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87 Cards in this Set
- Front
- Back
this amino acid used to synthesize catecholamine neurotransmitters
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tyrosine
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what enzyme hydroxylates tyrosine to form DOPA?
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tyrosine hydroxylase
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DOPA is a catechol-(blank)
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DOPA is a catechol-amino acid
therefore it can be readily transported by amino acid transporter into the brain |
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describe "adrenalin" mixture in adrenal medulla chromaffin cells
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80% EPI
20% NE |
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depolarization of a nerve terminal causes the opening of these channels
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voltage-gated calcium channels
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once a neurotransmitter is released, what dictates the response that is produced?
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type of receptors present on postsynaptic membrane
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presynaptic alpha-2 autoreceptors -- when stimulated -- decrease the release of this neurotransmitter at peripheral nerve terminals
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norepinephrine
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Epinephrine & dopamine are dose-dependent. What does that mean?
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Beta receptors are more sensitive, so they are preferentially stimulated at low doses of EPI. At higher doses of EPI, alpha receptors are stimulated.
Same principle applies for dopamine, except its preference is DA > beta > alpha |
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what is the major way by which the effect of monoamine trasmitters is terminated?
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reuptake of the transmitter back into the nerve terminal
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MAO acts at the (blank) end of catecholamines. MAO is present at (blank).
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MAO acts at the amine end of catecholamines. MAO is present at adrenergic synapses.
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describe 2 isozymes of MAO
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MAO-A: at most PNS terminals, gut, liver
MAO-B: at striatum in CNS, platelets |
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COMT acts at the (blank) end of catecholamines. COMTis located in the (blank) and (blank).
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COMT acts at the catechol end of catecholamines. COMT is located in the kidney and liver
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which is located at synapses: MAO or COMT or both?
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MAO is at synapses which makes it more important in the metabolism of neurotransmitters compared to COMT
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The final blood & urinary metabolite (after MAO & COMT) for EPI and NE is (blank).
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The final blood & urinary metabolite (after MAO & COMT) for EPI and NE is VMA.
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The final blood & urinary metabolite (after MAO & COMT) for dopamine is (blank).
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The final blood & urinary metabolite (after MAO & COMT) for dopamine is HVA.
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Adrenergic agonists produce sympathomimetic effects. The specific effect elicited by a person is influenced by these 2 factors.
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1. drug selectivity for receptor
2. lipid solubility & proportion of "indirect" vs. "direct" action |
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Bigger alkyl groups on phenyl-ethyl-amine backbone increases selectivity for which receptor?
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beta-receptor
(isoproterenol > EPI > NE) |
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Catechols have decreased lipid solubililty but maximum (blank).
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Catechols have decreased lipid solubililty but maximum potency.
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Which has a better lipid solubility: catechols or non-catechols
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non-catechols
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Catechol properties compared to non-catechol
1. lipid solubility 2. CNS activity 3. administration 4. duration of action |
Catechols (compaed to non-catechols) have...
1. less lipid solubility 2. little CNS activity 3. parenteral administration 4. shorter duration of action |
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The site of action for direct acting agonists is (post/presynapic).
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postsynaptic
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The site of action for indirect acting agonists is (post/presynaptic).
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presynaptic
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Describe how reuptake blockers affect direct and indirect acting agonists.
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Potentiation will occur in case of direct acting agonists.
Inhibition of indirect acting agonists will occur in the presence of reuptake blockers. |
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Tachyphylaxis develops in the presence of which agonist: direct or indirect?
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Indirect
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Name the mixed, direct acting adrenergic agonists
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Epinephrine
Ephedrine Pseudoephedrine Also mixed is Dopamine but its selectivity is DA>beta>alpha |
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These 2 drugs are mixed adrenergic agonists with both indirect and direct activity. Part of their action is due to NE release and they produce mild cardiac stimulation.
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Ephedrine
Pseudoephedrine |
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These indirect, mixed (alpha = beta) adrenergic agonists produce CNS activity.
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1. Amphetamine
2. Methamphetamine 3. Methylphenidate 4. Tyramine |
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These direct-acting alpha-2 agonists produce CNS activity.
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1. Clonidine
2. Brimonidine 3. Tizanidine |
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This agonist is useful for cardiac stimulation with few other ANS side effects because it is so selective.
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Dobutamine
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These agonists are useful as bronchodilators with few cardiac side effects.
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1. Albuterol
2. Levalbuterol 3. Salmeterol |
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Describe how Phenylephrine (a selective alpha agonist) produces bradycardia.
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1. acts directly on alpha-1 receptors, producing vasoconstriction
2. this increases PVR, leading to an increase in BP 3. baroreceptors sense the increasd BP 4. parasympathetic tone increases on heart |
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Describe how Epinephrine (a mixed agonist) produces a large increase in BP when first injected.
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1. at high dose, Epinephrine acts on alpha-1 receptors to produce vasoconstriction, leading to increased BP
2. Epinephrine also has effect on beta-1 receptors in heart to increase CO 3. eventually, at lower concentrations of Epinephrine, the alpha-1 receptors won't be stimulated as much and the BP will decrease |
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Describe how Isoproterenol produces a large increase in heart rate.
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1. directly stimulates beta-1 receptors in heart to increase HR and contractility
2. also stimulates beta-2 receptors on skeletal muscle blood vessels to produce vasodilation 3. lowered BP due to vasodilation is sensed by baroreceptors 4. increased sympathetic tone to heart |
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Mild adrenergic agonist toxicity results in these 3 things (according to notes; other symptoms also possible).
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1. anxiety
2. tachycardia 3. headaches |
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Alpha-agonists used as peripheral vasoconstrictor can cause this side effect.
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necrosis
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Long-term use of CNS drugs can result in (blank) and (blank).
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tolerance and dependence
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Methyldopa is converted to its active metabolite in the CNS. On which receptors does the metabolite act and how does it affect NE release?
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Methyldopa metabolite is alpha-methyl-NE. It acts on alpha-2 recptors and decreases NE release from nerve terminals by stimulated presynaptic alpha-2 autoreceptors.
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How does alpha-methyl-NE affect sympathetic outflow of PNS?
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alpha-methyl-NE is an alpha-2 agonist. It acts in the brain to decrease sympathetic outflow to PNS
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Agonists that act on (blank) receptors are used as cardiostimulants.
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Agonists that act on beta-1 receptors are used as cardiostimulants.
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Would you give an alpha-2 agonist to a person with high BP or low BP? Why?
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alpha-2 agonists are anti-hypertensive drugs.
The drugs act on alpha-2 receptors in the CNS to decrease sympathetic tone to the heart. |
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These adrenergic agonists dilate pupils.
(chose from alpha-1, alpha-2, beta-1 or beta-2) |
alpha-1 agonists dilate pupils
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CNS adrenergic agonists are used to treat these 4 things (according to notes).
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1. narcolepsy
2. ADHD 3. obesity 4. migraine headaches |
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Do alpha-1 blockers increase NE release?
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Nope. Alpha-1 receptors are located post-synaptically so an alpha-1 blocker would not increase NE release since the pre-synaptic alpha-2 receptors are unblocked. These alpha-2 receptors, then, can inhibit NE release when synaptic levels get too high.
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These 2 drugs are nonspecific alpha blockers (alpha1=alpha2). Which one is reversible?
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1. Phentoloamine = reversible
2. Phenoxybenzamine = irreversible |
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drugs ending in "---osin" are (blank).
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drugs ending in "---osin" are alpha-1 blockers.
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drugs ending in "----nidine" are (blank).
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drugs ending in "----nidine" are alpha-2 agonists.
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drugs endin in "----terol" are (blank).
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drugs endin in "----terol" are beta-2 agonists.
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Alpha-1 antagonists are used for treatment of hypertension and (blank).
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benign prostatic hyperplasia
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Which are better at treating hypertension on a long-term basis: nonselective alpha blocker or alpha-1 blocker?
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selective alpha-1 blockers are better since they have no effect on alpha-2 receptors in the CNS & presynaptic terminals
Nonselective alpha blockers will produce vasodilation due to alpha-1 block - just like the selective alpha-1 blockers. However, nonselective alpha blockers will ALSO block alpha-2 receptors in the brain. This is a double negative (remember that stimulation of alpha-2 receptors induces inhibition of NE release). Thus, a block of alpha-2 receptors will induce an INCREASE in NE release. This will increase SNS tone and produce tachycardia. |
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The effects of high concentrations of epinephrine can be reversed with (blank) blockers.
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alpha-blockers
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Alpha antagonists leads to (parasympathetic/sympathetic) predominance.
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parasympathetic (nasal stuffiness, urinary incontience, poor night vision)
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How do alpha-1 blockers facilitate urine flow in a man with BPH?
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The drugs block alpha-1 receptors so that they can no longer produce contractin of the urethral smooth muscle.
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Selective (blank) blockers are cardioselective agents.
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beta-1
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Some beta-blockers are membrane stabilizing. How do they do that?
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block sodium channels
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If a beta-blocker has partial intrinsic activity, what does that mean?
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the beta-blocker also has partial agonist action on the beta receptor.
This partial agonist action would result in less of an increase in PVR and HTN on initial administration. |
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Describe similarities and differences between beta-agonist structure and beta-blocker structure.
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beta-blockers hae large alkyl group on the amine jus like beta-agonists. this allows the beta-blocker to be selective for the beta receptor.
beta-blockers have larger ring structures and are not catechols. these larger structures allow receptor binding without intrinsic activity |
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drugs ending in "---lol" are (blank).
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beta-antagonists
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how do drugs ending in "----olol" differ from those ending in "----alol" or "----ilol"?
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"----olol"drugs have few other actions besides being a beta-antagonists
"---alol" or "---ilol" drugs are beta-antagonists but also have partial action on alpha receptors |
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These 2 beta-antagonist drugs have mixed beta>alpha selectivity.
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1. Labetalol
2. Carvedilol |
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This is the prototype for beta-antagonists.
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Propranolol
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This beta-1 selective antagonist has a very short half-life in the plasma
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Esmolol
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This non-selective beta antagonist is used to treat several eye disorders.
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Timolol
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Name the 2 beta-1 selective antagonists.
Name the 2 non-selective beta antagonists. Name the 2 mixed beta and alpha antagonists. |
beta-1 selective
1. Esmolol 2. Atenolol nonselective beta antagonists 1. Propranolol 2. Timolol mixed beta and alpha antagonists 1. Carvedilol 2. Labetalol |
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Explain why beta-blockers are good drugs for treating hypertension.
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Initially, the beta-blockers block the beta-receptors and produce an increased BP. Overtime, there is gradual decrease in BP due to
1. negative inotropic & chronotropic effects on heart 2. block of renin release 3. maybe effects on CNS beta receptors. |
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How will beta-blockers affect a patient's near/far vision?
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beta receptors cannot relax the ciliary muscles in the eye, leading to a more rounded lens and decreased far vision
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How will beta-blockers affect lipolysis and glycogenolysis?
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they will both be inhibited
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Toxic levels of beta-blockers can lead to these 2 cardiac side effects.
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1.CHF
2. AV block |
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What could be a major side effect in a Type II diabetic who is on a beta-blocker?
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hypoglycemia
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List the 4 groups of drugs that act at the presynaptic nerve terminal
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1. drugs that interfere with storage and/or release of neurotransmitter
2. DOPA drugs 3. drugs that block neurotransmitter reuptake 4. drugs that inhibit MAO and COMT |
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Why do adrenergic inhibitors of transmitter release have a long duration of action?
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they are inside the nerve terminal and are protected from diffusion & metabolism
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why does supersensitivity develop to direct-acting agonists after chronic use of drugs that inhibit transmitter release?
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Direct-acting agonists act on post-synaptic receptors and these receptors are not getting any stimulation in the presence of a transmitter-release inhibitor. Due to the lack of stimulation, the post-synatpic receptors are upregulated, leading to supersensitivity.
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mechanism of reserpine
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inhbits synaptic vesicle uptake pump,leading to depletion of monoamine neurotransmitters
gets into the brain and produces severe depression |
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mechanism of guanethidine
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accumulates in synaptic vesicles and causes slow release & depletion of NE
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mechanism of bretylium
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block of depolarization-induced NE release
does not affect NE stores in the vesicle, just the release |
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primary indication for the adrenergic inhibitors of transmitter release/storage
(Reserpine, Guanethidine, Betrylium) |
cardiovascular - they lower BP due to decreased CO and decreased PVR
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List the 3 DOPA drugs
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1. Levodopa
2. Carbidopa 3. Methyldopa |
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Can Levodopa get into the brain? Why? Why is it the drug of choice for Parkinsons?
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Levodopa gets in the brain b/c it is a catechol-amino acid. It is the precursor to dopamine which is why it is the drug of choice for Parkinsons.
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Which DOPA drug inhibits dopa decarboxylase enzyme so that DOPA is not converted to dopamine?
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Carbidopa. It can't cross BBB so it inhibits conversion of L-DOPA to dopamine in the PNS. Thus, there is increased availability of L-DOPA in the brain.
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Methyldopa has its primary effect in the (blank) and is used as an antihypertensive agent.
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primary effect is in CNS
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Methyldopa and this direct acting alpha-2 agonist have similar action.
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Clonidine
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2 examples of reuptake blockers
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antidepressants
cocaine |
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this non-clinical agent produces a large increase in dopamine levels in the brain, leading to euphoria
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cocaine
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example of MAOI
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selegiline
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what is octopamine?
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"false transmitter" from tyramine in the presence of MAOI
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How would the effects of Amphetamine be altered in the presence of a MAOI?
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Amphetamine effects would be potentiated
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Why is too much tyramine in the diet dangerous in a person taking a MAOI?
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MAOI + too much tyramine leads to lots of NE being released...which leads to increased CO, BP, HR
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Example of COMT inhibitor
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Entacapone
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