Adrenergic Receptors as Therapeutic Targets: Neurologic Implications Flashcards
Direct acting sympathomimetics
Analogs of EPI or NE that are agonists at alpha or beta adrenergic recpeotra
Indirect acting sympathomimetics
Mimic activation of symp nervous systme by mech other than direct receptor activation
Cocaine, amphetamine, tricyclic antidepressant mechs
Block NET and other monoamine transports
amphetamines also release NE from presynaptic nerve terminals
TCA mechanism
Inhibit NET leading to an increase of NE in the synaptic cleft
Results in improvmenet of depressive symtosm
Tricyclic AD facts and one example
Use has decreased signifcantly
Amitriptyline
Can also be used to tx neuropathic pain
Side effects of TCA
Sedation (antihistamine) Dry mouth (anticholinergic) Orthostatic hypotension (alpha 1 blockers) Arrythmias (block cardaic Na channels)
Dose response curve of TCAs
Small increases in dose can increase likelihood of toxicity
Cocaine mech
Inhibits NET
Also blocks the DAT SERT
Actions at DAT responsible for eurphoria
Cocaine therapeutic use
Limited use a local anesthetic and vasoconstricotr in specialized surgical procedures
Anesthetic action due to ability to block Na channels, NOT because of trnasporter effects
Cocaine toxicity- CNS
Anorexia Euphoria Agitation Hyperthermia Seizures
Cocaine VC
Hypertension
Coronary vasoconstriction
Arrythmias
MI
Pharmacodyanmis of cocaine
More rapid into circulation means faster onset of action and greater and faster effects
Amphetamine mech
Block NET and disruption of vesicular stoarge of NE resulting in efflux of NET throuh the NET
ALso blocks the DAT SET
Blockade of DAT responsible for euphoria and addictive properties
Therapeutic uses of amphetamines
ADHD
Narcolepsy
Appetite suppression
Amph in ADHD
Stimulation of post-synaptic alpha 2A-ARs in the prefrontal cortex
All approved ADHD meds increase catecholamine transmission in the prefrontal cortex
If overtreated with amphetamine
Misguided attention and mental inflexibility
Amph contraindictaions
Hypertension BPH Ischemic heart dz Glaucoma Hyperthyroidism
Amph drug interactions
Tricyclic antidepressatns
MAO-inhibitors
OTC cold meds
Toxicity of ampth
Similar to cocaine but longer duration
Ventriclular arrythmias, hyperthermia and tension, MI
Clonidine
Stimulates alpha 2 receptors in preforontal cortex to improve ADHD
Stimulates alpha 2 receptors in NTS to decrease sympathetic outflow decreasing peripheral vascular esistance
CLinical uses of clonidine
Hypertension ADHD Withdrawl Neuropathic pain Tourette's
Side effects of clonidine
Drowsiness or xerostomia
MAO inhibitors
Inhibit breakdown of NE
MAO-A vs. B
A - breaks down NE, SERT, and DA
MAO-B breaks down DA…at high contrations in synapses in striatum
Selegilin
Selective MAO-B inhibitor used in parkinsons dz
Tyramine
In certain foods and wine
If used with MAOIs then can cause a hypertensive crisis
