CAL 4 Flashcards
What is drug dependence
this refers to psychoactive substance in which the prolonged use can lead to dependency
what happens to chronic exposure to drugs
- adaptive neural mechanisms are activated to overcome the prolonged stimulation or inhibition produced by drugs
- often counteract the drug so that the drug is needed for normal function of the systems that are effected
what is drug withdrawl
refers to the cessation of drug administration to the point where the plasma levels and brain levels are negligible
what are abstience effects
- these are withdrawal side effects
withdrawal side effects
- drugs that reduce the CNS function can lead to convulsions
- drugs that increase the CNS function can lead to depression
what are the two types of drug dependence
- Psychological dependence
2. Physical dependence
What is psychological dependence characteristics
- Characterised by the compulsion, need or craving to take the drug.
- Produced by all drugs of dependence.
- Long lasting, e.g. smokers still experience craving, months after giving up.
- Due to effects in the limbic system of the brain.
- The only type of dependence produced by some drugs, e.g. cocaine, amphetamine, nicotine and caffeine.
what responses is the limbic system involved in
emotional responses
What does the limbic system consist of
The amygdala
Nucleus accumbens
Striatum
Cingulate gyrus
What are the withdrawal effects of psychological dependence
Withdrawal symptoms are emotional rather than physical, e.g.: Mood changes Anxiety Agitation Feeling unable to cope
What are the characterstics of physical dependence
- Characterised by a clear cut syndrome of physical symptoms of illness
- Only seen with some drugs of dependence
- Relatively short lived, e.g. has a duration of ~ 2 weeks
What are the withdrawal effects of physical dependence in
- opiates
- barbiturates
- benzodiazepines
- alcohol
Opiates
- Nausea/vomiting
- Hypertension
- Anxiety/agitation/apprehension
Barbiturates
- Sweating
- Tremors
- Delirium tremens (delirium/vivid hallucinations)
- Anxiety/agitation
Benzodiazepines
- Convulsions
- Panic Attacks
- Anxiety/agitation
Alcohol
- Sweating Tremors
- Delirium tremens (delirium/vivid hallucinations)
- Anxiety/agitation
what are the two types of tolerance
- Acute tolerance
2. Chronic tolerance
What are the two types of chronic tolerance
2a. Cellular tolerance
2b. Pharmacokinetic tolerance
what is drug tolerance
This refers to the phenomenon where the effects of the drug diminish with repeated, excessive usage.
name some examples of drugs that tolerance develops in
LSD
Glyceryl trinitrate
Anticholinesterases
What is acute tolerance
Acute tolerance or tachyphylaxis is a short lasting tolerance which occurs when a drug acts at a receptor which becomes desensitised by the first dose
in what does acute tolerance occur
Acute tolerance occurs with nicotine in tobacco
- Nicotine causes a depolarising block at some of the nicotinic receptors at which it acts.
- Over the smoking day, the nicotine- induced increase in heart rate (HR) diminishes.
- However, this effect recovers following overnight abstinence.
What are cellular tolerance and pharmacokinetic tolerance also referred to as
Cellular tolerance which is alternatively referred to as pharmacodynamic tolerance.
Pharmacokinetic tolerance which is alternatively referred to as metabolic tolerance.
What is the major contributor to drug tolerance and why
Cellular tolerance is the major contributor to drug tolerance and is due to neuroadaptive changes, occurring mainly in the brain, which produce diminished responses to the drugs.
when does cellular tolerance occur
Cellular tolerance occurs following chronic exposure to almost all drugs of dependence and can be measured as a reduced response for a given dose giving submaximal effect.
what is pharmokinetic tolerance due to
This is usually due to an increase in the metabolism of the drug caused by an induction of liver enzymes responsible for its degradation, and results in a diminished response per dose of drug. This type of tolerance can be overcome by taking larger and larger doses of the drug.
give an example of pharmokinetic tolerance
A proportion of the tolerance observed with barbiturates, e.g. amylobarbitone, is due to drug-evoked induction of cytochrome P450 enzymes in the liver, which results in faster metabolism of the barbiturates
how can pharmokinetic tolerance be over come
This type of tolerance can be overcome by taking larger and larger doses of the drug.
The diminishing effect of nicotine on changes in heart rate, which occurs during the smoking day, is an example of:
actue tolerance
What are the two kind of drugs that produce dependence
Psychomotor stimulants: drugs which cause excitation and stimulation of brain activity, often accompanied by increased locomotion.
CNS depressants: drugs whose overall effect is to depress brain activity and cause sedation.
what does nicotine do
- increase alertness
- improve psychomotor performance, especially under conditions of boredom or fatigue
- reduce the disruption in performance caused by stress
name some withdrawal effects of nicotine
- craving
- agitation/anxiety
- feelings of inability to cope in stressful situation
(thus they are mainly psychological)
What type of tolerance occurs with nicotine
- actue tolerance
- chronic - cellular and pharmokinectic
describe the types of tolerance that occur with nicotine
- Acute tolerance – many of the effects of nicotine, e.g. increase in heart rate and locomotor stimulation, show acute to short lasting tolerance to the drug due to desensitisation of the nicotinic receptors mediating these effects.
- Cellular tolerance
Chronic tolerance develops to many of the unpleasant effects of nicotine and tobacco, e.g. nausea, dizziness and sweating, which are usually experienced when people first start smoking. In fact, tolerance to these effects can be life-long. - Pharmacokinetic tolerance
Nicotine causes induction of its metabolic enzymes but only to a small degree. This is not a major contributor to the tolerance to nicotine.
why can acute tolerance not be overcome by increasing the dose
Acute tolerance cannot be overcome by increasing the dose. With this type of tolerance, which is due to desensitisation of the receptors, increasing the dose only deepens the block. The greater the dose, the longer the tolerance.
How does nicotine act
- Nicotine stimulates nicotinic acetylcholine receptors in the brain to produce its rewarding effects.
- The demonstration of this is that administration of mecamylamine, a nicotinic receptor antagonist which can enter the brain, can block the psychomotor stimulant and pleasurable effects of smoking.
Where does nicotine act
Nucleus accumbens
- stimulates nicotonic receptors on dopamine neurones leading to the release of dopamine
- helps develop dependence on nicotine
Hippocampus
- stimulation in this area increases attention and may underlie the improvement seen in nicotine
ventral tegmental area
- stimulates nicotonic receptors on dopamine
- this causes the release of dopamine from the nucleus accumbens and ventral tegemental area
- develops dependence
reticular formation
- increases alertness
name some different types of benzodiazepines
- anxiolytics
- sedatives
- hypnotics
- anticonvulsants
describe the different types of benzodiazepines
Anxiolytics – benzodiazepines are powerful anxiolytic drugs in man and animals. They are also used to tame animals, to allow them to be handled more easily.
Sedatives – To date, it has proved rather challenging to separate the anxiolytic and sedative effects of the benzodiazepines.
Hypnotics – at hypnotic doses, benzodiazepines induce sleep quickly and increase the duration of sleep.
Anticonvulsants – Diazepam, given intravenously, is one of the main treatments of status epilepticus (where the seizures occur repetitively with no intervening recovery) which is fatal if untreated.
describe the withdrawal side effects of benzodiazepines
Anxiety Agitation Convulsions Panic attacks (psychological)
What is iatrogenic
Imposed by clinical prescription rather than wilfully or self-imposed (derived from the Greek Iatros=doctor).
describe the tolerance experienced with benzodiazepines
- Tolerance of the cellular type, does occur to a limited extent following long term treatment with the benzodiazepines.
- However, this does not seem to lead to patients increasing their dosage.
- In fact the anxiolytic action for which many people are prescribed benzodiazepines is not as susceptible to tolerance.
- The main clinical tolerance appears to develop to the anticonvulsant actions of the drugs.
describe the mechanism of action of benzodiazepines
- Benzodiazepines (BDZs) bind to the GABAA receptor.
- this causes an allosteric (structural) modification of the receptor that results in an increase in GABAA receptor activity.
- BDZs do not act as a substitute agonist for GABA, but increase the frequency of channel opening events in the presence of GABA, which leads to an increase in chloride ion conductance and inhibition of the action potential.
Where do benzodiazepines act
Raphe nuclei
- stimulation of GABA receptors in the dorsal raphe nuclei attenuates the firing of 5HT neurones in this region, this mediates the anxiolytic effect
Reticular formation
- inhibit neurones in the reticular formation to cause sedation
What was the first clinically useful barbiturate
Phenobarbitone was the first clinically useful barbiturate
name examples of barbiturates and what they are used for
Phenobarbitone – an anticonvulsant, at very low doses
Thiopentane – an induction agent in general anaesthesia
Phenobarbitone has a slow onset and long duration of action and was used as a sedative. It is still in clinical use as an anticonvulsant drug; very low doses are effective and long lasting.
Pentobarbitone has a medium rate of onset and duration of activity (~ 6 hours) and was used as a sedative drug.
what do barbiturates do that can lead to death
Barbiturates will depress the activity of all cells such that at high doses, they depress the cardiovascular and respiratory systems causing death.
what do barbiturates produce in there clinical dose range
Over the clinical dose range, the effects they produce vary from anxiolytic to general anaesthesia with increasing doses
what are the main use of barbiturates
Euphoria – with most of the barbiturates taken orally, feelings of euphoria or well-being are experienced before sedation occurs
Anxiolytic effects - in low doses, barbiturates produce a sedated state where the patient is awake and less anxious
Sedation – all clinically effective doses of barbiturates cause sedation
Hypnotic effects – at slightly higher doses and especially with the drugs which have a medium duration of action e.g. pentobarbitone, amylobarbitone and hexobarbitone, sleep or hypnosis is induced relatively quickly.
Anticonvulsants – only some of the barbiturates have anticonvulsant activity, e.g. phenobarbitone, and this action occurs at doses which cause minimal sedation.
General anaesthesia - all barbiturates are capable of causing general anaesthesia, but with the long and medium acting drugs this does not occur without considerable respiratory depression. Therefore, only the highly lipid soluble, highly protein bound and therefore very quick onset and short acting barbiturates such as thiopentone, are used clinically as inducing agents in general anaesthesia.
Why is thiopentone not abused
Thiopentone is not abused probably because the anaesthetic effect occurs before the abuser has finished injecting the drug and they will not have experienced the euphoria.
do barbiturates have a high or low dependence
High dependence
what type of dependence do barbiturates have
The dependence is both physical and psychological
Name some withdrawal effects that can occur with barbiturates
- Anxiety – this is one of the first symptoms to appear after withdrawal of barbiturates and for those who were prescribed barbiturates as anxiolytic or antidepressant drugs, this may be a rebound re-emergence of the condition for which they were treated.
Insomnia – On withdrawal from barbiturates, insomnia occurs as a rebound to the sedation produced by these drugs.
Sweating
Delirium tremens – this is a major withdrawal reaction which is very characteristic of sedative hypnotic dependence i.e. not only barbiturates but also alcohol.
This is manifest as:
- Tremors
- Delusions
- Agitation
- Disorientation
- These symptoms usually take some days to develop and last approximately two weeks.
Confusion – this occurs before delirium tremens has fully developed.
Epileptic fits – these occur due to sudden abnormal discharges or firing of brain neurones. After withdrawal of barbiturates, grand mal seizures or status epilepticus can both occur some days after cessation of barbiturate administration in addicts and can be fatal.
What is delirium tremens
- withdrawal effect of barbiturates Delirium tremens – this is a major withdrawal reaction which is very characteristic of sedative hypnotic dependence i.e. not only barbiturates but also alcohol. This is manifest as: - Tremors - Delusions - Agitation - Disorientation - These symptoms usually take some days to develop and last approximately two weeks.
what are grand mal seizures
where large areas of the cortex are discharging causing loss of consciousness and/ or convulsions
