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85 Cards in this Set

  • Front
  • Back
Efficacy
Measure of the maximum response obtained with the highest concentrations of the agonist
EC50 (potency)
Measure of the concentration of agonist required to achieve 50% of the maximum response. In most cases, the EC50 is equivalent to the dissociation constant KD for the drug and receptor. This is similar to the Km in enzyme kinetics.
Antagonist
Agnet that binds to a receptor but cannot porduce the conformational change necessary to trigger the downstream events. NO response is seen when the antagonist is bound to itself
Competitive antagonists
Reversible binding. We CAN compete away the antagonist by increasing agonist concentrations
Competitive antagonism
Right shife. Efficacy unchanged. Higher concentrations needed to achieve same response.
Non competitive antagonists
inactivate receptor molecules or act a downstream site; decrease the maximum response of the agonist. Increasing agonist concentrations will NOT overcome this.
Non competitive antagonists
Potency unchanged; efficacy drops
Spare receptors
In α1 adrenergic pathway; activation at low concentrations with faster turn off.
Low pH
HA; uncharge, lipid soluble, protonated form of acid
High pH
B; lipid soluble, unprotonated form of base.
pH=pKa
unprotonated/protonated ratio is 50/50
1 pH unit is more alkaline
unprotonated/protonated ratio is 10/1
2 pH units more alkaline
unprotonated/protonated ratio is 100/1
Volume of distribution (Vd)
(amount administered)/(concentration at t=0)
Range of Vd values
5 -10 liter – drugs highly charged or bound to plasma protein; 20 - 40 liter – moderately lipid soluble; 40 liter – lipid soluble enough to distribute to total body water; >40 liter – highly lipid soluble; sequestered in fat, nervous tissue and muscle
CNS, BBB, Vd and lipid solubility
Large Vd values (>40 L), eliminated by hepatic drug metabolism (rather than renal excretion), HIGH lipid solubility
Urinary alkalinization
Use sodium bicarbonate; increases urine to pH8. Used when overdose of weak acids. ONLY works if pKa is in the range of 5-8.
Urinary acidification
Use ammonium chloride; lowers urine pH to 5. Used when overdose of weak bases. ONLY works if pKa is in the range of 5-8.
Ezetimibe
reduces the intestinal absorption of cholesterol
zero order
constant amount. N=0, [drug]^0=1. NOT dependent on drug concentration. Proceeds at a constant rate. Elimination--constant amount is lost per unit time.
zero order processes
drug administration; drug elimination in OVERDOSE situation; ALCOHOL
zero order graph
straight line on non-log plot; downward curve on semi-log plot
First order
constant percent. Rate of process directly dependent on the drug concentration. Elimination--constant percent is lost per unit time.
first order processes
drug metabolism under ordinary circumstances; renal excretion; ELIMINATION.
first order graph
straight line on log plot; exponential curve down on non-log plot
Rate of drug input
f(D/T)
elimination constant (ke)
ke=0.7/ t1/2
relationship between half life and ke
inversely related. As half life increases, ke decreases.
drug output rate (first order)
(X) (ke); X= C * Vd; C* Vd*ke
Steady state
Input rate=output rate; f(D/T) = Css * Vd * ke ; or f(D/T) = Css * CL
Time to steady state
4 * half life
Loading Dose
Css * Vd
Maintenance dose
Clearance * Css
Clearance
Vd * ke
Phase I metabolism reactions
oxidation, reduction, hydrolysis; located between absorption and metabolism
Phase II metabolism
conjugation--glucuronidation, sulfation, glutathione conjugation, acetylation, methylation, amino acid conjugation; located between metabolism and elimination
Oxidation Phase I
cytochrome P450 superfamily; LOSS OF ELECTRONS, GAIN OF OXYGEN, LOSS OF HYDROGEN
reduction phase I
intestinal microflora, mammalian enzymes; GAIN OF ELECTRONS, LOSS OF OXYGEN, GAIN OF HYDROGEN
hydrolysis
carboxylesterases, epoxide hydrolases
Phase III metabolism
transporter proteins that "pump" xenobiotics or their conjugates out of the cells
Most common P450's
CYP3A4/5; CYP2D6; CYP2C8/9; there are 57 human CYP's--18 families and 43 subfamilies
CYP's that are located in mitochondria
Steroidogenic
Basic reaction for CYP's
monooxygenation--one atom of oxygen is incorp into substrate and other is reduced to water. Reducing equivalents derived from NADPH
P450 cycle
Types of oxidative reactions by P450
Hydroxylation of an aliphatic or aromatic carbon
Types of oxidative reactions by P450
o Epoxidation of a double bond
Types of oxidative reactions by P450
o Heteroatom (S-, N- and I-) oxygenation and N-hydroxylation
Types of oxidative reactions by P450
o Heteroatom (O-, S- and N-) dealkylation
Types of oxidative reactions by P450
o Oxidative group transfer
Types of oxidative reactions by P450
o Cleavage of esters
Types of oxidative reactions by P450
o Dehydrogenation
Other oxidative enzymes Phase I
Flavin monooxygenases
Phase I reduction
azo and nitro reduction, carbonyl reduction, quinones
Phase I hydrolysis
carboxylesterases, epoxide hydrolases
Phase II glucuronidation
UGT's from co-factor UDP; includes carboxylic acids; UGT's are localized to microsomes
Phase II sulfation
PAPS cofactor, catalyzed by SULTs
Phase II glutathione conjugation
catalyzed by GST's; transfer of glutathione (Glu-Cys-Gly) to an electrophilic atom
Phase II acetylation
co factor--acetyl coA; substrates are amines; catalzyed by NAT1 & NAT2 located in cytosol
Phase II methylation
cofactor--SAM; transfer of a methyl group to O, N or S; catalyzed by COMT, POMT, PNMT, HNMT, NNMT, etc.
polymorphism
variation in DNA sequence that is present at a frequency of at least 1% in a population
Types of polymorphisms:
SNPs, Insertions/deletions (indels), copy number variants (CNV)
Excitatory AA's neurotransmitters
glutamate and aspartate
Inhibitory AA's neurotransmittors
glycine and GABA
Glutamate
activation of ionotropic receptors serves to depolarize the membrane via the passage of Na+ and Ca2+ down their electrochemical gradients. Mediates FAST synaptic transmission (AMPA and NMDA)
GABA
inhibitory neurotransmission--hyperpolarize the membrane via movement of Cl- down its concentration gradient.
Metabotropic G protein coupled receptors
modulate the properties of the neurons and how they respond to and integrate fast synaptic activity.
Beta adrenergic receptors, B1, B2 & B3
Gas--> Increased AC
Alpha 1 adrenergic receptors
Gaq/11--> increase PLCbeta
alpha 2 adrenergic receptors
Gai/o--> decrease AC
D1 like dopamine receptors D1 & D5
Gas-->increase AC
D2 like dopamine receptors D2, D3, D4
Gai/o--> decrease AC
M1, M3, M5
Gaq/11--> increase PLCbeta
M2, M4
Gai/o--> decrease AC
Primary neurotransmitter of DRG
glutamate, substance P, numerous other peptides.
Primary neurotransmitter of somatic motor neuron
acetylcholine
Primary neurotransmitter of preganglionic neuron
acetylcholine
primary neurotransmitter of postganglionic neuron
norepinephrine
cardiac effects of NE
increase BP, decreased heart rate, w/ atropine/prazosin, increased heart rate
cardiac effects of EPI
increase BP, increased heart rate
cardiac effects of PE
increase BP, decreased heart rate, w/atropine, no change in heart rate
cardiac effects of Ach
decrease BP, decrease HR, induce vasodilation via NO
succinylcholine molecular action
nicotinic receptor agonist
Atropine
drug that induces mydriasis and cycloplegia
Atenolol
Blocks the direct cardiac action of dobutamine
What distinguishes between an overdose of a ganglionic blocker versus a muscarinic blocker?
postural hypotension