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23 Cards in this Set
- Front
- Back
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CV effects of DOPAMINE @ low concentrations
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-@ low concentrations, activates D1 receptors in renal, mesenteric, and coronary beds
-inc cAMP and causing vasodilation -inc GFR, renal blood flow, Na+ excretion can be used in low cardiac output states with impaired renal function |
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CV effects of DOPAMINE @ high concentrations
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-at higher concentrations, activates cardiac Beta1 Rs causing positive inotropic effects
-at higher concentrations, activates alpha1 Rs causing vasoconstriction |
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CV effects of FENDOLOPAM
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-has high affinity for D1 and alpha2 Rs
-no affinity for alpha1 and beta Rs -dilates same vascular beds as Dopamine -used particularly in hypotensive emergencies as reduces BP rapidly while improving renal function -given IV and short t/2 -tx malignant HTN -derivative of Dopamine |
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Indirect Acting Amines
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-INDIRECT ACTING SYMPATHOMIMETICS ACT MAINLY BY PROMOTING NE RELEASE FROM NERVE TERMINALS
-these amines are all SUBSTRATES FOR NEURONAL UPTAKE |
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Indirect acting agents produce tachyphylaxis. What is this? Why does it occur?
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-same dose given repeatedly over short period of time has reduced effects
-non-exocytotic release |
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Indirect acting amines enter nerve thru reuptake pump and thru diffusion.
-Displace NE from vesicles |
-Displace NE
--leaves nerve on reuptake pump --and is partially deaminated by MAO -amphetamine is lipophilic and readily crosses membrane -xMAO... cannot deaminate NE |
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MAO inhibitors and Indirect-Acting Amines
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-MAO inhibitors allow more NE to accumulate in the nerve terminal
-thus indirect acting amines have more NE to displace - hence their actions are potentiated |
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MAO inhibitors and INdirect - Acting AMines
TYRAMINE |
-some indirect acting amines are present in certain foods (e.g. TYRAMINE) and are normally deaminated by hepatic and neuronal MAO
-hence MAO inhibitors increase their bioavailablility further potentiating their actions |
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MAO Inhibitors and Indirect-Acting Amines
What is the effect you would then be most concerned about? |
When displacing NE in large amounts, then raised BP
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What happens when patients are on MAO inhibitors, then eat foods or drink wine containing TYRAMINE?
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1. More of the TYRAMINE gets past the liver.
2. There is also more NE available for release within the nerve terminal 3. As a result, TYRAMINE releases an increased amount of NE 4. The important effect of this is an abrupt increase in BP 5. This often causes headache and even a CNS bleed. 6. To manage the increase in BP, we need to give an alpha- blocker (e.g. LABETOLOL or PHENTOLAMINE). |
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Clinical Uses of Indirect-Acting Amines
AMPHETAMINE |
-indirect-acting sympathomimetic
-causes mood elevation and decreased perception of fatigue (tx ADD or narcolepsy) -toxicity: causes psychological tolerance/dependence --tremor, irritability, insomnia, aggressiveness, anxiety, panic, suicidal ideation, etc -cardiovascular arrythmias, hypertension or hypotension, angina -with chronic abuse, picture like paranoid-schizophrenia -treatment of overdosage: --in hypertension, NITROPRUSSIDE OR ALPHA-AR ANTAGONIST --for CNS effects: sedative hypnotic drugs -therapeutic use (extremely limited now) --narcoplepsy (deposit of neurotransmitter in the brain) --ADHD --appetite suppression - thus was used for Obesity |
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Clinical Uses of Indirect-Acting Amines
METHYLPHENIDATE (RITALIN) |
-mild CNS stimulant, chemically related to amphetamine
-effects more marked on mental than motor activities -general pharmacological profile similar to amphetamine -major therapeutic uses: --narcolepsy --ADHD |
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PRESYNAPTIC ADRENERGIC PHARMACOLOGY
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PRESYNAPTIC ADRENERGIC PHARMACOLOGY
modulation of synthesis |
-synthesis can be inhibited by tyrosine hydroxylase step - not important clinically - rate limiting step
-can increase synthesis by supplying LEVODOPA- important use in Parkinsonism -false substrates can enter pathway at decarboxylation step (e.g. ALPHA-METHYLDOPA) results in formation of false neurotransmitter (e.g. ALPHA-METHYL-NE) |
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PRESYNAPTIC ADRENERGIC PHARMACOLOGY
the vesicular transport is irreversibly inhibited by... |
-RESERPINE
-early naturally occuring product -tx mild/mod HTN |
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Consequences of Inhibition of Vesicular Transport
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-when vesicular transport is inhibited, NE, DOPAMINE, and 5HT are exposed to deamination by MAO
-as a result, their levels fall in peripheral adrenergic nerves and in neurons in the CNS containing NE, DOPAMINE, AND 5HT |
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Because of a depletion of NE in adrenergic nerves there is a picture of PNS dominance with...
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-a fall in BP
-nasal stuffiness -and diarrhea |
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Because of the central depletion of amines, patients may complain of ...
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-depression (one of the findings leading to the Amine Hypothesis of Depression, due to depletion of NE and/or 5HT in CNS)
-Parkinsonism -Galactorrhea --due to depletion of DOPAMINE |
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Agent affecting NE release directly
Adrenergic Neuron Blockers |
-first, must enter neuron on neuronal transporter (results in possible interactions at transporter)
-then inhibits exocytotic release of NE (prolly thru LA action) -become obsolete in therapy because of unwanted side effects |
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Agents affecting NE release through presynaptic actions
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1. Following its release, NE activates presynaptic alpha2 Rs causing a reduction in NE release
2. Drugs that antagonize NE at alpha2 Rs increase NE release 3. A number of endogenous compounds can alter NE release through activation of other presynaptic receptors |
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Neuronal uptake is blocked by
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1. COCAINE
2. tricyclic antidepressants (e.g. IMPRAMINE) 3. newer antidepressants (e.g. the SNRIs DULOXETINE) 4. adrenergic neuron blockers -marked inc BP...causes ischemia |
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Effect of COCAINE on Responses
@ NE and SNS stimulation |
-responses will be POTENTITATED resulting in increased BP and HR
-if taken in overdose, can cause sev MI, heart attack or CNS bleed |
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Effect of COCAINE on Responses
Drugs that act by displacing NE from vesicles (the Indirect-Acting Sympathomimetic Amines)... |
-their action will be IMPAIRED because they cannot get to their site of action
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