drugs of abuse Flashcards
brain regions connected by the dopaminergic ‘reward’ pathway?
1.ventral tegmental area in the brainstem to the nucleus accumbens in the basal forebrain
2.then dopaminergic projects out to control the cortical and limbic regions
3.pathways are also known as the mesocortical and mesolimbic pathways as they project from the midbrain region of the brainstem to cortical and limbic systems respectively.
what is the transmitter receptor target of Marijuana ?
cannabinoid
what is the transmitter receptor target of cocaine?
dompamine
what is the transmitter receptor target of ketamine?
glutamate
what is the transmitter receptor target of valium?
GABA
what is the transmitter receptor target of heroin?
Opioid
what is the transmitter receptor target of ecstasy?
serotonin
what is the difference between abuse and misuse?
-consider misuse as using a substance for a purpose that it was not designed/prescribed for (e.g. taking a drug for ADHD to improve study capacity)
-whereas abuse is taking a substance in order to obtain a specific sensation (e.g euphoria/high/sedation
Alcohol
-due to the speed of onset of effect and ease of administration.
-It is rapidly absorbed from the small intestines as it is highly lipid soluble and non-tissue specific.
in what 3 ways does the CNS get effected by alcohol ?
1.Enhancing GABA activity
2.Inhibition of glutamatergic NMDA receptors
3.Inhibition of voltage dependent calcium channels (VDCC)
Chronic alcohol
leads to the inverse of effects occurring: reduction in GABAergic inhibition, increased NMDA receptor number and VDCC number, which may be linked to the increased levels of anxiety and insomnia associated with dependence
What would happen if you increased GABA activity in the hippocampus (remembering that this is a region involved in learning and memory and spatial awareness)?
ncreasing inhibition in the hippocampus (a region involved in learning and memory, emotions and spatial awareness) would reduce likelihood of deposition of memories/learning and also spatial awareness; leading to memory loss, confusion and disorientation, which are common side effects of too much alcohol.
what does nicotine act as?
stimulant and relaxant and is classed as a parasympathomimetic
what part of the brain region does nicotine act on ?
centrally in the brain and peripherally in the autonomic nervous system (ANS) ganglia
what receptor does nicotine bind to?
nicotinic cholinergic receptors (nAChR)
what 3 substance does nicotine release?
1.noradrenaline
2.acetylcholine
3.adrenaline
what 3 transmitters does nicotine ?
1.endorphins
2.dopamine
3.serotonin accounting for the positive mood effects and addictive quality of the substance
what provides positive reinforcement
cognitive enhancements and increase in fine tuning of movement
Opioids
class of drugs that mimic endogenous substances that bind to opioid receptors (endorphins), which are found in the central and peripheral nervous systems
what do opioids act as?
-neuromodulators
-best painkiller currently available is the opioid morphine
what are the four types of opioid receptor found in the nervous system?
µ (mu), κ (kappa), δ (delta) and NOP
how do opioids decrease neuronal transmission?
binding to the opioid receptors and causing
what 4 things does neuronal transmission cause?
1.Decreased opening of voltage-dependent Ca2+ channels
2.Increased K+ outflow via KATP and KIR channels
3.Decreased Ca2+ release from intracellular stores
4.Decreased exocytosis of transmitter vesicles
what are the 2 things that will decrease Ca2+ release, either from intracellular stores or entry reduce?
1.plastcity changes
2. activation of second messenger cascades, reducing activity in the neurons
How does increasing K+ outflow alter the neuron’s membrane potential?
Hyperpolarised
what is decreased exocytosis?
reduce cell-cell communication, disrupting transmission of the messages that the neurons are carrying.
what happens after the neuronal activity is dampened down in decreased exocytosis?
reduction in arousal, reducing physical activity and increasing in the parasympathetic activity within the autonomic nervous system
what is linked to k-receptor activation?
sigma receptor, where a lot of the psychoactive drugs act (e.g. pentazocine and phenazocine, which act at both kappa and sigma receptors)
what is opioid dependence associated with?
decrease in µ-receptor numbers over time and increase in κ-receptor, which probably explains the changing behavioural effects of addiction
Which opioid receptor antagonist can be used to prevent relapse in both opioid and alcohol dependence?
Naltrexone
physiological changes that you would expect to see in people taking opioids?
-constipation
-slower heart rate
-reduced sweating
-peripheral vasodilation
-slow cognition
-increase pleasurable sensation-through action on pleasurable sensation
what are the 2 types of cannabinoid receptors?
1.CB1
2.CB2
CB1
found mainly in the brain, but also in the liver
CB2
principally in the body, particularly in areas linked to the immune system, such as the spleen, but it has also been seen in the brain
what is the endogenous ligand?
these receptors is anandamide, this is a breakdown product of arachidonic acid, a fatty acid.
any conditions that are purported to be helped by the taking of cannabis?
-nausea e.g during chemotherapy
-mental health disorders e.g. anxiety and depression
Stimulant drugs
increase focus, energy and alertness and are so-called as they stimulate activity and communication in the nervous system
what feeling does stimulant drug release?
feeling of euphoria through activity on the reward system via increasing monoamine activity and are generally used to increase mood and activity, giving them the name ‘uppers.
how are stimulants drugs used clinically?
treat patients with ADHD and are of great interest as potential cognitive enhancers. We’ll consider these when we look at the study drugs.
Sedatives (or tranquilisers)
dampen arousal and activity in the central nervous system
what can sedatives be useful as adjucently?
-anaesthesia and for sedation and also potentially used to quickly dampen activity in severe, emergency cases of prolonged epilepsy.
-They are also used to induce euthanasia
tranquillisers
used to sedate, induce calmness and relaxation and also as antiepileptics (to calm hyperactivity within the brain)
what are the 2 groups of tranquillisers ?
1.Major – the antipsychotics, which are non-addictive
2.Minor – relaxants (muscle and neurological), which are addictive
number of tranquilisers are commonplace drugs of abuse
1.Benzodiazepines - these are commonly used as sedatives and as antipileptic drugs, but are also very useful as muscle relaxants
2.Barbiturates - these drugs can be used in exactly the same way as benzodiazepines, but are also commonly associated with euthanasia
what do Benzodiazepines and barbiturates act as?
positive allosteric modulators of GABAA receptors
what do GABA receptors bind to?
site adjacent to the GABA binding site to enhance the activation of the channel
If no GABA was present, would the benzodiazepines/barbiturates have an effect?
absence of GABA the channel cannot be opened, so no effect would be seen.
what do Benzodiazepines bind to?
γ (gamma) subunit
what do barbiturates bind to?
β (beta) subunit
Zolpidem
‘Z-class’ synthetic drug that is mechanistically identical to benzodiazepines
Psychotomimetics
generally cause changes in perception and sensory distortion including hallucination (gaining them the term hallucinogenic or psychedelic drugs)
what are the 2 groups of psychotomimetic drugs?
1.Drugs acting on 5HT – including LSD (‘acid’), mescaline (obtained from cactus) and MDMA (‘ecstasy’)
2.Drugs acting on glutamate receptors (NMDA) – including PCP and ketamine
NPS (new psychoactive substances)
‘legal high,’ many of the newer substances being sold as ‘for research use only.’
-Methylenedioxymethamphetamine (MDMA)
amphetamine analogue which acts as a psychostimulant by blocking the 5HT uptake transporter. It also blocks dopamine and noradrenaline reuptake
-used to give a feeling of euphoria and high levels of energy.
Adverse effects of MDMA include
hyperthermia, dehydration and associated loss of electrolytes
what is Sudden illness and death associated with?
acute hyperthermia, leading to damage of skeletal muscle and renal failure
what are changes in mitochondria function linked to?
sudden illness and death associated with MDMA use.
PCP - Phencyclidine
anaesthetic and painkiller, however the side effects (including sensory distortions/hallucinations (auditory and visual) and induction of transient psychotic states) led to its discontinuation as an anaesthetic for humans
Hyperactivation of which part of the nervous system is associated with the side effects?
Autonomic nervous system
what forms does phencyildine have?
oil, liquid, powder crystal and pills.
effects of Phencyclidine?
numbness and detachment (from self or surrounding) to increased positivity to panic and paranoia.
what is PCP’s main mechanism?
block the NMDA type of glutamate receptor. It binds to the PCP binding site inside the channel preventing influx of sodium and calcium
What type of enhancement (of neuronal activity) does the NMDA receptor play a key role in?
Long-term potentiation
Ketamine
-originated as a horse tranquiliser, replaced PCP as it is a very similar structure
- clinical use it comes in liquid form. On the street it is also available in powder, and is most often inhaled, or tablet form
-In liquid form it can be injected, increasing the risks of use.
- Ketamine is now a Class B drug
what ketamine associated with?
panic and agitation.
what does Paralysis and temporal sensory distortion lead to?
feeling of an ‘out of body’ experience.
Which receptor does ketamine bind to?
NMDA
withdrawal
deficit results in a severe stress reaction and rebound of the drug effects on the transmitter pathways that it affects
what does opioid dependency result in?
analgesia (reducing pain), muscle relaxation, psychological relaxation and pleasure, respiratory depression.
at what stage is the withdrawal stage the highest ?
2-3 days after withdrawal
-nervous system will start to reset the balance of transmitters and any receptor imbalance in order to restore functionality towards a more ‘normal’ state
- after focus is on resolving the psychological element of dependency, which is by far the hardest problem to tackle.
Which part of the nervous system is controlling the physiological responses seen in withdrawal? Which region of the brain controls this activity?
-sympathetic autonomic system
-in hypothalamus
Alcohol, one of the most prevalent substances of abuse, slows down the way the body functions. Which two transmitters can be over released in an attempt to return the body to a normal arousal state?
Adrenaline and noradrenaline
Adrenaline and noradrenaline
CNIII (Oculomotor)
Which opioid can be given as an adjunct to relieve the diarrhoea symptoms associated with withdrawal?
Loperamide
another therapy that complies with substitution therapy ?
random urinalysis
