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Pharmacology 3 > L20: Recreational Drugs > Flashcards

L20: Recreational Drugs Flashcards

1
Q

What are the two types of dependence? Describe them

A
  • Psychological dependence: desire to repeat the rewarding effect of a drug (craving); desire to avoid the physical or psychological effects of drug abstinence; can be triggered by environmental cues
  • Physical dependence: drug abstinence or withdrawal has adverse physiological effect; pharmacological treatment can alleviate some symptoms; shorter lasting and has less impact on relapse than psychological dependence
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1
Q

What is tolerance?

A

Decreased effect following repeat administration of a drug

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2
Q

What is addiction?

A

drug taking becomes compulsive and dominates lifestyle

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3
Q

What are the classes of commonly abused recreational substances? What are their examples?

A
  • Opioids: morphine, codeine, methadone, diamorphine
  • Stimulants: nicotine, amohetamines, cocaine, MDMA (ecstasy)
  • CNS Depressants: alcohol, barbiturates, ketamine, solvents
  • Psychotomimetics: lysergic acid diethylamide (LSD) and psilocybin, cannabis, phencyclidine (PCP)
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4
Q

What are the examples of ‘very strong’, ‘strong’, ‘weak’ and ‘weak or none’ dependence of drugs?

A
  • Very strong: morphine, heroin, methadone, nicotine, cocaine
  • Strong: amphetamine, ethanol, ketamine
  • Weak: cannabis
  • Weak or none: LSD, MDMA
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5
Q

Which neurotransmitter pathway and receptor do opiates target?

A

Neurotransmitter: endorphins
Receptor: mu and sigma opioid agonist

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6
Q

Which neurotransmitter pathway and receptor does nicotine target?

A

Neurotransmitter: Acetylcholine
Receptor: alpha-2 beta-4 nAChR agonist

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7
Q

Which neurotransmitter pathway and receptor do aphetamines target?

A

Neurotransmitter: Dopamine
Receptor: Dopamine transporter - reverse transport

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8
Q

Which neurotransmitter pathway and receptor does cocaine target?

A

Neurotransmitter: dopamine
Receptor: dopamine transporter antagonist

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9
Q

Which neurotransmitter pathway and receptor does MDMA target?

A

Neurotransmitter: dopamine, noradrenaline, serotonin
Receptor: monoamine transporter substrate

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10
Q

Which neurotransmitter pathway and receptor does LSD target?

A

Neurotransmitter: serotonin
Receptor: serotonin receptor agonist

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11
Q

Which neurotransmitter pathway and receptor does Cannabis target?

A

Neurotransmitter: endocannabinoids
Receptor: CB1 agonist

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12
Q

Which neurotransmitter pathway and receptor does ethanol target?

A

Neurotransmitter: GABA and glutamate
Receptor: GABAa agonist and NMDA receptor antagonist

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13
Q

Which neurotransmitter pathway and receptor does PCP and ketamine target?

A

Neurotransmitter: glutamate
Receptor: NMDA receptor antagonist

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14
Q

On which neurotransmitter do most pathways converge on? What are the functions of this pathway?

A

Dopamine
Functions:
- reward (motivation)
- pleasure (euphoria)
- compulsion
- perseveration
- motor function (fine-tuning)

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15
Q

What is the common feature of dependence-inducing drugs?

A

The activation of the mesolimbic dopaminergic pathway

16
Q

What are the two types of dopamine receptors? Are they inhibitory or excitatory?

A

D1 dopamine receptor - excitatory
D2 dopamine receptor - inhibitory

17
Q

Where does the mesolimbic dopaminergic pathway originate?

A

Pathway originates in substantia nigra and ventral tegmental area, afterwards sends signal to amygdala (prefrontal cortex)

18
Q

How do drugs of abuse increase dopamine transmission in the nucleus accumbens (NA)?

A

via:
- decreased GABAergic inhibition in VTA (preventing inhibition, more dopamine released)
- increased DA release
- decreased DA reuptake (uptake mechanism blocked, more DA in the synapse)

19
Q

Describe opioids (give examples, what are their structural similarities; what are they derived from; what is their effect)

A
  • morphine, heroin, codeine
  • Morphine and codeine are derived from the sap of opium poppy seedpod
  • Heroin (diamorphine) is synthesized from morphine and is converted into morphine in the body
  • causes intense rush, euphoria, relaxation
  • desire to repeat this rewarding experience leads to tolerance and dependence
20
Q

Why does dependence and tolerance on opioids develope?

A
  • opioid receptors might be lost due to frequent use (GPCRs), rapid dependence as more opioid is needed.
  • Downregulation of cAMP pathway in locus coeruleus neurons (noradrenergic) occurs as tolerance and dependence of opiates develops.
21
Q

What are the symptoms of opioid withdrawals?

A

Anxiety, insomnia, muscle aches, sweating, shivering, abdominal cramping, diarrhoea, dilated pupils, nausea and vomiting

22
Q

What is used for treatment of opioid dependence? Why? How does it work?

A

Methadone
- synthetic opioid with a longer half-life than morphine or heroin
- can stabilise heroin users during drug withdrawal (no rapid drop)
- a long lasting withdrawal from methadone also occurs but less intense
- also an NMDA receptor antagonist

Naltrexone
- opiate competitive antagonist can help recovering addicts from relapsing by preventing rewarding effects

23
Q

Describe nicotine (receptors that it binds to, mechanism of action and effects)

A
  • stimulant
  • binds to nicotinic acetylcholine receptors
  • activates ligand gated ion channel to depolarize neuronal membrane
  • effects in brain complex combination of inhibition and excitation
  • by binding directly to receptor, directly depolarizes membranes and increases dopamine release
24
Q

What kind of dependence and addiction does nicotine lead to?

A

Tolerance and strong dependence with very strong psychological dependence leading to addiction

25
Q

What can help reduce cravings and withdrawal symptoms of nicotine?

A

Nicotine replacement therapy can help alleviate withdrawal symptoms and reduce cravings
Varenicline - partial agonist at the alpha-4 beta-2 nAChR - impairs efficacy of nicotine and reduces effect

26
Q

Describe the effects of cocaine and amphetamines (tolerance, dependence)

A
  • locomotor stimulation
  • euphoria and excitement
  • insomnia
  • increased stamina
  • anorexia
  • anxiety
  • irritability
  • restlessness

Tolerance to amphetamine develops to some effects more readility than others. Tolerance to cocaine is less likely.
Psychological dependence occurs due to desire to repeat experience
Little evidence of physical dependence or withdrawal syndrome

27
Q

How does cocaine act?

A

Increase synaptic dopamine and noradrenaline via blocking reuptake by transporters. Behavioral effects likely due to increased dopamine.
Binds to DA transporters, blocks them, accumulation of DA in synaptic cleft.

28
Q

What could be used as a target for cocaine and opioids addiction treatment?

A
  • K+ channels as targets for treatment.
  • activation of G-protein coupled inwardly rectifying K+ (GIRK) channels is a common mechanism of many reward pathways
  • cocaine and opioids both reduce GIRK currents
  • re-activating GIRK channels may be a mechanism to overcome addiction pathways
  • Baclofen activates GIRK and has been used in treatment of alcohol dependence
29
Q

Describe amphetamines, how do they act?

A

Increase synaptic dopamine and noradrenaline via reverse transport from pre-synaptic terminals. Behavioral effects likely due to dopamine, allow accumulation of DA.

30
Q

Describe alcohol (ethanol) (its mechanism, dependence, withdrawals)

A
  • most common recreational drug
  • depressant (not dopamine pathways associated), relaxation (dopamine pathway)
  • increases GABAa receptor activity - inhibitory
  • acts as NMDA receptor antagonist
  • strong dependence and withdrawal symptoms
31
Q

Describe cannabis (active components, dependence, mechanism)

A
  • euphoria, relaxation, appetite
  • active components: tetrahydrocannabinol (THC), cannabinadiol (CBD)
  • CBD promising candidate for treating variety of conditions: anxiety, epilepsy, depression
  • complex, brain-wide effects (CB1 one of most abundant GPCRs)
  • THC - partial agonist at CB1/CB2 receptors
  • lower GABA release indirectly increases dopamine
32
Q

What are the drugs that target other neurotransmitter systems? Which systems?

A

serotonin pathway (function: mood, memory processing, sleep, cognition):
- ecstasy
- LSD + psilocybin

33
Q

Describe ecstasy (emotions, tolerance and dependence, mechanism)

A
  • emotions: euphoria, decreased anxiety, increased intimacy and sensations, mildly hallucinogenic
  • tolerance and dependence to ecstasy is uncommon (due to being a global effect)
  • ecstasy increases synaptic serotonin via blocking reuptake by serotonin transporters (false substrate, blocks, sustains reuptake)
  • similar effects dopamine and noradrenaline transporters.
34
Q

Describe LSD and Psilocybin (Tolerance, mechanism, which receptors does it act on)

A
  • psychotomimetic (distorted perception, hallucinations)
  • tolerance to effects occurs but no physical withdrawal symptoms
  • in clinical trials for depression, addiction, migraine, cluster headaches
  • agonist at 5-HT receptors and psychomimetic effects mainly tue to 5-HT2A subtype
  • inhibits 5-HT neurons in raphe nuclei
  • activating inhibitory autoreceptors

Pharmacology 3 (21 decks)

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