Psychiatric Disorder Drugs

Question 1

Describe all the stages of membrane depolarisation.

Answer 1

1. Resting membrane potential
2. Depolarisation
3. Repolarisation
4. Hyperpolarisation
5. Refractory period

Question 2

What are the important neurotransmitters?

Answer 2

1. Glutamate - major excitatory NT
2. GABA - major inhibitory NT
3. ACh
4. Dopamine

Question 3

What is the difference between an excitatory and inhibitory synapse?

Answer 3

• ES: presynaptic NT release causes postsynaptic depolarisation
• IS: presynaptic NT release depresses postsynaptic depolarisation

Question 4

Describe the synaptic transmission of neurotransmitters.

Answer 4

1. NT-containing vesicles are normally anchored to cytoskeleton (away from the active zone of the presynaptic membrane) by Ca2+-sensitive VAMPs
2. When action potential reaches presynaptic terminal, VGCCs are opened
3. Ca2+ influx causes VAMPs to release vesicles, which undergo exocytosis
4. Presynaptic autoreceptors also activated for regulation of NT release

Question 5

What are the two types of depression?

Answer 5

1. Unipolar - mood swings always in same direction; classified as reactive or endogenous
2. Bipolar - alternating depression / mania

Question 6

What are the five classes of antidepressants?

Answer 6

1. MAOIs
2. TCAs
3. SSRIs
4. SNRIs
5. S/NRIs

Question 7

Name a monoamine oxidase inhibitor.

Answer 7

Phenelzine

Question 8

How do MAOIs work?

Answer 8

1. Deficits in monoamine NTs can cause depression
2. Monoamine oxidase breaks down monoamines (MAO-A for serotonin, noradrenaline, dopamine; MAO-B for noradrenaline, dopamine)
3. MAOIs increase biological availability of monoamines

Question 9

What are the two adverse effects of MAOIs?

Answer 9

1. Restlessness, insomnia - increased CNS stimulation
2. Postural hypertension - increased dopamine accumulation in cervical ganglia inhibits SNS

Question 10

What is the sole contraindication of MAOIs?

Answer 10

1. No using with other serotoninergic drugs - causes hyperexcitability, myoclonus, and loss of consciousness

Question 11

Name four tricyclic antidepressants.

Answer 11

Imipramine, Amitriptyline, Nortriptyline, Desipramine

Question 12

How do tricyclic antidepressants work?

Answer 12

1. Tricyclic antidepressants inhibit serotonin and noradrenaline reuptake transporters
2. This increases biological availability of monoamines

• IAN are non-selective
• D is selective for NA reuptake transporter

Question 13

What are the adverse effects of tricyclic antidepressants?

Answer 13

1. Sedation - due to H1 receptor antagonism (histamine normally promotes wakefulness)
2. Postural hypertension - a-adrenoceptor block inhibits SNS
3. Xerostomia, miosis, constipation - muscarinic receptor antagonism

Question 14

What is necessary for tricyclic antidepressants?

Answer 14

Functional liver, for clearance

Question 15

Name two SSRIs.

Answer 15

Fluoxetine, citalopram

Question 16

How do SSRIs work?

Answer 16

• Inhibit serotonin reuptake receptors, thus increasing biological availability of serotonin
• Do not bind to a-adrenoceptors, histamine receptors (except citalopram), and muscarinic receptors = no CVS, sedation, or anticholinergic effects

Question 17

What is the benefit of SSRIs compared to other antidepressants?

Answer 17

More selective for serotonin, less adverse effects on other receptors

Question 18

What are the adverse effects of SSRIs?

Answer 18

1. Nausea and insomnia - withdrawal symptoms due to altered serotonin levels
2. Sexual dysfunction (delayed orgasm and ejaculation) - due to 5-HT2 stimulation
3. Serotonin syndrome (hyperexcitability, myoclonus, loss of consciousness) - DDIs with other serotoninergic drugs

Question 19

Name two SNRIs.

Answer 19

Reboxetine, maprotiline

Question 20

How do SNRIs work?

Answer 20

• Inhibit noradrenaline reuptake receptors, thus increasing biological availability
• Do not bind to a-adrenoceptors, histamine, and muscarinic receptors = no CVS, sedation, or anticholinergic effects (except maprotiline, which binds to a-adrenoceptors and histamine receptors, and can cause seizures)

Question 21

What are the adverse effects of SNRIs?

Answer 21

1. Insomnia - increased NA activity in CNS
2. Tachycardia, xerostomia, constipation - SNS

Question 22

Name three serotonin and noradrenaline reuptake inhibitors (S/NRIs).

Answer 22

Venlafaxine, Desvenlafaxine, Duloxetine

Question 23

How do S/NRIs work?

Answer 23

• Inhibit serotonin and noradrenaline reuptake receptors, thus increasing biological availability
• More effective in treatment-resistant patients

Question 24

What are the adverse effects of S/NRIs?

Answer 24

1. Nausea / Insomnia - withdrawal effects due to altered serotonin levels; stronger than SSRIs
2. Sexual dysfunction - due to increased 5-HT2 stimulation; can be treated with cyproheptadine
3. Serotonin syndrome (hyperexcitability, myoclonus, loss of consciousness) - DDIs with other serotoninergic drugs

Question 25

What is the difference between fear and anxiety?

Answer 25

- Fear is a response to a clear, imminent threat - Anxiety is a response to a vague, anticipated threat

Question 26

What responses do anxiety stimulate?

Answer 26

1. SNS 2. Stress > HPA axis > corticosteroids 3. Emotions, defensive behaviours

Question 27

What are the types of anxiety?

Answer 27

1. GAD - excessive, uncontrollable worrying over everyday matters for >6 months 2. Others - PTSD, phobias, OCD, panic disorder

Question 28

What are the general side effects of anxiolytics?

Answer 28

1. Sedation, occurs in low-dose 2. Hypnosis (drowsiness, sleep), occurs in medium-dose 3. Anaesthesia, occurs in high-dose

Question 29

What are the two classes of anxiolytics?

Answer 29

1. Benzodiazepines 2. Barbiturates

Question 30

Name two benzodiazepines used as anxiolytics.

Answer 30

Diazepam (longer-acting), Lorazepam

Question 31

How do benzodiazepines and barbiturates work?

Answer 31

- Bind to GABA-A receptors, and increase their affinity to GABA - GABA is an inhibitory NT, and causes Cl- influx = hyperpolarisation

Question 32

What are the adverse effects of benzodiazepines?

Answer 32

1. Drowsiness, confusion, amnesia, impaired muscle coordination 2. Overdose > severe respiratory depression, esp. with alcohol; can be treated with flumanezil, a benzodiazepine antagonist 3. Dependence and withdrawal - rebound anxiety, disturbed sleep, tremor, convulsiosn

Question 33

Name four barbiturates.

Answer 33

Phenobarbital, Pentobarbital, Amobarbital, Thiopental

Question 34

Arrange the barbiturates from longest- to shortest-acting.

Answer 34

Phenobarbital > Pentobarbital + Amobarbital > Thiopental

Question 35

What are the adverse effects of barbiturates?

Answer 35

1. Overdose > severe respiratory depression 2. Dependence / Withdrawal - sleep disturbances, rebound anxiety, tremors, convulsions

Question 36

What is schizophrenia?

Answer 36

Chronic mental disorder, highly-disabling

Question 37

What are the signs / symptoms of schizophrenia?

Answer 37

1. Positive - abnormal behaviours added (paranoid delusions, thought disorders, hallucinations) 2. Negative - normal behaviours subtracted (social isolation, flattened emotional responses, no self-awareness) 3. Cognitive - memory disorders, impaired selective attention span 4. Aggressive symptoms 5. Depression, anxiety

Question 38

What are possible causes for the positive symptoms?

Answer 38

1. Hyperactive dopamine / serotonin pathways 2. Hypoactive glutamate pathways

Question 39

Name two typical antipsychotics.

Answer 39

Haloperidol, Chlorpromazine

Question 40

How do typical antipsychotics work?

Answer 40

- Haloperidol antagonises D2 receptors - Chlorpromazine antagonises D2, a1, H1, and M1 receptors

Question 41

What are some chlorpromazine-specific adverse effects, given its a1, M1, and H1 antagonism?

Answer 41

1. Postural hypotension 2. Xerostomia, miosis, constipation 3. Sedation, weight gain

Question 42

What are the adverse effects of typical antipsychotics?

Answer 42

1. Acute dystonias - reversible Parkinsonism-like syndrome, due to D2 antagonism in nigro-striatal pathway 2. Tardive dyskinesias - potentially irreversible hyperkinetic movements (involuntary, repetitive movements of face, tongue, and limbs), due to LT D2 antagonism in nigro-striatal pathway 3. Akathisia - potentially irreversible involuntary movements and compulsions (associated with anxiety, restlessness, and agitation), due to LT D2 antagonism in nigro-striatal pathways

Question 43

Name four atypical antipsychotics.

Answer 43

Clozapine, Olanzapine, Risperidone, Amisulpride

Question 44

How do atypical antipsychotics work?

Answer 44

- Mixed antagonism of D, a1, H1, and M receptors - Less severe extrapyramidal symptoms - Amisulpride antagonises D2 and D3 receptors only

Question 45

What can the atypical antipsychotics be used for?

Answer 45

1. Negative symptoms - COR 2. Cognitive symptoms - CR 3. Mood stabilisation - COR

Question 46

What are the adverse effects of atypical antipsychotics?

Answer 46

1. Xerostomia, miosis, constipation (antimuscarinic; for CO) 2. Sedation, weight gain (antihistamine; for COR) 3. Postural hypotension (anti-adrenergic; for R) 4. Clozapine-induced agranulocytosis 5. Hyperprolactinemia (breast swelling, pain, lactation, gynaecomastia); for A