Module 3.1.1 (Drugs for Treatment of Alcohol Abuse) Flashcards
What are psychomotor depressants?
Benzodiazepines Barbiturates Opiates Alcohol GHB
- Administration results in sedation, reduced sensory and motor function, reduced anxiety and euphoria
Why are barbiturates not used as anxiolytics and hypnotics anymore?
Barbiturate overdoses are often fatal due to deep coma & respiratory arrest
- Barbiturates are now obsolete since they readily lead to psychological & physical dependence and small overdose can be fatal.
What is the MOA of barbiturates?
- Increase the duration of the GABA-gated chloride channel openings
- At high concentrations are GABA- mimetic by directly opening the chloride channels and they may also produce other inhibitory effects such as depression of excitatory neurotransmitter actions
What are examples of barbiturates? What do they do? Side effects?
E.g. Phenobarbitone, primidone, amylobarbital
- Enhances inhibition at synapses where GABA acts on GABAA receptors
- Abuse potential due to euphoric effects
- High risk of dependence
- Toxicity symptoms include nystagmus, ataxia, drowsiness, coma, respiratory depression, hypothermia, acute renal failure
- Should NOT be ceased abruptly
For GHB (gamma hydroxybutyrate):
A) What is it also known as
B) What are the 2 binding sites
A)
- Also known as liquid ecstasy, fantasy, juice or G
- Date rape drug
- Liquid, capsules or crystals
- Taken orally or injected
B)
- 2 distinct binding sites
- GHB receptor → excitatory
- GABAB receptor → inhibitory
> GHB exists endogenously at concentrations to activate GHB receptor but not the GABAB receptor
What are some properties of heroin - diacetylmorphine (opioids)?
Heroin more lipid soluble than morphine hence enters CNS more rapidly
- Significantly reduced by first pass metabolism by liver, hence injection and inhalation are preferred means of administration by illicit drug users
How is ethanol absorbed in the body and what is absorption rate increased by?
Mainly absorbed from small intestine and diffuses into nearly all tissues
Absorption rate increased by:
- rapid gastric emptying
- absence of fat, protein and carbohydrates
> 80% metabolized by liver to acetaldehyde
> 12% in stomach
> 5% excreted unchanged from lungs, sweat and urine
What is the MOA of ethanol?
Alcohol activates GABA receptors to cause sedation (in a similar way to BZD, barbiturates & GHB)
- Potent inhibitor of glutamate receptors
Explain the following that occurs with repeated exposure of ethanol:
A) Cellular or pharmacodynamic tolerance
B) Metabolic or pharmacokinetic tolerance
C) Physical addiction
D) Behavioural tolerance
A)
- Cell membrane alteration and complex neurochemical changes occur
B)
- After 1‐2 weeks drinking, daily rate of ethanol metabolism by liver increase 30%
C)
- Once cells have adapted, structural and biochemical changes may not return to original state for few weeks
D)
- Adaptation behaviour so one function better at the same blood alcohol concentration
What are the pharmacological efffects of ethanol in CNS?
depressant effects
- enhancement of both GABA‐ and glycine‐mediated inhibition
- inhibition of Ca2+ entry through voltage‐gated calcium channels –> reduce excitatory neurotransmitter release
- activation of certain types of K+ channel
- inhibition of ionotropic glutamate receptor function = CNS depressant effects
What are the behavioural effects of ethanol?
Slurring of speech, sedation
Impairment of intellectual
Impairment of motor function, staggering gait
Increased self‐confidence, euphoria, mood changes
Psychiatric symptoms with heavy drinkers
Loss of consciousness at high doses
Blackouts: episodes of forgetting all or part of what happened whilst drinking
Fragmented sleep
What are the adverse effects of ethanol?
Neurotoxicity
- Brain damage = irreversible
Effects on liver
- Liver damage
- Fatty liver
Effects on fetal development
- Fetal alcohol syndrome
- Alcohol related neurodevelopmental disorder (ARND)
Other effects –> thiamine deficiency
What are some withdrawal symptoms of ethanol? When does it begin and when is peak intensity?
Hand tremor, insomnia, difficulty in sleeping, feelings of generalized anxiety or panic attacks, autonomic system dysfunction including increased pulse, respiratory rate and body temperature, GI upset.
- Begins within 5 to 10 days of decreasing alcohol intake
- Peak intensity at day 2 or 3, usually improve by day 4 or 5
> Anxiety, insomnia and mild levels of autonomic dysfunction can persist for 6 months or more
> Seizures in small percentage of patients.
Explain how the following drugs treat alcoholism
A) BZD
B) Disulfiram
C) Naltrexone
D) Acamprosate
A)
- Alleviate the acute abstinence syndrome during ‘drying out’
B)
- To render alcohol consumption unpleasant
C)
- To reduce alcohol‐induced reward
D)
- To reduce craving
How does disulfiram work? What are the unpleasant symptoms associated with it? what benefits from it?
Blocks metabolism of alcohol –> inhibits aldehyde dehydrogenase –> blocks alcohol metabolism
- Concurrent alcohol intake results in raised blood acetaldehyde concentrations – unpleasant symptoms –> nausea, profuse vomiting, flushing, sweating, palpitations, tachycardia, dyspnoea, hyperventilation, headache
> encourages abstinence from ethanol use
> Severe reactions can cause cardiotoxicity, convulsions or loss of consciousness
> Only suitable for highly compliant motivated patients who understand the risk. Should be alcohol free for previous 24 hours
