PHARM - Drugs of Abuse - Week 9 Flashcards
Why does dependence to drugs occur?
Progressive pharmacological adaptation to the drug, resulting in tolerance
What happens to homeostasis in response to repeated drug exposure? What is a consequence of this?
It is reset. An individual in this state needs continuous drug administration to maintain normal function.
If there is a dependence on drugs, what happens if the drug is abruptly stopped?
Withdrawal symptoms occur
Define abstinence.
Practice of not doing something or having something that is wanted or enjoyable
Define psychological dependence, including the physiological basis for it, and what normally happens in individuals with no dependence.
Also called addiction - administration of substances or certain behaviours activate brain reward circuits.
These motivate normal behaviour which most people enjoy without being compelled to repeat them.
What occurs with reflexice acivation of reward circuits?
It becomes involuntary, drawing a person into compulsive repetition and putting focus on the immediate pleasure despite negative consequences.
Where is the primary action of drugs of abuse?
In the CNS - the brain reward circuits
What system specifically do addictive drugs activate? What consequence does this result in?
The mesolimbic dopamine system, producing a rewarding-reinforcing action.
What effect does alcohol have on the CNS?
Depressant
What neurotransmitter does alcohol bind to and increases transmission of what neurotransmitter?
Binds to GABA and increases GABA-ergic transmission
What two neurotransmitter receptors are altered by alcohol?
NMDA and 5-HT3 (serotonin)
Is alcohol rapidly or slowly absorbed and distributed?
Rapid
Describe how alcohol is processed by the body in terms of percentages (5).
90% is oxidised in the liver
The rest is eliminated via saliva, sweat, breath, and urine
Can an overdose of alcohol be fatal? Explain why.
Yes, due to the effects of being a depressant and acetaldehyde (a metabolite)
After what time period following cessation of heavy drinking does the dependence on alcohol become apparent?
6-12 hours
Name 5 withdrawal symptoms of alcohol after 6-12 hours.
Hand tremors
Nausea
Excessive sweating
Agitation
Anxiety
Name a withdrawal symptom of alcohol after 12-24 hours (1).
In some individuals, visual/tactile/auditory hallucinations may occur
Name a withdrawal symptom of alcohol after 24-48 hours (1).
In some individuals, siezures may occur
Name a withdrawal symptom of alcohol after 48-72 hours. What percentage of mortality is it associated with?
Delirium - 5-15% mortality
What is the standard first-line treatment for acute alcohol withdrawal symptoms?
Benzodiazepines
What is naltrexone and what does it prevent? How long is its action?
An opioid receptor antagonist
Prevents euphoria
Long action - 24-72h
How does naltrexone work (2)?
Blocks action of the endogenous opioids released by alcohol
Blocks activation of dopamine reward pathways
What overall effect will naltrexone have (2)?
Decreases pleasurable effects linked to alcohol consumption
Reduces cravings
Name 4 common adverse effects and one serious but rare adverse effect of naltrexone.
Insomnia
Headache
Fatigue
Dizziness
Hepatotoxicity
What must be monitored during naltrexone therapy?
Liver function
What does disulphiram promote?
Abstinence in motivated alcoholics after initial detoxification
What is disulphiram?
Aldehyde dehydrogenase inhibitor
How does disulphiram work (2)?
Blocks degradation of acetaldehyde to acetate
Acetaldehyde accumulates in the body and casues unpleasant symptoms
Name 7 symptoms of disulphiram and a reason why if applicable.
Intense flushing
Headache (throbbing)
Sweating
The above are caused due to acetaldehyde being a potent vasodilator
Nausea
Vomiting
BP changes
Hyperventilation
When is acamprosate used?
Maintenance of abstinence in alcohol dependence
What effect does acamprosate have on the CNS (2)?
Restores normal activity in glutamate and GABA systems.
How long does acamprosate therapy last?
Up to a year
What should be checked before acamprosate therapy?
Creatinine levels
Name 3 side effects of acamprosate.
Rash
Diarrhoea
Changes in libido
What addiction exceeds all others?
Nicotine addiction
What does nicotine cause the release of? Give 3 consequences of this. What do these 3 increase the risk of?
Catecholamine release
Increases heart rate, vascular resistance, and hypertension
Increases risk for coronary artery disease
What do catecholamines stimulate the mobilisation of?
Free fatty acids
How does nicotine affect LDLs and HDLs?
Increases LDLs and decreases LDLs
Mechanistically, how does nicotine act?
Acts as a nAChR agonist, increasing dopamine neuron activity
How do nicotine patches work?
Patch impregnated with nicotine, which provides slow absorption into the circulation.
Heps reduce cravings.
How does bupropion aid nicotine addiction?
Inhibits noradrenaline and dopamine re-uptake
Name 6 side effects of bupropion.
Insomnia
Agitation
Anxiety
Visual disturbances
Impaired concentration
Rash
What are opioids used for typically?
Treatment of pain
What do opioids do in addition to reducing the perception of pain?
Produce a state of well-being or euphoria
What is the most frequently abused opioid?
Heroid (diacetylmorphine)
What kind of drug is heroin (aside from being an opioid)?
Prodrug
What is heroin metabolised to?
Morphine
Why is heroin more effective than morphine (2)?
Greater lipid solubility - crosses the blood brain barrier more rapidly
Why does heroin cause respiratory depression?
It inhibits brainstem respiratory mechanisms
Name 6 adverse effects of heroin.
Antitussive effect
Miosis
Bradycardia
Nausea
Vomiting
Constipation
What are opioids agonists of?
G-protein coupled opioid receptors
Which receptor do heroin, morphine, codeine, and oxycodone act on?
μ receptor
Do all opioids induce tolerance and dependence upon cessation?
Yesd
What kind of drug is used for opioid overdose?
Opioid antagonists
Give an example of an opioid antagonist, what kind of overdose it is used to treat, and how quickly it acts.
Naloxone, short acting so used for acute opioid overdose
What is the main active constituent in cannabinoids?
THC
Name 4 beneficial therapeutic effects of THC (5).
Anti-emetic
Muscle relaxing effects
Improves seizure control in patients with epilepsy
Useful for anorexia linked to weight loss in cancer patients and patients infected with HIV (cachexia)
What is the main CNS action of THC? Name 2 effects this can have.
CB1 receptor
Can cause loss of coordination and painful muscle spasms
What kind of a drug is cocaine?
Psychostimulant and hallucinogen
Name three kinds of psychostimulants.
Cocaine
Ice Speed
What three effects do psychostimulants have?
Procudes excitement
Euphoria
Decreases fatigue
Name 4 hallucinogens.
LSD
PCP
Ecstasy
GHB (liquid ecstasy)
Are hallucinogens addictive?
No, theyre non-addictive drugs of abuse
Where do hallucinogens typically target?
Cortical and thalaic circuits rather than mesolimbic dopamine ones.
What do psychostimulants and hallucinogens interfere with?
Multiple neurotransmitter and receptor systems
In what three ways can cocaine be administered?
Injected
Snorted
Smoked
Is cocaine rapidly or slowly absorbed?
Rapid
Does cocaine cause CNS or PNS effects?
Both
What does cocaine block the uptake of (3)?
Neuronal uptake of dopamine, noradrenaline, and serotonin
What happens following a dose of cocaine (3)?
Intense euphoria
Dysphoria/irritability
Craving for more drug
Name 5 symptoms of cocaine overdose.
Acute fear
Psychotic symptoms
Hypertension
Tachycardia
Coronary vasospasm
Describe the mechanisms of amphetamines (2).
Acts as a competitive inhibitor reducing uptake of noradrenaline and dopamine
How do amphetamines enter neurons?
By uptake or diffusion
What do amphetamines do once inside the cell (3)?
Interact with VMAT and inhibit uptake of dopamine and noradrenaline into vesicles
What is LSD an agonist of and what does it increase transmission of?
Agonist of serotonin, increases glutaminergic transmission
What does LSD inhibit and where?
Inhibits 5-HT neurons from firing in raphe nuclei
What is PCP? Give its common name.
Phencyclidine - angel dust
What is PCP and antagonist to?
Glutamate NMDA-receptor
What four effects does PCP have on neurotransmitters?
Inhibits uptake of dopamine, noradrenaline, and serotonin
Stimulates dopamine release
What four behavioural effects does PCP have?
Euphoria
Excitation
Dysphoria
Aggression
What can chronic use of PCP lead to? Is it reversible or irreversible?
Irreversible schizophrenia-like psychosis
What is the common name for MDMA?
Ecstasy
What two neurotransmitters does MDMA stimulate the release of?
Dopamine and serotonin
What four things does MDMA affect?
Mood, sleep, memory, and apetite
What does acute toxicity of MDMA cause?
Hyperthermia
What is meant by serotonin syndrome, what drug is it caused by, and is it fatal?
Hyperserotoninergic state caused by MDMA
May be fatal
Name 12 symptoms of serotonin syndrome.
Abnormal muscle movements
Muscle rigidity
Sweating
Disruption in thermoregulation
Confusion
Agitation
Restlessness
Hallucinations
Tachycardia
Hypertension
Loss of control
Death
What is a common date rape drug and why?
GHB - it is an odourless liquid that readily mixes with alcohol
Causes euphoria, enhanced safety perceptions, social closeness, amnesia, then sedation/coma
