Mental Health Pharmacology

advertisement
Mental Health Pharmacology
Antipsychotics – Typical
Name
Haloperidol ,
chlorpromazine,
prochlorperazine,
flupentixol
Indication
 Schizophrenia
 Mania
 Sedation
 Anxiety and
psychomotor
agitation
 Nausea and
vomiting
Monitoring
ECG before initiating
treatment then annual
with some typical antipsychotics
MOA
Target: Muscarinic, histamine,
dopamine, serotonin and
adrenergic receptors.
MOA Mixed antagonists –
main action is through
antagonism of dopamine D2
receptors
The phenothiazine derivatives
can be divided into 3 main
groups:
 Group 1: chlorpromazine
hydrochloride,
levomepromazine, and
promazine hydrochloride,
 Group 2: pericyazine,
 Group 3: fluphenazine
decanoate, perphenazine,
prochlorperazine, and
trifluoperazine, generally
characterised by fewer
sedative and
antimuscarinic effects, but
more pronounced
extrapyramidal sideeffects than the others
 Butyrophenones
(benperidol and
haloperidol)
 Thioxanthenes
(flupentixol and
zuclopenthixol) have
moderate sedative,
antimuscarinic effects, and
extrapyramidal effects.
Diphenylbutylpiperidines
(pimozide) and the
substituted benzamides
(sulpiride) have reduced
sedative, antimuscarinic,
and extrapyramidal
effects.
Adverse Effects
 Extrapyramidal symptoms Hyperprolactinaemia
 Sexual dysfunction
 Cardio-side-effects - QTinterval prolongation
 Postural hypotension
 Hyperglycaemia and weight
gain
 Neuroleptic malignant
syndrome
Other
Drug interaction
- Phenothiazines (e.g.
chlorpromazine,
prochlorperazine) may
enhance the CNS
depressant effect of
opioids, anxiolytics,
sedatives, hypnotics
and alcohol
-
Antagonism of
sympathomimetics,
anticholinergics and
antiepileptic drugs may
occur.
-
↑ hypotensive effect
with ant-HTN agents
-
↑ risk of cardiac
arrhythmias (including
torsades de pointes)
with other drugs that
prolong the QT interval
Extrapyramidal symptoms consist of:

parkinsonian symptoms (including tremor), which may occur more commonly in adults or the elderly and
may appear gradually;

dystonia (abnormal face and body movements) and dyskinesia, which occur more commonly in children or
young adults and appear after only a few doses;

akathisia (restlessness), which characteristically occurs after large initial doses and may resemble an
exacerbation of the condition being treated;

tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw), which usually develops on
long-term therapy or with high dosage, but it may develop on short-term treatment with low doses—shortlived tardive dyskinesia may occur after withdrawal of the drug.
Antipsychotics – atypical
Name
MOA
Adverse Effects
Clozapine, olanzapine,
quetiapine, risperidone,
amisulpride
Atypical antipsychotics
act predominantly via
dopamine (D1 to D4) and 5HT receptors
 Sedation/agitation
 Postural
hypotension
 Antimuscarinic
effects.
 Weight gain.
 Neutropenia and
agranulocytosis
(clozapine only)
 Prolonged QT
interval
 Myocarditis and
cardiomyopathy
(clozapine only)
 Breast symptomsProlactin
(Risperidone)
Indications
 Schizophrenia and
other psychoses
 Mania and
hypomania
 Sedation
 Anxiety and
psychomotor
agitation
Monitoring
- FBC prior to starting
clozapine and initially
monitor counts
weekly.
- Cardiovascular
assessment prior to
starting clozapine
 Antipsychotic drugs
block post-synaptic
dopamine D2
receptors.
Drug bank  antagonism
at D2 receptors in the
mesolimbic pathway and
5HT2A receptors in the
frontal cortex. Antagonism
at D2 receptors relieves
positive symptoms while
antagonism at 5HT2A
receptors relieves negative
symptoms of schizophrenia.
Features that distinguish
second-generation
antipsychotics from firstgeneration agents are
improved efficacy in
‘treatment-resistant’
schizophrenia (particularly
true of clozapine) and
against negative symptoms,
and a lower risk of
extrapyramidal symptoms.
 Hyperglycaemia
(particularly
clozapine and
olanzapine)
Antipsychotics should
be used with caution in
patients with
cardiovascular disease.
Clozapine must not be
used in patients with
severe heart disease or
a history of
neutropenia.
Drug interaction and
Communication
Drug interaction
 Enhanced hypotensive effect
with antihypertensive agents.
 ↑ risk of cardiac arrhythmias
(including torsades de pointes)
with other drugs that prolong
the QT interval- amiodarone,
quinine, macrolide, SSRI
Communication
Worth reminding patient that they
should always inform any
healthcare professional involved in
their care what treatment they are
on.
This is particularly important for
antipsychotics as many other
medicines can interfere with the
way they work.
Patients taking clozapine should
know about the need for regular
blood test monitoring and of the
need to report infective symptoms
immediately
Benzodiazepine
Name
MOA
Adverse Effects
diazepam, temazepam
lorazepam,
chlordiazepoxide,
midazolam
 Bind to benzodiazepine receptors
that are coupled to GABA
receptors.





Indication
 Short-term use in
anxiety or
insomnia.
 Acute alcohol
withdrawal.
 Sedation.
 Status epilepticus.
 Muscle spasm
Monitoring
Monitor respiratory
effort and effect
(respiratory rate and
oxygen saturations).
 This increases the affinity of GABA
to its receptor and opens Cl
channels resulting in
hyperpolarisation of the cell
membrane, thereby preventing
further excitation.
 Benzodiazepines facilitate and
enhance binding of GABA to the
GABAA receptor.
 This has a widespread depressant
effect on synaptic transmission.
The clinical manifestations of this
include reduced anxiety,
sleepiness, sedation and
anticonvulsive effects.
Drowsiness
Light-headedness.
Dependence.
Confusion.
Amnesia
 The elderly should
receive a lower
dose.
 Benzodiazepines
are best avoided in
 respiratory
impairment or
neuromuscular
disease (e.g.
myasthenia gravis).
 They should be
avoided in liver
failure as they may
precipitate hepatic
encephalopathy
Drug interaction and
Communication
Drug interaction
Should not be taken with
alcohol due to increased
sedative effect
cytochrome P450 inhibitors
(e.g. amiodarone, diltiazem,
macrolides, fluconazole,
protease inhibitors) may ↑
their effects
Communication
Advise your patient that
pharmacological therapy is
only a short-term measure
Discuss the risks of
dependence, advising that
this can be minimised by
avoiding daily use if possible
and taking them for no
longer than 4 weeks.
Advise patients that they
should not drive or operate
complex or heavy machinery
after taking the drug, and
caution them that
sometimes sleepiness may
persist the following day.
Effect of excessive benzodiazepine use can be reversed by flumazenil. This is administered via IV route
Chlordiazepoxide can be used to lessen the symptoms of alcohol withdrawal. Chlordiazepoxide is given for a limited
time (3–10 days) in reducing doses but should not be given if a patient is likely to continue drinking alcohol
Carbamazepine
Name
MOA
Adverse Effects
Indication
1. Epilepsy: as a first
choice treatment
for focal seizures
with and without
secondary
generalisation and
for primary
generalised
seizures.
2. Prophylaxis of
bipolar disorder.
3. Trigeminal
neuralgia: as first
choice treatment
to control pain
and reduce
frequency and
severity of attacks.
Monitoring
No specific drug
monitoring required.
 Use-dependent blockade of
voltage-gated Na+ channels
responsible for propagation
of the action potential. Thus
carbamazepine preferentially
blocks the excitation of
neurones that are firing
repeatedly.
 Nausea and vomiting.
 Drowsiness.
 Generalised
erythematous rash.
 Cardiac conduction
disturbances.
 Leucopoenia
 It appears to inhibit neuronal
sodium channels, stabilising
resting membrane potentials
and reducing neuronal
excitability
 Carbamazepine
exposure in utero is
associated with neural
tube defects, cardiac
and urinary tract
abnormalities and cleft
palate
Reduces anticoagulant
effect of warfarin
 Carbamazepine should
be prescribed with
caution in patients
with hepatic, renal or
cardiac disease, due to
increased risk of
toxicity
Warn the patient to look out
for signs of severe
hypersensitivity, including
skin rashes; bruising,
bleeding, a high
temperature or mouth
ulcers (blood toxicity);
reduced appetite or
abdominal pain (liver
toxicity).
 Carbamazepine can be used
in the prophylaxis of bipolar
disorder if symptoms are not
responding to lithium
Drug interaction and
Communication
Drug interaction
Plasma levels can be
reduced by drugs that
potentiate Cytochrome
P450, including
phenytoin, phenobarbitone
and theophylline
Communication
Explain that treatment aims
to reduce seizure frequency.
For women, discuss
contraception and
pregnancy
Advise patients that they
must not drive unless they
have been seizure-free for
12 months (or have at least
a three-year pattern of
seizures while asleep only)
They should not drive for 6
months after changing or
stopping treatment.
Drugs for Dementia
Name
MOA
Adverse Effects
Donepezil,
galantamine and
rivastigmine
Memantine
Inhibition of acetylcholinesterase
thereby preventing the
breakdown of ACh;
 GI disturbance
 Gastric or duodenal
ulcers
 Drowsiness and
confusion
 Rarely, arrhythmias and
SA node/AV node block
Indication
1. Mild/moderate
dementia
2. Mild/moderate
dementia in
Parkinson’s
disease
(rivastigmine
only)
Monitoring
Monitor MMSE (mini
mental state
examination) score
every 6 months –
treatment should
only be continued
while score remains
at or above 10 (out
of 30).
NICE guidance (2007)
recommends the use
of
acetylcholinesterase
inhibitors in patients
with a MMSE score
between 10 and 20
points. NICE does
not recommend
memantine for
routine use
the cholinergic hypothesis suggests
that reduced ACh synthesis is a key
aetiological factor in Alzheimer’s
disease.
 Galantamine also acts as a
partial agonist at nicotinic
receptors.

Memantine – NMDAreceptor
antagonist that blocks the
effects of pathologically
elevated levels of glutamate
that may contribute to
neuronal dysfunction in
Alzheimer’s disease.
Drug interaction and
Communication
Drug interaction
risk of arrhythmias with
agents that reduce heart
rate (e.g. b blockers,
digoxin, amiodarone)
Effects antagonised by
antimuscarinics
Lithium
Name
Indication
 Treatment and
prophylaxis of
mania.
 Prophylaxis of
bipolar disorder
Monitoring
Check
- U&Es, LFTs and
TFTs prior to
initiating treatment.
-
Measure serum
lithium conc every 3
months (narrow
therapeutic index)
-
Monitor U&Es and
TFTs every 6–12
months on
stabilised regimen
MOA
Adverse Effects
Used for over 50 years in
treatment of bipolar disorder,
the mechanism of action is still
unknown.
 GI disturbance
 Fine tremor (common)
 Hyperparathyroidism
and hypercalcaemia
 Weight gain and
oedema
 Polyuria (inhibits
antidiuretic hormone)
 Hypothyroidism
CAUTIONS AND
CONTRAINDICATIONS.
 Renal disease.
 Untreated
hypothyroidism.
 Severe cardiac disease.
 Addison’s disease
Drug interaction and
Communication
Drug interaction
 Risk of lithium toxicity
with diuretics, ACEIs
and ARBs due to
reduced renal excretion.
 NSAIDs reduce lithium
excretion (reduce
afferent arteriolar
vasoconstriction).
 Increased risk of
ventricular arrhythmias
with amiodarone
Other
 Beneficial effects
take 3–4 weeks to
be seen.
 Dehydration,
reduced renal
perfusion and
infections
 In overdose, toxic
effects may clinically
manifest with
coarse tremor,
worsening GI
symptoms, blurred
vision, drowsiness,
ataxia and
dysarthria and
subsequently
convulsions,
psychosis and renal
failure
Monoamine Oxidase Inhibitors
Name
MOA
Phenelzine,
moclobemide,
selegiline
Inhibit MAO that degrades
monoaminergic
neurotransmitters in the synaptic
cleft.–
Indication
 Resistant
depression

Parkinson’s
disease (MAO-B
inhibitors only)
Monitoring
Monitor clinically for
adverse effects
MAO-A breaks down adrenaline,
noradrenaline, serotonin and
melatonin;
MAO-B breaks down
phenethylamine;
Adverse Effects




Postural hypotension
GI disturbance
Headache and dizziness
Rarely, hepatocellular
necrosis
 Monoaminergic crisis
(see below)
CAUTIONS AND CONTRAINDICATIONS
 Hepatic dysfunction
Both Subtypes degrade
 Phaeocromocytoma
dopamine.
(due to risk of
hypertensive crisis)
 Cerebrovascular
Some agents (e.g. phenelzine) are
disease
non-subtype specific whereas
others are specific (e.g.
moclobemide is selective for
MAO-A, selegiline is selective for
MAO-B).
Drug interaction and
Communication
Drug interaction
Accumulation of amine
neurotransmitters may result in
a hypertensive crisis,
hyperpyrexia and psychosis.
It occurs with numerous agents
including:
 Sympathomimetics (e.g.
in cough or
decongestant
medications)
 SSRIs and TCAs
 Levodopa
 Opioid analgesics
(especially pethidine)
 Tyramine-containing
foods (e.g. mature
cheese, broad beans,
beer, Marmite)
Sodium Valproate Anticonvulsant Oral
Name
MOA
Indication
Epilepsy – all forms
First choice drug for
the control of
generalised or
absence seizures and
as a treatment
option for focal
seizures.
 GI disturbance, Weight
Enhances the inhibitory effects of
gain
GABA within the brain, by
 Drowsiness
inhibiting enzymes that inactivate  Thrombocytopenia
GABA and block GABA reuptake
 Rarely pancreatitis
into neurones.
 Hyperammonaemia
 Reduced bone mineral
 The brain content of γdensity
aminobutyric acid (GABA), the
 Rarely liver dysfunction
principal inhibitory
(including fatal hepatic
neurotransmitter, which
failure)
regulates neuronal excitability.
 life-threatening
idiosyncratic adverse
This leads to inhibition of action
effects include severe
potential transmission both prepancreatitis, bone
and post-synaptically, thereby
marrow failure and
interrupting seizure activity
antiepileptic
hypersensitivity
syndrome
Bipolar disorder, for
the acute treatment
of manic episodes
and prophylaxis
against recurrence.
Monitoring
Monitor LFTs (6
monthly) and FBC
(prior to
commencing
treatment and
before surgical
procedures).
Adverse Effects
Drug interaction and
Communication
Drug interaction
Anticonvulsant effect
reduced by antidepressants
(SSRIs, TCAs), antimalarials
(mefloquine, chloroquine)
and MAOIs
Communication
Explain that the aim of
treatment is to reduce
frequency of seizures. Warn
patients that they may have
some indigestion or tummy
upset when starting
valproate, but that these will
settle in a few days and can
be reduced by taking tablets
with food.
It is the antiepileptic drug
associated with the greatest
risk of foetal abnormalities,
including neural tube
defects, craniofacial, cardiac
and limb abnormalities and
developmental delay.
It should be avoided in
patients with hepatic
impairment and dose
reduction is required in
patients with severe renal
impairment.
The usual daily starting dose of valproate is 600 mg for epilepsy and 750 mg for bipolar disorder, taken in 1–3
divided doses. The dose is increased to a usual daily maximum of 1–2 g.
Tricyclic antidepressant (TCAs)
Name
MOA
Adverse Effects
Other
Amitriptyline, lofepramine,
Imipramine, dosulepin
Indication
 2nd line treatment for
moderate-to-severe
depression where firstline serotonin-specific
reuptake inhibitors
(SSRIs) are ineffective.
Inhibit re-uptake of
noradrenaline and serotonin into
neurones, hence increasing
synaptic availability of
noradrenaline and serotonin.
 Blockade of
antimuscarinic
receptors causes dry
mouth, constipation,
urinary retention and
blurred vision.
Drug interaction
Should not be given with
MAOIs due to risk of
hypertensive crisis and
hyperpyrexia

The increased extracellular
concentration of
neurotransmitters allows greater
action potential transmission,
leading to clinical improvement in
symptoms
Neuropathic pain,
although they are not
licensed for this
indication.
TCA inhibit neuronal reuptake of
Monitoring
No specific drug monitoring serotonin (5-HT) and
noradrenaline from the synaptic
required
cleft, thereby increasing their
availability for neurotransmission
Tricyclic antidepressants also
block a wide array of receptors,
including muscarinic, histamine
(H1), α-adrenergic (α1 and α2)
and dopamine (D2) receptors.
 Blockade of
H1 and α1 receptors
causes sedation and
hypotension.
 Blockade of
dopamine receptors
cause breast
changes and sexual
dysfunction
 Anxiety, dizziness,
arrhythmias
CAUTIONS AND
CONTRAINDICATION
Immediately post-MI.
Cardiac arrhythmias
In manic phase of bipolar
disorder
Severe liver disease
↑ sedative effect when
taken with alcohol and
antihistamines
↑antimuscarinic side-effects
when taken with
antihistamines and
anticholinergics
TCAs antagonise the effects
of antiepileptic medication
Communication
 Advise patients that
treatment will improve
symptoms over a few
weeks, particularly sleep
and appetite.
 Discuss referring them
for psychological
therapy, which may
offer more long-term
benefits than drug
treatment.
 Explain that they should
carry on with drug
treatment for at least 6
months after they feel
better to stop the
depression from coming
back
 Warn them not to stop
treatment suddenly as
this may cause flulike withdrawal
symptoms and
sleeplessness. Should
reduce the dose slowly
over 4 weeks.
 Discussing at an early
stage what side effects
are expected may
encourage patients to
persist with treatment
SNRI (serotonin and noradrenaline reuptake inhibitor) – Antidepressant
Name
MOA
Adverse Effects
Other
Venlafaxine - 37.5 mg BD
Venlafaxine is a (SNRI),
interfering with uptake of these
neurotransmitters from the
synaptic cleft.
 gastrointestinal upset
(e.g. dry mouth,
nausea, change in
weight and diarrhoea
or constipation)
Drug interaction
Mirtazapine- 15 mg OD
Indication
 As an option for
treatment of major
depression where firstline selective serotonin
reuptake inhibitors
(SSRIs) are ineffective or
not tolerated.
 Generalised anxiety
disorder (venlafaxine).
Monitoring
No specific drug monitoring
required
Mirtazapine is an antagonist of
inhibitory pre-synaptic α2adrenoceptors.
Avoid combination with SSRI
Communication
 CNS effects (e.g.
headache, abnormal
dreams, insomnia,
Both drugs increase availability
confusion and
of monoamines for
convulsions).
neurotransmission, which is
the mechanism whereby they
 hyponatraemia
improve mood and physical
 serotonin syndrome
symptoms in moderate-to Suicidal thoughts and
severe (but not mild)
behaviour ↑
depression
 Prolonged QT interval
(venlafaxine)- Varrhythmias
Venlafaxine is a weaker
antagonist of muscarinic and
CAUTIONS AND
histamine (H1) receptors than
CONTRAINDICATION
TCA.
Mirtazapine is a potent
Cardiac arrhythmias
antagonist of histamine (H1) but Severe hepatic and renal
not muscarinic receptors.
impairment
 Advise patients that
treatment will improve
symptoms over a few
weeks, particularly sleep
and appetite.
They therefore have fewer
antimuscarinic side effects than
tricyclic antidepressants,
although mirtazapine commonly
causes sedation.
 Warn them not to stop
treatment suddenly as
this may cause flulike withdrawal
symptoms and
sleeplessness. Should
reduce the dose slowly
over 4 weeks.
 Discuss referring them
for psychological
therapy, which may
offer more long-term
benefits than drug
treatment.
 Explain that they should
carry on with drug
treatment for at least 6
months after they feel
better to stop the
depression from coming
back
 Discussing at an early
stage what side effects
are expected may
encourage patients to
persist with treatment
 Warn patients taking
mirtazapine to seek
medical advice for
symptoms of infection,
such as sore throat, so
that a blood test can be
taken to check for blood
disorders
SSRI- Antidepressant Selective serotonin reuptake inhibitors (SSRIs)
Name
MOA
Adverse Effects
Other
Citalopram, fluoxetine,
sertraline, escitalopram
(SSRIs) preferentially inhibit
neuronal reuptake of serotonin
(5-HT) from the synaptic cleft,
thereby increasing its
availability for
neurotransmission.
 GI disturbance
 Hypersensitivity
reactions
 Anorexia and weight
loss
 Dry mouth
 Headaches, sleep
disturbance
 Sexual dysfunction
 prolong the QT
interval and can
predispose to
arrhythmias
Drug interaction
Avoid combination with
MOAi due to risk of
serotonin syndrome
Indication
 Depression
 Panic disorder
 Obsessive–compulsive
disorder
 Generalised anxiety
disorder
Monitoring
No specific drug monitoring
required
This appears to be the
mechanism by which SSRIs
improve mood and physical
symptoms in depression and
relieve symptoms of panic and
obsessive disorders
Bleeding risk +anticoagulant
should not be combined with
other drugs that prolong the
QT interval, such as
antipsychotics.
Gastroprotection should be
prescribed for patients
taking SSRIs with aspirin
or NSAIDs due to an
increased risk of
gastrointestinal bleeding
 Serotonin
Rapid Pharmacology “The
syndrome triad of
monoamine hypothesis
autonomic
postulates that impairment in
hyperactivity, altered
central monoaminergic function
mental state and
with deficiencies in
Communication
neuromuscular
neurotransmitters (including 5excitation, which
HT) are key to the aetiology of
 Advise patients that
usually responds to
depression. SSRIs act to
treatment will improve
treatment withdrawal
increase concentrations of 5-HT
symptoms over a few
and supportive
by preventing the reuptake of 5weeks, particularly sleep
therapy.
HT back into the pre-synaptic
and appetite.
terminal; they block specific 5CAUTIONS AND
HT transporters thereby
 Discuss referring them
CONTRAINDICATION
increasing 5-HT binding at the
for psychological
post-synaptic receptors”
therapy, which may
There is a particular risk
offer more long-term
of adverse effects,
benefits than drug
including
treatment.
in epilepsy and peptic
ulcer disease.
 Explain that they should
carry on with drug
treatment for at least 6
months after they feel
better to stop the
depression from coming
back
 Warn them not to stop
treatment suddenly as
this may cause flulike withdrawal
symptoms and
sleeplessness. Should
reduce the dose slowly
over 4 weeks.
 Discussing at an early
stage what side effects
are expected may
encourage patients to
persist with treatment
 Warn patients taking
mirtazapine to seek
medical advice for
symptoms of infection,
such as sore throat, so
that a blood test can be
taken to check for blood
disorders
Download
Related flashcards
Create Flashcards