Psychopharmacology Flashcards
(159 cards)
1
Q
Learning objectives
A
- explore the journey of medication from consumption to action
- learn the various ways psychotropic medication interact with the brain
- develop awareness of the basic prescribing guidelines for major psychiatric disorders
2
Q
What are the different ways that medications can be formulated?
A
- tablets
- capsules
- velotabs
- quicklets
- solution
- slow release
- intramuscular
- depot
- intravenous
- subcutaneous
3
Q
What is the action of orodispersible tablets?
A
orodispersible tablets disintegrate in the mouth very quickly as they are formulated with disintegrants which are broken down by saliva in under one minute
4
Q
What are some slow release forms of medication?
A
- pills
- tablets
- capsules
5
Q
Which forms of medication increase compliance/ medication adherence?
A
Orodispersible tablets and slow release medications such as depots
6
Q
Why are slow-release medications more likely to increase medication adherence?
A
Drugs that are slowly released overtime need to be taken less frequently compared to immediate-release types
7
Q
What are depot medications also known as?
A
Long-acting injectables (LAI)
8
Q
What are long-acting injectables also known as?
A
Depot
9
Q
How to depot medications/ long-acting injectables work?
A
Long-acting injectables are injected intramuscularly which forms a depot that is slowly released into the bloodstream over weeks or months.
10
Q
What are the difficulties of depot medications?
A
Dosing - it may take some time to reach peak (therapeutic) levels and differs per antipsychotic medication.
Delays - it takes longer for therapeutic effects and for plasma levels to reach a steady state.
11
Q
What are the considerations for prescribing medication?
A
- check medication use
- adequate dosing and duration
- clearly communicate side effects
- consider different/ alternative drugs
- allergies
- homeopathic remedies
- past medical hx
- over the counter medications
- interactions
- recreational substances
- family hx
- what has worked before/ currently working
12
Q
What is the direction of movement of medication from mouth the liver?
A
Mouth → stomach → small intestine → bloodstream → liver
13
Q
How long do medications stay in the stomach?
A
45 minutes
14
Q
How do medications enter the liver from the blodstream?
A
via the portal vein
15
Q
What is the first pass effect?
A
A pharmacological phenomenon where medication undergoes metabolism at a specific location in the body
16
Q
What does the first pass effect do the concentration of antipsychotic drugs?
A
The first pass effect decreases the active drug concentration upon reaching system circulation or its site of action.
17
Q
Which organ is a major site of drug metabolism?
A
The liver
18
Q
Where else in the body does the first pass effect occur
A
- lungs
- vasculature
- gastrointestinal tract
- other metabolically active tissue
19
Q
Which route of administration is most greatly associated with the first pass effect?
A
Oral
20
Q
If the first pass effect is particular strong what considerations need to be made about drugs?
A
- alternative drug formulation (e.g. tablet, solution etc.)
- alternative route of adminstration (i.e. other than oral)
21
Q
The liver metabolises drugs into which two types of metabolites?
A
Active and inactive metabolites
22
Q
What determines the bio availability of of psychoactive medications?
A
The ratio of active to inactive metabolites
23
Q
Define
Bioavailability
A
The duration plus the intensity of a drugs pharmacological action
24
Q
What is the relationship between metabolic rate, active metabolites and bio availability?
A
Anything that increases the metabolic rate of an active metabolite decreases bioavailability (and vice versa)
25
What is the relationship between metabolic rate and enzyme activity?
Increased metabolic rate equals enzyme induction whilst a decreased metabolic rate equals enzyme inhibition.
26
# *define*
What is a prodrug?
A compund with little/ no pharmacological activity which once metabolised converts into a pharmacologically active drug compound
27
When can enzymes cause toxicity?
When an enzyme metabolises a prodrug into a drug enzyme induction can accelerate the prodrug to drug conversion increasing drug levels and potentially causing toxicity.
28
Which enzyme mediates the action of prodrug to drug conversion?
Cytochrome P450
29
Which factors influence drug metabolism?
* age
* genetic variation
* ethnicity
* enterohepatic circulation
* nutrition
* intestinal flora
* sex differences
30
Which age groups have slower metabolisms?
* fetuses
* neonates
* elderly
31
Which pathological disease factors influence metabolism
* liver disease
* heart disease
* kidney disease
32
Which antipsychotic drugs can be administered as long-acting injectables?
* olanzapine
* aripiprazole
* paliperidone
33
What effect on enzyme action needs to be considered with certain SSRIs?
Some SSRIs are potent inhibitors of individual or multiple hepatic cytochrome P450
34
What is the effect of fluoxetine (SSRI) on hepatic cytochrome P450?
Fluoxetine (SSRI) inhibits CYP2D6 which increases seizure risk of clozapine (antipsychotic)
35
What is the effect of smoking on Clozapine metabolism?
Smoking induces metabolism of Clozapine through CYP1A2
36
What is the effect of smoking on Clozapine dosage?
The clozapine dose would need to be increased to maintain therapeutic levels
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When does smoking becoming an increased risk factor for toxicity
If the individual stops smoking and continues to take the higher dose of clozapine (because of increased enzyme induction and metabolism of clozapine from smoking) the increased levels of clozapine can lead to toxicity.
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Which cells make up the blood brain barrier?
Glia and neurons
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How is the blood brain barrier formed?
Capillary endothelial cells are joined by tight junctions of high electrical resistance
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Capillaries are in contact with which type of glial cell?
Atrocyte foot processes
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Capillaries and foot processes of astrocytes separate which two types of cells?
Capillaries and neurons
42
Which compounds cannot enter the brain via the BBB?
* non-lipid soluble compounds
* most compounds with a molecular weight > 500 g/mol
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How do pharmacological drugs need to be formulated to cross the blood brain barrier?
*They need to be*:
* lipid soluble
* < 500 g/mol
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What are the different types of neurotransmitters?
* amines
* amino acids
* opioid peptides
* gases
* neurokinins
* purines
* lipids
* other peptides
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What are examples of amine neurotransmitters?
* serotonin
* dopamine
* noradrenaline
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What are examples of amino acid neurotransmitters?
* GABA
* glycine
* glutamate
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What are examples of opioid peptide neurotransmitters?
* endorphin
* enkephalin
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What is an example of a gas neurotransmitter?
Nitric oxide
50
What is an example of a neurokinin neurotransmitter?
Substance P
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What is an example of a purine neurotransmitter?
* ATP
* Adenosine
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What is an example of a lipid neurotransmitter?
Anandamide
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What is an example of a peptide neurotransmitter?
* bradykinin
* neurotensin
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Which hormones may/ may not be considered neurotransmitters?
* pituitary peptides (e.g. ACTH, GH, prolactin)
* circulating hormones (e.g. insulin, leptinm, cortisol)
* hypothalamic hormones (e.g. adrenaline)
55
When is adrenaline a hormone?
When it is secreted by the adrenal gland into the blood stream and affects the heart.
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When is adrenaline a neurotransmitter?
When it is released from a stimulated presynaptic nerve cell and acts on neighbouring post synaptic cells.
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What type of communication is the communication within neurons?
Electrical
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What type of communication occurs between neurons (across synapses)?
Chemical
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What are the two main types of receptors?
Ionotropic receptors and metabotropic receptors
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What are ionotropic receptors?
The second messenger can be an ion (e.g. calcium)
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What are metabotropic receptors?
Metabotropic receptors activate inside signal transduction pathways, and ultimately cellular responses (e.g. the cAMP signal pathway)
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What is the opposite of an agonist?
An inverse agonist
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What are inverse agonists?
Inverse agonists prevent the action of agonists but have no activity of their own in the absense of an agonist?
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What is the role of a parital agonist?
They stimulate receptors but to a lesser degress than agonists
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What is the least efficacious agonist relative to an endogenous agonist?
Full inverse agonist
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Which type of agoinst has a 0% efficacy relative to an endogenous agonist?
Silent agonist
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Which type of agonist has a 100% efficacy relative to an endogenous agonist?
Full agonist
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What causes depression?
| *neurotransmitter explanation*
A malfunction of the monoaminergic neurotransmitter system
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What are the three core features of depression
1. low mood
2. low energy
3. anhedonia
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What is first line treatment for depression?
Selective serotonin reuptake inhibitors
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What are examples of SSRIs?
* fluoxetine
* paroxetine
* citalopram
* escitalopram
* sertraline
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What percentage of patients with moderate depression recover with no treatment?
20%
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What percentage of patients with moderate depression response to placebo?
30%
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What percentage of patients with moderate depression response to antidepressants?
50%
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What is discontinuation syndrome?
The effect of stopping a drug which may cause returning or new symptoms
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Which factors increase the risk of discontinuation syndrome?
* drugs with a short half life
* missing doses
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NaSSA
Noradrenergic and Specific Serotinergic Antidepressant
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What is an example of an NaSSA?
Mirtazapine
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What is the action of NaSSAs
* D2 receptor antagonist
* blocks three serotonin receptors
* blocks histamine 1 receptor
* increased release of noradrenaline and serotonin
* as effective as an SSRI
* anxiolytic
* sleep restoration
* no sexual dysfunction
* improves appetite
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SNRI
Serotonin and noradrenaline reuptake inhibitor
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What effect does SNRI dosage have on inhibition/ reuptake
Lower doses inhibit serotonin uptake more whilst higher doses inhibit noradrenaline uptake
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What line of treatment are SNRIs recommended?
Second line
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What is an adverse physiologically response to SNRIs?
Increased risk of hypertension
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What is the first line of treatment for anxiety?
Psychological therapy
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Anxiety disorders
* generalised anxiety disorder
* social anxiety
* OCD
* PTSD
* panic disorder
* specific phobias
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What is the brain's main inhibitory neurotransmitter?
GABA
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What is the action of bezodiazepines?
Benzodiazepines enhance GABA
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What are the adverse effects of benzodiazepines?
* addictive
* withdrawal
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What are the considerations for prescribing benzodiazepines?
* use the lowest effective dose for the least amount of time
* use for a maximum of four weeks
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What is the advice for prescribing SSRI/SNRI for generalised anxiety disorder?
* start with half of the usual dose used to treat depression
* titrate up to normal antidepressant range
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Pregabalin
* licensed to treat generalised anxidety disorder
* stopping suddenty can cause a return of symptoms and increase the risk of seizures
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# *Treatment*
Panic disorder
* first line treatment is SSRIs
* CBT based self help
* do not prescribe benzodiazepines
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# *Treatment*
Generalised anxiety disorder
* first line treatment is SSRIs
* alternative treatment is SNRIs and pregabalin
* high intensity psychological intervention
* CBT based self help
* benzodiazepines in severe cases but only for 2-4 weeks
95
# *Treatment*
OCD
| ***(with moderate-severe functional impairment)***
* first line treatment in an SSRI or high intensity CBT
* SSRI ***and*** high intensity CBT if response to one treatment alone is suboptimal
* Clomipramine (TCA) if SSRI is not working
* Clomipramine ***and*** antipsychotic (citalopram) if clomipramine only is not working
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# *Treatment*
Insomnia
* zolpiderm
* zopiclone
* temazepam
* promethazine
* melatonin
97
Zopiderm
* short half life
* for people who find it hard to get to sleep
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zopiclone
* long half life
* for people who find it hard to stay asleep
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temazepam
* short half life
* increased risk of dependency
100
promethazine
* antihistamine
* sedative
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What is melatonin and where is it produced?
Melatonin is a hormone produced by the pineal gland in a circadian rhythm
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What is the action of melatonin?
Melatonin rises in the evening. The rise in melatonin is preceded by the onset of natural sleep by approx. 2 hours.
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What is the role of melatonin in sleep?
Melatonin is involved in falling asleep and synchronising circadian rhythms.
104
# True or false
Melatonin can safely be used in neuropsychiatric disorders and children
True
105
What is the underlying pathophysiology of psychosis?
* abberant neurodevelopment
* inflammation
* oxidative stress
* abberant dopaminergic neurotransmission
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What does abberant mean?
Deviating from normal
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What are five of the dopamine pathways in the brain?
* mesolimbic
* mesocortical
* tuberofundibular
* nigrostriatal
* thalamic
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What is the mesolimbic pathway?
The mesolimbic pathway projects from the ventral tegmental area in the brain stem to the nucleus accumbens in the ventral striatum.
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What is the effect of hyperactivity in the mesolimbic pathway?
hallucinations and delusions
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What is the mesocortical pathway?
The mesocortical pathway projects from the ventral tegmental area to the prefrontal cortex and the ventromedial prefrontal cortex.
112
What symptoms are associated with the prefrontal cortex?
Cognitive symptoms
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What symptoms are associated with the ventromedial prefrontal cortex?
Affective symptoms
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What is the tuberofundibular pathway?
The tuberofundibular pathway projects from the hypothalamus to the anterior pituitary gland.
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What does the anterior pituitary gland do?
The anterior pituitary gland controls the release of prolactin and dopamine which inhibits the release of prolactin.
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Is the tuberfundibular pathway normal or abnormal in schizophrenia?
Normal
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What is the nigrostriatal pathway?
The nigrostriatal pathway projects from teh substantia nigra to the basal ganglia and plays a key role in regulating movements.
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What are the motor symtpoms associated with low dopamine?
Parkinsonism
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What are the non motor symptoms associated with excess dopamine?
* tics
* dyskinesia
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Is the nigrostriatal pathway normal or abnormal in schizophrenia?
Normal
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What is the role of the thalamic pathway?
The thalamic pathway may be involved in slee[ and arousal?
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Is the thalamic pathway normal or abnormal in schizophrenia?
Normal
123
Which three dopamine pathways are normal in schizophrenia
* tuberofundibular
* nigrostriatal
* thalamic
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What is parkinsonism?
Bradykinesia (slowness of initiation of voluntary movements with progressive reduction in speed and amplitude or repetitive actions) and at least one of the following:
* muscle rigidity
* 4 - 6 Hz resting tremor
* postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
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Dystonia
Sustained muscle contractions which cause twisting and repetitive movements or abnormal posturing.
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Tardive dyskinesia
Repetitive, involuntary, purposeless movements such as:
* grimacing
* tongue movements
* lip smacking
* lip puckering
* pursing of the lips
* excessive eye blinking
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What are typical antipsychotics?
| Also conventional or first generation antipsychotics
D2 antagonism that ameliorates positive symptoms but also blocks reward circuits causing apathy, anhedonia, lack of motivation and extrapyramidal side effects (e.g. involuntary movements, muscle contractions, tremors)
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Which receptors do typical antipsychotics work on?
D2
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What are some typical antipsychotics?
* chlorpromazine
* haloperidol
* flupenthixol
* zuclopenthixol
* pipothiazine
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What are atypical antipsychotics?
| Also second generation antipsychotics
Atypical or second generation antipsychotics readily dissociate from dopamine receptors. They may act as serotonin agonists, D2 partial agoinsts or serotonin partial agonists.
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What is the effect of atypical, second generation antipsychotics?
Lower rates of extrapyramidal symptoms compared to typical/ first generation antipsychotics and increased effectiveness in targeting negative symptoms.
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What are the side effects of atypical/ second generation antipsychotics?
They may cause more metabolic side effects such as weight gain and diabetes.
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What are some atypical antipsychotics?
* olanzapine
* risperidone
* quetiapine
* aripiprazole
* lurasidone
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What is refractory schizophrenia?
Schizophrenia that is resistant to treatment
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Which medication is given in refractory schizohrenia?
Clozapine
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How is treatment resistance defined?
Treatment resistance is established when a patient has already tried two different antipsychotics with suboptimal effects.
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Adverse side effects depend on which two factors?
Dose and titration
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What is the number one rule when prescribing antipsychotic medications?
Start low and go slow
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Why is it important to start at a low dose and increase slowly?
Starting at a low dose ensures the patient recieves a therapeutic effect.
Increasing slow is to avoid agranulocytosis.
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What is agranulocytosis?
An acute condition where white blood cells are severly and dangerously lowered causing neutropenia in the circulating blood, leading to sepsis.
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What is the effectiveness of clozapine?
| Clozapine is used to treat treatment-resistant schizophrenia/ psychosis
* after 6 weeks 30% of patients improve
* a further 30-40% of patients improve by 6 months
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Clozapine
| cheat sheet
* used in treatment resistant psychosis
* reduced suicide risk
* increases risk of seizures in high doses
* weight gain
* hypersalivation
* myocarditis
* close monitoring is needed
* agranulocytosis occurs in 0.5-2% of patients
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Which measures need to be monitored in all antipsychotics?
* baseline full blood count (FBC)
* urine and electrolytes (U&E)
* liver function test (LFT)
* electrocardiogram (ECG)
* blood pressure (BP)
144
Which additional measures need to be monitored in patients who take olazapine?
* baseline glucose
* glucose at 1,4 and 6 months
* lipids 3 monthly for the first year then yearly after that
145
Bipolar II
Bipolar II disorder is a milder form of mood elevation, and mild episodes of hypomania that alternate with periods of severe depression.
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Which additional measures need to be monitored in patients who take risperidone, amisulpride and sulpiride?
* basline prolactin
* prolactin at 6 months and then yearly after that
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Bipolar I
Bipolar I disorder is characterised by periods of severe mood episodes from mania to depression.
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Bipolar affective disorder
Rapid cycling between depression and mania with four or more episodes of hypomania or depression that occur in a 12 month period.
* less responsive to treatment than non cycling bipolat
* high morbidity
* increasesd risk of suicide
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# Treatment
Bipolar
Antipsychotics (e.g. olanzapine)/ mood stabilisers (e.g. lithium, sodium valproate are effective treatment for mania and hypomania. These effects may be increased using sedatives and axiolytics (e.g. benzodiazepines).
149
Lithium
* an ion that involves secondary messenger systems and gene expression regulation
* mood stabilising
* reduces relapse (mood stabilising)
* minimises suicide risk (mood stabilising)
* narrow therapeutic window (monitoring)
150
Valproate
Thought to increase the action of GABA/ and or inhibit voltage sensitive sodium channels.
* avoid in women of child bearing age
151
What is first line treatment for rapid cycling bipolar (bipolar affective disorder)?
Lithium (only) or lithium and valproate
152
What type of disorder is bipolar?
Relapsing-remitting
| *Yay! that means we can use prophylactic treatments*
153
What is the prophylactic first line treatment for bipolar affective disorder?
Lithium
154
What is the prophylactic second line treatment for bipolar affective disorder?
Valproate
155
What are alternative prophylactic second line treatments for bipolar affective disorder?
* olanzapine
* quetiapine (if previously effective during a manic or depressive episode)
156
What is the prophylactic third line treatment for bipolar affective disorder?
An alternative antipsychotic that has previously been effective during an acute episode (e.g carbamezapine, lamotrigine)
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