CAL 4 Flashcards
1
Q
What is drug dependence
A
this refers to psychoactive substance in which the prolonged use can lead to dependency
2
Q
what happens to chronic exposure to drugs
A
- 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
3
Q
what is drug withdrawl
A
refers to the cessation of drug administration to the point where the plasma levels and brain levels are negligible
4
Q
what are abstience effects
A
- 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
5
Q
what are the two types of drug dependence
A
- Psychological dependence
2. Physical dependence
6
Q
What is psychological dependence characteristics
A
- 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.
7
Q
what responses is the limbic system involved in
A
emotional responses
8
Q
What does the limbic system consist of
A
The amygdala
Nucleus accumbens
Striatum
Cingulate gyrus
9
Q
What are the withdrawal effects of psychological dependence
A
Withdrawal symptoms are emotional rather than physical, e.g.: Mood changes Anxiety Agitation Feeling unable to cope
10
Q
What are the characterstics of physical dependence
A
- 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
11
Q
What are the withdrawal effects of physical dependence in
- opiates
- barbiturates
- benzodiazepines
- alcohol
A
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
12
Q
what are the two types of tolerance
A
- Acute tolerance
2. Chronic tolerance
13
Q
What are the two types of chronic tolerance
A
2a. Cellular tolerance
2b. Pharmacokinetic tolerance
14
Q
what is drug tolerance
A
This refers to the phenomenon where the effects of the drug diminish with repeated, excessive usage.
15
Q
name some examples of drugs that tolerance develops in
A
LSD
Glyceryl trinitrate
Anticholinesterases
16
Q
What is acute tolerance
A
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
17
Q
in what does acute tolerance occur
A
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.
18
Q
What are cellular tolerance and pharmacokinetic tolerance also referred to as
A
Cellular tolerance which is alternatively referred to as pharmacodynamic tolerance.
Pharmacokinetic tolerance which is alternatively referred to as metabolic tolerance.
19
Q
What is the major contributor to drug tolerance and why
A
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.
20
Q
when does cellular tolerance occur
A
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.
21
Q
what is pharmokinetic tolerance due to
A
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.
22
Q
give an example of pharmokinetic tolerance
A
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
23
Q
how can pharmokinetic tolerance be over come
A
This type of tolerance can be overcome by taking larger and larger doses of the drug.
24
Q
The diminishing effect of nicotine on changes in heart rate, which occurs during the smoking day, is an example of:
A
actue tolerance
25
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.
26
what does nicotine do
- increase alertness
- improve psychomotor performance, especially under conditions of boredom or fatigue
- reduce the disruption in performance caused by stress
27
name some withdrawal effects of nicotine
- craving
- agitation/anxiety
- feelings of inability to cope in stressful situation
(thus they are mainly psychological)
28
What type of tolerance occurs with nicotine
- actue tolerance
| - chronic - cellular and pharmokinectic
29
describe the types of tolerance that occur with nicotine
1. 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.
2. 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.
3. 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.
30
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.
31
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.
32
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
33
name some different types of benzodiazepines
- anxiolytics
- sedatives
- hypnotics
- anticonvulsants
34
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.
35
describe the withdrawal side effects of benzodiazepines
```
Anxiety
Agitation
Convulsions
Panic attacks
(psychological)
```
36
What is iatrogenic
Imposed by clinical prescription rather than wilfully or self-imposed (derived from the Greek Iatros=doctor).
37
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.
38
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.
39
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
40
What was the first clinically useful barbiturate
Phenobarbitone was the first clinically useful barbiturate
41
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.
42
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.
43
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
44
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.
45
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.
46
do barbiturates have a high or low dependence
High dependence
47
what type of dependence do barbiturates have
The dependence is both physical and psychological
48
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.
49
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.
```
50
what are grand mal seizures
where large areas of the cortex are discharging causing loss of consciousness and/ or convulsions
51
What are status epilepticus seizures
grand mal with no intervening recovery of consciousness – this leads to death
52
what type of tolerance occurs in barbiturates
Cellular tolerance
| Pharmacokinetic tolerance
53
How do barbiturates work
At clinically relevant doses they:
Potentiate(increase) the effects of GABA at GABAA receptors in the brain. - they do this by increasing the amount of time that the channel remains open allowing more chloride through and allowing more hyperpolarisation
Since GABA is the major inhibitory transmitter in the brain, their CNS depressant effects are mediated by their action on this system.
54
What is the major inhibitory transmitter in the brain
GABA
55
What two receptors does GABA act on
GABAA: Postsynaptic, ligand-gated ion channel
GABAB: Presynaptic, G-protein coupled, linked to second messenger systems
56
what causes withdrawal insomnia
GABAA receptor
| On withdrawal from barbiturates, insomnia occurs as a rebound to the sedation produced by the drugs.
57
Where do barbiturates work
Raphe nuclei
- stimulation of GABA nuclei in the dorsal raphe nuclei increases 5HT neurones in this region, they mediate an anxiolytic effect
reticular formation
- inhibit neurones in the reticular formation and cause sedation
58
What are the classical signs of alcohol intoxication
- Slurred speech
- Staggering gait
- Intellectual and motor impairment
- Mood and behavioural changes
- Sedation – as intoxication progresses beyond the euphoric and excitable stage, the person becomes sedated, and at higher levels of intoxication, coma can result and sometimes death from respiratory depression when the blood alcohol reaches ~400 mg/100 ml.
- emesis
- Euphoria – or feeling of well-being is one of the first effects to occur on consuming alcohol.
59
What changes in mood and behaviour can be seen in alcohol intoxication
– the effect that alcohol has on mood and behaviour depends on:
- Dose
- Rate of rise of blood ethanol concentration
- Personality – shy people can become gregarious as the alcohol depresses their inhibitions
- Mental state – emotionally labile people can become euphoric, hyperexcitable, aggressive (sometimes to the point of manic rage), morose and depressed with the effects occurring successively.
60
what blood alcohol level can kill you
400 mg/100 ml
61
What is the most common cause of alcohol induced death
inhalation of vomit
62
What are the three phases of alcohol withdrawal
```
Phase 1
This occurs ~8 – 24 hours after the last drink and is manifest as:
nervousness
apprehension
tremor
nausea
butterflies in the stomach
```
```
Phase 2
This occurs >24 hours after last drink and manifests as:
agitation
muscle cramps
nausea/vomiting
hypertension
tachycardia
insomnia
```
Phase 3
This occurs ~2-4 days after last drink and manifests as:
confusion
disorientation
delirium tremens
epileptic fits – occurs in severe cases and can be fatal if not treated
63
How much of the worlds population become alcohol dependent
only ~10% of the alcohol consuming population become alcoholic,
64
What three types of tolerance can occur with alcohol
- actue
- cellular
- pharmokinetics
65
describe the three types of tolerance that can occur with alcohol
Acute tolerance – this is seen after one drinking bout, where the effects wear off even when the blood alcohol level is maintained
Cellular tolerance – this occurs with regular drinking, where one has to consume more alcohol to produce the motor impairment seen in an abstainer. It occurs with or without dependence.
- It occurs readily with regular alcohol consumption, such that even moderate drinkers, who are not dependent upon alcohol, require 2-3 times the amount of alcohol it initially took them to become intoxicated.
Pharmacokinetic tolerance – this only occurs in severe alcoholics.
- With high levels of chronic exposure to alcohol, its metabolic enzymes, which are part of the cytochrome P450 group of oxidative liver enzymes, are induced.
- This is really only manifest in alcoholics and may account for the cross tolerance to barbiturates that is seen in alcoholics
66
How does cellular tolerance happen in people who drink alcohol
- The mechanism involves at least partly changes in the lipid content of membranes which make them less susceptible to alcohol.
- Acute alcohol, like many of the anaesthetic drugs, increases membrane lipid fluidity.
- This effect is reduced following repeated exposure to alcohol.
- Interestingly, alcoholics require larger doses of anaesthetics, suggesting cross tolerance occurs with this effect.
67
what is the difference between first order kinetics and zero order kinetics in the body
Zero-order kinetics - A drug concentration independent elimination rate process i.e. drug is eliminated at a constant rate.
First-order kinetics - A drug concentration dependent elimination rate process i.e. more drug is present, the more drug will be eliminated
68
what type of kinetics does alcohol show
zero order kinetics
- Alcohol metabolism shows zero order kinetics since the elimination is linear with time. This is because alcohol dehydrogenase, the main enzyme for metabolising alcohol, has an apparent Km for alcohol of ~8mg/100ml of blood. Since a pint of beer will produce blood levels of ~35 mg/100 ml, then the rate limiting enzyme is saturated and the reaction progresses at a constant rate until the blood level falls to levels of ~8 mg/100 ml.
69
How does alcohol work
- tend to act on the voltage gated calcium channels inactivating them and therefore reducing the transmitter release
70
Where does alcohol work
reticular formation
- Depress the firing of ascending inhibitory neurones at low intake this causes the initial disinhibitory behaviour
Frontal cortex
- higher doses of alcohol inhibit the cortical neurones resulting in hypnotic effects and loss of consciousness
71
What is the active ingredient of cannabis
The active ingredient of cannabis is delta-9-tetrahydrocannabinol (9-THC) and it is thought to exert its effect by binding to cannabinoid CB1 receptors in the brain.
72
describe how cannabis works
- 9-THC binding to CB1 receptors activates G-proteins, that can ultimately activate or inhibit a number of signal transduction pathways.
- The G-proteins directly inhibit N and P/Q-type voltage dependent calcium channels and sodium channels, and indirectly inhibit other calcium channels via inhibition of adenylate cyclase.
- 9-THC binding and G-protein activation also can ultimately activate inwardly rectifying potassium channels and the MAP kinase signalling pathway.
The cumulative complex effect of these pathways is reflected behaviourally in the euphoric feeling
73
Name some opiates
```
Morphine
Heroin (diacetylmorphine)
Codeine
Pethidine
Methadone
```
74
Describe how heroin is made
It is produced synthetically by acetylation of morphine to diacetylmorphine of diamorphine.
- It is a more potent drug than morphine.
75
describe methadone
- It has a similar 3-dimensional structure to morphine although it is chemically different.
- It is longer acting and more active orally than morphine and heroin and so is used as replacement therapy in drug treatment centres.
76
name some effects of opiates
Analgesia – Opiates are very potent painkillers and this is the main clinical indication of use for these drugs especially post-operatively and in the relief of the pain of terminal cancer.
Cough suppression – codeine is more potent than morphine at inhibiting the cough reflex and is effective at doses which are sub-analgesic. Codeine has been commonly used in cough medicines.
Respiratory depression – The opiates cause respiratory depression even at therapeutic doses and this is the main cause of death from opiate overdose.
Sedation – opiates cause sedation at therapeutic doses.
Constipation – opiates act partly by an action in the CNS and partly by a direct action in the gut, to increase tone and decrease motility of the gut which results in constipation.
Pupillary constriction – the pin-point pupil which opiates produce is an important diagnostic indicator of an opiate overdose since dilated rather than constricted pupils are normally associated with respiratory depression and coma.
Nausea and vomiting
Euphoria
77
what do opiates do to the CNS
- they cause CNS depression
78
What is the main cause of death from opiate overdose
Respiratory depression
79
what withdrawal side effects occur with opiates
psychological and physiological
80
name some withdrawal side effects that occur with opiates
```
diarrhoea
nausea/vomiting
abdominal cramps/GI tract discomfort
sweating/shivering
hypertension
convulsions
anxiety/agitation/apprehension
goosebumps – the occurrence of goosebumps gave rise to the street term ‘cold turkey’ commonly used to describe opiate withdrawal
```
81
describe tolerance to opiates
- Tolerance of the cellular type occurs to many of the effects of the opiates, especially to the nausea and vomiting, which can occur within 24 hr of morphine treatment.
- Tolerance also occurs to the euphoric, analgesic and respiratory depression following excessive use such that, in the case of the latter effect, an addict could take 50 times the normal analgesic dose and show relatively little respiratory depression, while this dose would kill non-addict.
- However, not all of the effects of morphine show tolerance to the same degree. The constipation and pupillary constriction do not readily show tolerance.
82
what receptors do opiates act on
Opiates act on specific opioid receptors of which there are three main types:
- Mu – type receptors – This type of receptor is mainly responsible for the euphoria, analgesia, respiratory depression and constipation caused by opiates
- Kappa – type receptors – These receptors play a role in analgesia at the spinal level and cause sedation but do not contribute to the dependence on opiates.
- Delta – type receptors – These receptors also play a role in analgesia.
83
what are the endogenous ligands for opiate receptors
The endogenous ligands for these receptors are:
- Beta – endorphin – This is a 31 amino acid peptide which is equally active at all three opioid receptors.
- Leucine- enkephalin or leu-enkephalin – This is a pentapeptide (Tyr-Gly-Gly-Phe-Leu) which is most active on delta type receptors.
- Methionine-enkephalin or met-enkephalin – This is a pentapeptide (Tyr-Gly-Gly-Phe-Met) which is most active on mu and delta –type receptors.
- Dynorphin – This is a 17 amino acid peptide which is most active at kappa type receptors.
84
what are the dependence of opiates due to
The dependence producing properties of the opiates are due to the stimulation of mu-type opioid receptors.
- Opiates stimulate mu – receptors and cause hyperpolarisation by increasing K+ conductance.
85
What is the net effect of opiates
The net effect of opiates is to:
- inhibit nerve cell firing
- inhibit transmitter release
86
where do opiates act
nucleus accumbens
- contains mu-opiate receptors
- stimulation mediates the eurphoric and dependence effects
periaquaductal grey
- stimulation of Mu opiates receptors in this region leads to analegic effects
- opiates also acts directly as anaselgic effects on the kappa opaite receptor stimulating by inhibiting pain transmission in the dorsal root of the spinal cord
ventral tegmental area
- stimulation of Mu opiates, this increases the firing of dopamine neurones
- thus this increases the release of dopamine in the nucleus accumbens
- this contributes to the euphoria and development of dependence
reticular formation
- stimulation of this area causes sedation and can lead to respiratory depression
area postrema
- contains the chemoreceptor trigger zone and this causes nausea and vomiting
87
What does cocaine cause to happen
```
Causes euphoria
Increases energy levels
Enhances physical performance
Suppresses appetite
Local anaesthetic
```
88
what is cocaine used for clinically
- Cocaine is a relatively potent local anaesthetic which is still used clinically as an ophthalmic anaesthetic, where it is applied locally, to the cornea, rendering it insensible.
- In addition, it causes dilatation of the pupils, mydriasis, and reduces intra-ocular pressure due to its potentiation of catecholamine activity.
89
what type of dependence does cocaine lead to
psychological but not physical
90
name some withdrawal effects of cocaine
i) craving for the drug
ii) acute depression
iii) anxiety/agitation
iv) intense fatigue
91
What is dependence liability
is the potential of the drug to induce dependence in people who self administer the drug chronically.
- Great dependence liability is seen in drugs which will induce dependence in a majority of users after relatively short periods of chronic treatment. For example, cocaine has great dependence liability since virtually all people who experiment with cocaine daily for a few weeks will become dependent on the drug.
92
How can cocaine be adminstered
```
A = Intranasal of 'snuff' - medium dependence
B = Intravenous - high dependence
C = Inhalation of 'crack - high dependence
D = Oral - low dependence
```
93
What are the symptoms of cocaine induced psychosis
- paranoid delusions
- auditory and visual hallucinations
- tactile hallucinations (the addicts believe they have insects crawling under their skin) (formication)
94
what do cocaine users have a higher risk of
- heart attack and stroke
95
How does cocaine work
- Potentiates actions of the catecholamines in the brain but not directly
96
what mechanism of action do both cocaine and amphetamines share
- inhibition of dopamine uptake transporter, but cocaine is not a substrate for the dopamine uptake transporter
97
Where does cocaine act
nucleus accumbens
- causes euphoria
- development of dependence
reticular formation
- increases alertness
hypothalamus
- increases temperature
- decreases food consumption
98
what does caffeine normally stimulate
- a reduction in fatigue
| - increased arousal
99
What are the withdrawal effects of caffeine
craving
fatigue
irritability
headaches
100
Which drink contains the most caffeine per average cup?
| - tea or coffee
- they are both equal
101
what type of dependence develops with caffeine
mainly psychological
102
what type of tolerance can develop with caffeine and describe this
- cellular tolerance
- in people who do not normally drink coffee they can experience palpitations, irritability and nervousness after consuming a strong cup of coffee but these show tolerance within a matter of days
103
What class fo compounds a caffeine a member of
Methylxanthines
104
What sites of action does caffeine/methylxanthines act on
- They inhibit phosphodiesterase (the enzyme hydrolyses cyclic AMP to the inactive 5’AMP).
- They inhibit adenosine type (A1) receptors (stimulation of these receptors inhibits cyclic AMP production).
- Both of these actions result in an increase in cyclic AMP, a second messenger for G-protein coupled receptors including some catecholamine receptors e.g. the beta-adrenergic and dopamine type 1 (D1) receptors.
- It is likely that the psychostimulant effects of caffeine are related to its ability to potentiate catecholamines in the brain due to potentiation of the cyclic AMP – dependent catecholamine receptors.
105
where does caffeine work in the brain
nucleus accumbens
- increases the amount of dopamine that is released
- mediates the pleasurable and dependence part of caffeine
reticular formation
- increases alertness
106
What drugs are in the category of amphetamine
Amphetamine
Dexamphetamine
Methylamphetamine
107
what is the difference between dexamphetamine and amphetamine
Amphetamine is optically active and dexamphetamine, which is the (+) or dextro form of amphetamine is the more active isomer.
108
What are the three types of amphetamine
The three types of amphetamine are:
Racemic amphetamine – Benzedrine
Dexamphetamine – dextro (+) – amphetamine – Dexedrine
Levamphetamine – levo(-)-amphetamine
109
what is the difference between methylamphetamine and amphetamine
- Methylamphetamine (also called metamphetamine or methedrine) differs from amphetamine in that one of the hydrogens on the terminal amine group is replaced by a methyl group.
- This drug has similar potency and dependence producing potential to amphetamine.
110
what type of dependence liability do amphetamines have
- have a high dependence liability, therefore chronic exposure will readily produce dependence
- This occurs when the drug is administered orally or intravenously
111
What type of dependence do amphetamines have
- psychological dependence and no physical dependence
112
name some withdrawal effects of amphetamines
- anxiety
- acute depression
- craving for the drug
113
What type of tolerance develops with amphetamines
- cellular type
- For instance, the high blood pressure which occurs due to the excess sympathetic stimulation of the cardiovascular system is subject to tolerance, such that a dose of drug which would produce severe hypertension in a non-addict would have little effect on the cardiovascular system of an addict.
114
What happens when you inject amphetamine intravenously
- Many amphetamine addicts inject amphetamine (commonly known as speed) intravenously in order to experience an intense euphoria of ‘flash’
- With this type of excessive use, tolerance can develop to the euphoric effects of amphetamines, which leads the addict to keep escalating the dose to overcome the tolerance.
- This frequently leads to psychosis with symptoms similar to those seen in schizophrenia
115
What psychosis effects are seen in amphetamine
Paranoid delusions
Auditory hallucinations
Compulsive, repetitive behaviour, e.g. hand washing
Jaw grinding
116
How long can you esculate amphetamine doses
a few days
| - after this they fall into a deep sleep or depression due to exhaustion of neurotransmitters in the brain
117
What is the structure of amphetamines like in the brain
The structure of amphetamine is similar to the catecholamines, e.g. dopamine (DA), noradrenaline and adrenaline
118
What are amphetamines
Amphetamines are indirectly acting sympathomimetics which act to potentiate the effects of catecholamines in the brain
119
How do Amphetamines work
Amphetamines are indirectly acting sympathomimetics which act to potentiate the effects of catecholamines in three ways:
1. Stimulate release of catecholamines
2. Inhibit their recapture by the uptake system
3. Inhibit monoamine oxidase (MAO) activity
120
Describe how amphetamines work
1, Stimulate the release of catecholamines
Amphetamine increases the release of catecholamines by being taken up by the DA uptake transporter system and displacing catecholamines into the synaptic cleft.
2, inhibit their recapture by the uptake system
Amphetamine competes with dopamine (DA) for the DA uptake transporter, therefore the uptake of dopamine is competitively inhibited.
3, inhibit MAO activity
Dopamine is metabolised by monoamine oxidas (MAO) to dihydroxyphenylacetic acid (DOPAC). At high doses, MAO is blocked by amphetamine.
121
In what part of the brain do amphetamines act
Nucleus accumbens
- euphoria
- development of dependence
hypothalalmus
- increases temperature
- decreases food consumption
reticular formation
- increases alertness
122
Cellular tolerance is the major contributor to drug tolerance which develops with chronic use of drugs of dependence.
- true or false
true
123
Which of the following give rise to physical dependence as well as psychological dependence with chronic use?
Alcohol, barbiturates, benzodiazopines, caffeine and opiates all cause physical dependence as well as psychological dependence.
124
Name some psychomotor stimulants
- cocaine
- caffiene
- nicotine
- amphetamines
125
Name some CNS depressants
- Barbiturates
- alcohol
- opiates
- benzodiazopines
