Psychiatry: Pharmacology Flashcards
Benzodiazepines
MoA
- 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)
Benzodiazepines
Indications
- Insomnia
- Parasomnias
- Anxiety disorders
- CNS withdrawals, e.g. DELIRIUM TREMENS
Benzodiazepines
Side effects
7
- Dependence (therefore should only be prescribed for 2-4 weeks at a time)
- Tolerance
- Somnolence
- Cognitive defects
- Amnesia
- Disinhibition
- Do NOT let them drive
Benzodiazepines
Examples (5)
- Lorazepam
- Diazepam
- Temazopam
- Clonazepam
- Chlordiazepoxide (Delirium tremens)
Benzodiazepines
Rapid withdrawal symptoms
- Insomnia
- Irritability
- Anxiety
- Tremor
- Loss of appetite
- Tinnitus
- Perspiration
- Perceptual disturbances
- Seizures
Discuss antidepressants in general
- 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
1st line for new depressed patient?
Sertraline
SSRIs
MoA
Selective inhibition of serotonin pumps within synapses with high potency
No effect on noradrenaline
SSRIs
Examples
Sertraline Citalopram Fluoxetine Escitalopram Paroxetine
SSRIs
Side effects
- Nausea/headache/GI upset (5-HT3) (5-HT2): - Insomnia - Agitation - Anxiety - Tremor - Extrapyramidal signs - Dyspepsia - Bloating - Sweating - Dry mouth - Sexual dysfunction - Hyponatraemia (SIADH) - SUICIDALITY!
Tricyclic antidepressants
MoA
- 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)
Tricyclic antidepressants
Examples
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
Tricyclic antidepressants
Side effects
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
Monoamine oxidase inhibitors (MAOIs)
MoA
- Binds irreversibly to MAO
- Prevents inactivation of amines (noradrenaline, serotonin and dopamine)
- Increases synaptic levels
Monoamine oxidase inhibitors (MAOIs)
Indications
- Atypical depression (e.g. hyperphagia)
- Other psychiatric disorders
Monoamine oxidase inhibitors (MAOIs)
Examples
- Phenelzine
- Isocarboxazid
- Moclobemide
- Tranylcypromine
Monoamine oxidase inhibitors (MAOIs)
Side effects
(Same as TCA)
- Confusion
- Constipation
- Difficulty micturition
- Dry mouth
- Drowsiness
- Sexual dysfunction
- Postural hypotension
- Headache
- Dizziness
- Insomnia
- Tremor
- Sweating
- Serotonin syndrome
Monoamine oxidase inhibitors (MAOIs)
Interactions
Tyramine-rich foods:
- Cheese
- Wine
- Beer
- Broadbeans
- Aged foods
- Bovril/Oxo
- Marmite
Drugs:
- Opiates
- Cocaine
- Insulin
- L-dopa
SNRIs
MoA
- Selectively inhibits both serotonin and noradrenaline pre-synaptic receptors and reduces reuptake
- NO antihistaminic, anticholinergic or antiadrenergic effects
SNRIs
Examples
- Venlafaxine
- Duloxetine
SNRIs
Indications
- Major depressive disorder
- GAD
- Social anxiety disorder
- Panic disorder
- Menopausal symptoms
- Chronic/neuropathic pain (Duloxetine)
Sodium valproate
MoA
- Increases GABA activity
- Mood stabiliser
Sodium valproate
Indications
- Mania or depression prophylaxis
Sodium valproate
Side effects
- Sedation
- Tremor
- Nausea/vomiting
- Thrombocytopaenia
- Platelet dysfunction
- Weight gain and increased appetite
- P450 inhibitor
- Ataxia
- Alopecia: regrowth may be curly
- Pancreatitis
- SEVERELY TERATOGENIC
Sodium valproate
Monitoring
- FBs/U&Es/Creatinine
- Pregnancy test (hCG)
Lithium
Indications
- Long-term prophylaxis of Bipolar Affective Disorder (controls depression and mania)
- Only medication to reduce suicide rates (15% in BAD)
Lithium
Side effects
- 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
Lithium
Monitoring
- 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!
Lithium
MoA
- 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)
Lithium toxicity
Lithium levels
Generally occurs following concentrations > 1.5 mmol/L
Lithium toxicity
Precipitating factors
- Dehydration
- Renal failure
Drugs:
- Thiazide diuretics/Loop diuretics
- ACE-Is/ARBs/NSAIDs/Metronidazole
Lithium toxicity
Mild levels/features/management
1.5 - 2.0 mmol/L
- D+V
- Ataxia
- Dizziness
- Slurred speech
- Nystagmus
Management: volume resuscitation with saline (forced alkaline diuresis)
Lithium toxicity
Moderate levels/features/management
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)
Lithium toxicity
Severe levels/features/management
> 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
Typical antipsychotics (First generation)
MoA
- 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
Typical antipsychotics (First generation)
Examples
- Haloperidol (high potency)
- Chlorpromazine (low potency)
Typical antipsychotics (First generation)
Side effects
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
Caution of all antipsychotics
Elderly: increased risk of VTE or stroke
Atypical antipsychotics (Second generation)
MoA
Serotonin-dopamine 2 antagonists
Pathways: mesolimbic and serotonin
Atypical antipsychotics (Second generation)
Indications
First-line for schizophrenia/psychosis
Atypical antipsychotics (Second generation)
Examples
- Risperidone
- Olanzapine (higher risk of dyslipidaemia and obesity)
- Quetiapine
- Clozapine
- Amisulpride
- Aripiprazole (low prolactin levels)
Atypical antipsychotics (Second generation)
Side effects
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
Aripiprazole
MoA
- 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
Hyperprolactinaemia
- 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
Paliperidone
- 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
Clozapine toxicity
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
Modafinil
MoA
- 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
Modafinil
Indications
- Narcolepsy-related sleepiness
Modafinil
CIs
- Allergy and hypersensitivity
Methylphenidate
Indications
- ADHD
- ADD
- Narcolepsy
Methylphenidate
Side effects
- N+V, stomach pain
- Reduced appetite
- Vision problems
- Dizziness
- Headaches
- Sweating
- Rash
- Anxiety/insomnia
- Weight loss
- Potentially cardiotoxic: baseline ECG first
Z-drugs
MoA
- Act on the alpha2-subunit of GABA receptor
- Similar effects to benzos but different structurally
Z-drugs
Examples
- Imidazopyridines: e.g. ZOLPIDEM
- Cyclopyrrolones, e.g. ZOPICLONE
- Pyrazolopyrimidines, e.g. ZALEPLON
Z-drugs
Adverse effects
- Similar to benzos
- Increased risk of fall in the elderly
Serotonin syndrome
Causes
- MAOIs
- SSRIs (St John’s Wort can interact with SSRIs to cause it)
- Ecstasy
- Amphetamines
Serotonin syndrome
Features
Classic triad:
- Neuromuscular excitation (hyperreflexia, myoclonus, rigidity)
- Autonomic nervous system excitation (e.g. hyperthermia)
- Altered mental state
Serotonin syndrome
Management
- Supportive, including IV fluids
- Benzodiazepines
- Cyproheptadine (5-HT2 antagonist) or Chlorpromazine
Neuroleptic malignant syndrome
Causes
- Antipsychotics
- Levodopa
Neuroleptic malignant syndrome
Mechanism
- Dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage
Neuroleptic malignant syndrome
Features
- 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
Neuroleptic malignant syndrome
Management
- 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
Dystonia
Extra-pyramidal SEs:
- Parkinsonism
- Acute dystonia: sustained muscle contraction
- Akathisia (restlessness)
- Tardive dyskinesia (choreoathetoid movements - chewing/pouting/excessive blinking)
MANAGE WITH PROCYCLIDINE
Mesolimbic system
Hyperactivity is responsible for POSITIVE symptoms
Mesocortical system
Underacvitiy if responsible for NEGATIVE symptoms
Tuberoinfundibular pathways
Activation is involved in secretion of prolactin
Nigrostriatal pathway
Activation involved in voluntary movement
Lithium
Measurements before starting
- BMI
- FBC
- U&Es
- TFTs
- eGFR
- ECG
Lithium
Measurements every 6 months
- Serum lithium (0.4-1.0)
- BMI
- U&Es
- TFTs
- eGFR
- Calcium
