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Phase 3A Medicine > Psychiatry: Pharmacology > Flashcards

Psychiatry: Pharmacology Flashcards

1
Q

Benzodiazepines

MoA

A
  • GABA-A agonist in mesolimbic system
  • Increase the FREQUENCY of chloride channels opening
  • Therefore increasing inhibitory effect of GABA on neuronal excitability

Frequently Bend - During Barbeque
(Benzos - Frequency; Barbiturates - Duration)

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2
Q

Benzodiazepines

Indications

A
  • Insomnia
  • Parasomnias
  • Anxiety disorders
  • CNS withdrawals, e.g. DELIRIUM TREMENS
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3
Q

Benzodiazepines

Side effects

7

A
  • Dependence (therefore should only be prescribed for 2-4 weeks at a time)
  • Tolerance
  • Somnolence
  • Cognitive defects
  • Amnesia
  • Disinhibition
  • Do NOT let them drive
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4
Q

Benzodiazepines

Examples (5)

A
  • Lorazepam
  • Diazepam
  • Temazopam
  • Clonazepam
  • Chlordiazepoxide (Delirium tremens)
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5
Q

Benzodiazepines

Rapid withdrawal symptoms

A
  • Insomnia
  • Irritability
  • Anxiety
  • Tremor
  • Loss of appetite
  • Tinnitus
  • Perspiration
  • Perceptual disturbances
  • Seizures
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6
Q

Discuss antidepressants in general

A
  • Typical delay of 3-6 weeks before therapeutic dose is achieved
  • If no signs of improvement after 2 months -> switch antidepressant, augment with other treatment or reconsider psychological interventions
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7
Q

1st line for new depressed patient?

A

Sertraline

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8
Q

SSRIs

MoA

A

Selective inhibition of serotonin pumps within synapses with high potency

No effect on noradrenaline

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9
Q

SSRIs

Examples

A 
Sertraline
Citalopram
Fluoxetine
Escitalopram
Paroxetine
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10
Q

SSRIs

Side effects

A 
- Nausea/headache/GI upset (5-HT3)
(5-HT2):
- Insomnia
- Agitation
- Anxiety
- Tremor
- Extrapyramidal signs
- Dyspepsia
- Bloating
- Sweating
- Dry mouth
- Sexual dysfunction
- Hyponatraemia (SIADH)
- SUICIDALITY!
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11
Q

Tricyclic antidepressants

MoA

A
  • Blocks reabsorption/reuptake of serotonin (5-HT) and noradrenaline (NA) pumps in pre-synaptic terminals
  • Also acts as competitive antagonistic on post-synaptic terminals alpha cholinergic (alpha-1 and alpha-2), muscarinic and histaminergic receptors (H1)
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12
Q

Tricyclic antidepressants

Examples

A

More sedative:

  • Amitriptyline - used for neuropathic pain
  • Clomipramine - 2nd line for panic disorder/OCD
  • Dosulepin
  • Trazadone

Less sedative:

  • Imipramine - 2nd line for panic disorder
  • Lofepramine
  • Nortriptyline
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13
Q

Tricyclic antidepressants

Side effects

A

Lengething of QT interval!

“Can’t pee, can’t see, can’t spit can’t shit”

Due to anticholinergic effects:

  • Cognitive impairment
  • Blurred vision
  • Tachycardia
  • Dry mouth
  • Constipation
  • Urinary retention
  • Sexual dysfunction

Due to adrenergic effects:

  • Drowsiness
  • Postural hypotension

High risk of overdose! One week supply can be lethal.

  • Safest: Lofepramine
  • Worst: Amytriptiline and Dosulepin
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14
Q

Monoamine oxidase inhibitors (MAOIs)

MoA

A
  • Binds irreversibly to MAO
  • Prevents inactivation of amines (noradrenaline, serotonin and dopamine)
  • Increases synaptic levels
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15
Q

Monoamine oxidase inhibitors (MAOIs)

Indications

A
  • Atypical depression (e.g. hyperphagia)

- Other psychiatric disorders

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16
Q

Monoamine oxidase inhibitors (MAOIs)

Examples

A
  • Phenelzine
  • Isocarboxazid
  • Moclobemide
  • Tranylcypromine
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17
Q

Monoamine oxidase inhibitors (MAOIs)

Side effects

A

(Same as TCA)

  • Confusion
  • Constipation
  • Difficulty micturition
  • Dry mouth
  • Drowsiness
  • Sexual dysfunction
  • Postural hypotension
  • Headache
  • Dizziness
  • Insomnia
  • Tremor
  • Sweating
  • Serotonin syndrome
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18
Q

Monoamine oxidase inhibitors (MAOIs)

Interactions

A

Tyramine-rich foods:

  • Cheese
  • Wine
  • Beer
  • Broadbeans
  • Aged foods
  • Bovril/Oxo
  • Marmite

Drugs:

  • Opiates
  • Cocaine
  • Insulin
  • L-dopa
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19
Q

SNRIs

MoA

A
  • Selectively inhibits both serotonin and noradrenaline pre-synaptic receptors and reduces reuptake
  • NO antihistaminic, anticholinergic or antiadrenergic effects
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20
Q

SNRIs

Examples

A
  • Venlafaxine

- Duloxetine

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21
Q

SNRIs

Indications

A
  • Major depressive disorder
  • GAD
  • Social anxiety disorder
  • Panic disorder
  • Menopausal symptoms
  • Chronic/neuropathic pain (Duloxetine)
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22
Q

Sodium valproate

MoA

A
  • Increases GABA activity

- Mood stabiliser

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23
Q

Sodium valproate

Indications

A
  • Mania or depression prophylaxis
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24
Q

Sodium valproate

Side effects

A
  • Sedation
  • Tremor
  • Nausea/vomiting
  • Thrombocytopaenia
  • Platelet dysfunction
  • Weight gain and increased appetite
  • P450 inhibitor
  • Ataxia
  • Alopecia: regrowth may be curly
  • Pancreatitis
  • SEVERELY TERATOGENIC
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25
Q

Sodium valproate

Monitoring

A
  • FBs/U&Es/Creatinine

- Pregnancy test (hCG)

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26
Q

Lithium

Indications

A
  • Long-term prophylaxis of Bipolar Affective Disorder (controls depression and mania)
  • Only medication to reduce suicide rates (15% in BAD)
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27
Q

Lithium

Side effects

A
  • Lowers seizure threshold
  • Cognitive slowing
  • Fine tremor
  • Reduced appetite
  • Nausea/vomiting/diarrhoea
  • Polyuria/polydipsia (secondary to nephrogenic diabetes insipidus)
  • Interstitial renal fibrosis
  • Thyroid enlargement –> hypothyroidism
  • Hair loss
  • Acne
  • Leucocytosis
  • Hyperparathyroidism and hypercalcaemia
  • ECG: T-wave flattening/inversion
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28
Q

Lithium

Monitoring

A
  • When checking, the sample should be 12 HOURS post-dose
  • Lithium levels should be checked WEEKLY and after each DOSE CHANGE until concentrations are stable
  • Once established, should be checked every 3 MONTHS
  • Thyroid and renal function checked every 6 MONTHS
  • Patients should have information book, alert card and record book!
29
Q

Lithium

MoA

A
  • Interferes with inositol triphosphate formation
  • Interferes with cAMP formation
  • It has a very narrow therapeutic range (0.4-1.0 mmol/L)
  • Long plasma half-life
  • Excreted primarily by the kidneys
  • Inhibits dopamine neurotransmission
  • Promotes GABAnergic transmission (inhibitory)
  • Downregulates NMDA glutamate receptor (excitatory)
30
Q

Lithium toxicity

Lithium levels

A

Generally occurs following concentrations > 1.5 mmol/L

31
Q

Lithium toxicity

Precipitating factors

A
  • Dehydration
  • Renal failure

Drugs:

  • Thiazide diuretics/Loop diuretics
  • ACE-Is/ARBs/NSAIDs/Metronidazole
32
Q

Lithium toxicity

Mild levels/features/management

A

1.5 - 2.0 mmol/L

  • D+V
  • Ataxia
  • Dizziness
  • Slurred speech
  • Nystagmus

Management: volume resuscitation with saline (forced alkaline diuresis)

33
Q

Lithium toxicity

Moderate levels/features/management

A

2.0 - 2.5 mmol/L

Same as mild, PLUS:

  • Blurred vision
  • Anorexia
  • Delirium
  • Clonic limb movement
  • Convulsions
  • Syncope

Management: volume resuscitation with saline (forced alkaline diuresis)

34
Q

Lithium toxicity

Severe levels/features/management

A

> 2.5 mmol/L

  • Generalised convulsions
  • Acute confusion
  • Oliguria
  • Renal failure
  • Hyperreflexia
  • Coarse tremor (fine tremor seen in therapeutic levels)
  • Coma

Management:

  • HAEMODIALYSIS (or peritoneal)
  • Sodium bicarbonate is used in some cases
35
Q

Typical antipsychotics (First generation)

MoA

A
  • D2 dopamine antagonists: block dopaminergic transmission in the mesolimbic pathways
  • High potency: high specificity and high risk of extrapyramidal side effects
  • Low potency: low specificity and high risk of cardiotoxic and anticholinergic side effects
    Pathways: mesolimbic, mesocortical, tuberoinfundibular, nigrostrital cholinergic
36
Q

Typical antipsychotics (First generation)

Examples

A
  • Haloperidol (high potency)

- Chlorpromazine (low potency)

37
Q

Typical antipsychotics (First generation)

Side effects

A

Extra-pyramidal (Haloperidol):

  • Parkinsonism
  • Acute dystonia: sustained muscle contraction
  • Akathisia (restlessness)
  • Tardive dyskinesia (choreoathetoid movements - chewing/pouting/excessive blinking)
  • MANAGED WITH PROCYCLIDINE

(Chlorpromazine)

  • Anti-muscarinic/anti-cholinergic: Dry mouth, blurred vision, urinary retention, constipation
  • Cardiotoxic: longer QT interval, reduced HR

Others:

  • Weight gain
  • Sedation
  • RAISED PROLACTIN (possibly galactorrhoea) (due to inhibition of dopaminergic tuberoinfundibular pathway)
  • Impaired glucose tolerance
38
Q

Caution of all antipsychotics

A

Elderly: increased risk of VTE or stroke

39
Q

Atypical antipsychotics (Second generation)

MoA

A

Serotonin-dopamine 2 antagonists

Pathways: mesolimbic and serotonin

40
Q

Atypical antipsychotics (Second generation)

Indications

A

First-line for schizophrenia/psychosis

41
Q

Atypical antipsychotics (Second generation)

Examples

A
  • Risperidone
  • Olanzapine (higher risk of dyslipidaemia and obesity)
  • Quetiapine
  • Clozapine
  • Amisulpride
  • Aripiprazole (low prolactin levels)
42
Q

Atypical antipsychotics (Second generation)

Side effects

A 
Risperidone:
- EPSEs
- Hyperpraloctinaemia
- Weight gain
- Sedation
Olanzapine:
- Significant weight gain
- Hyperlipidaemia
- Transaminitis
- Hyperprolactinaemia
Quetiapine:
- Weight gain
- Hyperlipidaemia
- Transaminitis
- Orthostatic hypotension
Clozapine:
- Reserved for treatment-resistant patients due to side effects, as discussed on another card
43
Q

Aripiprazole

MoA

A
  • Dopamine D2 partial agonist
  • Weak 5-HT1a partial agonist and 5-HT2a receptor antagonist
  • Not as effective as other antipsychotics so usually used in conjunction with other anti-psychotics to REDUCE PROLACTIN LEVELS
44
Q

Hyperprolactinaemia

A
  • Sexual side effects
  • Breast discharge (galactorrhoea)
Can also be caused by:
- Smoking
- Hyperlipidaemia
- Obesity
- Diabetes
So work out the cause and establish lifestyle changes before resorting to Aripiprazole
45
Q

Paliperidone

A
  • A metabolite of risperidone
  • Can be given as 1 month or 3-month injections

1 monthly: Xeplion
3 monthly: Trevicta
- Less breakthrough symptoms
- Must have been on Xeplion and reached the correct dose with no SEs before beginning on Trevicta

46
Q

Clozapine toxicity

A

Clozapine should be introduced if schizophrenia is not controlled despite the sequential use of two or more antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for at least 6–8 weeks.

LIFE-THREATENING = AGRANULOCYTOSIS/NEUTROPAENIA

  • Reduced seizure threshold
  • Constipation
  • Myocarditis: baseline ECG must be taken before starting
  • Hypersalivation
  • Hyperlipidaemia and hyperglycaemia
  • Weight gain
  • Liver dysfunction
47
Q

Modafinil

MoA

A
  • Inhibit the reuptake of dopamine by binding to the dopamine reuptake pump
  • Lead to an increase in extracellular dopamine
  • Modafinil activates glutamatergic circuits while inhibiting GABA
48
Q

Modafinil

Indications

A
  • Narcolepsy-related sleepiness
49
Q

Modafinil

CIs

A
  • Allergy and hypersensitivity
50
Q

Methylphenidate

Indications

A
  • ADHD
  • ADD
  • Narcolepsy
51
Q

Methylphenidate

Side effects

A
  • N+V, stomach pain
  • Reduced appetite
  • Vision problems
  • Dizziness
  • Headaches
  • Sweating
  • Rash
  • Anxiety/insomnia
  • Weight loss
  • Potentially cardiotoxic: baseline ECG first
52
Q

Z-drugs

MoA

A
  • Act on the alpha2-subunit of GABA receptor

- Similar effects to benzos but different structurally

53
Q

Z-drugs

Examples

A
  • Imidazopyridines: e.g. ZOLPIDEM
  • Cyclopyrrolones, e.g. ZOPICLONE
  • Pyrazolopyrimidines, e.g. ZALEPLON
54
Q

Z-drugs

Adverse effects

A
  • Similar to benzos

- Increased risk of fall in the elderly

55
Q

Serotonin syndrome

Causes

A
  • MAOIs
  • SSRIs (St John’s Wort can interact with SSRIs to cause it)
  • Ecstasy
  • Amphetamines
56
Q

Serotonin syndrome

Features

A

Classic triad:

  • Neuromuscular excitation (hyperreflexia, myoclonus, rigidity)
  • Autonomic nervous system excitation (e.g. hyperthermia)
  • Altered mental state
57
Q

Serotonin syndrome

Management

A
  • Supportive, including IV fluids
  • Benzodiazepines
  • Cyproheptadine (5-HT2 antagonist) or Chlorpromazine
58
Q

Neuroleptic malignant syndrome

Causes

A
  • Antipsychotics

- Levodopa

59
Q

Neuroleptic malignant syndrome

Mechanism

A
  • Dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage
60
Q

Neuroleptic malignant syndrome

Features

A
  • Pyrexia/fever
  • Tremor
  • Muscle cramps
  • Autonomic instability: HTN, tachycardia, tachypnoea
  • Delirium and confusion (agitated)
  • Muscle rigidity
  • Raised creatinine kinase (Ck) - can progress to rhabdomyolysis/acute kidney injury!
  • Leukocytosis
61
Q

Neuroleptic malignant syndrome

Management

A
  • Stop antipsychotic
  • Medical ward: ITU
  • IV fluids to prevent renal failure
  • DA agonists: BROMOCRIPTINE
  • Cooling devices/antipyretics
  • Treat rhabdomyolysis
  • Dantrolene may be useful in selected cases
62
Q

Dystonia

A

Extra-pyramidal SEs:

  • Parkinsonism
  • Acute dystonia: sustained muscle contraction
  • Akathisia (restlessness)
  • Tardive dyskinesia (choreoathetoid movements - chewing/pouting/excessive blinking)

MANAGE WITH PROCYCLIDINE

63
Q

Mesolimbic system

A

Hyperactivity is responsible for POSITIVE symptoms

64
Q

Mesocortical system

A

Underacvitiy if responsible for NEGATIVE symptoms

65
Q

Tuberoinfundibular pathways

A

Activation is involved in secretion of prolactin

66
Q

Nigrostriatal pathway

A

Activation involved in voluntary movement

67
Q

Lithium

Measurements before starting

A
  • BMI
  • FBC
  • U&Es
  • TFTs
  • eGFR
  • ECG
68
Q

Lithium

Measurements every 6 months

A
  • Serum lithium (0.4-1.0)
  • BMI
  • U&Es
  • TFTs
  • eGFR
  • Calcium

Phase 3A Medicine (17 decks)

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