WEEK 2: MECHANISMS OF PSYCHOTROPIC DRUG ACTIONS Flashcards
Outline the different types of antidepressants.
1.Serotonin selective reuptake inhibitors
2.Serotonin norepinephrine reuptake inhibitors
3.Triacyclic antidepressants
4.Monoamine oxidase inhibitors
5.
Describe the MOA of serotonin selective reuptake inhibitors
SSRIs treat depression by increasing levels of serotonin in the brain. Serotonin is one of the chemical messengers (neurotransmitters) that carry signals between brain nerve cells (neurons).
SSRIs block the reabsorption (reuptake) of serotonin into neurons. This makes more serotonin available to improve transmission of messages between neurons. SSRIs are called selective because they mainly affect serotonin, not other neurotransmitters. They inhibit SERT (serotonin transporter.
SSRIs may also be used to treat conditions other than depression, such as anxiety disorders.
Describe the MOA of serotonin-norepinephrine reuptake inhibitors.
SNRIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, SNRIs work by ultimately effecting changes in brain chemistry and communication in brain nerve cell circuitry known to regulate mood, to help relieve depression.
SNRIs block the reabsorption (reuptake) of the neurotransmitters serotonin (ser-o-TOE-nin) and norepinephrine (nor-ep-ih-NEF-rin) in the brain.
They inhibit SERT and NET to increase NE and serotonin in synaptic cleft.
EFFECTS
*Sexual dysfunction
*Serotonin syndrome
*Tachycardia / Hypertension
*Sweating
Outline pharmacodynamics of selective serotonin reuptake inhibitors
Pharmacokinetics
* absorbed slowly - reach peak levels after 4-8 hours
* t½ for PAROXETINE and SETRALINE is about 24 hrs; t½ for FLUOXETINE is 48-72 hrs
* eliminated by hepatic metabolism
* FLUOXETINE is metabolized to norfluoxetine, which is also a potent 5-HT uptake blocker and has a half-life of 7-9 days
* SERTRALINE is metabolized to desmethylsertraline which has a half-life of 2-3 days and is 5-10 times less potent than the parent compound
Outline the pharmacodynamics of selective serotonin re-uptake inhibitors
Pharmacodynamics
* long term administration results in:
* 5-HT2 receptor function
* 5-HT1 receptor function post-synaptically
* 5-HT1A receptors pre-synaptically
*serotonin syndrome
*Disrupt sleep (insomnia/hypersomnia)
*high serotonin results in low libido hence sexual dysfunction
*Most of them lead to Qt prolongation:
QT prolongation occurs when the heart muscle takes longer to contract and relax than usual
*Results into increased risk of fall as they are sedative
Describe the MOA of tricyclic antidepressants
*inhibit both SERT and NBET
*Acts as muscarinic and histamine antagonists (side effects)
Describe the pharmacodynamics of tricyclic antidepressants
Pharmacodynamics
* blockade of Ach muscarinic receptors
* blockade of histamine H1 receptors
* blockade of alpha-1 adrenoceptors
* blockade of 5-HT2/1C serotonergic receptors
* membrane stabilization
State the side effects of tricyclic antidepressants
Side effects:
* Anticholinergic effects
dry mouth
constipation
impaired visual accommodation/ blurred vision
difficulty in micturition & urinary retention
worsening of glaucoma
confusion
- 1-adrenoceptor blocking effects
drowsiness
postural hypotension (especially in the elderly)
sexual dysfunction
cognitive impairment - Histamine H1-receptor blockade
drowsiness
weight gain
Describe the MOA of Monoamine Oxidase inhibitors
*It inhibit MAO enzyme by binding to MAO-A AND B
*Result in increased levels of E, NE, serotonin and dopamine
SIDE EFFECTS
*Serotonin syndrome
*Hypertension
*Cns stimulation
Define antipsychotics
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of other psychotic disorders.
Distinguish between the two types of antipsychotics
CONVENTIONAL
* more affinity for Dopamine (D2) receptors, More extra pyramidal side effect (EPSE), e.g., Haloperidol, Chlorpromazine.
ATYPICAL
* Newer agents, less affinity for D2 and more for serotonin (5HT) receptors, less EPSE, more metabolic side effects. E.g., Olanzapine. Clozapine
State the side effects of conventional antipsychotics
1.Extrapyramidal symptoms (EPS)/ Parkinsonism
*Tardive Dyskinesia (TD) :
is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips.
*Akathisia :
is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still.
2.sedation - due to alpha1 adrenergic and H1 blockade
3.muscarinic blockade
- dry mouth
- urinary hesitancy
- constipation
- blurred vision and worsening of glaucoma
4.alpha 1 adrenergic blockade
- postural hypotension
- impotence
- ejaculatory failure
- nasal congestion
5.Endocrine: dopamine receptor blockade in H-P-A axis > increased prolactin
- amenorrhoea: missed menstrual period - galactorrhoea: milk flow from the breasts - impotence: erectile dysfunction - infertility
What is Neuroleptic malignant syndrome (NMS) ?
It is an idiosyncratic response to neuroleptics, thought to be due to complete dopamine blockade, although exact mechanism unclear
Neuroleptic malignant syndrome (NMS) is a reaction to some specific types of medications. It’s characterized by symptoms like very high fever, rigid muscles, and rapid heartbeat.
Describe MOA of ATYPICAL ANTIPSYCHOTICS
Atypical Antipsychotics
E.G., Risperidone
Pharmacological properties
* serotonin-dopamine atypical antipsychotic (SDA)
* higher affinity for the 5-HT2A receptor than the D2 receptors
* antagonist at Histamine and NA receptors
State the side effects of ATYPICAL ANTIPSYCHOTICS
- incidence of EPS is no greater than placebo
- at higher doses (> 8 mg), RISPERIDONE can cause EPS at a similar rate to typical drugs
- dose-related hyperprolactinemia (and sexual side effects) may be a problem
- insomnia
- headache
- anxiety
- weight gain
State the side effects of ATYPICAL ANTIPSYCHOTICS
- incidence of EPS is no greater than placebo
- at higher doses (> 8 mg), RISPERIDONE can cause EPS at a similar rate to typical drugs
- dose-related hyperprolactinemia (and sexual side effects) may be a problem
- insomnia
- headache
- anxiety
- weight gain
What is a placebo?
It is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
What is an anxiolytic?
An anxiolytic is a medication or other intervention that reduces anxiety
Describe the mechanism of action of Benzodiazepines
Method of action
* receptors are in a supramolecular complex with GABAA receptors (BZ/GABA) and chloride ion channel
* BZDs bind to the GAMMA 2 subunit
* they enhance GABA neurotransmission, thereby altering indirectly the activity of other systems s
- two types of receptor: BZ1, BZ2
- the BZ2 receptor may mediate anti-anxiety effects of BZDs
- BZ2 receptor is concentrated in the amygdala and septo-hippocampal pathways
- action may be to open chloride channel or increase chloride ion movement
- chloride ion moves into cell and inhibits depolarization
- makes neurone less reactive
- tribulin in human breast milk binds to B2 receptor
DBI (diazepam binding inhibitor) - a natural neuropeptide - displaces DIAZEPAM from binding sites, and produces ‘anxiety’ in rats
uch as noradrenaline and 5-HT - BZDs do not work in the absence of GABA
What is efficacy of a drug?
It is the ability of a drug to bring about pharmacological/ therapeutic effect
What is DBI (diazepam binding inhibitor) ?
- a natural neuropeptide - displaces DIAZEPAM from binding sites, and produces ‘anxiety’ in rats
Outline the withdrawal symptoms of diazepam
- symptoms usually develop within 2-3 days of stopping a short-acting one (e.g. LORAZEPAM) and within 7 days after stopping a longer acting BZD (e.g. DIAZEPAM)
- the symptoms last 3 -10 days, peak at 7-8 days
- characterized by anxiety, restlessness, apprehension, insomnia, nausea, tremor, muscle tension, sweating and heightened sensitivity to perceptual stimuli (e.g. hyperacusis)
- less common: malaise, blurred vision, nightmares, depression, hyperreflexia, ataxia, metallic taste in the mouth
- rare: tinnitus, perceptual disturbances (illusions, macropsia, micropsia, and occasionally hallucinations)
- epileptic seizures have been reported
What are mood stabilizers?
Mood stabilizers are psychiatric medications that help control mood swings, such as mania and depression, in mood disorders like bipolar disorder and schizoaffective disorders
What are mood stabilizers?
Mood stabilizers are psychiatric medications that help control mood swings, such as mania and depression, in mood disorders like bipolar disorder and schizoaffective disorders
How does lithium acts as a mood stabilizer?
affects the flow of sodium through nerve and muscle cells in the body. Sodium affects excitation or mania.
Outline disorders which are treated by mood stabilizers
*mania (feeling highly excited, overactive or distracted)
*hypo-mania (similar to mania, but less severe)
regular periods of depression, where treatment with other medicines has not worked
*bipolar disorder, where your mood changes between feeling very high (mania) and very low (depression)
*Lithium can also help reduce aggressive or self-harming behaviour.
