CNS Stimulants Flashcards
Psychomotor stimulants
Amphetamines and related drugs
Methylxanthines
Nicotine
Psychotimimetic Agents (Hallucinogens)
Cannabinoids
Ketamine
Psychomotor stimulants have a marked effect on mental function and behavior such as:
Produce excitement and euphoria
Reduce sensation of fatigue
Increase in motor activity
Amphetamines include:
amphetamine
dextroamphetamine
methylphenidate
dexmethylphenidate
MOA of psychomotor stimulants:
Acts by releasing monoamines, primarily NE and DA from intracellular vesicular storage sites
Block or reverse the direction of transporters that mediate the reuptake of NE, DA, 5-HT
Act on LOCUS CERULEUS NEURONS IN THE PONS:
- ASCEND adrenergic projections throughout HYPOTHALAMUS+THALAMUS, Cerebral cortex, spinal cord
- DESCEND adrenergic projections to the medulla and spinal cord
Act on midbrain DA neurons associated with the reward pathway
With long term use, amphetamines are neurotoxic and can lead to ________ of amine-containing nerve terminals and eventually _______ can occur.
With long term use, amphetamines are neurotoxic and can lead to DEGENERATION of amine-containing nerve terminals and eventually CELL DEATH can occur.
Due to a combined action of NE and DA, amphetamine stimulates the entire cerebrospinal axis, cortex, brain stem and medulla leading to:
Increased alertness
Decreased fatigue
Depressed appetite
Insomnia
Locomotor stimulation
Tolerance and Dependence of Amphetamines:
RAPID tolerance and dependence to EUPHORIC and ANOREXIC actions
SLOW tolerance and dependence to LOCOMOTOR STIMULATION
No w/d symptoms compared to opioids
Methylphenidate acts by:
blocking DA and NE transporters leading to increase concentrations of amines in synaptic space.
MOA of methylxanthines:
Inhibition of phosphodiesterase leading to increases in cellular cyclic AMP and cyclic GMP concentrations.
Blockade of presynaptic adenosine receptors on dopaminergic and adrenergic terminals.
Blockade of adenosine receptors on cortical neurons.
Caffeine is used in combination with other drugs for the
treatment of the following disorders:
Musculoskeletal Disorders: Caffeine plus aspirin
Dysmenorrhea: Caffeine plus acetaminophen plus pyrilamine
Migraine and headache: Caffeine plus butalbital plus codeine;
Caffeine plus ergotamine or dihydroergotamine
Pain Management: Caffeine plus dihydrocodeine; caffeine plus
acetaminophen plus dihydrocodeine; caffeine plus aspirin
plus acetaminophen
Nicotine MOA
Nicotine activates nicotinic ACh receptors that are located centrally, peripherally and at the neuromuscular junction.
Cholinergic neurons leaving the laterodorsal tegmental area
(near the border of the midbrain and pons) activate muscarinic
and nicotinic receptors on dopaminergic neurons in the
ventral tegmental area.
Activation of the nicotinic receptors stimulates the dopaminergic reward system.
TorF: Activation of presynaptic nicotinic receptors on dopaminergic
terminal facilitates the release of dopamine
True
TorF: High doses of nicotine produce weak analgesia and low doses causes tremors leading to convulsions.
False Low doses produce weak analgesia; high doses causes
tremors leading to convulsions.
Pharmacological actions of nicotine on the CNS:
Stimulant action on respiration:
Large doses via a direct action the medulla
Small doses via an indirect action by reflex stimulation of chemoreceptors in the carotid and aortic bodies
Induces vomiting by both central and peripheral actions
Central:
Central: due to stimulation of the chemoreceptor trigger
zone in the area postrema of the medulla oblongata
Peripheral:
due to activation of vagal and spinal afferent nerves that form part of the sensory input of reflex pathways involved in the act of vomiting.
Nicotine action of PNS
Transient stimulation followed by a more persistent
depression of all autonomic ganglia
Low doses stimulate ganglion cells directly and may facilitate impulse transmission.
High doses cause initial stimulation which is followed quickly by blockade of transmission.
Effect of Nicotine on CVS
Increase in blood pressure and heart rate:
Due to stimulation of the sympathetic ganglia and
adrenal medulla
Nicotine-induced vasoconstriction can decrease coronary
blood flow.
Psychotomimetics or hallucinogens mainly affect:
Thought patterns and perception: tends to become distorted and dream-like (rather than being sharpened or dulled).
Mood: produce changes in mood that is more complex
than a simple shift in the direction of euphoria or depression.
TorF: Psychotomimetic agents do not cause dependence
True. Psychotomimetic agents do not cause dependence even
though the psychological actions overlap those of the highly addictive psychostimulants (such as cocaine and amphetamines).
Cannabinoids MOA:
Act on G protein-coupled receptors:.
CB1-receptors are mainly found in the CNS
CB2-receptors are found in the periphery
CB1-receptors are localized presynaptically where
they inhibit neurotransmitter release. They are concentrated in the hippocampus, cerebellum, hypothalamus, substantia nigra and prefrontal cortex.
CB2-receptors are located mainly in lymphoid tissue (spleen,
tonsils, thymus and circulating lymphocytes and tissue mast cells) and microglia-immune cells of the CNS.
Endogenous ligands for CB receptors are known as
endocannabinoids:
Anandamide
2-arachidonoyl glycerol (2-AG)
The pharmacological effects of THC varies with:
Dose Route of administration Experience of the user Vulnerability to psychoactive effects Setting of use
