight - kg and ideal body weight body surface area basal metabolic rate - temp affects pathologic state genetic profile
pharmicokinetics
the actions of the body on the drug
absorption, distribution, metabolism, elimination
absorption
Route - PO, IM, IV, rectal
first pass effect - PO and rectal pass through liver first which extracts and/or metabolizes some of the drug
bioavailability
the extent to which a drug reaches it effect site after its introduction into the circulatory system
affected by lipid solubility, solubility in aqueous and organic solvents, molecular weight, pH, pKa, and blood flow
distribution
(alpha phase) the plasma concentration of the drug declines
two compartment model
distribution phase – decrease in plasma level – elimination phase
redistribution
termination of effect
plasma level decreases to the point that the drug moves out of the vessel rich central group and is then taken into the peripheral group
elimination
beta phase
involves metabolism and excretion, clearance of drug
Vessel rich
brain, heart, liver, kidney, endocrine
receives 75% of cardiac output (only 10% body mass)
lean muscle
muscle and skin
receives 19% of cardiac output (50% body mass)
fat
receives 6% of cardiac output (20% body mass)
vessel poor
bone ligament and cartilage
receives 0% of cardiac output (20% body mass)
metabolism pathways
oxidation
reduction
hydrolysis
conjugation
Phase 1 metabolism
oxidation, reduction, hydrolysis
increases the drugs polarity
phase 2 metabolism
conjugation
drug or metabolites are covalently linked to a highly ionized molecule
the resulting conjugate is more water soluble for excretion
sites of metabolism
hepatic microsomal enzymes plasma - hoffmann elimination lungs kidneys GI tract
cytochrome P450 enzymes
hepatic microsomal enzymes mostly
oxidative metabolism of most drugs
enzyme induction
the ability of drugs or chemicals to stimulate activity of the cytochrome p450 system
may be due to increased synthesis of cytochrome p450 and cyt p450 reductase
can be revved up
noncytochrome p450 enzymes (esters)
nonmicrosomal enzymes
metabolism by conjugation, hydrolysis, and some oxidation and reduction
largely in liver and some GI
not inducable, genetically determined.
phase 1 enzymes
cytochrome p450
nonmicrosomal enzymes
noncytochrome p450 enzymes (esters)
phase 2 enzymes
glucoronosyltransferases
gluthathione-s-transferases
n-acetyl-transferases
sulfotransferases
what meds metabolized by glucoronosyltransferase
morphine, propofol, and midalozam
n-acetyl-transferases
have fast and slow acetylators
slow acetylators are at greater risk for side effects because you dont metabolize drugs as fast
gluthione-s-transferases
a defensive system for detoxification and protection against oxidative stress
elimination 1/2 life
the time for the drug in the plasma to decrease by 50%
affected by volume of distribution and changes in clearance
context sensitive half time
the time for the plasma drug concentration to decrease 50% after discontinuing a continuous infusion of a specific duration
(the longer the infusion the longer the half time)
effect-site equilibration time
the time between IV injection into the plasma and the delivery of the drug to its site of action
important to consider for redosing, don’t want to redose if drug hasn’t made it to site of side effect
volume of distribution
number to describe the apparent volumes of compartments that constitute the compartmental model.
Dose of drug given divided by the amount in plasma prior to elimination.
volume of distribution (Vd) effected by
lipid solubility
binding to plasma proteins
molecular size
ionized
water soluble, poorly lipid soluble
ex: Neuromuscular blockers
non-ionized
lipid soluble, diffuses easily across lipid barriers like blood-brain barrier, GI endothelium, hepatocytes, renal tubular epithelium, placenta
protein binding
effects distribution of drugs as only unbound drug can cross cell membranes
agonist + agonist
1+1=2
ex nitrous and sevo
synergistic
1+1=3
ex: fentanyl and benzos (increases impact of resp depression, sedation)
potentiation
1+0=3
enhancement of one drug action by second drug with no action of its own
antagonistic
1+1=0
ex: fentanyl + narcan
hyperreactive
having or showing abnormally high sensitivity to stimuli
ex: vasodilators and dehydration
hypersensitive
abnormally susceptible physiologically to a specific agent
typically immune mediated response
hyporeactive
having or showing abnormally low sensitivity to stimuli
safety margin
therapeutic vs lethal dose
tolerance
the capacity of the body to endure or become less responsive to a substance (as a drug) or a physiological insult especially with repeated use or exposure
tachyphylaxis
diminished response to later increments in a sequence of applications of a physiologically active substance [med]
Inverse agonist
A drug or endogenous chemical that binds to a receptor, resulting in the opposite action of an agonist. May have a theoretical advantage over antagonists in situations in which a disease state is partly due to an up regulation of receptor activity,
Ligand
Molecule that is able to bind and form a complex with a receptor to produce a biological response. Are endogenous chemicals
Quantal drug response
Using dose response curves, the actions of a drug can be quantified and expressed as the effective dose ED50, toxic dose TD50, and lethal dose LD50. The therapeutic index is LD50/ED50
Ceiling effect
Refers to the dose beyond which there is no increase in effect. Additional dosing often leads to adverse effects.
