Antidepressants Flashcards
What are the causes of depression?
- Originally thought that low levels of serotonin was the cause.
- Now not so clear but likely reduction in serotonin receptors in hippocampus.
- Would help explain why SSRI takes so long to work.
- Many studies show people with depression having what is assumed to be normal levels of serotonin.
Describe the action of Mono Amine Oxidase Inhibitors.
Give examples of these drugs and list the side effects.
- Inhibit the activity of MAO enzymes.
- They were the first class of antidepressants developed.
- MAO breaks down norepinephrine / serotonin and dopamine.
- Inhibiting MAO increases level of all three transmitters.
- Examples:
- Phenelzine
- Selegilline - also used in Parkinsons (helps control symptoms)
- Tranylcypromine
- Side effects:
- Weakness
- Dizziness
- Headache
- Fatigue
- Weight gain
- Impotence
What are the interactions with MAOIs?
- Should not be used in combination with SSRI / Tricyclic as well as some analgesics such as morphine / tramadol as they will increase serotonin to potentially dangerous levels causing confsion, hypertension, tremor, coma, and possibly death i.e. neuroplastic malignant syndrome.
- Foods high in tyramine may also cause ahypertensive crisis:
- Cheese
- Certain meats such as venison
- Alcohol
- Some green vegetables i.e.broad beans
Describe the action of reversible MAOIs.
- Moclobeminde:
- Reported to act by reversible inhibition of MAO type A.
- Therefore called RIMA.
- Tyramine has less of an effect (fewer interactions).
- Short acting so medications can be changed with only one week washout period.
What is the mechanism of action of tricyclic antidepressants?
- Act by inhibiting re-uptake of norepinephrine and serotonin by blocking the transporters responsible for re-uptake of these neurotransmitters.
- Increasing concentration of neurotransmitters in the synapses and triggering further neurotransmission.
What are the uses of tricyclic antidepressants?
- Depression
- Anxiety
- Chronic pain (i.e. fibromyalgia, reflex sympathetic dystrophy
- syndrome)
- IBS
- Neuralgia
- OCD
- Nocturnalenuresis
- PTSD
- The main ones!
In which condition should tricyclic antidepressants be used with extreme caution?
Tricyclics should be used with caution in cardiovascular disease due to risk of arrythmias.
What are the side effects of tricyclic antidepressants?
- Tricyclics should be used with caution in cardiovascular disease due to risk of arrythmias.
- Tricyclics have antimuscarinic activity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility.
- They can induce bradycardia followed by tachycardia, reduce bronchial secretions, urinary retention, dry mouth and confusion.
Give examples of tricyclic antidepressants?
Which is the most common (first line in Fife)?
- Amitriptyline - most common and first line in Fife.
- Clomipramine
- Imipramine
- Lofepramine
- Nortriptyline
What are the concerns about prescribing tricyclic antidepressants?
Tricyclics are very dangerous in overdose so beware of how much you prescribe for a patient and use with caution in patients at high risk of suicide.
Describe the mechanism of action of Selective Serotonin Re-Uptake Inhibitors (SSRIs).
- Believed to work by increasing levels of neurotransmitter serotonin by limiting its re- absorption and pure SSRI have only a weak affinity for norepinephrine and dopamine transmitters.
- Serotonin receptors are know as 5- hydroxytryptamine (5-HT).
- They are, therefore, cleaner with generally fewer side effects and better tolerated by patients.
- 5-HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission.
- These receptors modulate the release of many neurotransmitters
- GABA
- Dopamine
- Epinephrine
- Norepinephrine
- Acetylcholine
- They influence aggression, anxiety, cognition, learning memory, mood and sleep.
What are the uses of SSRIs?
- They are the most widely prescribed antidepressants
-
Uses:
- Depression
- Anxiety
- OCD
- Panic disorder
- PTSD
- Eating disorders
What are the side-effects of SSRIs?
- Sexual: dysfunction and reduced libido.
- Cardiac: some, especially citalopram, to be used with caution as can cause QT interval prolongation therefore dose dependant with citalopram.
- Bleeding: affects anticoagulants (i.e. warfarin and aspirin) and also increased risk of GI bleeds.
- Suicide: possible increased risk of suicide especially in children and adolescents.
- Overdose: safer than other antidepressants
- Epilepsy: may reduce fit threshold
-
Others include:
- Nausea
- Rash
- Muscle aches
- Insomnia
- Sweating
Describe the toxicity of SSRIs when used in overdose.
What is Duloxetine?
What are its uses and side effects?
- SNRI (serotonin norepinephrine uptake inhibitor).
-
Uses:
- Depression
- Neuropathic pain (diabetes, fibromyalgia)
- Stress urinary incontinence
-
Side effects:
- Nausea
- Insomnia
- Dizziness
What is mirtazapine?
What are its uses and side effects?
- A presynaptic alpha2-adrenoreceptor antagonist. Also a noradrenergic and specific serotonergic antidepressant NaSSA.
-
Uses:
- Depression
- Anxiety
- PTSD
-
Side effects:
- Low dose causes drowsiness so best taken at night
- Higher dose more stimulant effect
What is venlafaxine?
What are its uses and side effects?
- Serotonin-norepinephrine re-uptake inhibitor (SNRI).
-
Uses:
- Major Depressive Disorder
- Anxiety
- Panic
- Social phobia
- Metabolized in the body into desvenlafaxine (by cytochrome P206 isoenzyme in the liver)
- Often used in treatment of resistant depression
Give examples of other drugs with antidepressant properties.
- Antipsychotics such as risperidone.
- Lithium used in bipolar/mania mood stabilization possible adverse affects on kidney and thyroid function.
Describe how antidepressants work for pain.
- Can be used to treat nerve damage or abnormal nerve function (neuropathic) and some muscle pains.
- Direct effect on the mechanisms of the pain, and not through any effect on mood.
- Tricyclics work by blocking the re-uptake of Noradrenaline and Serotonin (5-HT) into the nerve endings and increasing their levels in the pain control pathways.
- Their benefit arises: by their direct effect on pain, and also through beneficial effects on sleep.
What are the antidepressants commonly used for pain?
- Commonly used antidepressants:
- Amitriptyline
- Nortriptyline
- Duloxetine
- Duloxetine is also licensed for diabetic neuropathy
Describe drug-induced QT prolongation.
- Prolongation of the QT interval can lead to a life threatening arrhythmia known as torsades de pointes.
- Recent warnings have highlighted the risk of QT prolongation with citalopram.
- Use of more than one drug that prolongs the QT interval increases the risk of torsades de pointes and ventricular arrhythmia.
Which drugs can cause drug-induced QT prolongation?
Which patients are at greater risk of drug-induced QT prolongation?
- People who have more risk factors for QTc prolongation than the general population are particularly vulnerable to drug-induced LQTS.
- Major psychiatric disorders
- Cardiovascular disease
- The elderly
- Women
