Pharm 4 Flashcards
Pharmacodynamics
action of the drug inside the body. deals with physiological/biochemical effects of drugs, their mechanism of action at macromolecular/subcellular/organsystem levels
how do drugs work
modifying underlying biochemical/physicological process_..NOT de novo
physical properties of drugs
mass, adsorptive property, osmotic activty, radioactivty
how do laxatives work
draw water into lumen
mass examples
bulk laxatives –> bran,
methylcellulose
adsorbtion
binding to a drug
adsorptive property examples
charcoal, kaolin
osmotic activity examples
magnesium sulfate, mannitol
example of a diuretic
mannitol draws water into the kidney to remove water
radioactivity example
iodine
chemical properties
antacids like Al(OH)3,
Mg(OH)2 neutralize gastric HCL
example of a drug acting on an enzyme
enalapril inhibits ACE
example of drug acting on receptor
most durgs
actions of drug receoptr interaction
molecular/conformational changes,
alteration of enzyme activity,
changes in permeability/transport processes,
cascade of changes leading to a response
types of drug action
stimulation,
depression,
replacement,
cytotoxic
stimulation
selective enhancement of the level of activity of specialized cells
epinephrine stimulates
heart
pilocarpine stimulates
salivary gland - PNS stimulant
depression
selective diminution of activity of specialized cells
barbiturates depress
cns reticular activating system and produce sleep
quinidine depresses
heart - antiarrithemic
drugh that stimulates one cell and depresses another cell type
acetylcholine
replacement examples
insuline in diabetes mellitus,
levodopa in parkinsonism
cytotoxic effects examples
anticancer drugs produe cytotoxic actions against neoplastic cells,
antibiotics produce cytotoxic action against microbes
most drugs act by
binding to receptors
functions of receptors
propagation of signals from outside to inside,
amplify the signal,
adapt to short term and long term changes
receptor families
channel linked/ligand gated,
g protein linked/coupled,
kinase linked,
intracellular receptor
channel linked (ligand gated)
ionotropic,
selective ion channel Na, K, Ca, Cl,
drug binding results in opening or closing of chnnel,
fastest (milliseconds)
g protein linked/coupled
metabotropic - cell membrane receptors linked through g proteins to effector mechanisms which include –adenylyl cyclase, phospholipase C,
channel regulation,
takes seconds to produce
kinase linked
(minutes) enzyme linked receptor,
phosphorylation of tyrosines .
Mst imp is to transport glucose receptors to surface
intracellular receptor
(hours) in cytosol or nucleus,
take longer time bc proteins need to be made,
eg steroids
channel linked examples
nicotinic cholinergic receptors,
GABA a and NMDA receptors
g protein examples
alpha and beta adrenergic receptors,
histamine receptors
kinase linked examples
insuline
intracellular receptor examples
steroids, tyroxine, vit-D
ligand gated ion channel example
cholinergic nicotinic receptors
affinity
the bility of the drug to bind to the receptors
intrinsic activity (IA)
ability of a drug to activate the receptor and produce the response
agonist
drug which binds to the receptor, activates it and produces the response
what has both affinity and intrinsic activity
agonist
examples of agonists
morphine, epinephrine, acetylcholine
antagonist
binds to the receptor but will not activate the receptor
what has affinity but no intrinsic activity
antagonist
examples of antagonists
prazosin (alpha rec), atenolol (beta rec), atropine (muscarinic rec)
partial agonist
it will activate the receptor but produce submaximal response (however, antagonizes the action of a full agonist)
example of a partial agonist
pentazocine –partial agonist at opioid receptor
what agonist will produce unsurmountable antagonism
noncompetitive binding at an alosteric site
inverse agonist
activates the receptors to produce an effect in the opposite direction to that of agonist
example of inverse agonist
beta carbolines produce the effects opposite to diazepam
affinity + IA (1)
agonist
affinity + IA (0)
antagonist
affinity + IA (0 to 1)
partial agonist
affinity + IA (0 to -1)
inverse agonist
drug potency
the amount of drug needed to produce the response (lower the doe required, higher will be the potency and vice versa)
drug efficacy
the maximum response of the drug (more important)
the position of the dose response curve on the dose axis is an index of
drug potency
the upper limit of the drug response curve is an index of
efficacy of the drug
steep slope in the DRC indicates
small increase in does markedly increases the response
the steepest part of the DRC is witing
25-75% of drug dose (30-70% is said to be linear)
types of dose response relationships
graded dose response, quantal(all or none) dose response
graded dose response
gradual increase in concentration and thereby response in one individual, animal, or tissue but only to a limit
ceiling effect
seen when further increase in dose does not exhibit the increase in response which occurs at a ceiling dose. Denotes all receptors are occupied.
shape of graded dose response relationship
hyperbolic curve plotting dose, sigmoid if plotting log dose
graded dose response relationship is significan in
studying the effect of drug on single tissue or animal,
determining the potency and efficacy of drugs,
studying the comparison between agonists and antagonists
quantal (all or none) dose response
studies the influence of the magnitude of the dose on the proportion of a population that response;
shows if the determined response is seen with a given dose or not at all
is quantal dose response a continuous relationship
no
quantal dose response is significant in determining
median effective dos (ED50) median lethal does (LD50) and therapeutic index (TI)
therapeutic index formula
TI = LD50/ED50
the gap btw the therapeutic and adverse DRC indicates
safety margin of the drug or therapeutic index
the higher the therapuetic index
the better bc a small increase won’t lead to toxicity
combined effects of drugs
synergism and antactonism
interaction of drugs can occure on a
parmacokinetic level or pharmacodynamic level
synergism
when the action of one drug is faciitated or inreased by the other
types of synergism
additive and supraadditive (potentiation)
does a synergistic drug have to produce an effect if given alone
no
additive synergism
effect of (A + B) = effect of A + effect of B
additive synergism: asprine + acetaminophen
an analgesic/antipyretic
additive synergism: nitrous oxide + ether
general anesthetic
additive synergism:ephedrien + theophylline
bonchodialator
supraadditive (potentiation) synergism
when 2 or more drugs are given together the effecto of combination is greater than the individual effects of the comonents : effect of (A + B) > effect of A + effect of B
supraadditive (potentiation) synergism: acetylcholine + physostigmeine
physostigmine prevents the breakdown of acetylcholine
supraadditive (potentiation) synergism: levodopa + carbidopa
carbidopa is a dopacecarboxylase inhibitor–>less levodopa metabolism/ dopamine prodicued in the periphery, more for CNS
supraadditive (potentiation) synergism: sulfamethoxazole + trimethoprim
sulfamethoxazole blcks folate synthase and trimethoprim blocks folate reductase. Individually they are bacteriostatic but together they are bacteriocidal (cotrimoxazoles). Sequential blockade/folate inhibition
antagonism
when one drug decreases or inhibits the action of another: effect of (A + B) < effect of A + effect of B
types of antagonism
physico-chemical, physiological/functional, receptor/pharmacological
physicochemical antagonsim
two drugs that react chemicallly and form an inactive product
Physico-chemical example
EDTA (anticoagulant and metal chelator) complex with heavy metals
physiological/functional antagonism
tow drugs actig through different receptors or mechanisms produce opposite effects
physiological/functional antagonsim example
histamine and epinephrine on bronchial tissue (epi will reduce bronchoconstriction but they act on their own receptors), insuline and glucagon on blood glucose levels
receptor/pharmacological antagonism
two drugs action through the same receptors or mechanisms produce opposite effects or one prevents another from producing pharmacological effects
receptor/pharmacological antagonism example
beta blockers occupy beta receptors and preent epinephrine from binding and producing effects–stimulation of the heart is decreased
types of receptor/pharmacological antagonsim
competitive/equilibrium/reversible type, noncompetitive/nonequilibrium/permanent type
receptor - comp vs noncomp
same rec vs different allosteric site
compared to agonist - comp vs noncomp
resembles agonist vs does not resemble agonist
DRC - comp vs non comp
parallel rightward shift vs flattening
effect - comp vs noncomp
reduces affinity/potency by inactivating agonist molecules vs reduce intrinsic activity by inactivating receptors
intensity of response - comp vs noncomp
depends on concentration of both agonist and antagonist vs depends only on the concentration of the antagonist
competitive antagonist examples
Ach - atropine,
morphine - naloxone,
prazosin - epinephrine
noncompetitive antagonist
diazepam–bicuculline,
phenoxybenzamine (irreversible alpha 1 blocker) and epinephrine
