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Drugs and the Brain > Stimulants > Flashcards

Stimulants Flashcards

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1
Q

what are the two
categories of stimulants

A

psychomotor and psychotomimetic

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2
Q

what do psychomotor stimulant do?

A
  • 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
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3
Q

What does prolonged use of psychomotor stimulants results in?

A

neurotoxicity

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4
Q

what are the chemical properties of psychomotor stimulants?

A
  • small ring structures with a proximal amine group
  • similar to neurotransmitters like noradrenaline and dopamine
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5
Q

what pathways are associated with psychomotor stimulants?

A

noradranergic, dopaminergic and serotonergic

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6
Q

what is the amfetamine mode of action? (long)

A
  • 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
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7
Q

what are the beahvioural effects of amfetamine? (6)

A
  • Locomotor stimulator
  • Euphoria and excitement
  • Insomnia
  • Increased stamina
  • Anorexia
  • Raised BP and inhibition of gastric motility
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8
Q

what are the clinical uses for amfetamines?

A
  • 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
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9
Q

what does chronic use and dependence of amfetamines result in?

A
  • induce schizophrenia and psychosis
  • tolerance develops rapidly
  • dependence result of unpleasant after-effects and memory of euphoria
  • rodents self-administer until death
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10
Q

What neurotransmitter systems does cocaine incorporate?

A
  • acts similarly to amfetamine - noradrenergic, dopaminergic and serotonergic
  • free base vaporises at 90 degrees - can be smoked which is crack cocaine
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11
Q

what does chronic use and dependance of cocaine result in?

A
  • Toxic effects are common, mainly cardiovascular, can be acute or chronic
  • Strong psychological dependence (not addiction)
  • Foetal malformation if used in pregnancy
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12
Q

What is caffeine’s mode of action?

A
  • 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
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13
Q

What was the name of the psychomotor stimulant used frequently in WWII?

A
  • Pervitin – non-prescription brand of methamphetamine.
  • Hitler a heavy user – and the German, American, British and Japanese armies
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14
Q

what are psychotomimetic stimulants? overview

A
  • 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
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15
Q

what are the effects of LSD/Psilocybin/mescaline? (long)

A
  • 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
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16
Q

what are the pharmacological effects of LSD? (long)

A
  • 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
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17
Q

What are the pharmacological effects of mescaline and psilocybin?

A
  • 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
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18
Q

What are the adverse effects of LSD/psilocybin/mescaline?

A
  • bad trip
  • bad flashbacks
  • no physical withdrawal symptoms
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19
Q

What are the pharmacological effects of MDMA

A
  • changes in noradrenaline
  • changes in 5HT via action on 5HT transporter
  • at higher doses dopamine released
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20
Q

What are the adverse effects of MDMA?

A
  • sudden illness and death
  • Acute hyperthermia
  • Excess water intake
  • Heart failure
  • long term affects on memory
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21
Q

what is ketamine and phencyclidine?

A

Ketamine = dissociative anaesthetic agent used in veterinary practice and science
Phencyclidine = analogue of ketamine, less used
both produce euphoria and at higher doses - hallucinations

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22
Q

what is the Ketamine/phencyclidine mode of action?

A
  • block NMDA receptor and long duration of NMDA action
23
Q

what are the side effects of ketamine/phencyclidine?

A
  • long term use = paradoxical bladder defects
  • dangerous in overdose
24
Q

What are 4 examples of convulsants?

A

pentylenetetrazol, Penicillin, bicucilline, strychnine

25
Q

what is pentylenetetrazol used for?

A

Used to induce seizures

26
Q

What does pentylenetetrazol act on?

A

Its a GABAa receptor antagonist

27
Q

How is Penicillin used for its convulsant properties?

A

widely used as a seizure inducing agent to test anti-convulsives. Applied to cortical surface, doesn’t cross bloob-brain barrier

28
Q

What do Bicuculline and gabazine do?

A

They are GABAa receptor antagonists, used experimentally to block GABAa activity and induce seizures.

29
Q

What is Strychnine used for?

A

induces seizures by acting as a glycine antagonist within the spinal cord.

30
Q

Where does Strychnine come from?

A

It is an alkaloid form the seed of the Nux Vomica tree.

31
Q

What are convulsants generally used for?

A

To induce seizures or reduce central inhibition. No longer have any real medicinal use

32
Q

How do convulsants work?

A

They block activity of central inhibitory transmitters

33
Q

nicotine mode of action

A
  • 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
34
Q

what are the behavioural effects of nicotine?

A
  • inhibits spinal reflexes –> muscle relaxation
  • low nicotine doses cause central arousal
  • large doses cause sedation
  • excitation in the meso-limbic dopaminergic reward system
35
Q

chronic use and dependence in nicotine?

A
  • can get psychological and physical dependence
  • tolerance also
36
Q

What are the harmful effects of nicotine?

A
  • cough
  • cancer
  • coronary heart disease
  • death…
37
Q

What are the active ingredients in cannabinoids

A

Mainly THC
Also cannabidiol (CBD) and cannabinol

38
Q

What is the solubility in water of THC

A

0.0028mg/mL

39
Q

What are the pharmacological effects of cannabinoids on the CNS

A
  • relaxation
  • sharpened awareness
  • slowing of time
  • analgesia
  • anti-emetic
40
Q

What are the pharmacological effects of cannabinoids on the PNS

A
  • tachycardia
  • vasodilation
  • reduction in intraocular pressure
  • bronchodilation
41
Q

what happens in the exogenous cannabinoid system

A
  • 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
42
Q

What happens in the endogenous cannabinoid system?

A

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

43
Q

What receptor does the endocannabinoid system act through in the CNS

A

CB1

44
Q

What receptor does the endocannabinoid system act through in the PNS

A

CB2

45
Q

How is endocannabinoid system distributed?

A

it is NOT homogenously distributed

46
Q

Does the endocannabinoid system decrease excitatory or inhibitory release?

A

BOTH, hence its complexity

47
Q

What are newly developed CB receptor antagonist drugs targeting?

A

Obesity
tobacco dependence
drug addiction
alocoholism

48
Q

What are newly developed CB receptor agonist drugs targeting?

A
  • Galucoma
  • nausea
  • reducing weight loss
  • neuropathic pain
  • tics (tourette’s)
  • epilepsy
49
Q

What are all the psychomotor stimulants?

A

Amfetamine (and methamfetamine), cocaine, MDMA, caffeine

50
Q

How is cocaine metabolised?

A

Rapidly, in the liver

51
Q

What are examples of psychomimetic stimulants? (6)

A
  • LSD, psilocybin, mescaline, MDMA, ketamine and phencyclidine
52
Q

What does repeated use of psychomotor stimulants result in?

A

tolerance and dependence –> can affect cardiovascular system

53
Q

What dopaminergic pathways does cocaine use?

A

nigrostriatal and mesolimbic pathways

54
Q
A

Drugs and the Brain (9 decks)

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