Psych Pharmacology Flashcards
Name the main drug classes of antidepressants
- SSRIs
- SNRIs
- TCAs
- NaSSAs
- SARIs
- MAOIs
What does SSRI stand for?
Selective Serotonin Reuptake Inhibitor
What does SNRI stand for?
Serotonin and noradrenaline reuptake inhibitor (SNRI)
What does TCA stand for?
Tricyclic antidepressant
What does NaSSA stand for?
Noradrenergic and specific serotonergic antidepressant (NaSSA)
What does SARI stand for?
serotonin reuptake inhibitor (SARI)
What does MAOI stand for?
Monoamine oxidase inhibitor (MOAI)
Name some egs of SSRIs
- Fluoxetine,
- sertraline,
- paroxetine,
- citalopram,
- fluvoxamine
Name some egs of SNRIs
- Venlafaxine,
- Duloxetine
Name some egs of TCAs
- Amitriptyline,
- lofepramine,
- clomipramine,
- imipramine
Name an eg of NaSSAs
Mirtazapine
Name an eg of SARIs
Trazodone
Name some egs of MAOIs
- Phenelzine,
- tranylcypromine,
- isocarboxazid
What are the actions of SSRIs
Antagonises:
- serotonin reuptake pump
What are the actions of SNRIs
Antagonises:
- serotonin reuptake pump
- noradrenaline reuptake pump
- dopamine reuptake pump (in high doses)
What are the actions of TCAs
Antagonises:
- serotonin reuptake pump
- noradrenaline reuptake pump
- a-adrenergic receptor
- dopamine reuptake pump (slightly)
- muscarinic receptors
- histaminergic receptors
What are the actions of NaSSAs
Antagonises:
- 5HT (serotonin) receptor
- a2-adrenergic receptor
- muscarinic receptor (slightly)
- histamine-1 receptor
What are the actions of SARIs
Antagonises:
- a1-adrenergic receptor
- muscarinic receptor (slightly)
- histamine-1 receptor
What are the actions of MAOIs?
Nonselective and irreversible inhibition of:
- monoamine oxidase A and B
What are the SEs of SSRIs?
What are the SEs of SNRIs?
Same as SSRIs but greater
What are the SEs of TCAs?
What are the SEs of NaSSAs?
What are the SEs of SARIs?
same as TCAs
What are the side effects of MAOIs?
- Hypertensive crisis (secondary to tyramine ingestion i.e. cheese reaction)
-
Serotonin syndrome
- Occurs because MAOIs increase 5-HT
- Giving other antidepressants with a strong serotonergic effect (SSRIs, clomipramine, imipramine) at the same time as MAOIs increases the risk of serotonin syndrome; so does giving opiates
- Triad of neuromuscular abnormalities, altered consciousness, autonomic instability
Which food/drugs must be avoided in conjunction with MOAIs?
What is discontinuation syndrome?
- abrupt withdrawal of any antidepressant (except fluoextine)
- SSRIs with short half-lives (e.g. paroxetine, sertraline) and venlafaxine are particular culprits
- ~ → discontinuation syndrome
- symptoms:
- GI disturbance,
- agitation,
- dizziness,
- headache,
- tremor
- insomnia.
Name egs of mood stabilisers
lithium
anticonvulsants:
- sodium valproate,
- carbamazepine
- lamotrigine
How does lithium work as a mood stabiliser?
modulate the neurotransmitter-induced activation of second messenger systems
How do sodium valproate, carbamazepine and lamotrigine work as mood stabilisers?
- inhibit activity voltage-gated sodium channels
- enhance GABA- ergic neurotransmission
What are the indications of lithium?
- Acute mania
- Prophylaxis of bipolar affective disorder (prevention of relapse)
- Treatment-resistant depression (lithium augmentation)
What are the indications of sodium valproate?
- Epilepsy
- Acute mania
- Prophylaxis of bipolar affective disorder (second-line)
What are the indications of Carbamazepine?
- Epilepsy
- Prophylaxis of bipolar affective disorder (third-line)
What are the indications of Lamotrigine?
- Epilepsy
- Prophylaxis of depressive episodes in bipolar affective disorder (third-line)
What is the therapeutic window of lithium?
Therapeutic levels:
- 0.4–0.8 mmol/L when used adjunctively for depression;
- 0.6–1.0 mmol/L for treatment of acute mania and for bipolar disorder prophylaxis
When might lithium levels in the blood rise, other than due to increased dose?
Decreased clearance:
- renal impairment (e.g. in older adults, dehydration)
- dehydration (D&V, inadequate fluid intake)
- sodium depletion.
Drugs that increase lithium levels:
- diuretics (especially thi- azides),
- NSAIDS
- angiotensin-converting enzyme (ACE) inhibitors
What are the SEs of lithium?
-
General:
- Thirst, polydipsia, polyuria, weight gain, oedema, Fine tremor, Precipitates or worsens skin problems, Teratogenicity
-
Neuro:
- Concentration and memory problems
-
Endo:
- Hypothyroidism, Hyperparathyroidism
-
Renal:
- Impaired renal function
-
Cardiac:
- T-wave flattening or inversion
-
Haem:
- Leucocytosis
What are the signs of lithium toxicity?
-
1.5–2mmol/L:
- GI: nausea and vomiting,
- neuro: apathy,
- MSK: coarse tremor, ataxia, muscle weakness
-
>2mmol/L:
- neuro: nystagmus, dysarthria, impaired consciousness, hyperactive tendon reflexes, convulsions, coma
- renal: oliguria,
- CV: hypotension
Which Ix are required before starting lithium?
- FBC
- U&Es
- Calcium
- Thyroid function
- Pregnancy test (in women of childbearing age)
- ECG (if cardiac disease or risk factors)
Describe the blood monitoring prior to lithium Tx
Lithium blood levels:
- monitored weekly after starting Tx until a therapeutic level has been stable for 2 consecutive weeks
- then every 3 months for the 1st year,
- then every 6 months (unless the patient is at high risk for complications from lithium or has poor concordance).
Renal function, calcium and thyroid function:
- monitored every 6 months or more frequently if there is any evidence of impairment
What are the SEs of sodium valproate?
-
GI:
- Increased appetite and weight gain
- Nausea and vomiting
-
Neuro:
- Sedation and dizziness
-
CVS:
- Ankle swelling
-
Misc:
- Hair loss
- Tremor
- Haematological abnormalities (prolongation of bleeding time, thrombocytopenia, leucopenia)
- Raised liver enzymes (liver damage very uncommon)
What are the SEs of carbamazepine?
-
GI:
- Nausea and vomiting
- Raised liver enzymes (hepatic or cholestatic jaundice, rarely)
-
Derm:
- Skin rashes
-
Neuro:
- Blurred or double vision (diplopia)
- Ataxia
- drowsiness,
- fatigue
-
Haem:
- Hyponatraemia and fluid retention
- Haematological abnormalities (leucopenia, thrombocytopenia, eosinophilia)
What are the SEs of lamotrigine?
-
GI:
- Nausea and vomiting
-
Derm:
- Skin rashes (consider withdrawal) - ?Stephen-Johnsons syndrome (particularly in first 8 weeks of use)
-
Neuro:
- Headache
- Aggression, irritability
- Sedation & dizziness
-
Misc:
- Tremor
Compare the different monitoring required of different mood stabilisers
-
Lithium:
-
Prior to starting:
- Medication review, blood tests (FBC, U&Es, eGFR, TFTs, Ca), pregnancy test, (ECG if CVD)
-
Once started:
- Lithium plasma levels weekly (12hrs post-dose), until level has been stable for 4wks, then every 3 months (start monitoring from start if dose changed);
- Every 6 months: FBC, U&Es, eGFR, TFTs, Ca
-
Prior to starting:
-
Sodium valproate:
-
Prior to starting:
- BMI, FBC, LFTs, pregnancy test
-
Once started:
- BMI, FBC, LFTs & prothrombin time 6 months after treatment initiated, and yearly thereafter
-
Prior to starting:
-
Carbamazepine:
-
Prior to starting:
- FBC, U&Es, LFTs
-
Once started:
- Periodic FBC, U&Es, LFTs
-
Prior to starting:
-
Lamotrigine
- none required
Compare NICE guidelines for women of childbearing age using the different mood stabilisers
- Lithium → use reliable contraception, but avoid in those breastfeeding
- Sodium valproate → use with extreme caution in women of childbearing age (risk of foetal malformations if taken during pregnancy) → enrol on pregnancy prevention programme
- Carbamazepine → no teratogenic effects
- Lamotrigine → no teratogenic effects
What are the contraindications of lithium?
-
Lithium:
- untreated hypothyroidism,
- heart failure,
- cardiac arrhythmia
- Pregnancy and breastfeeding
- Caution in renal disease, cardiac disease and thyroid disease
- Caution in conditions causing Na imbalance, e.g. Addison’s disease
What are the contraindications of sodium valproate?
- Hepatic dysfunction
- Porphyria
- Pregnancy and breastfeeding
What are the contraindications of carbamazepine?
- Atrioventricular conduction abnormalities (unless paced)
- History of BM depression
- Acute porphyria
- Pregnancy and breastfeeding
What are the contraindications of lamotrigine?
- Caution in myoclonic seizures and Parkinson’s (may be exaggerated)
- Caution in hepatic and renal failure
Summarise the contraindications of the mood stabilisers
-
Lithium:
- untreated hypothyroidism,
- heart failure,
- cardiac arrhythmia
- Pregnancy and breastfeeding
- Caution in renal disease, cardiac disease and thyroid disease
- Caution in conditions causing Na imbalance, e.g. Addison’s disease
-
Sodium valproate:
- Hepatic dysfunction
- Porphyria
- Pregnancy and breastfeeding
-
Carbamapezine:
- Atrioventricular conduction abnormalities (unless paced)
- History of BM depression
- Acute porphyria
- Pregnancy and breastfeeding
-
Lamotrigine:
- Caution in myoclonic seizures and Parkinson’s (may be exaggerated)
- Caution in hepatic and renal failure
Name the typical antipsychotics
- Chlorpromazine
- Haloperidol
- Sulpiride
- Flupentixol
- Zuclopenthixol
Name the atypical antipsychotics
- clozapine
- olanzapine
- quetiapine
- risperidone
- aripiprazole
Which antipsychotics can be given IM (long-acting depot)?
Typical:
- haloperidol
- flupentixol
- zuclopenthixol
Atypical:
- Olanzapine
- Risperidone
- Aripiprazole
How do all antipsychotics work (except clozapine)?
Therapeutic effect:
- Antagonism of dopamine D2 receptors in the mesolimbic dopamine pathway
Side-effects
- Antagonism of dopamine D2 receptors throughout the brain
- Antagonism of muscarinic, histaminergic and α-adrenergic receptors
Summarise the dopamine pathways in the brain
Which dopamine pathways cause the positive and negative symptoms of schizophrenia?
How does clozapine work?
- antagonism of 5-HT-2A receptors and D4 receptors,
- among many other receptor targets.
What are the common side effects of all antipsychotics?
What are EPSEs? What is the Tx for each of them?
Name the SEs that are specific to atypical antipsychotics
- greater risk of metabolic syndrome than typical antipsychotics
- less risk of EPSEs than typical antipsychotics
What are the SEs that are specific to clozapine?
- greater risk of metabolic syndrome than typical antipsychotics
- agranulocytosis
- myocarditis
- cardiomyopathy
What are the SEs specific to clozapine?
- greater risk of metabolic syndrome than typical antipsychotics
- agranulocytosis
- myocarditis
- cardiomyopathy
How does monitoring vary between typical, atypical antipsychotics and clozapine?
-
Typical:
- BP,
- pulse,
- ECG
-
Atypical:
- weight,
- BP,
- ECG,
- lipids,
- glucose/HbA1c,
- FBC,
- U&Es,
- LFTs
-
Clozapine:
- weight,
- lipids,
- ECG,
- LFTs
- Before starting, weekly FBC for 1st 18wks, then fortnightly, then monthly
- If leukocyte count <3000/mm3 or absolute neutrophil count <1500mm3 → discontinue permanently and refer to haematologist
How do contraindications vary according to typical, atypical antipsychotics and clozapine?
-
Typical:
- Parkinson’s,
- Bradycardia,
- QT prolongation
-
Atypical:
- CVD,
- metabolic syndrome,
- epilepsy
- elderly
-
Clozapine:
- Severe cardiac disease,
- Acute liver disease,
- Severe renal impairment,
- History of bone marrow disorders
Compare and contrast neuroleptic malignant syndrome (due to antipsychotics) and serotonin syndrome (due to antidepressants)
