Stimulants Flashcards
what are the two
categories of stimulants
psychomotor and psychotomimetic
what do psychomotor stimulant do?
- Induce euphoria, reduced sense of fatigue
- Increase motor output
- Act on central modulatory catecholaminergic pathways and other similar pathways
- peripheral as well as central actions
What does prolonged use of psychomotor stimulants results in?
neurotoxicity
what are the chemical properties of psychomotor stimulants?
- small ring structures with a proximal amine group
- similar to neurotransmitters like noradrenaline and dopamine
what pathways are associated with psychomotor stimulants?
noradranergic, dopaminergic and serotonergic
what is the amfetamine mode of action? (long)
- slows down transport of noradrenaline and dopamine, increasing concentration in the synapse and the terminal
- Amfetamine is also a monoamine oxidase inhibitor, which further increases cytosolic noradrenaline/dopamine
- increased conc. of these transmitters reverses action of NET and DAT
- as a result transmitters get pushed into synaptic cleft
what are the beahvioural effects of amfetamine? (6)
- Locomotor stimulator
- Euphoria and excitement
- Insomnia
- Increased stamina
- Anorexia
- Raised BP and inhibition of gastric motility
what are the clinical uses for amfetamines?
- Narcolepsy (Modafinil)
- ADHD (ritalin) - reasons they work are unkown. Atomoxetine a newer alternative
- Selective noradrenaline reuptake inhibitor (used in combo with methyphenidate) also used for ADHD
- Modafinil also used as a selective noradrenaline reuptake inhibitor, bad side effects
what does chronic use and dependence of amfetamines result in?
- induce schizophrenia and psychosis
- tolerance develops rapidly
- dependence result of unpleasant after-effects and memory of euphoria
- rodents self-administer until death
What neurotransmitter systems does cocaine incorporate?
- acts similarly to amfetamine - noradrenergic, dopaminergic and serotonergic
- free base vaporises at 90 degrees - can be smoked which is crack cocaine
what does chronic use and dependance of cocaine result in?
- Toxic effects are common, mainly cardiovascular, can be acute or chronic
- Strong psychological dependence (not addiction)
- Foetal malformation if used in pregnancy
What is caffeine’s mode of action?
- Inhibit central adenosine receptors
- Also inhibits phosphodiesterase enzyme, which increases local cAMP
- Mental functions improved by moderate doses, but impaired at higher doses
- not dependence-inducing, social dependence can occur
What was the name of the psychomotor stimulant used frequently in WWII?
- Pervitin – non-prescription brand of methamphetamine.
- Hitler a heavy user – and the German, American, British and Japanese armies
what are psychotomimetic stimulants? overview
- drugs capable of psychotic-like effects
- potential treatments for mental health
- Affect thought, perception and mood, no psychomotor stimulation or depression
- Autonomic side-effects low
- Little or no dependence liability
what are the effects of LSD/Psilocybin/mescaline? (long)
- Somatic – dizziness, weakness, etc
- Perceptual – altered shapes and colors, sharpened sense of hearing
- Psychic – alterations in mood, tension, distorted sense of time etc
- Psilocybin loosens up fixations on negative connections that can cause depression – at the right dose!
- only need one dose for weeks/months
what are the pharmacological effects of LSD? (long)
- potent partial agonist activity at 5HT-2A receptors within the cingulate cortex
- not fully understood, likely double action on the same system
- activates postsynaptic cells via 5-HT2a agonism in cingulate cortex – but slows raphe firing rate via 5-HT1a in raphe nuclei
- complex inhibition and activation happening at same time
What are the pharmacological effects of mescaline and psilocybin?
- Mescaline also acts on 5-HT2a
- Psilocybin metabolised to a compound active at several 5HT receptors therefore most clinical interest is in 5-HT2a action
- Effects are subjective so difficult to measure
What are the adverse effects of LSD/psilocybin/mescaline?
- bad trip
- bad flashbacks
- no physical withdrawal symptoms
What are the pharmacological effects of MDMA
- changes in noradrenaline
- changes in 5HT via action on 5HT transporter
- at higher doses dopamine released
What are the adverse effects of MDMA?
- sudden illness and death
- Acute hyperthermia
- Excess water intake
- Heart failure
- long term affects on memory
what is ketamine and phencyclidine?
Ketamine = dissociative anaesthetic agent used in veterinary practice and science
Phencyclidine = analogue of ketamine, less used
both produce euphoria and at higher doses - hallucinations
what is the Ketamine/phencyclidine mode of action?
- block NMDA receptor and long duration of NMDA action
what are the side effects of ketamine/phencyclidine?
- long term use = paradoxical bladder defects
- dangerous in overdose
What are 4 examples of convulsants?
pentylenetetrazol, Penicillin, bicucilline, strychnine
what is pentylenetetrazol used for?
Used to induce seizures
What does pentylenetetrazol act on?
Its a GABAa receptor antagonist
How is Penicillin used for its convulsant properties?
widely used as a seizure inducing agent to test anti-convulsives. Applied to cortical surface, doesn’t cross bloob-brain barrier
What do Bicuculline and gabazine do?
They are GABAa receptor antagonists, used experimentally to block GABAa activity and induce seizures.
What is Strychnine used for?
induces seizures by acting as a glycine antagonist within the spinal cord.
Where does Strychnine come from?
It is an alkaloid form the seed of the Nux Vomica tree.
What are convulsants generally used for?
To induce seizures or reduce central inhibition. No longer have any real medicinal use
How do convulsants work?
They block activity of central inhibitory transmitters
nicotine mode of action
- acts on nAChR’s, complex effects
- nAChR’s located pre and post synaptically, they enhance transmitter release and increase excitability
- nicotine activates receptors and induces desensitisation
- overall effect is a balance of the two
what are the behavioural effects of nicotine?
- inhibits spinal reflexes –> muscle relaxation
- low nicotine doses cause central arousal
- large doses cause sedation
- excitation in the meso-limbic dopaminergic reward system
chronic use and dependence in nicotine?
- can get psychological and physical dependence
- tolerance also
What are the harmful effects of nicotine?
- cough
- cancer
- coronary heart disease
- death…
What are the active ingredients in cannabinoids
Mainly THC
Also cannabidiol (CBD) and cannabinol
What is the solubility in water of THC
0.0028mg/mL
What are the pharmacological effects of cannabinoids on the CNS
- relaxation
- sharpened awareness
- slowing of time
- analgesia
- anti-emetic
What are the pharmacological effects of cannabinoids on the PNS
- tachycardia
- vasodilation
- reduction in intraocular pressure
- bronchodilation
what happens in the exogenous cannabinoid system
- THC binds to CB1 receoptor at dopamine synapse
- releases cAMP
- results in less Ca2+
- less depolarisation
- less GABA release, neuron is more excitable
- known as the exogenous cannabinoid system
What happens in the endogenous cannabinoid system?
The biosynthesis/inactivation of endocannabinoids
- rise in Ca2+ is key trigger
- 2-AG and anadamide synthesised from membrane lipids which are activated on demand
- not vesicular release
- post-synaptically produced, acts on presynaptic cells = retrograde
What receptor does the endocannabinoid system act through in the CNS
CB1
What receptor does the endocannabinoid system act through in the PNS
CB2
How is endocannabinoid system distributed?
it is NOT homogenously distributed
Does the endocannabinoid system decrease excitatory or inhibitory release?
BOTH, hence its complexity
What are newly developed CB receptor antagonist drugs targeting?
Obesity
tobacco dependence
drug addiction
alocoholism
What are newly developed CB receptor agonist drugs targeting?
- Galucoma
- nausea
- reducing weight loss
- neuropathic pain
- tics (tourette’s)
- epilepsy
What are all the psychomotor stimulants?
Amfetamine (and methamfetamine), cocaine, MDMA, caffeine
How is cocaine metabolised?
Rapidly, in the liver
What are examples of psychomimetic stimulants? (6)
- LSD, psilocybin, mescaline, MDMA, ketamine and phencyclidine
What does repeated use of psychomotor stimulants result in?
tolerance and dependence –> can affect cardiovascular system
What dopaminergic pathways does cocaine use?
nigrostriatal and mesolimbic pathways
