Psychopharmacology Flashcards by Jack Wildman

What is clomipramine and how does it work at lower vs higher doses?

A TCA that works as a SSRI at lower doses and NaRI at higher doses

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How does clomipramine metabolism affect its action? What clinical bearing does this have?

The metabolite of clomipramine (desmethylclomipramine) acts as a NaRI
So rapid metabolisers see less of an effect for clomipramine e.g. In OCD
Monitoring levels of clomipramine and desmethyclomipramine can guide dosage

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6 examples of TCAs?

Amitriptyline
Clomipramine
Imipramine
Lofepramine
Dosulepin
Doxepin

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How do TCAs work?

5-HT and NA uptake blockade via SERT and NET blockage - a bit like SNRIs

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What 4 receptors do TCAs antagonise for their side effects?

M1 muscarinic
H1 histaminergic
a1 alpha receptor
NMDA receptors

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What effect do TCAs have on DA?

None directly

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What TCA is the best tolerated in terms of side effects and OD toxicity? What role does it therefore have?

Lofepramine

So is second line in primary care

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What TCA is 2nd or 3rd line for OCD?

Clomipramine

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What role may amitriptyline play in severe depression?

Maybe more effective than SSRIs

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What receptors/channels are involved in the cardiotoxicity of TCAs?

Na channels

L-type Ca channels

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What antiarrythmic activity do TCAs have?

Class 1A antiarrythmics

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Antimuscarinic side effect profile?

Dry mouth, dry nose
Blurred vision
Constipation
Urinary retention
Cognitive impairment
Increased temp

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What are antihistaminergic side effects?

Sedation

Weight gain

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What is the major alpha blockade side effect?

Hypotension

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What 3 side effect profiles are seen in TCAs?

Antihistaminergic
Antimuscarinic
Anta-alpha adrenergic

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What drugs must you be wary of using alongside TCAs and why?

Enzyme inducers or inhibitors - P450 metabolism
Long QT drugs as can cause ventricular dysrhythmia
Alcohol and other CNS depressants
Other antimuscarinic drugs
Other 5-HT drugs, MAOIs etc. Due to serotonin syndrome

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TCA overdose profile?

Mega Anticholinergic effect so high temp, tachycardia, mydriasis, reduced consciousness
Cardiac - transient hypertension then profound hypo, dysrhythmias
CNS - seizures, syncope, coma, myoclonus, hyperreflexia
CNS depression and hypoventilation
GI constipation and vomiting
Grabby and hallucinating

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Within how long of ingestion will TCA OD effects become apparent?

1 hour or so

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Management of TCA overdose?

Gastric decontamination if within 1-2 hour (activated charcoal)
Monitoring - BP, ECG, pH - assess for resp support and ICU need
Treat metabolic acidosis with IV sodium bicarbonate
Treat dysrhythmias

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What acid base disturbance is seen in TCA OD? How do you treat?

Metabolic acidosis

Treat with sodium bicarb

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How do you treat the cardiovascular effects of a TCA OD?

Sodium bicarb IV

also non-1A antiarrythmics, magnesium sulphate

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What is often defined as medically clear following TCA OD?

ECG normal for 24 hours

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What management might be considered for severe refractory TCA OD?

IV lipid emulsion therapy

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5 examples of SSRIs?

Fluoxetine = Prozac
Sertraline = Zoloft/Lustral
Paroxetine = Seroxat
Citalopram
Escitalopram

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How do SSRIs work?

Inhibition of 5-HT reuptake

What is a 5-HT 1 agonist side effect seen in SSRIs?

Early increased anxiety

What is early increased anxiety likely a result of in SSRIs?

5-HT 1 agonism

What is a side effect of 5-HT 2 agonism in SSRIs?

Sexual dysfunction

What likely causes sexual dysfunction in SSRIs?

5-HT2 agonism

What is a side effect of 5-HT 3 agonism in SSRIs?

Nausea

What is nausea in SSRIs likely a result of?

5-HT 3 blockade

What is ondansetron and how does it work?

5-HT3 antagonist used as an anti-emetic

What are the 3 most common side effects of SSRIs?

Nausea Sexual dysfunction Early increase in anxiety

4 less common side effects of SSRIs?

Akathisia Photosensitivity Increased risk of osteoporosis and fractures Increased risk of bleeding with anticoagulants

What SSRI has the most likely discontinuation syndrome? Sx?

Paroxetine | Electric shock like sensations, headache, malaise, anxiety, insomnia

Which SSRI has the least bad discontinuation syndrome and why?

Fluoxetine - long half life

What is the worst SSRI to OD on? Why?

Citalopram - can prolong QTc and cause arrhythmias

What are the 3 general areas of Sx of serotonin syndrome?

Autonomic e.g. High temp, ANS instability, sweating, tachy and high BP, vasoconstriction, mydriasis, nausea, diarrhoea Cognitive/CNS e.g. Clonus, myoclonus, brisk reflexes, tremor, seizures Somatic e.g. Metabolic acidosis, rhabdomyolysis, renal failure, DIC

Common drugs responsible for serotonin syndrome?

``` SSRIs MAOIs Lithium TCAs Linezolid Tramadol MDMA Pethidine St Johns Wort SNRIs Buspirone Triptan Mirtazapine ```

2 common painkillers that can cause serotonin syndrome?

Tramadol | Pethidine

What do MAOIs and tryptans (tryptamine/tryptophan) result in?

Mega high BP, bit like serotonin syndrome

Differentials for serotonin syndrome?

``` Carcinoid syndrome NMS Malignant hyperthermia Meningitis Heat stroke ```

Example of a NaRI? Another that is sort of NaRI?

Reboxetine | Lofepramine sort of is

What is reboxetine?

NaRI

What is the role of reboxetine?

Well tolerated, but possibly not very potent antidepressant used as an alternative to SSRIs

Apart from depression, what is reboxetine used for off license?

Panic disorder | ADHD

2 examples of SNRIs?

Venlafaxine | Duloxetine

How do SNRIs work?

Inhibit reuptake of serotonin, noradrenaline and DA

What drug class has a similar pharmacological profile to TCAs? What advantage do they have over TCAs?

SNRIs | Advantage is that they don't have the M1/H1/a1 antagonistic activity so better tolerated

How does the pharmacological profile of SNRIs change with dose?

``` Low = 5-HT blockade Med = Na blockade High = DA blockade ```

How does mirtazapine work? 3 ways

NaSSa - noradrenaline and selective serotonin antagonist Works by blocking presynaptic a2 heteroceptors, which has the net effect of raising intrasynaptic 5-HT1 transmission Blocks 5-HT2 so is anxiolytic Blocks H1 so causes sedation

2 major side effects of mirtazapine? Why?

Sedation and weight gain | Due to dual H1 blockade and 5-HT2 blockade

Advantages of mirtazapine over SSRIs?

More potent | Less sexual dysfunction side effects

How does trazadone work? What effect profile does this give?

5-HT2 antagonist | Less depression and anxiety

What role may trazadone have in antidepressant therapy?

Good anxiolytic and probably less potent but good adjunct to SSRI, SNRI

What is moclobemide?

A reversible MAOI

2 examples of MAOIs?

Phenelzine | Selegiline

How does vortioxetine work?

Blocks 5-HT uptake Also binds several 5-HT receptors Improves cognition

How does agomelatine work?

M1 and M2 agonist | 5-HT2c antagonist

What must be checked in agomelatine use?

LFTs

2 examples of NaSSAs?

Mirtazapine | Mianserin

How do Z drugs work?

GABAergic activity so inhibitory

What is the difference between anxiolytics and hypnotics?

Hypnotics are anxiolytics with shorter half lives

Broadly how might you pharmacologically manage anxiety?

Start on antidepressants which may take 6-8 weeks to work | Plus benzos for first 1-2 weeks

How does buspirone work? What's it for?

5-HT 1A agonist | For anxiety disorders e.g. GAD

2 examples of typical antipsychotics?

Haloperidol | Chlorpromazine

7 examples of atypical antipsychotics?

``` Clozapine Olanzapine Risperidone Olanzapine Amisulpride Aripiprazole Lurasidone ```

What is the key receptor blockade for classical antipsychotic activity?

What side effect profiles do typical antipsychotics have?

Antagonise H1, M1 and NA for side effect profiles | Also EPSEs come from D2 antagonism

What are the 2 core receptors in atypical antipsychotics?

5-HT2A | D2

Advantages and disadvantages of clozapine?

Really good antipsychotic for resistant schizophrenia Has less EPSEs than others Disadvantages include long term cardiac risk and possibility of agranulocytosis and neutropenia

What particular symptoms of schizophrenia does clozapine have a significant effect on?

Negative symptoms

How does amisulpride work?

D2/3 blockade alone

What antipsychotic works by D2/3 antagonism alone?

Amisulpride

How does Aripiprazole work?

Dopamine partial agonist

What antipsychotic works as a partial DA agonist?

Aripiprazole

How do quetiapine, risperidone and olanzapine work?

5-HT2 and D2 antagonism

Apart from anti psychosis, what else are atypical antipsychotics used for?

Mania Severe or psychotic depression BPAD Sometimes anxiety

Which atypical antipsychotic is particularly associated with akathisia?

Aripiprazole

Which two atypical antipsychotics have the lowest risk of hyper prolactin?

Quetiapine | Olanzapine

Which antipsychotic has the best evidence in bipolar disorder?

Quetiapine

What risk is associated with Lamotrigine and how is this reduced?

Stevens Johnson syndrome | Slowly up titrate and monitor for rashes

How often should you monitor lithium levels and why?

3 monthly due to narrow therapeutic range

What bloods should you check for lithium and how often?

TFTs Renal function 6 monthly

What is the risk of stopping lithium acutely?

50% risk of mania

What birth anomaly is associated with lithium use?

Ebsteins anomaly

What advantages does quetiapine have over other atypicals?

Fewer issues with weight gain or prolactin

Which atypical antipsychotic has a key risk of prolonging QTc?

Amisulpride

What constitutes a clozapine screen and why?

Fbc (WCC over 3.5), blood group Temp, heart rate, weight Myocarditis screen - cardiac enzymes, echo after 6m

3 examples of typical antipsychotics given as depot?

Haloperidol Flupenthixole Fluphenazine

How do you treat antipsychotic associated EPSEs?

Can reduce dose if poss or consider changing | Anticholinergics e.g. Benztropine, trihexyphenidyl

What is prochlorperazine?

A D2 receptor antagonist typical antipsychotic also used as an antiemetic (nausea, vertigo)

What is promethazine?

An antihistamine, sedative and weak antipsychotic (D2 blockade)

Common side effects of lithium?

Increased urination Tremor Thirst

Common signs of lithium OD?

``` Nausea, diarrhoea, vomiting Cognitive impairment Ataxia Somnolence and depressed consciousness Tinnitus ```

Long term SEs of lithium?

Tremor Diabetes insipidus Hypo/hyperthyroidism Acne

Why does lithium cause dehydration and associated Sx?

Inhibits ADH so had diuresis effect | Then dehydration also raises lithium levels and so can worsen

What ECG changes are commonly seen in lithium?

Benign T wave changes

What heart defect is associated with maternal lithium use?

Ebsteins anomaly

What neuromuscular signs may be seen in lithium use?

``` Hyperreflexia Myoclonus Tremor Headache Transient muscle weakness ```

Drug interactions with lithium?

Diuretics esp loop and thiazides NSAIDs ACEis Can all raise lithium level and can cause renal failure

3 drugs which can increase lithium excretion and lower levels?

Theophylline Caffeine Acetazolamide

What effect may increasing dietary sodium intake have on lithium levels?

May lower due to increasing excretion

How is lithium excreted?

Glomerular filtration | Some reabsorbed in proximal tubule related to salt and water concentrations

What effect does sodium depletion have on lithium concentrations?

Low sodium causes increased reabsoprtion of sodium in proximal tubule Lithium and sodium are co absorbed so increases lithium absorption Leading to high lithium levels