Psychopharmacological Therapy

What are monoamine NTs?

serotonin and dopamine

Do we know how monoamine NTs work?

not really

How long does it take monoamines to work?

several weeks even with acute changes (possible chronic adaptation)

What functional group are monoamines derived from?

amines → ammonia

Where is serotonin produced in the brain?

raphe nuclei

What bodily functions does serotonin impact?

1. GI

2. arousal

3. vascular

4. clotting

5. inflammatory response

What are the 2 serotonin receptors?

• 5HT1a - treating depression

• 5HT2a

• 5HT3 - N/V

Which drug types bind to 5HT2a?

1. atypical antipsychotics antagonists → (STOP hallucinations)

2. Agonists → CREATE hallucinations

   1. LSD/shrooms (psilocin)

What is the receptor most associated with serotonin syndrome?

5HT2A

Which meds bind to 5HT3?

ondansetron and all the -setrons

What do SRIs block?

reuptake of serotonin from cleft back into presynaptic neuron → enhances serotonergic neurotransmission

What are common side effects of serotonergic drugs?

sedation, anticholinergic (overheating, inc. HR), orthostatic hypotension

What were the first antidepressants?

TCAs

What is significant about TCAs chemical structure?

3 rings

Which serotonin drugs have the most anticholinergic activity?

TCAs

In what population is TCAs side effects seen more in?

elderly

Why aren’t TCAs used anymore?

their side effects

Norepi & Multimodal serotonin drugs have the most …

sedation compared to other drug classes

Norepi & Multimodal serotonin drugs have moderate …

anticholinergic properties

What are examples of TCAs?

mirtazapine and doxepin

What is the half-life of serotonin drugs?

5-7 days

Drugs with shorter … have more severe ….

half-lives; withdrawals

Which SRIs have shorter half-lives?

1. paroxetine

2. venlafaxine

3. duloxetine

“tine” and “xines”

What are the effects of SRI discontinuation syndrome?

flu-like symptoms and brain-zaps

Is SRI discontinuation syndrome dangerous?

no

How do you treat SRI discontinuation syndrome?

take the med

Should SRIs be discontinued in peri-operative period?

no, except MAOIs

Which lab value can SRIs impact?

sodium → clinically significant hyponatremia

• DO NOT TREAT FAST (perm neuro changes)

What is serotonin syndrome a problem of?

ANS excitability

What are symptoms of Serotonin Syndrome?

ANS:

1. hyperreflexia - knee jerk

2. diaphoresis

3. rigidity

4. hyperpyrexia - extreme fever

Mental:

1. anxiety

2. confusion

For all of the syndromes, what temp does the fever get too?

40 degrees, except malignant hyperthermia → 46 degrees

What is important to consider when trying to treat drug syndrome?

what is the person taking. which drug

What is mad-hatter syndrome associated with?

anticholinergic syndrome → muscarinic antagonists

Which non-psychiatric drugs can cause serotonin syndrome?

1. methylene blue

2. Opoids

   1. demerol

   2. tramadol

   3. fentanyl

3. dextromethorphan

what is the treatment for serotonin syndrome?

• Stop the drug

• 5-HT2A antagonist interventions

  • Cyproheptadine

    • serotonin receptor antagonist

    • H1 blocker → antihistamine

What drug class is Buspirone?

serotonin 5-HT1A agonist

What does buspirone treat?

anxiety

Why is buspirone okay to give with anesthesia?

bc it has no effects on GABA receptors → no cross-reactivity with benzos, barbs, or alcohol

Which drug class has the largest immediate anesthesia implications?

MAOIs

What can MAOIs cause?

severe life-threatening hypertension

What is the diet consideration for MAOIs?

tyramine limit → creates catecholamines

What foods do people taking MAOIs need to avoid?

1. cheese

2. sour cream

3. yeasts

4. yogurt

what is the mechanism of action of MAOIs?

irreversible enzyme inhibition; permanent

What does monoamine oxidase break down?

serotonin, catecholamines, tyrosine

What is the pathway of catecholamine biosynthesis?

phenylalanine

⬇

tyrosine

⬇

dopa

⬇

norepi

⬇

epi

what is the amino acid that all catecholamines come from?

tyrosine

MAO-A and MAO-B both metabolize …

dopamine

Drugs that inhibit MAO-B have fewer … and rarely …

side effects; dietary restrictions

Beside dopamine, what does MAO-A metabolize?

norepi

Why are MAO-Bs used to treat PD?

fewer major side effects

the 2 forms of monoamine oxidase enzyme exhibit …

substrate selectivity

which breakdown products detect/help diagnose pheochromocytoma?

Homovanillic Acid (HCA) and Vanilmandelic acid (VMA)

When selegiline is used to treat PD, what does it selectively inhibit?

MAO-B → patients do not need to follow a tyramine-free diet

What does selegiline elicit?

massive release of endogenous catecholamines

They clinical symptoms of selegiline are the same as …

pheochromocytoma

Which drugs do people taking selegiline need to avoid?

SSRIs, SNRIs, TCAs, and ephedrine

Why should ephedrine be avoided with selegiline?

may cause lethal dose of catecholamines; should use direct acting catecholamines instead

What dose of direct acting catecholamines should be used with selegiline?

1/3 of normal dose

What is the 1st line treatment for MAOI induced HTN crises?

peripheral vasodilators → nitroglycerin/nitroprusside

What are secondary arrhythmias of MAOI HTN crises treated with?

lidocaine or B1-adrenergic antagonist

What are the anesthesia considerations for people taking MAOIs?

1. can have anesthesia with precautions

2. avoid sympathetic stimulation → intubation will do this

3. avoid ephedrine

4. regional anesthesia better

5. avoid opioids

What are the symptoms of TCA overdose?

anticholinergic toxicity

1. sz’s → acidosis - give bicarb

2. heart block - isoproterenol

3. Ventricular cardiac arrhythmias → acidosis - give bicarb

4. hypotension

How does TCA overdose usually occur?

polypharmacy with OTC medications with anticholinergic effects

What populations is at risk for TCA overdose?

elderly → with anticholinergic effects

What kind of therapeutic window do TCAs have?

narrow

Hallmarks of TCAs’ therapeutic window.

1. overdose usually fatal

2. drug is cardiotoxic

3. predispose to seizure and sedation

4. More lethal when taken for suicide

What is anticholinergic poisoning also called?

matter hatter syndrome

What are the symptoms of anticholinergic poisoning?

2. anhydrosis

3. dry mucous membranes

4. mydriasis → giving atropine alters pupil size assessment

   1. cannot be diagnosed as non-reactive a/f atropine

5. altered mental status

6. tachycardia

7. urinary retention

Anticholinergic effects!!

What drug class is bupropion?

norepi dopamine reuptake inhibitor

What is bupropion usually used in?

depression and smoking cessation

How does bupropion affect smoking cessation?

increased dopamine levels lessens withdrawal and prevents crave to smoke

What is the risk of taking bupropion?

seizures related to stimulant effect

What is bupropion contraindicated with?

taking MAOIs

What is the drug “class” of methylphenidate?

drugs with primarily dopaminergic activity

What is the mixed structure of methylphenidate?

mixed amphetamine salts (levo/dextro amphetamine)

What are the side effects of methylphenidate?

anxiety, appetite suppression, and cardiac stimulation

What is the anesthesia consideration for methylphenidate?

• holding prior to anesthesia is reasonable unless chronically on it

• hemodynamic instability → but not really

What is the drug class of modanifil?

dopamine reuptake inhibitor

What is modafinil and what does it promote?

a pyschostimulant and wakefulness

What is modafinil indicated in?

narcolepsy, shift work sleep disorder, and OSA

True or false. Modafinil has a higher abuse potential than amphetamines.

false

What are the types of extrapyramidal symptoms?

1. akathisia - restlessness/fidgeting

2. dystonia - muscles contract on their own

3. parkinsonism - parkinson like

4. tardive dyskinesia - involuntary facial movements

What are the categories of dopamine related drug side effects?

extrapyramidal symptoms

restless legs syndrome (RLS)

Why does RLS occur?

Lowered dopamine levels

• health or drug problem

• any drug that antagonizes dopamine

What is RLS characterized by?

unpleasant sensations in ankles/feet that occur at night and relieved by walking

What is RLS not?

feet moving on their own; it’s an uncomfortable sensation

What are examples of dystonic reactions?

1. oculogyric crises from metoclopramide - eyes stuck looking up

2. opisthotonos - arched back

3. neck dystonias

these are tardive dyskinesias

What are tardive dyskinesias/dystonic reactions treated with?

benadryl

What are the 4 types of neck dystonias?

1. torticollis

2. laterocollis

3. retrocollis

4. antecollis

what is the drug class of benztropine?

anticholinergic and dopamine re-uptake inhibitor

Which receptors do benztropine bind to?

M1: potent and selective muscarinic-1 antagonist

What symptoms do M1 receptors cause?

1. significant dry mouth

2. urinary retention

3. confusion

4. memory issues

benztropine has limited use because of this

What is benztropine used in conjunction with?

D2 receptor-blocking drugs

What is benztropine used for?

prophylactic or antidote to acute drug-induced EPS

Benztropine has multiples uses …

secondary to its ability to enhance dopamine concentrations

• RLS, acute EPS, parkinson’s disease

What do D2/D3 receptor agonists treat?

1st line treatment for PD and RLS

What is the limiting factor for D2/D3 receptor agonist?

drug augmentation in chronic treatment

Why are D2/D3 receptor agonist preferred in PD?

to delay use of carbidopa/levodopa

What are the dopamine pathways?

1. Mesolimbic

2. Mesocortical

3. Nigrostriatal (SN)

4. Tuberoinfundibular

What does the mesolimbic pathway target?

antipsychotic efficacy