Lecture 7: Indirect-acting Sympathomimetics Flashcards
Indirect-acting sympathomimetics
-promote release of NE (dopamine)
-reverse action of plasma membrane transporter (NET and DAT)
types of indirect-acting sympathomimetics
-amphetamine
-pseudoephedrine
-ephedrine
-tyramine
indirect sympathomimetic uses
-amphetamines: ADHD, narcolepsy, anorexiant
-others: nasal congestant
Structures
structures
Amphetamine use
-narcolepsy
-ADHD
-also used as appetite suppressant
Amphetamine problems
-anorexia
-poor growth
-sleep disturbances
-jitteriness
Toxic dose of Amphetamine
-INcrease BP, HR via NE signaling
-potential for stroke, arrhythmia, MI, sudden death
-agitation, confusion, addiction
Amphetamine also releases
-dopamine
=CNS effects
Phentermine/Topiramate
-weight loss
-Phen: sympathomimetic
-Topir: antiepileptic
-avoid: HTN, heart disease, pregnancy (birth defects)
- Ephedrine and + Pseudoephedrine
-indirect sympathomimetics
-alkaloid obtained from stems of ephedra
-also found in mahuand
D–Ephedrine structure
-desired R config at B-OH and S config at a carbon
-direct a and B agonist activity at receptors
L-+-pseudoephedrine
-SS diasteromer
-S config of B-OH
-REDUCES agonist activity
-major mech is via reversal of transporter
Pseudoephedrine use
-nasal congestion
Ephedrine use
-DIRECT a B effects
-banned as weight loss supplement bc BP, stroke, death
Ephedra
-combo of ephedrine and pseudoephedrine enatiomers
Problems with pseudo/ephedrine
-increase BP
-increase HR
-via NE signaling from SNS
Pseudo/ephedrine warning
-do not use if taking MAO-inhibitor
-can be used to make meth
Indirect sympathomimetics vs NE and Epi
-indirect are ORALLY active
-due to methyl substitution that blocks oxidation by MAO
MAO inhibitors
-indirect-acting sympathomimetic
-decrease breakdown of tyramine
=bolus release of NE
-could lead to HTN crisis
MAO inhibitor medications
-phenelzine (antidepressant)
-selegiline
-
Tyramine
-indirect sympathomimetic in meats and cheese
-digested by MAO
other indirect sympathomimetics
-amphetamine
-methylphenidate
-pseudoephridrine
NET blockers
-norepineephrine reuptake inhibitors
-cocaine, methylphenidate
-tricyclic antidepressants
Cocaine action
-block NET and DAT
-decrease uptake
-enhance NE signaling by keeping more transmitter in synaptic cleft
Cocaine clinical use
-local anesthetic
-sodium channel blocker
-nasal mucosa and vasoconstriction
Cocaine side effects
-increase BP and HR
-potential for stroke, MI, death
-euphoria, alertness, arrousal, addiction
Methylphenidate
-NET and DAT inhibitor
-riatlin
methylphenidate action
-block NE and DA reuptake transporters from transporting monoamines from synaptic cleft back to pre-synaptic terminal
=enhance NE and DA signaling
Methylphenidate use
-ADHD
-narcolepsy
Methylphenidate problems
-similar to amphetamine
-priapism (prolonged erection)
-addictive potential via enhanced DA signaling
Atomoxetine action
-NET inhibitor
-enhance NE levels
Atomoxetine clinical use
-ADHD
-not controlled, not a stimulant
Atomoxetine problems
-suicide
-priapism
-take longer/maybe not as effective as stimulants
Non-stimulants for ADHD
-guanfacine (a2 agonist)
-clonidine (a2 agonist)
-atomoxetine (NET inhibitor)
Stimulants for ADHD
-amphetamine
-methylphenidate
