Term
step 1 of catecholamine synthesis:
_______ is taken up into adrenergic neurons and is then converted to _______ by the action of ___________. |
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Definition
| L-tyrosine (from blood); L-dopa; tyrosine hydroxylase |
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Term
step 2 of catecholamine synthesis:
L-dopa is converted into ________ by the action of ___________. |
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Definition
| dopamine; dopa decarboxylase (aka l-amino acid decarboxylase) |
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Term
| what happens to dopamine molecules after they are synthesized by dopa decarboxylase? |
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Definition
| they are transported into storage granules (vesicles) by an active transport carrier. |
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Term
| what happens to the dopamine in the vesicles of dopamine and norepinephrine neurons? |
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Definition
| It can be released from dopamine neurons, but NE neurons must use dopamine beta-hydroxylase (present in vesicles) to convert dopamine to NE. |
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Term
| How is epinephrine synthesized? |
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Definition
| In epinephrine neurons, a cytoplasmic enzyme, phenylethanolamine N-methyltransferase (PNMT) converts cytoplasmic NE (either from re-uptake or internal release from vesicles) to epinephrine |
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Term
| besides converting L-dopa to dopamine, what else can dopa decarboxylase do? |
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Definition
| convert alpha-methyldopa to alpha-methyldopamine which can be further converted to alpha-methylnorepinephrine, which are false transmitters |
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Term
| what is a false transmitter? |
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Definition
| they can be stored in pre-synaptic vesicle, but have little effect on post-synaptic receptors. |
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Term
T/F. NE acts in a feedback loop?
What does this mean? |
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Definition
| TRUE. It works on enzymes tyrosine hydroxylase and dopa-decarboxylase to modify production of NE. If there is excessive NE release there will be less NE in cytoplasm and this will trigger more rapid synthesis. |
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Term
| What is the ratio of epi to NE release from adrenal medulla chromaffin cells? |
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Definition
| 80% Epi to 20% NE. This is important for sympathetic response b/c epi has a longer duration than NE in the blood stream |
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Term
| Explain release of adrenergic NT's |
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Definition
| impulse travels down neuron and triggers Ca++ inflow at nerve terminal. This causes release of NT. Same thing happens in adrenal chromaffin cells, but the NT is released to blood vessels |
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Term
| following release, approximately ___% of NE is retrieved by reuptake pumps back into the cytoplasmic pool (most important mechanism in stopping neurotransmitter action at the receptor sites.) |
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Definition
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Term
| What are the two enzymes responsible for metabolism of catecholamines? |
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Definition
| monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) |
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Term
| MAO has two major forms (A&B). Which one is most active form for metabolism of NE, DA, EPI, and Serotonin? |
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Definition
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Term
| Where do MAO and COMT exist? |
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Definition
| MAO is mainly on the outer surface of mitochondria in sympathetic neurons and COMT is located mainly in the synaptic cleft. The liver has a lot of MAO and COMT, thus rapidly metabolizing circulating catecholamines. |
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Term
| What is the order of alpha agonist potency b/w dopamine, epinephrine, isuprel, and norepi? |
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Definition
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Term
| What is the order of beta agonist potency between dopamine, epinephrine, isuprel, and norepi? |
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Definition
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Term
| alpha 1 (postsynaptic) stimulation |
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Definition
| vasoconstriction, mydriasis, relaxation of GI tract, contraction of GI sphincters and bladder sphincters |
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Term
| apha 2 (presynaptic) stimulation |
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Definition
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Term
| alpha 2 (postsynaptic) stimulation |
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Definition
| platelet aggregation, hyperpolarization of cells in the CNS |
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Term
| beta 1 (postsynaptic) receptors |
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Definition
| increases HR and contractility |
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Term
| Beta 2 (postsynaptic) stimulation |
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Definition
| vasodilation, bronchodilation, GI relaxation, uterine relaxation, glycogenolysis, lipolysis |
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Term
a. dopamine 1 (postsynaptic) stimulation
b. dopamine 2 (presynaptic) stimulation |
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Definition
a. vasodilation
b. inhibition of NE release |
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Term
| how do alpha 2 antagonists work? |
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Definition
| they cause sympathetic overstimulation because the neuron thinks there is not enough NT and will continue to release it because the feedback mechanism that stops release is stimulation of alpha 2 receptors. |
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Term
| Norepinephrine (Levophed) |
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Definition
1. Stimulates alpha and beta receptors (more alpha than beta)
2. increases coronary artery blood flow
3. causes glycogenolysis, inhibition of insulin release, and lipolysis (all less than epinephrine)
4. reflexive vagal stimulation secondary to increased total peripheral resistance and BP slows the HR and increases stroke volume
5. Does not cross BBB
6. does not increase myocardial O2 consumption
7. rapid onset, duration only 1-2 mins. |
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Term
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Definition
1. Potent alpha and beta agonist (non-selective adrenergic agonist)
2. combined with other drugs (LA's, eye drops) to decrease absorption so the drug lasts longer
3. potent bronchodilator
4. alpha1 action causes vasoconstriction
5. alpha2 action causes decreased NE release from neurons
6. Beta 1 action causes inc HR and inotropy
7. Beta 2 causes arteriolar dilation, bronchodilation, and glycogenolysis. Also decreases mast cell histamine release
8. lowers intraocular pressure (wide angle glaucoma) d/t vasoconstriction. W.A.G.=overproduction of aqeous humor
9. increased risk of arrhythmias
10. coronary artery dilation
11. alpha stimulation in liver increases gluconeogenesis and inhibits insulin release.
12. beta 2 stimulation at skeletal muscle and liver inc. glycogenolysis
13. does not cross BBB well
14. with small doses see more beta activity and with large doses see potent alpha activity |
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Term
| T/F. Most drugs that stimulate both alpha and beta will stimulate beta more at low doses and alpha more at high doses. |
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Definition
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Term
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Definition
1. potent non-selective beta agonist
2. potent bronchodilator and inotrope
3. very little alpha activity
4. increases blood flow (vasodilation) and relaxes GI smooth muscles
5. IV onset RAPID, duration < 1 hour
6. used for acute bronchospasm, bradycardia, asthma, etc. |
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Term
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Definition
1. selective beta 1 agonist (minor beta 2 or alpha effects)
2. causes increased inotropy and chronotropy
3. systolic pressure increased due to increased SV. little change in DBP
4. increases coronary blood flow and myocardial O2 demand
5. Unlike dopamine, does not increase NE release from sympathetic nerves
6. administered by gtt because 1/2 life only 2 mins. |
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Term
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Definition
1. works at dopamine receptors to dilate renal arterioles and increase renal blood flow and GFR
2. At low doses causes vasodilation in renal, mesenteric, and coronary vessels
3. At moderate doses stimulates B1 receptors which increase inotropy and chronotropy
4. at high doses, stimulates alpha receptors increasing TPR
5. does not cross BBB
6. given by gtt b/c 1/2 life 2 mins.
7. used for heart failure and shock |
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Term
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Definition
1. synthetic compound similar to Isuprel
2. More B-2 selective than Isuprel (but less than albuterol)
3. used exclusively as bronchodilator
4. Not used much b/c there are better beta-2 agonists |
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Term
| albuterol (Ventolin, Proventil, ProAir) |
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Definition
1. Selective beta-2 agonist
2. indicated for bronchospasm in pts with COPD and asthma
3. adverse reactions are nervousness, tremor, palpitations, and tachycardia |
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Term
| T/F. Tachycardia after albuterol is most likely due to some beta 1 stimulation. |
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Definition
| FALSE. It is a compensatory reaction to vasodilation |
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Term
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Definition
1. relatively selective Beta 2 agonist
2. structurally similar to albuterol
3. used for asthma and bronchospasms |
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Term
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Definition
1. Beta 2 agonist (much more selective than albuterol)
2. used for chronic treatment of asthma (BID dosing d/t longer half life)
3. S/E: tachycardia, palpitations, hypersensitivity, temor, headaches |
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Term
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Definition
1. Beta 2 agonist
2. Used for bronchospasm, asthma, and emphysema
3. S/E: tremor, nervousness, tachycardia, palpitations, N/V |
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Term
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Definition
1. selective alpha 2 agonist
2. more CNS activity than peripheral
3. Alpha 2 stimulation in the CNS leads to decreased sympathetic outflow and increased PSNS outflow
4. indicated for control of HTN
5. S/E: dry mouth (even with inc. PSNS outflow), skin irritation |
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Term
| phenylephrine (Neosynephrine) |
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Definition
1. alpha agonist (alpha 1 mostly)
2. causes vasoconstriction, nasal decongestion, and mydriasis (without cycloplegia)
3. S/E: bradycardia, decreased CO, arrhythmias, angina, dizziness, and CNS excitation |
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Term
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Definition
1. parenterally administered potent vasoconstrictor (alpha 1)
2. Used to prevent hypotension from spinal anesthesia
3. S/E: anxiety, cardiac arrhythmias, and HTN |
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Term
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Definition
1. forms alpha-methylnorepinephrine which acts as a false transmitter that is less potent than NE
2. Used to treat HTN
3. C/I in pts with hepatic dz.
4. S/E: angina, CHF, orthostatic hypotension, bradycardia, many others |
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Term
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Definition
1. inhibits amine re-uptake pumps thus causing increased stimulation
2. has LA effects d/t Na channel blockade of nerve membranes
3. S/E: vasoconstriction, mydriasis, nervousness, resp. failure, cardiac arrest, general CNS stimulation |
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Term
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Definition
1. stimulates sympathetic neurons to release neurotransmitter
2. Also has direct post-synaptic effect
3. Used for narcolepsy, ADD, obesity
4. C/I in any CV disease, HTN, hyperthyroidism
5. S/E: palpitations, tachycardia, HTN, psychoses, insomnia, H/A, temor, general CNS stimulation |
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Term
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Definition
1. stimulates both alpha and beta receptors
2. indirect effect= release of NE
3. direct effect at adrenergic receptors also
4. therapeutic doses produce smooth muscle relaxation, cardiac stimulation, and increased SBP&DBP |
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Term
| pseudoephedrine (Sudafed) |
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Definition
1. Direct a1, b1, and b2 activity in addition to triggering release of catecholamines from nerve termminal
2. used mainly for asthma, nasal decongestion
3. C/I in CV disease and HTN
4. S/E: CNS excitation, tremors, insomnia, nervousness, palpitations, tachycardia, cardiac arrhythmias, headache, sweating |
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Term
| phenoxybenzamine (Dibenzyline) |
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Definition
1. alpha 1 and 2 antagonist
2. binds covalently so is irreversible
3. lasts at least 3 days
4. most effective at smooth muscle and exocrine glands
5. Used for pre-op treatment of pheochromocytoma to block potential hypertensive crisis during surgery, also for sweating and HTN caused by pheochromocytoma, certain vasospastic disorders, and frostbite therapy
6. S/E: dizziness, decreased ejaculation ability, fatigue, miosis, orthostatic hypotension, tachycardia |
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Term
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Definition
1. alpha 1 & 2 competitive antagonist
2. shorter duration than phenoxybenzamine
3. Used for pheochromocytoma diagnosis, pheochromocytomectomy, MAO induced hypertensive crisis, impotence
4. S/E: dizziness, decreased ejaculation ability, flushing, hypotension, sinus tachycardia |
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Term
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Definition
1. selective alpha 1 antagonist
2. used for tx of HTN
3. S/E: dizziness, headaches, drowsiness, palpitations, tachycardia, orthostatic hypotension
4. Does not block a-2 receptors so there is no excessive release of NE from neurons and less risk of reflex tachycardia that is seen with other alpha blockers |
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Term
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Definition
1. selective alpha 1 antagonist
2. closely related to prazosin but less potent
3. 1/2 life 12 hours so can be used once a day
4. used for treatment of HTN and BPH (mostly) |
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Term
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Definition
1. selective alpha-1 antagonist
2. 1/2 life 20 hrs. Can be used once daily
3. used for treatment of HTN and BPH |
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Term
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Definition
1. selective alpha-1 antagonist
2. 1/2 life 3-5 hours
3. Used for BPH |
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Term
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Definition
1. selective alpha-1a antagonist (alpha 1b is what controls vascular smooth muscle)
2. 1/2 life 5-10 hrs
3. metabolized by P450 system |
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Term
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Definition
1. selective Alpha 2 antagonist
2. blocks central A-2 receptors leading to inc. BP and HR
3. possible aphrodisiac properties
4. S/E: antidiuretic effects, CNS excitation, HTN, tachycardia, increased motor activity, nervousness, irritability, N/V
5. local injections into penile shaft to increase erections |
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Term
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Definition
1. prototype beta blocker
2. Non-selective (blocks both beta 1&2)
3. used for HTN, angina, arrhythmias, migraines, pheochromocytoma
4. has membrane stabilizing effect which enhances anti-arrhythmic properties (most beta blockers share this property)
5. C/I: shock, bradycardia, asthma, CHF
6. S/E: bradycardia, CHF, hypotension, heart block, insomnia, hallucinations, bronchospasms |
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Term
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Definition
1. non selective beta antagonist
2. used for angina and HTN
3. C/I: bradycardia, bronchial asthma, shock, heart block, MI
4. S/E: bradycardia, cardiac failure, conduction disturbances, arrhythmias, dizziness, bronchospas,, diarrhea, impotence, decreased libido, blurred vision |
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Term
|
Definition
1. Non-selective beta antagonist
2. used for HTN, ocular HTN (wide angle glaucoma)
3. C/I: asthma, COPD, bradycardia, heart failure
4. S/E: fatigue, bradycardia, dizziness, cold hands and feet |
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Term
|
Definition
1. non-selective beta antagonist with some sympathetic agonist activity
2. strong B2 agonist- vasodilation
3. not as much bronchoconstriction as with other beta blockers
4. Used for HTN
5. C/I: bradycardia, COPD, heart failure
6. S/E: fatigue, dizziness, diarrhea, cardiac failure |
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Term
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Definition
1. alpha 1, beta 1, and beta 2 antagonist
2. 7x more beta blockade than alpha blockade
3. used for HTN
4. C/I: asthma, cardiac failure, severe bradycardia
5. S/E: Postural hypotension, sweating, dizziness, N/V, nasal stuffiness, bradycardia, impotence |
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Term
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Definition
1. alpha 1, beta 1&2 antagonist
2. Has even higher beta to alpha blockade than labetalol
3. used for angina, heart failure (NYHA class II&III), and HTN
4. C/I: bronchospasm, emphysema, COPD, asthma, bradycardia, DM, hear failure (NYHA class IV), liver disease, pheochromocytoma
5. S/E: bronchospasm, diarrhea, dyspnea, fatigue, headaches, hypotension, peripheral edema, bradycardia, syncope |
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Term
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Definition
1. Beta 1 antagonist
2. used to treat HTN and angina pectoris
3. C/I: bradycardia, heart block, shock, MI
4. S/E: dizziness, bradycardia, nightmares, CHF, peripheral edema, bronchospasm, nausea, diarrhea |
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Term
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Definition
1. mostly beta 1 blockade but is also partial sympathetic agonist
2. used in reductionof HTN and to control Vent arrhythmias
3. not as much bronchoconstriction as non-selective beta blockers
4. less likely to cause bradycardia than other beta1 blockers d/t to intrinsic sympathomimetic activity
5. S/E: alopecia, dizziness, angina, fatigue, heart failure |
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Term
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Definition
1. beta 1 antagonist
2. used for afib/flutter, PSVT
3. C/I: bronchospasms, bradycardia, shock
4. S/E: AV block, cardiac arrest, hypotension, bradycardia
5. half-life only a few minutes |
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Term
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Definition
1. inhibits tyrosine hydroxylase
2. used for pheochromocytoma
3. C/I: hepatic disesae, parkinson's
4. S/E: anxiety, confusion, crystalluria, depression, parkinsonism, salivation |
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Term
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Definition
1. blocks catecholamine release from nerve terminal
2. used for Vtach and prophylaxis of VFib
3. S/E: hypotension, bradycardia |
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Term
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Definition
1. inhibits storage of catecholamines (and serotonin) in granules, leading to depletion
2. initial effects may cause transient release
3. Used for HTN, schizophrenia
4. C/I: mental depression, peptic ulcer, ulcerative colitis
5. S/E: vomiting, diarrhea, dry mouth, syncope, angina |
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Term
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Definition
| Symptoms of myocardial ischemia that occur when myocardial oxygen supply is insufficient to meet demand. |
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Term
| What are the symptoms of angina? |
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Definition
1. chest discomfort often described as heaviness, pressure, and squeezing.
2. symptoms last 1-5 mins
3. usually occurs with exertion |
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Term
| What is Prinzmetal's angina? |
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Definition
| chest discomfort caused by coronary vasospasm |
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Term
| alpha 2 receptors inhibit ________ by G protein interaction, causing ________. |
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Definition
| adenylate cyclase; hyperpolarization |
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Term
| alpha 1 stimulation triggers increased intracellular ______ release by activation of ___________, which is also G protein mediated |
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Definition
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