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110 Cards in this Set
- Front
- Back
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Drug bioavailability
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fraction of unchanged drug that reaches the systemic circulation
affected by first pass metabolism |
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Half life
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time it takes for plasma drug concentration to be reduced by 50%
applied only to drug eliminated by first order kinetics |
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bethanechol
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cholinergic agnoist
choline ester used to increase parasympathetic tone acts at the muscarinic receptors |
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pilocarpine
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cholinergic agonist
natural alkaloid topical agent for glaucoma and xerostomia |
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cevimeline
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cholinergic agonist
M3 specific agoinst excellent treatment for xerostomia |
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contraindications of cholinergic agonists
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patients with asthma
heart disease (reflexive sympathetic action may cause arrythmias) |
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why can Ach not be used effectively as a pharmacological agent?
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because pseudocholinesterases are found throughout the body to eliminate Ach
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endrophonium
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reversible, short acting ACE inhibitor
used to diagnose myasthenia gravis |
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physotrigmine
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reversible, intermediate acting ACE inhibitor
treatment for hypotonic bladder, glaucoma can cross the BBB |
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neostigmine
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reversible, intermediate acting ACE inhibitor
myasthenia gravis treatment because effect at NMJ is greater than phyostigmine |
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pyridostigmine and ambenonium
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reversible, intermediate acting ACE inhibitor
myasthenia gravis treatment |
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rivastigmine, donepezil, tacrine, and galantamine
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reversible, intermediate acting ACE inhibitor
alzheimers treatment because it can cross the BBB |
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ecothiophate
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irreversible, long acting ACE inhibitor
synthetic organophosphate used to treat glaucoma |
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isoflourophate
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irreversible, long acting ACE inhibitor
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how to insecticides and nerve gases cause the most damage?
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in the process of aging in which ACE is permanently inhibited through phosphorylation
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post-exposure treatment for nerve gas
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high doses of atropine or scopolamine followed by an injection of pralidozine
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atropine
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muscarinic receptor antagoinst
belladona alkaloid used to reverse severe bradycardia, produce mydriasis, antispasmodic |
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scopolamine
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muscarinic receptor antagonist
belladona alkaloid prophylactic for motion sickness crosses the BBB more readily than atropine |
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ipratropium bromide
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synthetic muscarinic receptor antagonist
used in asthma and COPD because it has a minimal inhibitory effect on mucocilliary clearance when compared to atropine |
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tiotropium
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synthetic muscarinic antagonist
used in asthma and COPD much more selective for M3 so it has much more selective action at the bronchioles |
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tolterodine
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synthetic muscarinic antagoinst
used to treat overactive bladder blocks M3 receptors to diminish the urge to go and prevent leaks not appropriate for patients with BPH |
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nicotinic ganglionic antagonists
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very few used because they block the parasympathetics and sympathetics
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nicotinc NMJ antagonists
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block cholinergic transmission in skeletal muscle so can be used as muscle relaxants
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non-depolarizing NMJ blockers
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act as competitive blockers at the NMJ whose effect can be overcome with more Ach
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antracurium
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non-polarizing NMJ blocker
not used because of its toxic breakdown products |
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cistracurium
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non-depolarizing NMJ blocker
spontaneously degrades in plasma so it's safe for renal patients and ventilated patients |
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mivacurium
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non-depolarizing NMJ blocker
recovery from blockade is more rapid, making this ideal in short surgical procedures |
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rocurium
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non-depolarizing NMJ blocker
rapid onset makes this useful for tracheal intubation |
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pancuronium
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non-depolarizing NMJ blocker
causes rapid HR |
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tubocurarine
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non-depolarizing NMJ blocker
may induce histamine release and lower BP |
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succinyl choline
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depolarizing NMJ blocker
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half life
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time it takes for the PLASMA concentration to be reduced by 50%
applied to drugs eliminated by 1st order kinetics |
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steady state
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rate of drug elimination balances drug input rate
4-5 half-lives to reach steady state 3.3 half-lives to reach 90% steady state |
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therapeutic window
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= minimum [effective]/minimum [toxic]
= 10 or less is usually highly toxic |
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drug absorption
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transfer of drug from site of admin to blood stream
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facilitated diffusion
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L-dopa is the only drug that uses this
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pinocytosis
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used by iron-transferrin, vitamin B-12, intrinsic factor
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if pH of solution is below pKa
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acids will be unionized (and will be absorbed)
bases will be ionized |
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proximal intestines absorb
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weak acids
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distal intestines absorb
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weak bases
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drug distribution
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process by which a drug reversibly leaves the blood stream and enters the intersitium
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due to competition for binding site, which drugs are contraindicated in infants?
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sulfonamides, which tend to displace bilirubin
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volume of distribution
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dose/concentration in plasma at time 0
relates the volume of drug in the body to the concentration in blood |
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biotransformation can be affected by
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prior admin
physiological status age genetics liver function |
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phase 1 of biotransformation
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non-microsomal enzyme reactions (hydrolysis, ETOH metabolism)
cytochrome P450 reactions |
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which cytochrome metabolizes 70% of all drugs
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3a4
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CYP450 inhibitors (3)
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grapefruit juice
cimetidine (H2 antagonist) azole antifungals |
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CYP450 inducers (3)
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barbituates
all anticonvulsants rifampin (causes oral contraceptive failure) |
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what allows drugs to proceed into phase II
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lipid solubility
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5 steps of phase II of biotransformation
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glucuronidation
sulfonation transcyclase acetylation inactivation of and increased solubility of drugs |
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slow acetylators
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HIP drugs will result in the butterfly rash of lupus
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poor metabolizers
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caucasians = 5-10%
african americans = 2-5% |
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ultra-rapid metabolizers
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ethiopians = 20%
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normal GFR
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120 (25% RPF)
if GFR <80, you must adjust the dose of the drug |
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creatine clearance
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women = 87-104
men = 90-140 |
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net renal excretion
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= GFR + amt of drug selected by active transport in the kidney - amt of drug reabsorbed throughout the tubule
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Clearance (Cl)
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= volume of blood cleared per unit time
= GFR when there is no reabsorption or secretion = free fraction x GFR |
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first order elimination
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dependent on half life
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zero order elimination
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no fixed half life
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acidifiers of urine (3)
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increases the ionization of weak bases (quinidine) and thus renal excretion
NH4Cl cranberry juice vitamin C |
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alkalizers of urine (1)
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increases ionization of weak acids (aspirin) and thus renal excretion
NaHCO3 |
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Loading Dose
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= (Vd x Cp) / f
Vd = volume distribution Cp = plasma concentration f = bioavailability |
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maintenance dose
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= (Cl x Cp) / F
F=bioavailability |
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five principles of pharmacology and drug theory
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bind specifically
alter existing pathways activate/inhibit compare to basal proportional response |
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site of action (3)
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membrane protein (adrenergic receptor)
cytoplasmic/extracellular enzyme (gastric proton pump, COX) nucleic acid (alkylating agents) |
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G-protein time frame
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minutes
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G-protein endogenous activators (5)
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nor epi
serotonin Ach histamine alpha |
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desensitization
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decreased effect of a drug in the acute sense due to the phosphorylation and internalization of the receptor
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down regulation/tolerance
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decreased response due to chronic exposure and effects are long lasting due to degradation of the receptor
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sensitization
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increased response due to increased synthesis of receptors
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ligand gated ion receptor time frame
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miliseconds
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ligand gated ion receptor examples (2)
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nicotinic Ach activator
GABA receptor |
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tyrosine kinase receptor effects
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effects are on cellular function as well as the regulation of the transcription of genes involved in cell growth and differentiation
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tyrosine kinase time frame
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minutes/hours/days
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tyrosine kinase endogenous activators (4)
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insulin
epidermal growth factor platelet derived growth factor atrial natiuritic factor |
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cytokine receptor keys (2)
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JAK
regulates genes involved in synthesis and release of many inflammatory mediators and hematopoetic factors |
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cytokine receptor time frame
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hours/days
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cytokine receptor endogenous activators (3)
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growth hormone
erythropoitin interferon |
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intracellular receptor functional domains (3)
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hormone binding domain
DNA binding domain transcription activating domain |
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intracellular receptor time frame
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hours/days
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intracellular receptor endogenous activators (5)
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glucocorticoids
mineralcorticoids sex steroids vitamin D thyroid hormone |
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binding affinity
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Kd = [L][R]/[L-R]
concentration of drug required to bind 1/2 the receptors range = 1mM-1pM higher Kd = lower affinity |
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efficacy
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the ability of the ligand to induce the receptor to adopt an active conformation to generate a biological response
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chemical antagonist
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direct chemical interaction between the agonist and antagonist that renders the agonist inactive
ex chelating agents |
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physiological antagoinst
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interaction of two agonists that act independently of each other but happen to cause opposite effects
ex epi and ach on HR |
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indirect antagonist
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those that work further down the chain reaction so adding more reactant does not overcome the antagonist
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competitive antagonist
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have affinity but no efficacy
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reversible antagonist
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equilibrium competitive
can be overcome by adding more agonist |
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irrerversible antagonist
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nonequilibirum competitive
cannot be overcome by increasing amount of the agonist |
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graded dose response curve
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depicts how many people respond to a certain dose (specific to that dose amount)
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ED50
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= dose required to produce 1/2 of its own maximum response
thus max response must be known to calculate ED50 |
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potentcy
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compares ED50 values
ED50 cannot be compared to Kd |
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intrinsic activity
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the ability of receptors in certain tissues to response to agonist stimulation (may be used interchangeably with efficacy)
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sympathetic activity in the eye
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mydriasis via alpha 1
constriction of vascular bed via alpha dilation of the vascular bed via beta 2 |
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parasympathetic activity in the eye
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miosis
accomodation via M3 |
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sympathetic activity in the trachea and bronchioles
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dilates via beta 2 receptors
mucosal secretions increase with beta 2 agonists mucosal secretions decrease with alpha agonists |
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parasympathetic activity in the trachea and bronchioles
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bronchoconstriction via M3
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parasympathetic activityin the lacrimal glands
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stimulates tears via VII and M3
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sympathetic activity in the salivary glands
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thick, viscous secretions
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parasympathetic activity in the salivary glands
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copious, watery secretion
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sympathetic activity on HR
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via beta 1, increase via SA node, ventricular pacemakers, AV node, and his-purkinje system
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sympathetic activity on contractility of the heart
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via beta 1, increase via atira and ventricles
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parasympathetic activity on HR
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right CNX on M2 receptor of SA node
left CNX on M2 receptor of AV node you are hyperpolarizing by increasing potassium currents out of the cell |
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parasympathetic activity on heart contractility
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vagal effects on atrial muscle
slight decrease in ventricular contractility |
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sympathetic effect on GI
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decrease in muscle motility and tone
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parasympathetic activity on GI
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M3 receptors
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sympathetic activity in kidneys
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secretion of renin
beta 1 increases, alpha 1 decreases |
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sympathetic activity on ureters and bladder
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relaxes detrussor (beta 2)
contraction of sphincter (alpha 1) |
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parasympathetic activity on ureters and bladder
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relaxes sphincter
contraction of detrussor (M3) |
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sympathetic activity in genetalia
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stimulates ejaculation in males
stimulates relaxation of the uterus in females |
