Antidepressants Flashcards
What are the natural and synthetic catecholamine agonists?
- natural
- epinephrine
- norepi
- dopamine
- synthetic
- isoproterenol
- dobutamine
The receptors that are termed alpha receptors respond to the catecholamines in what order of potency?
Norepi > epi > isoproterenol
The receptors that are termed beta receptors respond to the natural and synthetic catecholamines in what order of potency?
Isoproterenol > epi > norepi
What is serotonin?
Where is it found in the highest concentration?
- 5-Hydroxytryptamine (5-HT)
- neurotransmitter and local hormone
- highest concentration:
- wall of intestine
- blood
- CNS
What are the three types of antidepressants?
- Selective serotonin reuptake inhibitors
- tricyclic antidepressants
- Monoamine Oxidase Inhibitors
What are SSRI’s used for?
- treat mild to moderate depression
- anxiety disorder
- panic disorder
- OCD
- post-traumatic stress disorder
- social phobia
- bi-polar depressive episodes
What is the MOA of SSRI’s?
- All block reuptake of serotonin
- New SSRI’s act on serotonin, NE, and/or dopamine
- some produce alpha 2 receptor blockade
What makes an SSRI atypical?
If it acts on dopamine
What are the typical SSRIs?
- Fluoxetine (prozac)
- Sertraline (zoloft)
- Paroxatine (paxil)
- Fluvoxamine (Luvox)
- Escitalopram (Lexapro)
Which antidepresent is the most potent inhibitor of CYP450?
Fluoxetine (prozac)
Why are SSRIs the anti depressant of choice?
- Higher safety index than other classes
- minimal effects on blood pressure
- no issues with cardiac conduction
- no changes in seizure threshold
What are the side effects of SSRI’s?
- Insomnia/ fatigue
- agitation
- orthostatic hypotension
- headache
- nausea/vomiting
- sexual dysfunction
- increased appetite
What are the anesthetic considerations for SSRIs?
- inhibition of CYP450
- may increase plasma concentration of certain drugs
-
Antiplatelet activity
- increased risk of bleeding
- Serotonin syndrome-medication
- confusion, fever, shivering, ataxi, diaphoresis, hyperreflexia, muscle rigidity
What are tricyclics used to treat?
- depression
- chronic pain syndrome in lower doses
- chemical structure is similar to local anesthetics and phenothiazines
- inhibits overactive inflammatory response systems
- Potentiation of endogenous opioids
Tricyclic MOA
- Blocks reuptake of serotonin and/or NE at presynaptic terminals
- tertiary amines- inhibits serotonin and NE reuptake
- secondary amines- inhibit NE reuptake
What are the tertiary amine tricyclics?
- Amytriptyline (elavil)
- Imipramine (tofranil)
- clomipramine (anafranil)
What are the secondary amine tricyclic medications?
- Desipramine (norpramin)
- nortriptyline (pamelor)
What are the pharmacokinetics of tricyclics?
- highly lipid soluble
- strongly PB
- long elimination 1/2 time
- 10-80 hours
- metabolized in liver
- all have active metabolites
What are side effects of tricyclics?
- Anticholinergics
- dry mouth, tachycardia, urinary retention, ileus, slow gastric emptying
- cardiovascular
- orthostatic hypotension, modest increase in heart rate, depresses conduction through the atria & ventricles
- Central nervous system
- lower sz threshold, weakness, fatigue
- **these effects can be fatal with overdose
Why would you not give a tricyclic with an MAOI?
- Can cause CNS toxicity
- hyperthermia
- sz
- coma
What anesthetic drugs can have potential interactions with tricyclics?
- sympathomimetics
- IA
- anticholinergics
- antihypertensives
- opioids
What should you consider when administering sympathomimetics to a patient on tricyclics
- response unpredictable
- exaggerated responses to indirect acting due to larger amounts of NE available to stimulate post synaptic receptors
- Use lower doses of direct acting
- decrease by 1/3
- Book says you could use an indirect acting sympathomimetic if the patient had been on their tricyclic chronically, but that gets fuzzy and riskly. We are risk avoiders.
What should you expect regarding your volatile anesthetics if your patient is on tricyclics?
may need a higher MAC because of the extra NE that is not be re-taken up (theoretical, may not translate to practice)
What should you expect if you administer epinephrine, opioids, or barbs to a pt on tricyclics?
What is the take home?
- They will have a greater response to all these meds
- decrease dose
- don’t forget about epi in a LA
What should you expect if you administer anticholinergics to a pt on tricyclics?
- They may have an exaggerated response
- more likely to have post op delirium and confusion
- glyco is better
What does anticholinergic toxicity or central anticholinergic syndrome look like?
- flushing
- dry mouth
- skin
- mydriasis (pupil dilation)
What can an overdose of tricyclics cause?
How does this present?
- life threatening intractable myocardial depression or ventricular dyrshythmias
- present as:
- agitation
- excitement and deliuium
- sz
- progresses to coma
- resp depression
- cardiac dyrshythmias
- sudden death
- hypotensive
- anticholinergic effects
How is a tricyclic overdose treated?
- ventilatory support
- manage CNS and cardiac toxicity
- physostigmine for anticholinergic psychosis
- acidosis may increase unbound drug–more dyrshythmias
- use bicarb
What does the MAO enzyme system deactivate?
dopamine
serotonin
epinephrine
norepi
What is the MOA of MAOIs?
- blocks the enzyme that metabolized biogenic amines, increasing the availability of these neurotransmitters in the CNS and PNS
- forms a stable, irreversible complex with MAO enzyme
Why aren’t MAOIs used often?
- side effects
- lethal in overdose
- difficult dosing
- pt must follow a tyramine free diet
What are the MAO A’s?
MAO B?
- MAO A
- serotonin
- NE
- epi
- MAO B
- phenylethylamine
What disease have we recently learned about that might be treated with an MAO B?
What should be considered in the dosing of this drug?
- Parkinson’s
- If the dose is >30 mg, it is no longer selective and will work on A enzymes as well
- if this happens, the patients diet will matter, just like it does with an MAO A
What are the side effects of MAOIs?
- Orthostatic hypotension (especially in elderly)
- anticholinergic like effects
- impotence/anorgasmy
- weight gain
- sedation or mild stimuland effects
What are the dietary restrictions for MAOIs?
why?
- tyramine- derived from tyrosine and can act as an idirect catecholamine releasing diet
- must follow diet that is low in tyramine
- to avoid Hypertensive crisis, CVA
- ex:cheese, fava beans, wine, avocado, liver, cured meats
What drugs should you use with caution with MAOIs?
- cyclic antidepressants
- opioids
- cold-allergy drugs
- sympathomimetics
- nasal decongestants
- SSRIs
- no meperidine
What symptoms should patients on MAOIs report that might indicate they are experiencing a catecholamine surge?
serious headache
vomiting
chest pain
Whats the deal with Demerol and pts on MAOIs?
- excitatory (type 1)- caused by enhanced serotonin activity in the brain
- agitation
- skeletal muscle rigidity
- hyperpyrexia
- depressant (type 2)- slowed breakdown of meperidine
- hypotension
- respiratory depression
- coma
Anesthetic considerations for MAOIs are basically the same as for tricyclics. What are they?
- caution with sympathomimetics- no direct acting!
- caution with opioids- no demerol!
- may need higher MAC with VA
- minimize possibility of sympathetic nervous stimulation or drug induced hypotension
What are the symptoms of MAOi overdose?
- excessive sympathetic discharge
- tachycardia
- hyperthermia
- mydriasis
- sz–>coma
- treatment
- supportive care
- maybe dantrolene
What symptoms may be experienced when antidepressents are discontinued?
How can this be avoided?
- dizziness
- myalgias
- parasthesia
- irritability
- insomnia
- visual disturbances
- tremors
- lethargy
- N/V/D
- wean off over two weeks
