CNS stimulants Flashcards
What are the 3 main categories of harm from drugs?
Physical harm;
- Acute vs chronic risks
- Route of administration (both primary and secondary risk)
Dependence;
- Intensity of pleasure (“rush”, “high”)
- Tolerance, craving, withdrawal
- Physical vs psychological dependence
Social harms
What is the UK misuse of drugs act?
It classifies controlled drugs into 3 classes;
Class A;
- Deemed “most dangerous”
- Carry the harshest punishments
Class B
Class C;
- Deemed to have “least capacity for harm”
- Act demands more lenient punishment
What are the types of CNS stimulants we have ?
Convulsants & respiratory stimulants;
- Doxapram
Psychotomimetic drugs;
- Hallucinogens (LSD, psilocybin, mesacaline, MDMA)
- Dissociative anaesthetics (ketamine, PCP)
- Cannabis
Psychomotor stimulants;
- Amphetamines, khat, cocaine, nicotine
- Methylxanthines (caffeine, theophylline)
What are some features of Convulsants and Respiratory Stimulants ?
Convulsants and Respiratory Stimulants
A diverse group of drugs that have little clinical use
Doxapram;
- Short acting respiratory stimulant used in respiratory failure, e.g;
- Post-operative respiratory depression
- Acute respiratory failure
- Neonatal apnoea
What are the features of Psychotomimetic drugs?
Psychotomimetic drugs
Relating to or denoting drugs which are capable of producing an effect on the mind similar to a psychotic state
Hallucinogens !
Drugs that after on 5HT receptors and transporters;
- LSD (D-lysergic acid diethylamine)
- Psiolocybin (magic mushrooms)
- Mescaline
- MDMA (Ecstasy)
Where do serotonin pathways in the brain go?
5-HT was identified as a neurotransmitter in the serotonin pathway thanks to LSD
Locus coeruleus - Sensory signals
Raphe nuclei - Sleep, wakefulness and mood
What are the pharmacological effects of Hallucinogens ?
The main effect are on mental processes;
- 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 menacing quality
- may be accompanied by paranoid delusions
‘Flashbacks’
- can be reported weeks or months later
Some say due to environment, some say due to mental health issues etc
What is Tolerance, Dependence and Risks associated with Hallucinogens ?
Tolerance;
- develops quickly (plus cross-talk between drugs)
There is no physical withdraw syndrome;
- Psychological effects (“flashbacks”, psychosis)
Risks;
- Risk of injury and accidental death while intoxicated
- Poisoning due to mistaken identity
- Adrenergic effects with LSD (can cause cardio risk as well)
- GI effects with psilocybin
Not drug itself, due to behaviour when taking to or taking something else that you thought was LSD
What are the features of Dissociative anaesthetics ?
Phencyclidine (PCP, ‘Angel Dust’)
- synthesised as a possible i.v general anaesthetic
- found to produce disorientation and hallucinations
Ketamine;
- used for induction and maintenance of anaesthesia
Effects resemble those of other psychotomimetic drugs;
- also an analgesic
- causes stereotyped motor behaviour like amphetamine
- can give a ‘bad trip’ as LSD
Both are NMDA receptor antagonists (similar effects but different mechanisms)
What is the Tolerance, Dependence and Risks involved with Dissociative anaesthetics ?
Tolerance;
- Rapid over regular, repeated doses
Dependence (physical & psychological) and withdrawal syndromes with PCP
Risks;
- Accidents / Loss of control / Autonomic behaviour
- PCP: Hyperthermia, convulsions
- Ketamine: Overdose with heart attack / respiratory failure (rare)
What is another big Psychotomimetic drug?
Cannabis ! (THC)
What are some Psychomotor stimulants and their features ?
Psychomotor stimulants;
“drugs that act on the CNS to increase alter ness, elevate mood, and produce a sense of well being”
Amphetamine, dextroamphetamine and methylamphetamine (crystal meth)
- Very similar chemical and pharmacological properties
Main effects are;
- Locomotor stimulations
- Euphoria and excitement
- Insomnia
- Anorexia (diminishes with continued use)
- Stereotypic behaviours (chronic use)
Methylphenidate, 3,4-methylenedioxymethamphetamine (MDMA)
- Chemically related, but considered separately
What are the actions of Amphetamine ?
Behavioural effects portably due to the release of dopamine rather than noradrenaline
- Subjects becomes 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
What is the mode of Action of Amphetamines?
- Competitive inhibitors of monamine uptake
- Displace monoamines (i.e noradrenaline, dopamine) from vesicles into cytoplasm
- Inhibits MAO at high concentrations
- Cause NET to work in “reverse”
Displace monoamine and catecholamine
NET - norepinephrine transport - usually takes back into cells to get packaged into vesicles but acts as pump to push into synaptic region and prevent reuptake
What the 3 simplified dopamine pathways in the Brain?
Nigrostiatal;
- Motor control
Mesolimibc & mesocortiyal;
- Behaviours effects
Tuberohypophyseal system
- Endocrine control
If target dopamine affect all of these pathways
High uses of amphetamine can lead to schizophrenia states in brain
What the 2 simplified noradrenaline pathways in the Brain?
Locus coeruleus;
- Wakefulness, alterness
Medulla / hypothalamus;
- Blood pressure regulation
What is the Tolerance, Dependence and Risks involved with Amphetamines ?
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;
- Vascular accidents (e.g tachycardias, arrhythmias, increased BP)
- Cerebral convulsions & coma
- Excitation syndrome (hyperthermia / tachycardia)
- Anorexia
- Chronic paranoid psychosis
- Cognitive impairment
- Personality / mood
- Chronic paranoid psychosis
What are the clinical uses of amphetamine (or amphetamine like) drugs?
Clinical uses of amphetamine (or amphetamine like) drugs;
Lisdexamfetamine mesylate;
- ADHD (changes peoples ability to focus)
Phentermine and diethylpropion;
- Weight loss
- Prescription only, not on NHS (i.e private only)
What are some Psychomotor Stimulants ?
Psychomotor Stimulants;
- Khat (contains cathinone, an amphetamine like stimulant)
- Nicotine
- Cocaine
What are the features of Cocaine?
Cocaine leaves of South American shrub, Erythroxylum Coca
Potent inhibitor of catecholamine take into nerve terminals - especially dopamine
Effects resemble that of amphetamine:
- Euphoria (related to decreased dopamine and 5-HT reuptake)
- Alterness and wakefullness
- Increased confidence and strength
- Heightened 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
What is the Tolerance, Dependence and Risks involved with Cocaine ?
Tolerance to occurs rapidly
Physical dependence mild but a strong psychological dependence occurs
Risks (acute);
- Cardiovascular (BP increases, tachycardia, ventricular fibrillation, heart attack, respiratory arrest, stroke)
- Muscle spasms, tremor
- Hyperthermia
- Seizures, headaches, excited delirium
Risks (chronic);
- 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)
What are the features of Methyxanthines ?
Various beverages (e.g tea, coffee, cocoa) contain methyxanthines which have mild CNS stimulant effects = STARBUCKS!
Main two are caffeine & theophylline
- CNS stimulants
- Diuretics
- Cardiac muscle stimulants
- Smooth muscle relaxants (especially bronchial - use in airway dilation)
Main psychological effects are to reduce fatigue and improve mental performance without any euphoria
What is the mechanism of action of Methylxanthines, their tolerance, habituation and clinical uses?
Methylxanthines
Mechanism of action;
- Inhibit cAMP / cGMP phosphodiesterase
- Block purine receptors (adenosine receptors of the A1 and A2 subtype)
- Diuresis possibly due to vasodilation of the afferent glomerular arterioles causing increased GFR
Tolerance and habituation develop to a small extent
Few clinical uses for caffeine but theophylline can be used as a bronchodilator in serve asthma attacks
What are Eugeroics and their features?
Eugeroics are “wakefulness-promoting agents” - clinically used in treatment of narcolepsy
Not 100% in the “psychostimulant” category, but have some commonalities and prone to abuse (“smart drugs”)
Modafinil;
- Mechanisms not 100% clear but has some activity as a DA reuptake inhibitor
Solriamfetol;
- NA and DA reuptake inhibitor
Pitolisant;
- H3 receptor antagonist
What drugs fall into which categories ?
Class A;
- Cocaine, mephamphetamine, LSD, ecstasy
Class B;
- Amphetamine, ketamine, cannabis, methylphenidate
Class C;
- Khat
