Module 1.4.1 (Drugs for Bipolar Disorders) Flashcards
What is bipolar disorder?
Bipolar disorder is a severe biologic illness characterised by fluctuation of mood
- Alternating episodes of mania and depression
- Onset of symptoms occurs in adolescence or early childhood
What are the types of mood episodes seen in BPD?
Mania
- Persistent elevated, expansive or irritable mood
- Hyperactivity
- Reduced need for sleep
Hypomania
- Mild form of mania
- Not severe to cause social impairment
Manic Depression
- Depressed mood
- Loss of pleasure or interest
- Sleep disturbances
Mixed episodes
- Mania and depression simultaneously
- Agitated and irritable (mania)
- Worthless, guilt, feeling (depression)
- High risk of suicide
What is:
A) bipolar I disorder
B) bipollar II disorder
C) rapid-cycling bipolar disorder
A)
- manic or mixed episodes and usually depressive episodes as well
B)
- hypomanic or depressive episodes
- not manic or mixed episodes
C)
- four or more episodes per year (can be any type of episodes)
What are drug therapies used in the treatment of bipolar disorder. THREE different types of drugs.
Mood stabilisers
- Lithium
- Anticonvulsants
- Valproate, carbamazepine, lamotrigine
Antidepressants
- Venlafaxine, fluoxetine, sertraline
Antipsychotics
- Olanazapine, risperidone, quietapine
How do mood stabilisers work? What is the drug of choice?
- Relieve symptoms during manic and depressive episodes
- Prevent recurrence
- Do not worsen symptoms of mania and depression
- Do not accelerate the rate of cycling
- Lithium (Li) remains the drug of choice for acute mania and prophylaxis.
What is used in the acute phase of the manic episode in patients who have bipoalr and why?
In the acute phase of the manic episode, antipsychotic drugs and benzodiazepines are usually needed to provide symptom relief, reduce self-injury and reduce risk to others, because lithium and sodium valproate onset of action is delayed for 1-2 weeks
What is the MOA of lithium?
- Inhibit synthesis and release of NA, 5HT and dopamine –> enhance the action of reuptake transporters
- Reduce formation of intracellular second messengers - IP3, DAG and cAMP –> decreases neuronal activity
In BPD there may be an excessive activity in neuronal pathways involved with intracellular second messengers; IP3, DAG and cAMP
How does lithium impair sodium action?
Lithium is treated like sodium in body, can alter the distribution of ions critical for neuronal function (Ca2+, Na+, and Mg2+)
- Transport specific ions from one side of the membrane to another
- Ion channel (or gates) open to allow the selective transfer of ions down their concentration gradients
> Na+ and Ca2+ will diffuse into cell making cytosol more positive and causing depolarisation
> K+ will diffuse out making the cytosol more negative and inhibit depolarisation
> Cl- diffuses into cell making cytosol more negative and inhibit depolarisation
What are the indications for lithium?
- Treatment of acute mania
- Prevention of manic or depressive episodes in bipolar disorder
- Schizoaffective disorder and chronic schizophrenia
For lithium
A) Which patients to use it in caution with
B) Can it be used in pregnancy
C) Can it be used in lactation
A)
Use with caution in patients with renal impairment
- Even relatively mild renal dysfunction requires dose reduction to avoid lithium accumulation and toxicity
B)
Pregnancy category D
- Avoid lithium use especially during first trimester
C)
Lithium enters breastmilk and can accumulate to potentially harmful level
How to monitor plasma lithium levels? What are the ideal levels?
- Low therapeutic index
- Plasma monitoring is essential
- Monitor serum lithium concentration (at least 8-12 hours after last dose), once or twice weekly until stabilised, then every 3 months –> monitor more often during illnesses, changes in diet or temperature, drug treatment
Keep below 1.5 mmol/L
Initial level 0.8-1.5 mmol/L
Maintanence level 0.4-1.0 mmol/L
What are the adverse effects that occurs for lithium when the plasma level is:
A) <1.5 mmol/L
B) 1.5-2.0 mmol/L
C) 2.0-2.5 mmol/L
D) >2.5 mmol/L
A)
- Nausea, vomiting, diarrhoea, thirst, polyuria, lethargy, muscle weakness, fine hand tremor
B)
- Persistent GI upset, coarse hand tremor, confusion, hyperirritability of muscles, sedation, incoordination, ECG changes
C)
- Ataxia, giddiness, blurred vision, tinnitus, severe hypotension, extensive diuresis, seizures, serious ECG changes, coma, death
D)
- Symptoms progress rapidly to generalised convulsion, oliguria, and death
What are the common adverse effects associated with lithium?
Early adverse effects: metallic taste, nausea, diarrhoea, epigastric discomfort, anorexia, fatigue, headache, confusion
Tremor: fine hand tremor augmented by stress, fatigue, certain drugs (antidepressants, antipsychotics, caffeine)
Polyuria: 50-70% of pateint has daily urine output >3L
Hypothyroidism and Goitre: acne, psoriasis and leucocytosis –> benign changes in T wave of ECG
What are the infrequent/rare adverse effects of lithium? What needs to be monitored?
- nephrogenic diabetes insipidis with polydipsia and polyuria
- memory impairment
- hair loss
- parathryoidism
> need to monitor renal function with serum creatinine and electrolytes every 3 to 6 months
> thryoid function test every 6 to 12 months
For ltihium toxicity:
A) What is mild to moderate toxicity?
B) What is severe toxicity?
A)
- Blurred vision, frequent diarrhoea, nausea, vomiting,
- muscle weakness,
- drowsiness, apathy, ataxia, flu-like illness.
B)
- Increased muscle tone, hyperreflexia
- myoclonic jerks, coarse tremor
- disorientation, psychosis
- seizures, coma
