To understand the mechanism of action of mental illness drugs. A basic understanding of what neurotransmitters are involved is important. While there are many neurotransmitters within the nervous system. When focusing on the neurotransmitters relating to mental illness the following are the most important.

Inhibitory neurotransmitters cause potassium to flow out of neurons. Post synaptic neurons become more negative (hyperpolarised). This lessens the chance of the neuron responding to or creating an action potential. Inhibitory neurotransmitters do not stimulate the brain, the are responsible for calming the brain. Excessive inhibitory neurotransmitters can cause fatigue, low motivation, and low mood.

Inhibitory neurotransmitters include:

  • GABA
  • Serotonin
  • acetylcholine

 

Excitatory neurotransmitters cause an influx of sodium into neurons. Post synaptic neurons membrane potential becomes less negative and increases their likelihood to generate an action potential. Excitatory neurotransmitters stimulate the brain and in excessive amounts they can lead to agitation, restlessness, insomnia, and seizures.

Excitatory neurotransmitters include

  • Glutamate
  • Dopamine
  • Nor/adrenaline
  • Acetylcholine

 

Both inhibitory and excitatory neurotransmitters levels are affected with mental illness. The drugs used to treat these illness attempt to restore a normal balance of these to allow individuals to return to normal functioning.

 

 

Antipsychotics

Psychotic symptoms a result of over activity in the mesolimbic dopamine pathway,. This class of medication can be used to treat mania, bipolar, schizophrenia, severe depression and anxiety.

Typical

  • Haloperidol– Antagonist of dopamine and 5HT (serotonin). Side effects: Extrapyramidal effects, hyperprolactinemia, muscle weakness, rigidity, or tremor, sexual dysfunction.
  • Clozapine– Antagonist of dopamine and 5HT receptors. Side effects: agranulocytosis, hyper-salvation, metabolic syndrome

Atypical

  • Olanzapine– Antagonist of dopamine, muscarinic and 5HT receptors. Side effects: Tremor, insomnia, dry mouth, hypotension, weight gain, + BSL, extrapyramidal effects, sexual dysfunction.
  • Aripiprazole– partial dopamine agonist lowers dopamine neurotransmission in the mesolimbic pathway. Side effects: hyper salvation, weight gain, insomnia, GI upsets, dizziness
  • Quetiapine– Antagonist of dopamine and 5HT receptors. Side effects: hyperprolactinaemia, GI upsets, + appetite, weight gain, drowsiness
  • Risperdal– Antagonist of dopamine and serotonin. Side effects: extrapyramidal effects, dizziness, fatigue, dry mouth, + appetite, weight gain

 

Anxiolytics

Anti-anxiety drugs act by enhancing the GABA neurotransmitter which sends inhibitory messages and slows neuron firing down. This class of drugs affect 40% of neurons. GABA balances overstimulation of excitatory neurotransmitters such as dopamine noradrenaline.

  • Benzodiazepines –pams

Decrease anxiety, promote sleep, muscle relaxant, amnesia (short term for pain)

Side effects: Respiratory distress, affect REM sleep, orthostatic hypotension, sedative, can have paradoxical effect. These drugs can be addictive and abused

Beta blockers can be used to relieve side effects from anxiety

 

Lithium

Alters sodium transportation in nerves and muscle cells. Regulates glutamate to a healthy level within the brain and also inhibits dopamine and noradrenaline.

In dehydrated patients, lithium is reabsorbed in the proximal tubule and follows water. The increased level causes toxicity. Early signs are confusion, muscle tremor, slurred speech and drowsiness. Late signs are blurred vision, convulsions, sever trembling, increased urine and arrhythmias.  Common side effects include nausea, diarrhoea, dizziness, muscle weakness, fatigue, thirst and weight gain.

 

Antidepressants

Works on the key neurotransmitters dopamine, serotonin, and noradrenaline

MAOI: monoamine oxidase inhibitors- moclobemide

TCAs: tricyclic – amitriptyline

SSRIs: selective serotonin reuptake inhibitor -Citalopram, fluoxetine

SNRI: serotonin noradrenaline reuptake inhibitor – venlafaxine

Side effects: anticholonergic effects (decreased Parasympathetic response, dry mouth, suicidal ideation, depressed mood, weight gain/loss, fatigue, insomnia, libido changes, constipation.

 

 

 

References

Bryant, B., & Knights, K. (2015). Pharmacology for health professionals (4th ed.). Sydney, Australia: Mosby Elsevier.

Johnston, A. (2015). Structure and function of the neurological system. In J. Craft & C. Gordon (Eds.), Understanding pathophysiology (2nd ed., pp. 89–136). Sydney, Australia: Mosby Elsevier.

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