Selective serotonin reuptake inhibitors

Selective Serotonin Reuptake inhibitors, or SSRIs, are mainly used to treat major depressive disorder. This disorder causes a persistent feeling of sadness and loss of interest in everyday activities.

Even though the exact cause of depression is still unknown, there's some evidence that suggests it’s related to low levels of neurotransmitters like serotonin, norepinephrine, and dopamine.

Selective serotonin reuptake inhibitors work by increasing the levels of serotonin to alleviate the symptoms of depression.Now, serotonin is a neurotransmitter that helps regulate mood, emotions and feeding behavior.

Presynaptic serotonergic neurons use the amino acid tryptophan to synthesize serotonin, which is also called 5-hydroxytryptamine, or 5-HT.

Once synthesized, serotonin is stored in small vesicles within the presynaptic neuron. When an action potential reaches the presynaptic membrane, the vesicles fuse with the membrane and release the serotonin into the synaptic cleft.

The serotonin drift around until they bind to 5HT2 receptors on the postsynaptic neuron, and cause it to fire off its own action potential.

As long as there’s a high enough concentration of serotonin in the synaptic cleft, the postsynaptic neuron will continue to fire.

On the presynaptic neuron, there are serotonin reuptake transporters or SERTs. This protein functions like a little trap door on the cell membrane; when a sodium, a chloride and a serotonin binds to the surface of this protein on the extracellular side, it flips over and sends the serotonin and the ions into the cell.

When a potassium ion binds to the protein on the intracellular side, the trapdoor resets again, so more serotonin can attach.

This way, serotonin is taken back into the presynaptic neuron, its concentration in the synaptic cleft decreases, and the postsynaptic neuron stops firing.Now, in conditions such as major depressive disorder, where there’s a low serotonin level, selective serotonin reuptake inhibitors are the first-line therapy due to their milder side effects.

Common medications in this class include escitalopram, fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram. They bind to serotonin reuptake transporters and inhibits them, which increases the serotonin level within the synaptic cleft.

It's important to note that these medications are slow-acting because it takes time for serotonin to accumulate within the synaptic cleft.

Because of this, it usually takes 4-6 weeks before improvements can be seen. Other conditions that can be treated with SSRIs include chronic anxiety, post traumatic stress disorder, or PTSD, obsessive-compulsive disorder, or OCD, and eating disorders like bulimia.Common side effects of SSRIs include anxiety, insomnia or drowsiness, GI distress, sexual dysfunction, and syndrome of inappropriate antidiuretic hormone or SIADH.

The most dangerous, however, are suicidal ideations, especially in individuals under 25, and serotonin syndrome. Serotonin syndrome is a life threatening condition caused by serotonin accumulation which causes overstimulation of the nervous system.

This syndrome is characterized by skin flushing, hyperthermia, agitation, muscle rigidity, seizure, and coma. It usually occurs in individuals treated with a combination of SSRIs and other antidepressants that increase serotonin level, such as monoamine oxidase inhibitors.

Treatment of serotonin syndrome consists of administration of benzodiazepines and supportive care, and in severe cases administration of cyproheptadine, which is an antihistamine that can also block 5HT2 receptors.

If SSRIs are discontinued abruptly, some people can experience withdrawal syndromes like irritability, headaches, and insomnia.

For medicine specific side effects, citalopram causes prolongation of the QT interval, which could cause ventricular arrhythmias.

Most of the SSRIs are considered to be pregnancy category C, which means there could be potential risks, however paroxetine is category D, and it's been shown to cause congenital heart defects.

Finally, fluoxetine, fluvoxamine, and paroxetine, are inhibitors of cytochrome P450 enzymes. These liver enzymes are responsible for the metabolism of a variety of drugs and toxins in our body.

So, when combined with other drugs that are metabolized by cytochrome P450 enzymes, such as benzodiazepines, SSRIs will reduce their rates of elimination and cause them to build up in the body.Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts!

First, let’s have an escalator for escitalopram. At the bottom, is a serpent for sertraline.

At the top, fluoxetine and fluvoxamine are represented by 2 oxen in a plane, as they try to escape from the snake. They drop off their buddy, an ox with a parachute for paroxetine, and this ox is trying to land in a snake-free citadel representing citalopram.

For the indications, There’s a weeping soldier from the citadel representing depression and PTSD. Next to him, is an anxious medical student obsessively going over flashcards, representing chronic anxiety and OCD.

He's also eating a big slice of cake for eating disorders. For the more dangerous side effects of SSRIs, let’s start with serotonin syndrome, which will be represented by a dead knight who’s about to be cremated.

He’s stiff, so there’s muscle rigidity, the hot fire represents hyperthermia, and the armor is glowing red for flushing.

The knight was only faking his death, so he starts squirming from the heat to represent agitation. No one believed he's alive though, since he left behind a suicide note.

For the less dangerous side effects, let’s have a man sitting up in bed since he has insomnia. His too anxious to sleep because he’s been having diarrhea in bed.

He's wearing antidiuretic diaper representing SIADH, but wearing a diaper is not very attractive, so he got the ones with little hearts on them to help him overcome his sexual dysfunction.

For medication specific side effects, let’s have the three oxen shoot at a flying, chrome colored cell for cytochrome p450 inhibition.

Paroxetine panics and drops the baby he was carrying, so it’s the most unsafe for pregnancy. Finally, in the citadel lives a long tailed squirrel who’s a real cutie, because citalopram causes long QT syndrome.

All right, as a quick recap. Selective serotonin reuptake inhibitors, or SSRIs, are antidepressant medications that prevent serotonin reuptake from the synaptic cleft, thus increasing the amount of serotonin binding to 5HT2 receptors.

Aside from major depressive disorder, SSRIs can also treat PTSD, OCD, chronic anxiety and eating disorders. These medications have a few dangerous side effects like increased risk of suicide and the life threatening serotonin syndrome.

inhibitors or SSRI are antidepressant medications that prevent serotonin reuptake from the synaptic clap Thus increasing the amount of serotonin binding to five HT two receptors Aside from major depressive disorder ssris can also treat PTSD OCD Chronic anxiety Patients exhibits SS a few have the side effect though like increased risk of suicide and the life-threatening serotonin syndrome But wait there's more here's a mind map with all of the pneumonic from the video Go ahead and pause the video so you can test yourself to see what you remember Stay tuned for the answers