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