Pharm--Stimulants and Dependency Flashcards
Explain the mechanisms of action of drugs that are used to treat ADHD, and list the neurotransmitters
that are elevated in extracellular synapses by each drug.
adderall–amphetamine–causes monoamine release and inhibits MAO, risk of sudden heart attack, abuse, or death
methylphenidate–same as amphetamine, but with slightly less abuse potential
atomoxetine–selective NE reuptake inhibitor, side effect of orthostatic HTN, sexual dysfunction because of clonidine-like effect (decreases sympathetic outflow)
List drugs that are used to treat narcolepsy and explain their mechanism of action and the strategy for
their use.
modafinil–mechanism unclear, inhibits NET and DAT (NE and DA(dopamine) transporters) to increase their concentrations along with 5HT and glutamate while reducing GABA, used by military, low abuse and side effects
Describe the brain systems (targets) that are involved in the reinforcing effects of addictive stimulants
like amphetamine and cocaine
the main target is the nuccleus accumbens, which when inhibited produces pleasure
neurons of Nuc Accu are GABA-ergic with D2-Receptors, inhibition of them causes pleasure
dopaminergic neurons project from vental tegmental area to nuc accu
Explore the underlying changes that occur in the brain following the prolonged use of drugs like
amphetamine; include in your discussion changes in the storage levels of catecholamines and changes in
receptor density and sensitivity.
amphetamine causes chronic overstimulation of D2 GABA ergic neurons in nuc accu, D2 receptors become desensitized and down reg’d while DA is depleted from the VTA neurons, the GABA ergic neurons synth more cAMP
opiates deserve special notice for their ability to both cause release of dopamine from VTA neurons and to directly inhibit the nuc accu; thus they are extremely addictive
Identify the sites of action of opiates in the VTA and NAc. Explain how opiates elevate extracellular
dopamine.
opiates act on Mu opiod receptors on the GABAergic neurons of the nuc accu to depolarize them via GCPR activity
they also act on mu opiod receptors in VTA neurons to cause DA release
List the major side effects of stimulants and other addictive drugs
the monoamine transporter blocking stimulants can cause clonidine-like side effects (orthostatic HTN, sexual dysfunction) in addition to euphoria (nuc accu) and anorexia
What part of the brain contains NE?
locus coeruleus
what part of the brain contains 5HT?
raphe nucleus
what part of the brain contains dopamine?
SNr and ventral tegmental area (VTA)
how do stimulants alter catecholamine levels in the brain?
they raise all catecholamine levels
what does cocaine do?
block monoamine reuptake protein
what do amphetamines do?
they cause release of monoamines
what’s methylphenidate’s mechanism ?
works like cocaine
what’s atomoxetine’s mechanism and side effects?
NE-specific reuptake inhinbitor
erectile dysfunction and dry vag, orthostatic tachycardia
what’s modafinil used for, mechanism, and side effects?
used as a wakefulness agent in narcolepsy
inhibits NE and dopamine transporters, increases serotonin and glutamate, and decreases GABA
low abuse and side effect profile
