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77 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Agonist
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binds receptor and actively changes concentration of intracellular receptors
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Antagonist
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bind receptor and passively change concentration of intracellular messengers.
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passive because they can block the ongoing stimulation of a receptor by another compound.
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Ligand-gated ion channel
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agonist opens aqueous ion channel
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ex- GABA mediated Cl- channel
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voltage-sensitive ion channel
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membrane depolarization opens aqueous ion channel
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ex- Na+ channels in heart and neurons
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GPCR
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receptors linked to G-proteins that activate or inhibit enzymes or ion channels when activated
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increased Na+ conductance
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rapid depolarization
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increased K+ conductance
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hyperpolarizes membrane
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therefore, decreased K+ conductance decreases membrane potential difference, easier to fire AP
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increased Cl- conductance
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hyperpolarizes membrane
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Increased Ca++ conductance
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slow depolarization
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nicotinic receptor
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responds to ACh, opens Na+ channel
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N1 receptor
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responds to ACh at sympathetic and parasympathetic ganglia
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increases Na+ conductance- depolarization
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N2 receptor
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responds to ACh at NMJ
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increases Na+ conductance- depolarization
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Inhibitory amino acids
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increase Cl- conductance, hyperpolarize cell
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GABA
glycine |
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GABA-a receptor stimulation enhanced by
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benzos, barbiturates, volatile anesthetic gases, propofol, ethanol
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even greater increase in Cl- conductance
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Excitatory amino acids
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increase Na/Ca conductance, depolarize cell
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glutamate
aspartate |
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Serotonin increases...
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Na+ conductance via 5-HT3 receptor
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adrendoreceptors
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alpha 1 & 2, beta 1 & 2
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GPCR
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serotonin receptors
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5-HT1, 5-HT2, 5-HT4
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GPCR
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Muscarinic cholinergic receptors
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M1, M2, M3, M4
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GPCR
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GPCR other than adrenoreceptors, serotonin receptors, and muscarinic chonlinergic
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GABA-b, V1 & V2, H1 & H2, ACPD gluatmate receptors
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GABA-a receptor increases Cl- ion conductance, GABA-b is a GPCR
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B-adrenoreceptors
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activates G protein -- activates adenyl cylcase -- cAMP- cAMP dependent kinases
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cAMP is degraded by
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PDEase -- 5'AMP, inhibited by
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theophylline, caffeine, papverine
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Many GPCRs active....
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IP3-DAG to cause smooth muscle contraction and glandular secretion
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lipid-soluble compounds can...
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freely cross cell membrane, effects are slow because they usually alter transcription, examples:
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estrogen, adnrogens, thyroxine
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Phospholipase C
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releases IP3 & DAG from PIP-2.
IP3 releases Ca from SR DAG activates phosphokinase C's |
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Phospholipase A2
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releases arachidonic acid from cholesterol, triglyceride, phospholipid esters
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In general, drugs...
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alter the rate of ongoing biochemical processes in the body
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increased membrane potential difference...
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cell is hyperpolarized
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decreased membrane potential differnce
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cell is depolarized (not necessarily at threshold)
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ions that can depolarize cells
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Na+, Ca ++
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Na is faster than Ca
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increased cAMP causes...
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signal amplification
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albuterol
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b-2 receptor selective agonist, bronchodilation. Works in a few minutes.
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Affinity
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ability of a drug to form a stable complex with a receptor
1/Kd |
Small Kd=high affinity
Large Kd=low affinity |
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Intrinsic activity
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biological effectiveness of a drug receptor concept
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Competitive antagonism
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slope of dose response curve stays the same, requires more agonist to get the same response
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Noncompetitive antagonism
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slope and maximum effect decreases
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bind covalently, so receptor is permanently blocked
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partial agonist as an antagonist
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decreases response if a full agonist is around because partial agonist occupies receptor and cannot elicit full response
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Tolerance, dose-response curve
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Curve shifts to the right
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pharmacokinetic tolerance
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when one drug induces the metabolism of another drug
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pharmacodynamic tolerance
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when the tissue response decreases
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EtOH can cause pharmacodynamic tolerance
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cross-tolerance
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tolerance to one drug from prior exposure that results in tolerance in another drug
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ex- heavy drinker responds less to benzos
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receptor upregulation
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too little signal from: denervation, receptor blockade, decreased neurotransmitter release
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Efficacy
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maximal clinical effect on dose-response curve
more efficacious=greater clinical effect |
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Potency
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the dose of drug required to achieve a certain clinical effect
smaller the effective dose, the more potent |
when potency increases, dose-response curve shifts to the left
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therapeutic index
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LD50/ED50
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Cpo= (Xo x F)/Vd
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Estimated plasma concentration of a dose (Xo) at time zero
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Vd = (Xo x F) / Cpo
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Volume of distribution can be determined if you know the dose, bioavailability, and plasma concentration
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Vd
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Volume of distribution (L)
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elimination rate constant, k
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k=0.7 / t1/2
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Clearance
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Cl= rate out / Cp
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rate out =
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Cu X Uvol/t
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Rule of 4's
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It takes 4 half lives for a drug to reach steady-state concentration
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Steady State
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rate in = rate out
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Rate in for IV dose
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Xo / t
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Rate in for po dose
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(Xo x F) / t
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Pulse pressure
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SBP-DBP, the pressure created by one beat
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Windkessel function
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stretching of large arteries during systole, return to normal during diastole
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TPR determined by
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arterioles (4th/5th order)
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LV- End Diastolic Volume determined by
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blood volume
blood distribution venous capacitance atrial contractility |
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Major determinant of stroke volume
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Venous Return
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Frank-Starling Law
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The heart pumps what it gets, venous return is the most important determinant of stroke volume
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Cardiac output is primarily determined by
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Stroke Volume (mostly depends on venous return!)
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Afterload
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arterial impedence, TPR, DBP
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Carotid Baroreflex
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when BP decreases, CBR causes an increase in sympathetics and decrease in vagal activity
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increased heart rate and pressure
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Carotid Baroreflex, pressure increase
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decrease in efferent sympathetics, increase in vagal efferent activity
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decreased heart rate and pressure
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Carotid Baroreflex mediated tachycardia
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drop in pressure results in tachycardia because CBR stimulates sympathetic efferents and decreases vagal efferents
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Decreased stimulation of B-1 in heart....
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decreases HR, CO falls
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but not by much! HR is not a major determinant of CO
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Decreased stimulation of A-1 in resistance arterioles...
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passive vasodilation, decrease in DBP
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Decreased stimulation of A-1 in veins causes
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passive vasodilation which reduces venous return and therefore cardiac output because the veins can hold more volume
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Increased efferent vagal activity...
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decrease in HR
decrease in atrial contractility slight decrease in ventricular contractility |
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Stimulating A-2 receptors in the RVLM...
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decreases sympathetics and slows HR
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Clondine
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A-2 adrenoreceptor agonist, suppresses neuronal activity of RVLM, decreases sympathetics, therefore decreases pressure
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alpha-methyldopa
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metabolized to alpha-methyl-NE, A-2 receptor agonist, suppresses sympathetics in RVLM, decreases pressure
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isoproterenol
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Beta agonist, increases HR by direct stimulation of SA node
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Hydralazine
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arterial vasodilator, decreases pressure, CBR mediated tachycardia
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pilocarpine
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cholinergic agonist, decreases HR by direct action on SA node
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Norepinepherine
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constricts resistance arterioles and increases pressure, CBR mediated bradycardia
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