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Drug action > Drugs To Treat Depression & Recreational Drugs > Flashcards

Drugs To Treat Depression & Recreational Drugs Flashcards

(52 cards)

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1
Q

Monoamine hypothesis of depression

A

Predicts that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, noradrenaline, and/or dopamine in the CNS long term
Results in underactivity of serotonin at NA synapses
A number of antidepressants target the serotonergic (and NA) and neurotransmission system

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2
Q

Unipolar depression

A

Average age of onset is 35-45
Incidence of 9-15%
Higher in women than men
Genetic component; 25% of cases have familiarly links

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3
Q

Bipolar disorder

A

Depression with mania
Affects men and women equally
Average age onset around 30
Twin studies show significant concordance

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4
Q

Affective disorder

A

Disturbance of mood rather than thought or cognition

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5
Q

Unipolar depression is defined as

A

Suffering from five or more symptoms daily for at least two weeks

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6
Q

Symptoms of unipolar depression

A

Significant weight change
Sleep disturbance
Fatigue/loss of energy
Depressed or irritable mood
Reduced interest in pleasurable activities
Psychomotor agitation
Loss of self worth, excessive guilt
Diminished ability to think
Suicidal thoughts

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7
Q

Usual symptoms of mania

A

Unnaturally elevated mood
Over-activity
Loss of inhibitions
Irritability
Loss of sleep and appetite

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8
Q

Additional symptoms of mania, present in ~10% of patients

A

Delusions
Hallucinations

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9
Q

Manic episodes are treated….

A

…separately from depressive episodes

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10
Q

Monogamie oxidase inhibitors

A

Among the first antidepressants to be introduced
Use declined due to side-effects and advent of new drugs
eg -> Tranylcypromine, moclobemide

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11
Q

Tranylcypromine

A

Irreversible block of MAOI
Non-selective

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12
Q

Moclobemide

A

Reversible block
MAO-A selective

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13
Q

Mechanism of monoamine oxidase inhibitors

A

Blocking breakdown of 5-HT and NA increases their levels at the synapse.
This is expected to increase release of these transmitters -> receptor activation should increase.
MAO-A is more selective for serotonin & NA (selective action reduces side-effects).

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14
Q

Tricyclic antidepressants (TCAs)

A

Early class of antidepressants
Non-selective transporter block
eg -> dibenzazepines, dibenzycycloheptenes

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15
Q

Dibenzazepines

A

Imipramine (non-selective for NA/-HT uptake)
Desipramine (selective for NA uptake)

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16
Q

Dibenzcycloheptenes

A

Amitriptyline (non-selective for NA/5-HT uptake)

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17
Q

Mechanism of monoamine reuptake inhibitors

A

Blocking reuptake of 5-HT and NA from the synapse prolongs monoamine signalling at the synapse. -> as with MAOIs, this should lead to an increase in receptor activation.

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18
Q

Monoamine uptake inhibitors

A

Selective Reuptake Inhibitors (SSRIs)
Other reuptake inhibitors, eg SNRIs and NRIs

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19
Q

What is SERT?

A

A type of monoamine transporter proteins that transports serotonin from the synaptic cleft to the presynaptic neuron

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20
Q

SERT and SSRIs

A

SSRIs bind at the central binding pocket of SERT

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21
Q

Other antidepressants

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A

Noradrenergic and Specific-Serotonergic Antidepressants (NaSSAs)

22
Q

Action of NaSSAa

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A

Selectively antagonise alpha-2AR and various 5-HT receptors
Prevents the negative feedback effect of synaptic NA on 5-HT and noradrenaline neurotransmission
Increases the concentration of 5-HT in the synaptic cleft
The enhances signalling at certain NA and 5-HT synapses

23
Q

How are manic episodes treated?

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A

Mood stabilisers

24
Q

Most widely used mood stabiliser

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A

Lithium (Li2CO3)
Its mechanism is unclear but it may result from inhibition of phosphatidyl inositol (PI) metabolism
Very narrow therapeutic window; toxic at high doses

25
Problems with current antidepressants
Only around half of patients are fully responsive to current drugs Drug treatments can take several weeks to take effect Even the newest drugs have potentially problematic side effects
26
Potentially problematic side effects of monoamine oxidase inhibitors
Dry mouth Hypertensive effects from ingested tyramine Postural hypotension Tremors
27
Potentially problematic side effects of tricyclic antidepressants
Dry mouth Sedative Postural hypotension Dysrhythmias (in overdose)
28
Potentially problematic side effects of reuptake inhibitors
Nausea
29
Potentially problematic side effects of St John's Wort
Indices metabolism of other drugs
30
Recreational drugs - caffeine
Caffeine and four other methylxanthines found in tea and coffee and psychostimulants They act as competitive antagonists at adenosine A1 and A2A receptors It's been suggested that caffeine consumption may protect dopaminergic neurones against the degeneration found in Parkinson's disease
31
Recreational drugs - nicotine
Neuroactive substance in tobacco Agonist at nicotinic acetylcholine receptors, exerting its CNS effects through the alpha-4-beta-2 subtype
32
Effects of nicotine on nicotinic acetylcholine receptor
These receptors are involved in cognition and the dopamine reward pathway Nicotine desensitises them, leading to an increase in their surface expression by a reduction in their responsiveness
33
Recreational drugs - ethanol
General CNS depressant Pharmacological effects resemble volatile general anaesthetics Acts via GABA-A receptors, inhibiting NMDA receptors, 5HT3 receptors, L-type voltage gated Ca2+ channels Activates dopaminergic reward pathway Opiate receptor antagonist naltrexone inhibits ethanol consumption and craving in alcoholism
34
Recreational drugs - Psychostimulants: cocaine amphetamine
Induce a psychosis that resembles schizophrenia Potentiate monoaminergic transmission through inhibition of dopamine, 5-HT, and noradrenaline reuptake Euphoria is mostly due to effects on dopamine
35
Recreational drugs - hallucinogens examples
LSD Mescaline Phencyclidine Ketamine
36
Hallucinogens - LSD and mescaline
Partial agonists at 5HT-2A receptors, which affect memory and perception
37
Hallucinogens - phencyclidine and ketamine
Channel blockers at NMDA receptors, which are a class of ionotropic glutamate receptor
38
Ketamine: a new hope for depression?
Can have dissociative, anaesthetic, and and hallucinogenic effects Approved as anaesthetic in 1970 Off label use for treatment of resistant depression - fast acting
39
Recreational drugs - marijuana and cannabinoids
Cannabis is the most commonly used illicit drug in the western world Therapeutic role as an analgesic agent, particularly in MS and to treat the nausea related to cancer chemotherapy
40
What is the main psychoactive ingredient of cannabis?
Theta-9-tetrahydrocannibinol (THC), which is an agonist at the GPCR CB1 cannabinoid receptor
41
Where are the GPCR CB1 cannabinoid receptors?
The brain areas associated with cognition (cerebral cortex) and memory (hippocampus)
42
Cannabinoids receptor ligands - endocannabinoids
Endogenous agonists for CB1 receptor have been identified as anandamide and sn-2 arachidonylglycerol (2-AG) Development of cannabinoid antagonists has shown that cannabis produces dependence and leads to withdrawal effects
43
THC and mental health
An association has been identifies between cannabis use and the appearance of psychoses or schizophrenia The risk of developing these conditions is approximately doubled in cannabis users
44
What might the association between cannabis and schizophrenia & psychoses be due to?
THC inducing or worsening psychoses in susceptible individuals OR Individuals who are susceptible to psychoses being more likely to become regular cannabis users
45
The link between CB receptors and schizophrenia may involve...
… the dopamine reward pathway
46
Drug abuse
The self-administration of drugs beyond approved cultural norms
47
Dependence
A state in which "an organism only functions normally in the presence of a drug". Stopping the drug will lead to withdrawal.
48
Addiction
A state in which "an organism engages in compulsive behaviour". This is thought to involve the dopamine reward pathway
49
Tolerance
The need for a significantly increased dose to achieve the same effect, or a reduction in effect when doses are constant
50
Withdrawal
Withdrawal effects generally oppose the normal effects of the drug
51
Plasticity - possible method for tolerance
Plasticity reduces the effect of the drug through changes in protein expression patterns Drugs that inhibit a response could similarly leads to a compensatory effect in the opposite direction Changes can also occur at the cellular and anatomical levels
52
Plasticity and withdrawal
When the drug is removed, the response will fall below the 'normal' level until the plasticity has time to reverse

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