Drugs Used In The Treatment Of Affective Disorders Flashcards
What is bipolar disorder?
Bipolar disorder is a mental illness marked by extreme shifts in mood ranging from a manic to a depressive state.
A person with mania will feel excited, impulsive, euphoric, and full of energy. He or she might engage in risky or unhealthy behavior. Drug use, spending sprees, and impulsive or unprotected sex are common during manic episodes
The depressive episodes might bring on deep sadness and hopelessness. Depression causes a loss of energy and interest in activities the patient once enjoyed.
This phase can include periods of too little or too much sleep. Also, suicidal thoughts or attempts may come with deep depression
Briefly describe the types of bipolar disorders
- Bipolar I disorder will show at least one manic episode and one or more major depression episodes. Bipolar I disorder is equally common in men and women. The first episode in men is usually mania. In women, the first episode is typically major depression
- bipolar II experience major depression. But instead of mania they experience hypomania. With hypomania, a person will still exhibit high energy, impulsiveness, and excitability. However, the mood is not as extreme as full-fledged mania, and these patients never experience hallucinations or delusions during a hypomanic episode.
- Cyclothymic Disorder This is a “mild” form of bipolar disorder, with mood swings that are less severe and episodes shifting from hypomania to mild depression
What are the common signs and symptoms of mania?
Feeling unusually “high” and optimistic or extremely irritable
Unrealistic, grandiose beliefs about one’s abilities or powers
Sleeping very little, but feeling extremely energetic
Talking so rapidly that others can’t keep up
Racing thoughts; jumping quickly from one idea to the next
Highly distractible, unable to concentrate
Impaired judgment and impulsiveness
Acting recklessly without thinking about the consequences
Delusions and hallucinations (in severe cases)
What common symptoms of bipolar depression?
Feeling hopeless, sad, or empty
Irritability
Inability to experience pleasure
Fatigue or loss of energy
Physical and mental sluggishness
Appetite or weight changes
Sleep problems
Concentration and memory problems
Feelings of worthlessness or guilt
Thoughts of death or suicide
Depression is secondary to…?
- Organic problems like hypothyroidism, dementia, anemia
- Psychiatric problems like schizophrenia, drug abuse, anxiety disorders
- Use of depressants drugs such as alcohol
Describe the monoamine hypothesis of depression
The first major theory about the biological aetiology of depression hypothesized that depression was due to a deficiency of monoamine neurotransmitters, notably norepinephrine (NE), dopamine (DA) and Serotonin
Which classes of drugs are used to treat affective disorders?
Anti-psychotic drugs
Anti-seizure drugs
Antidepressants
Which antidepressants are used to treat affective disorders?
- Tricyclic anti-depressants (TCAs)
- Selective serotonin reuptake inhibitors (SSRIs)
- Monoamine oxidase inhibitors (MAOIs)
- Atypical anti-depressants
List the TCAs used
amitriptyline,
imipramine,
nortriptyline,
desipramine,
dosulepin (dothiepine) and
lofepramine
What is the MoA of TCAs?
Block uptake of noradrenaline and 5-HT into the presynaptic terminal (inhibit the re-uptake pumps)
TCAs also block muscarinic, histamine H1 and alpha-adrenergic receptors (this contributes to their unwanted effects)
What are the adverse effects of TCAs?
Dry mouth, blurred vision, constipation, postural hypotension, increased risk of arrhythmias, sedation, weight gain
What are the results a TCA overdose?
Arrhythmias, shock, respiratory depression, seizures, coma and death (have a narrow therapeutic index)
What are the contraindications of TCAs?
Arrhythmias, recent myocardial infarction, manic phase, severe liver disease, seizure disorders, and patients taking lignocaine, anticholinergic drugs or alcohol
List the SSRIs used
flouxetine, fluvoxamine, citalopram, paroxetine and sertraline
What is the MoA of SSRIs?
Selectively inhibit the reuptake of serotonin into presynaptic nerve terminals
Similar efficacy to TCAs
They are better tolerated than TCAs and MAO inhibitors, and are safer in overdose
What are the adverse effects of SSRIs?
Headache, nausea, vomiting, diarrhoea, insomnia, anxiety, agitation, sexual dysfunction
May induce suicidal ideation in children, adolescents and young adults
List the MAOIs used
phenelzine, tranylcypromine, isocarboxazide and moclobemide
What is the MoA of MAOIs?
Inhibit monoamine oxidase (MAO), the enzyme that metabolizes monoamines (noradrenaline, serotonin and dopamine)
Inhibition of MAO-A which preferentially degrades norepinephrine and serotonin is responsible for the therapeutic efficacy of MAOIs (MAO-B degrades dopamine preferentially)
Moclobemide is selective for MAO-A
What are the adverse effects of MAOIs?
Headache, CNS excitement, tremors, postural hypotension, dry mouth, blurred vision, sexual dysfunction (phenelzine), weight gain and sleep disturbances
What is the result of an MAOI overdose?
Agitation, hyperthermia, seizures, hypotension or hypertension
Describe the drug food interaction of MAOIs
MAOIs inhibit the metabolism of indirectly acting sympathomimetic drugs (e.g. phenylephrine, ephedrine and pseudoephedrine) and tyramine from certain foods such as cheese, mature wines, yeast, fish, sausages). These amines are metabolized by MAO.
The result of the inhibition is severe hypertension and arrhythmias. These effects are due to increased noradrenaline release resulting from increased levels of the amines.
Describe the drug-drug interaction of MAOIs
MAOIs interact with SSRIs, TCAs, tramadol and pethidine resulting in the “serotonin syndrome” (characterised by tremor, hyperthermia, muscle rigidity and cardiovascular collapse)
MAOIs result in additive sedation and CNS depression when given concurrently with benzodiazepines, barbiturates, ethanol and opioids
Briefly write on the use of Venlafaxine
Inhibits reuptake of noradrenaline and serotonin. Adverse effects include nausea, dizziness, sexual disturbances, anxiety and insomnia. Useful in patients not responding to other anti-depressants.
Briefly write on the use of Reboxetine
Selectively inhibits reuptake of noradrenaline
Briefly write on the use of Mirtazapine
Blocks alpha2-adrenoceptors thereby increasing noradrenaline release. Is very sedative and causes weight gain
Briefly write on the use of Trazodone
Inhibits serotonin reuptake. Adverse effects include postural hypotension and priapism. Safer than TCAs in overdose
Briefly write on the use of Nefazodone
Inhibits serotonin reuptake. Causes sedation and mild postural hypotension. Used in the prophylaxis of recurrent depression
What is the treatment plan for bipolar?
Bipolar disorder is treated with a combination of mood stabilizers and anti-depressants, and sometimes anti-psychotics (anti-psychotics are given during the manic phase)
Mood stabilizers prevent mood swings that are seen in bipolar disorder
Which mood stabilizers are used in the treatment of bipolar?
lithium, carbamazepine, valproate, lamotrigine and gabapentin
What is the MoA of lithium?
Inhibits inositol monophosphate, thereby decreasing the activity of the second messengers diacylglycerol and inositol-1,4,5-triphosphate
Has anti-manic and anti-depressant activity
What are the clinical indications of lithium?
(1) Prophylaxis and treatment of bipolar disorder
(2) Prophylaxis and treatment of acute mania
(3) Prophylaxis of resistant recurrent depression
What are the adverse effects of lithium?
Adverse effects include thirst, nausea, vomiting, diarrhoea, tremor and polyuria. Late adverse effects include weight gain, oedema, acne, nephrogenic diabetes insipidus and hypothyroidism.
High plasma concentrations result in drowsiness, confusion, ataxia, blurred vision, nystagmus and seizures
What are the results of a litium overdose?
Delirium, muscle twitching, convulsions, arrhythmias and renal failure and death
How do you treat lithium toxicity?
Discontinue lithium administration, haemodialysis and anti-convulsants
What are the contraindications of lithium?
Contraindications: Antipsychotics, NSAIDs, diuretics, pregnancy, breastfeeding
Diuretics deplete sodium and this depletion results in increased renal reabsorption of lithium thereby increasing lithium toxicity
NSAIDs decrease the renal clearance of lithium resulting in increased risk of toxicity
