antidepressants and stimulants

8/4/2019 Antidepressants and Stimulants

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Antidepressants and Stimulants


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Depression


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What is REALDepression ?

Apathy, low self esteem, insomnia, personal neglect, loss

of appetite, loss of libido, pessimism, lack of motivation

NOT thought disturbances

Types ofDepression

Exogenous Depression: Associated with a life crisis event

Endogenous Depression: Not associated with any trigger

Depressive Syndromes : Unipolar and Bipolar AffectiveDisorder

(more on these later)


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Pathophysiology ofDepression

Monoamine Theory ofDepression

1960s proposed that depression was caused by reduced levels of

monoamines in the brain

Important monoamines being Noradrenaline and Serotonin

Antidepressant Drugs increase Noradrenaline and Serotonin levels

in the CNS


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Noradrenaline and 5-HT in the CNS

Arousal and Mood(also BR, HR)

Behaviour, Sleep, Mood, Food Intake

Body Temp,

NA 5-HT


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Monoamine Nerves: Neurotransmission

Action potential

Release of neurotransmitter (NA or 5-HT)Acts on specific receptors (for NA or 5-HT)

Excess transmitter release inhibited by presynaptic receptors (NA via E2)

Neurotransmitter removed from synapse by amine uptake pump

Excess neurotransmitter in presynaptic neuron degraded by Monoamine

oxidase (MAO)


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Sites of Action for Anti-Depressants

5-HT re-uptake inhibitors

Monoamine (NA and 5-HT) re-uptake pump inhibitors

Blockade of pre-synaptic E2 receptors

Inhibition of MAO enzyme

5-HTreuptake

and


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5-HT Reuptake Inhibitors

Now the most prescribed anti-depressant

Specifically block the re-uptake of 5-HT by the presynaptic neuron

Results in increased 5-HT in the synapse

Not many Side Effects (compared to tricyclics)

eg. Fluoxetine (Prozac)5-HT reuptake

inhibitor


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Tricyclic Antidepressants (TCA)


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Tricyclic Antidepressants (TCA)

Block the amine reuptake pump

Block the reuptake of 5-HT AND Noradrenaline

More effective than 5-HT reuptake inhibitors in severe depression

Side EffectsAnti Muscarinic p dry mouth, urine retention, constipation, blurredvisionAntihistamine p sedation

Antiadrenergicp

postural hypotension

Contraindicated in people with cardio problems (infarction, arrhythmias)and Epilepsy

eg. Imipramine


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Tetracyclic Antidepressants


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Tetracyclic Antidepressants

Block presynaptic E2 receptors

Increase Noradrenaline levels in synapse

Also block reuptake NA and to lesser extant 5-HT

Also blocks some 5-HT receptors

Side EffectsAntihistamine:Drowsiness

eg. Mianserin


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Monoamine Oxidase Inhibitors (MAOI)


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Breaks down monoamines (NA,Dopamine, 5-HT)

Increased levels of NA 5-HT in presynaptic neuron; more for release

Enzyme within the mitochondria of presynaptic nerve

Block MAO

MAO in the gut and breaks down tyramine

So what you ask

Two forms of MAO. MAOA and MAOB


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Excess tyramine (amino acid) in circulation causes the release ofnoradrenaline from sympathetic nerves

Increased BP, increased HR, increased SV

People taking MAOIs for depression should avoid foods rich in tyramine

(Beer, wine,hot dogs, beans, sour cream)

MAOIs are contraindicated in people with CV disease,hepatic

disease, epilepsy. People taking sympathomimetics, levodopa

MAOI inhibitor eg. Phenelzine


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Newer MAOIs are specific for MAOA.

MAOA is involved in controlling NA and 5-HT levels in

depression pathways

Still have to be careful with tyramine consumption in diet

Less Side Effects

Dont work as well

eg. Moclobemide


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5-HT and

NA reuptake

inhibitor

Noradrenaline-Serotonin Reuptake Inhibitors


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Noradrenaline-Serotonin Reuptake Inhibitors

New class of antidepressants

Work similar to Tricyclic Antidepressants BUT dont have

antihistamine, antiadrenergic, anticholinergic effects

May be more effective than 5-HT reuptake inhibitors

eg. Venlafaxine


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CNS Stimulants


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CNS Stimulants

Used forWeight Loss (Anorectics)

Attention Deficit Disorder

Attention Deficit HyperactivityDisorder


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Anorectics

Why stimulants for weight loss ?

Most are sympathomimetics

(mimick sympathetic nervous system)

Restless euphoric sense of well being talkative increased libido

Forget about food

InsomniaRebound

Depression

Side Effects

eg. Phentermine

CNS Effects


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ADD and ADHD

Neurochemical imbalance ??

Mainly affects children

Obsessiveness, forgetfulness, frustration,

daydreaming, aggressiveness, uncooperative

+ in ADHDhyperactive as well

Controversial in terms of its diagnosis and treatment

It is ironic that ADDADHD patients respond to CNS stimulants


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ADD and ADHD

ADD and ADHD treated with CNS stimulants

eg. Methylphenidate (Ritalin) and Dexamphetamine

Increase monamines (NA and 5-HT) in CNS

Reduction in appetite, euphoria, insomnia

Side Effects: headache,hypertension, growth retardation, palpatations


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Drugs to know

Antidepressants

Fluoxetine

Imipramine

Mianserin

Phenelzine

Moclobemide

Venlafaxine

CNS Stimulants

Phentermine

MethylphenidateDexamphetamine

antidepressants and stimulants

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