CNS Stimulants Flashcards
three categories of drug
- convulsants & respiratory stimulants
- Psychotomimetric drugs
- Psychomotor stimulants
Misuse of drugs act
A - deemed most dangerous
B
C - Deemed to have least capacity for harm
- act demands more lenient punishment
Convulsants & respiratory stimulants
– Doxapram
– short-acting respiratory stimulant used in respiratory failure, e.g.
• post-operative respiratory depression
• acute respiratory failure • neonatal apnoea
Psychotomimetic drugs - relating to or denoting drugs which are capable of producing an effect on the mind similar to a psychotic state
– Hallucinogens (LSD, psilocybin, mescaline, MDMA)
– Dissociative anaesthetics (ketamine, PCP)
– Cannabis
Psychomotor stimulants
– Amphetamines, khat, cocaine, nicotine
– Methylxanthines (caffeine, theophylline)
Hallucinogens
Drugs that act on 5-HT receptors and transporters: – LSD (D-lysergic acid diethylamine) – Psilocybin – Mescaline – MDMA (Ecstasy)
where does serotonin work in the brain
Locus coeruleus
• (sensory signals) Raphe nuclei
• (sleep, wakefulness and mood)
main effects of hallucinogens
– alter perception of sights and sounds
– hallucinations (visual, auditory, tactile or olfactory)
– sounds can be perceived as visions
– thought processes illogical and disconnected
‘Bad trip‘
– hallucinations can take on a menacing quality
– may be accompanied by paranoid delusions
tolerance and risks of halluncinogens
Tolerance
– develops quickly (plus cross-talk between drugs)
There is no physical withdrawal syndrome
Risks
– Psychological effects (“flashbacks”, psychosis)
– Risk of injury and accidental death whilst intoxicated
– Poisoning due to mistaken identity
– Adrenergic effects with LSD
– GI effects with psilocybin
Dissociative anaesthetics
Phencyclidine (PCP, ‘Angel Dust’)
Ketamine
Both are NMDA receptor antagonists
tolerance to dissociative anaesthetics
Tolerance
– Rapid over regular, repeated doses
Dependence (physical & psychological) and withdrawal
syndromes with PCP
Risks
– Accidents/loss of control/automatic behaviour
– PCP: hyperthermia, convulsions
– Ketamine: overdose with heart attack/respiratory failure (rare)
Cannabis (Cannabis sativa, indica)
Tetrahydrocannabinol (THC) and 11-hydroxy-THC
Psychomotor Stimulants - “drugs that act on the central nervous system (CNS) to increase alertness, elevate mood, and produce a sense of well-being”
Amphetamine, dextroamphetamine and methylamphetamine
main effects of Psychomotor Stimulants
– Locomotor stimulation
– Euphoria and excitement
– Insomnia
– Anorexia (diminishes with continued use) – Stereotypic behavior (chronic use)
Action of Amphetamine on behaviour
probably due to the release of dopamine rather than noradrenaline
– Subjects become confident, hyperactive and talkative
– Sex drive is said to be enhanced
– Fatigue (both physical and mental) is reduced
– Does not enhance mental performance, just ability to concentrate for longer
Mode of Action of Amphetamines
Competitive inhibitors of monoamine uptake
Displace monoamines (i.e. noradrenaline, dopamine) from vesicles into cytoplasm
Inhibit MAO at high concentrations
Cause NET to work in “reverse”
what are the dopamine pathways in the brain
Nigrostriatal
• (motor control) Mesolimbic & Mesocortical
• (behavioural effects) Tuberohypophyseal system
• (endocrine control)
Simplified noradrenaline pathways in the brain
Locus coeruleus
• (wakefulness, alterness) Medulla/hypothalamus
• (blood pressure regulation)
Amphetamines: Tolerance, Dependence, Risks
Rapid tolerance to euphoric and anorexic effects, slowly for other effects.
Moderate dependence potential due euphoria it produces.
“Amphetamine psychosis”
– If taken repeatedly over a few days
– Almost indistinguishable from an acute schizophrenic attack
– Stereotypic behaviour
– After cessation, usually a period of deep sleep
• After which subject may feel lethargic, depressed, anxious & often very
hungry
risks of an amphetamines
– Vascular accidents (e.g. tachycardias, arrhythmias, ↑BP) – Cerebral convulsions & coma – Excitation syndrome (hyperthermia/tachycardia) – Anorexia – Chronic paranoid psychosis – Cognitive impairment – Personality/mood – Chronic paranoid psychosis
Lisdexamfetamine mesylate - like amphetamine
• Attention-deficit hyperactivity disorder
Phentermine and diethylpropion - like amphetamine
- Weight loss
* Prescription-only, not on NHS (i.e. private only)
Khat - Psychomotor Stimulants
Contains cathinone, an amphetamine-like stimulant
Cocaine - Erythroxylum Coca
Potent inhibitor of catecholamine uptake into nerve terminals
– (especially dopamine)
Effects resemble that of amphetamine:
– Euphoria (related to↓dopamine and 5-HT re uptake)
– Alertness and wakefulness
– Increased confidence and strength
– Heighted sexual feelings
– Indifference to concerns/cares
Readily absorbed by many routes
– Nasal administration damages the nasal mucosa and septum
– Free-base form (‘crack’) can be smoked
Cocaine: Tolerance, Dependence
Tolerance to occurs rapidly.
Physical dependence mild. Strong psychological
dependence occurs. Risks (acute)
– Cardiovascular (↑BP, tachycardia, ventricular fibrillation, heart attack, respiratory arrest, stroke)
– Muscle spasms, tremor
– Hyperthermia
– Seizures, headaches, excited delirium
risks of cocaine
– Heart attacks due to furring of coronary arteries
– Malnutrition & weight loss
– Decreased libido and impotence
– Personality/mood
• (e.g. anxiety, depression, repetitive behaviours, delusions, psychosis)
– “Toxic syndrome”
• similar to acute paranoid schizophrenia
Methylxanthines
Various beverages (e.g. tea, coffee, cocoa) contain methylxanthines which have mild CNS stimulant effects
Main two are caffeine & theophylline – CNS stimulants
– Diuretics
– Cardiac muscle stimulants
– Smooth muscle relaxants (especially bronchial)
Main psychological effects are to reduce fatigue & improve mental performance without any euphoria
Methylxanthines mechanism of action
– Inhibit cAMP/cGMP phosphodiesterases
– Block purine receptors
• adenosine receptors of the A1 and A2 subtype
– Diuresis possibly due to vasodilation of the afferent glomerular arterioles causing ↑ GFR
Tolerance and habituation develop to a small extent Few clinical uses for caffeine but theophylline can be
used as a bronchodilator in severe asthma attacks
Eugeroics
Not 100% in the “psychostimulant” category, but have some commonalities and prone to abuse (“smart drugs”)
Modafinil
• Mechanism not 100% clear, but has some activity as a DA reuptake inhibitor
Solriamfetol
• NA and DA reuptake inhibitor
Pitolisant
• H3 receptor antagonist
