PHARM - Drugs Used to Treat Depression and Bipolar Disorders - Week 9 Flashcards
What are affective disorders?
Those which influence affect or mood
What happens with mood swings?
Extreme elation and hyperexcitability to extreme melancholia and withdrawal
Do unipolar/major depression have manic episodes?
No
What are the two kinds of unipolar/major depression? Are their causes known?
Reactive - known cause
Endogenous - no known/apparent cause
What are the two kinds of mood disorders?
Unipolar
Bipolar
What are three neurotransmitters implicated in mood?
Noradrenaline
Serotonin
Dopamine
What are mood disorders characterised by?
Longlasting changes to mood
What are 6 symptoms of depression?
Intense sadness/despair
Diminished interest/pleasure in daily life
Loss of concentration
Sleep disturbance
Anorexia
Disruption to normal rhythm
List three psychological risk factors for mood disorders.
Early parental loss
Childhood abuse
Stressful life events
List three biological risk factors for mood disorders.
Hormonal
Genetic
Biochemical (monoamines)
Describe the monoamine theory of depression.
Drugs that interfere with monoaminergic transmission influence mood.
Depletion results in depression.
Do drugs that elevate mood make good antidepressants? Explain (3).
No as they can cause dependence (dopamine related) and toxicity
How long do antidepressants take to have effect?
2-6 weeks
Describe the action of cocaine on a neuron.
It blocks the uptake of noradrenaline by the neuron.
Describe the action of amphetamine on a neuron.
Forces the release of noradrenaline
List two 1st generation unipolar antidepressant drugs.
Tricyclic antidepressants
Monoamine oxidase inhibitor
List two 2nd generation unipolar antidepressant drugs.
Selective serotonin uptake inhibitors
Selective serotonin/noradrenaline uptake inhibitors
List two 3rd generation unipolar antidepressant drugs.
Novel monoaminergic drugs
Non-monoaminergic drugs
(these are known as atypical antidepressants)
List two bipolar antidepressant drugs.
Lithium
Some anti-epileptics
What generation of unpolar antidepressant drugs led to the monoamine theory of depression?
1st generation - MAOi and TCAs
What effect do MAOi and TCAs have? Describe each.
They prolong the action of NA
MAOi decreases NA metabolism
TCA blocks neuronal uptake of NA
Which MAO do MAOi inhibit?
Both MAO A and MAO B
Inhibition of which MAO is related to antidepressant activity and side effects?
Inhibition of MAO A
What is the mechanism of action of MAOi? What effect does it have on monoamine concentrations in the cytoplasm?
It is similar in structure to MAO substrates
It increases monoamine concentration in the cytoplasm
What is the mechanism of action for tricyclic antidepressants?
Blocks re-uptake of NA and 5HT into nerve terminal
In addition to their mechanism of action, what else to TCAs allow for?
Downregulation of post-synaptic receptors
List 6 side effects of TCAs. Is an overdose dangerous?
Sedation
Anti-cholinergic side effects
Decreased blood pressure
Increased weight gain
Cardiac effects
Seizures
Dangerous in overdoses
Describe how quickly the pharmacological effects of TCAs manifest vs how long it takes to have an antidepressant effect. Give a reason for this disrepancy (2).
Takes weeks to develop despite pharmacological effects manifesting in hours.
Adaptive changes in neuronal function likely underlie antidepressant activity like changes in receptor sensitivity and density.
Increased levels of transmitter can downregulate receptor number/function.
Do TCAs have a wide or narrow therapeutic window?
Is their efficacy good or limited?
Narrow
Limited efficacy
Do TCAs have a long or short half-life? Can it accumulate?
Long
Gradual accumulation is possible
Describe the mechanism of action for selective serotonin reuptake inhibitors (SSRI). Does it have any effect on NA or DA?
It is selective for 5HT uptake - exact mechanisms unknown
Has weak inhibition of NA/DA uptake
How are SSRIs administered?
Orally
What do SSRIs interact with directly?
hSERT
List 5 adverse effects of SSRIs. List one advantage it has. Does it have many or few drug interactions (mention 1st gen antidepressants)?
Nausea
Insomnia
Agitation
Weight change
Loss of libido
Advantage - much safer in overdose
Numerous drug interactions, including with MAOi and TCAs
Are 3rd gen atypical antidepressants TCAs?
Are non TCAs
Are 3rd gen atypical antidepressants short or long acting?
Short acting
Do 3rd gen atypical antidepressants have a common mechanism of action?
No
Which has more adverse effects, TCAs or 3rd gen atypical antidepressants?
TCAs
3rd gen has fewer
How do some common 3rd gen atypical antidepressants work (4)?
Block a2 adrenoceptors, histamine and serotonin receptors.
No effect on uptake.
What is the drug of choice for acute manic illness (a bipolar depression)? What is its mechanism of action?
Lithium
Mechanism unclear
Why must plasma levels be monitored when administering lithium?
It becomes toxic quickly and the therapeutic range is very low and close to toxic levels.
In what form is lithium administered?
Lithium carbonate
List 5 side effects of lithium.
Nausea
Tremor
Impaired renal (polyuria), thyroid, and neurological function
