PSYCHOPHARMACOLOGY Flashcards
1
Q
full agonists
A
- can take place on both ionotropic and metabotropic receptors
- endogenous factors naturally act as full agonists (eg NTs, hormones)
- some psychotropic drugs can also stimulate agonistic action, triggering a full signal transduction
- in metabotropic receptors process takes place through second messengers
- in ionotropic receptors, agonists can cause the ion channel to open as wide as possible and at the highest frequency
2
Q
direct action of full agonist
A
binds to receptor, producting the sequence of events
3
Q
indirect action of full agonist
A
assists in full agonistic action of endogenous ligands.
4
Q
partial agonists
A
ionotropic and metabotropic
some intrinsic action that places them between competitive and full agonists
activity depends on density and expression of receptors, and efficiency of effector systems
4
Q
antagonists
A
ionotropic and metabotropic
act by binding with receptor without triggers direct action or known signal transduction.
work by blocking the binding of natural NT agonists
can be competitive or non-competitive.
competitive is reversible
5
Q
inverse agonists
A
ionotropic and metabotropic
bind to receptors but bring about opposite result
reduce signal transduction lower than receptors baseline
6
Q
pharmacodynamics - up regulation
A
number of receptors on a cell increases as a response to an external message
increases the sensitivity of the cell to molecules
eg critical for the development of dependence on nicotine in smokers
7
Q
pharmacodynamics - down regulation
A
number of receptors on a cell reduces as a response to an external message
decreases the sensitivity of the cell to molecules
eg tolerance in opioid use
8
Q
affinity
A
the ability of a drug to bind to its relevant receptor tightly or not
thermodynamic forces determine affinity
8
Q
sensitisation
A
increases of the pharmacological action of a drug following repeated exposure to it
9
Q
potency
A
amount of drug needed to produce a desired effect
high potency = desired effect at lower concentrations
10
Q
efficacy
A
‘intrinsic activity’
‘a proportionality factor denoting the amount of physiological response a given ligand imparts to a biological system for a given amount of receptor occupancy’
11
Q
potency of a drug determined by… (3)
A
proportion of the drug reaching the receptor
affinity for the receptor
efficacy
12
Q
GABA
A
major inhibitory NT in the brain
binds to GABAa and GABAb
eg benzos
13
Q
Serotonin
A
involved in depression phenotypes
5-HT rec approx 15 subtypes
most are excitatory
14
Q
dopamine
A
involved in salience and reinforcement
related to schizophrenia and parkinsons
can be excitatory or inhibitory
receptors D1-D5
D2 receptors responsible for EPSEs of antipsychotics
D3 and D4 receptors play a role in the negative sx of schizophrenia
15
Q
glutamate
A
major excitatory NT involved in learning and memory
4 types of receptors:
NMDA, AMPA, kainite (all ionotropic)
mGluR (metabotropic)
eg memantine
16
Q
acetylcholine
A
excitatory and inhibitory
CNS and PNS
related to cognition and memory
nicotinic rec and muscarinic rec
nicotinic are excitatory
17
Q
norepinephrine
A
involved in attention and flight or flight
binds to adrenergic receptors
18
Q
glycine
A
inhibitory
sensory and motor pathways
18
Q
histamine
A
H1 and H2 rec mediated actions mainly excitatory
H3 actions inhibitory
sleep wake cycle, learning and memory
19
Q
types of metabolisers (genetic)
A
poor metabolisers (no alleles)
intermediate metabolisers (one allele)
extensive metabolisers (two alleles)
ultra rapid metabolisers (three alleles)
20
Q
4 core components of pharmacokinetics
A
absorption
distribution
metabolism
elimination
21
Q
drug absorption
A
after administration, released from pharmaceutical formulation to enter the person’s blood stream
22
bioavailability
how much of the original drug enters the bloodstream unchanged
IV = 100%
22
drug distribution
the transfer of a drug from one point to another in the body
23
drug metabolism
the biotransformation of compounds into new compounds, in order that they are made more water-soluble and can be more easily excreted from the body
24
drug elimination and potential routes (8)
can be excreted unaltered or in the form of metabolites
breast milk, faeces, urine, breath, tears, hair, saliva, sweat
25
first pass metabolism
intestinal and hepatic degradation or alteration of a drug or substance take by mouth after absorption, removing some of the active substance from the blood before it enters the general circulation
reduces bioavailability
26
factors affecting bioavailability (5)
formulation of the drug
with vs without food
interactions with food
interactions with other drugs
diseases affecting liver or GI tract
27
diazepam PO bioavailability
almost 100%
28
diazepam rectal bioavailability
around 90%
29
diazepam time to peak plasma levels oral administration
30-90 minutes
30
diazepam time to peak plasma level IM administration
30-60 min
31
half life
time taken to eliminate 50% of absorbed dose of a drug from plasma
32
drug clearance
the volume of plasma form which the drug is completely removed, or cleared, in a given time period
33
steady state
when the intake of a drug is at the same overall rate as its excretion or elimination, so there is no net change in the amount of drug in the persons system
usually 4-5x half life
33
dietary CYP450 inhibitors
grapefruit
soya
caffeine
34
first order kinetics
same fraction of a drug is eliminated per unit time, regardless of plasma levels of the drug
the actual amount of drug eliminated over a certain time period decreases proportionally with the amount of drug in the body
clearance of a drug is constant
34
zero order kinetics
the fraction of drug eliminated per unit time varies. the amount of drug eliminated for each time interval is constant, regardless of the amount o drug in the body
35
ssri longest half life
fluoxetine
least likely to experience withdrawal effects
36
ssri shortest half life
paroxetine
37
CVS changes with ageing
cardiac output slowly and steadily decreases
BP tends to increase
arteriosclerosis more prevalent
38
renal changes with ageing
renal size and function decrease with age
total number of glomeruli decreases
renally excreted drugs can have significantly higher half lives in elderly
39
respiratory system changes with ageing
vital capacity and other functional respiratory measurements eg FEV decrease
40
endocrine changes with ageing
peripheral insulin resistance worsens
diabetes
osteoporosis increasing issue
menopause an issue for women
41
GI and liver changes with ageing
atrophic gastritis more frequent
decreased intestinal motility
liver volumes decrease, but functional differences not always marked
hepatic half lives can be prolonged
42
skin changes with ageing
skin cell replacement slows
appearance, tone and elasticity change
43
MSK changes with ageing
degenerative joint disease
overall decrease in muscle mass
44
age - absorption
changes in gastric pH can lead to differences in absorption
45
age - distribution
typically fat levels increase with age, therefore lipophilic or lipid soluble drugs tend to be more widely distributed in older people than younger people
water soluble drugs tend to be less well distributed
46
age - metabolism
with reduced liver activity and perfusion, first pass metabolism can be reduced, leading to higher than expected levels of unchanged drugs when administered orally, or lower than expected levels of metabolites
47
age - excretion
reduction in renal function can lead to decreased clearance of drugs, and this can lead to higher serum levels and even toxicity in older patients
48
CYP450 poor metabolisers eg
asian population
african american populations
49
CYP450 ultrarapid metabolisers eg
middle eastern and north african populations
50
pregnancy - absorption
changes to rate of gastric emptying and pH during pregnancy
need to consider N+V in pregnancy
51
pregnancy - distribution
water content rises quite markedly, fat stores also rise
can lead to dilution and lower plasma levels of drugs
52
pregnancy - metabolism
some CPY450 enzymes inducted by hormone changes in pregnancy, others can be reduced by competitive inhibition
metabolism of drugs can be increased or decreased during pregnancy
53
pregnancy - excretion
increased blood flow during pregnancy, kidney clears out a lot more drug during pregnancy.
54
concentration steady state
when rate of administration equals rate of elimination
usually 5-7 half lives
plasma concentrations remain constant
55
therapeutic window
between minimum effective and maximum safe plasma drug concentration range
56
factors affecting metabolism (8)
genetic polymorphisms
CYP450
ethnicity
enzyme induction/inhibition by other drugs
liver disease
smoking
diet
caffeine
57
examples of drugs that increase plasma clozapine concentration (inhibitors) (4)
theophylline
caffeine
cimetidine
fluoxetine
58
cigarette smoke mainly induces which hepatic cytochrome
1A2
58
examples of drugs that decrease plasma clozapine concentration (inducers) (4)
carbamazepine
smoking
st john's wort
phenytoin
59
clozapine optimal plasma level
0.35-0.6 mg/L
60
maximum acceptable clozapine level
1
61
lithium excretion
at least 95% renally excreted
62
norclozapine
major clozapine metabolite
longer t1/2 than clozapine, so can accumulate
ratio important in determining compliance
63
optimum lithium plasma range
0.6-0.75 mmol/L
may be higher in treatment of acute mania
64
lithium drug interactions (5)
! drugs that alter sodium handling
NSAIDS
angiotensin II receptor antagonists
ACE inhibitors
thiazide diuretics
65
amitriptyline active metabolite
nortriptyline
66
imipramine active metabolite
desipramine
66
fluoxetine active metabolite
norfluoxetine
67
sertraline active metabolite
desmethylsertraline
68
venlafaxine active metabolite
desmethylvenlafaxine
69
who introduced insulin therapy for schizophrenia
sakel
69
who introduced convulsive therapy for schizophrenia using metrazol?
meduna
69
who developed ECT
cerletti and bini
70
who developed frontal leucotomy for schizophrenia and depression
moniz
71
who invented disulfiram
jacobsen and hald
72
who discovered lithiums antimanic effect
cade
73
who invented chlorpromazine
charpentier
74
who first used reserpine as an antipsychotic
kline
75
who found imipramine had antidepressant effect
kuhn
75
who invented haloperidol
janssen
76
who discovered fluoxetine
eli lilly and company
76
who first used chlorpromazine
delay and deniker
76
who invented chlordiazepoxide
sternbach
77
who first used imipramine TCA
kuhn
78
mechanism of ssri
increase levels of serotonin in synaptic cleft
79
common SSRIs
fluoxetine
paroxetine
citalopram
escitalopram
sertraline
fluvoxamine
80
examples of tertiary amines TCAs
imipramine
amitriptyline
clomipramine
dothiepin/dosulepin
80
common SSRI side effects
GI
dizziness
sexual dysfunction
hyponatraemia
81
how do TCAs work
increasing levels of serotonin and noradrenaline
82
examples of secondary amines TCAs
desipramine
amoxapine
nortriptyline
protryptiline
83
TCA side effects
hypotension
tachycardia
QTc prolongation
very toxic in overdose
84
how do MAOIs work
increase levels of serotonin, noradrenaline and dopamine
85
available reversible MAOI
moclobemide
reversible inhibitor of monoamine oxidase type A
86
3 irreversible MAOIs
phenelzine
isocarboxazid
tranylcypromine
87
SNRI examples
venlafaxine
milnacipran
duloxetine
88
NARI exmaples
reboxetine
atomoxetine
89
DARI example
buproprion
dopamine reuptake inhibitors
90
SARI
serotonin antagonist and reuptake inhibitors
trazodone
91
NaSSA
noradrenergic and specific serotonergic antagonists
mirtazapine
mianserin
92
how to typical / first gen antipsychotics work
antagonists at the postsynaptic dopamine receptors
93
group 1 typical antipsychotics
chlorpromaxine
levomepromazine
promazine
pronounced sedative effects
moderate antimuscaric
moderate EPSEs
94
group 2 typical antipsychotics
pericyazine
pipotiazine
moderate sedative effects
fewer EPSEs than groups 1 or 3
95
group 3 typical antipsychotics
fluphenazine
prochlorperazine
perphenazine
trifluperazine
characterised by fewer sedative and antimuscarinic SEs than groups 1 and 2
96
atypical antipsychotic examples (8)
risperidone
paliperidone
olanzapine
amisulpride
clozapine
quetiapine
aripiprazole
ziprasidone
97
does clozapine undergo first pass metabolism
yes
98
clozapine receptor action
high affinity for 5-HT receptors
antagonist at adrenergic, cholinergic and histaminergic receptors
occupies D2 receptor sites in a less tight bonding
99
clozapine common side effects
hypersalivatio
drowsiness
orthostatic hypotension
hypertension
weight gain
hyperthermia
100
serious clozapine side effects
constipation
agranulocytosis
myocarditis
NMS
seizures
101
rate of agranulocytosis in clozapine patients
1-2%
more common in first 18 weeks, but can occur at any time
102
constipation treatment in clozapine
bulk forming laxative as monotherapy or in combination with stimulant laxatives
103
clozapine bloods
FBC weekly for first 18 weeks
fortnightly 18-52 weeks
then if stable, every 4 weeks
monitoring continued for 4 weeks after stopping clozapine
104
lithium common side effects
metallic taste
GI side effects
weight gain
polyuria and polydipsia
interstitial nephropathy
benign T-wave changes and sinus node dysfunction
alopecia
acne
worsening of psoriasis
leukocytosis
hyperthyroidism
hypothyroidism
hyperparathyroidism
hypercalcaemia
parathyroid adenoma
physiological tremor if used long term
105
teratogenic effects of lithium
Ebstein's anomaly - prolapse of the tricuspid valve into the right ventricle
1:1000
contraindicated in breastfeeding
106
how does carbamazepine work
stabilising sodium channels
narrow therapeutic window
evidenced in treating rapid cycling
107
carbamazepine side effects
dizziness
drowsiness
cardiac conduction deficits
rash
neural tube defect in 0.1-1% of the population
108
sodium valproate mechanism
GABA agonist
109
sodium valproate side effects
nausea
lethargy
weight gain
alopecia (with curly regrowth)
thrombocytopenia
leucopenia
tremor
sedation
hyponatraemia due to SIADH
PCOS
110
topiramate side effects
1.5% develop renal caluli (10x placebo)
used in refractory or rapid cycling bipolar
111
phenytoin side effects
sedation
ataxia
diplopia
acne
gingival overgrowth
hirsuitism
osteomalacia
hematotoxicity
112
lithium and pregnancy
high red USS and echo at 6 and 18 weeks
intensive monitoring and lithium levels in third trimester
serum levels 4 weekly up to 36w then weekly
also level taken within 24 hours after birth
113
carbamazepine and pregnancy
should be avoided during pregnancy
lower risk than valproate
lower risk of neural tube defects compared to depakote
prophylactic vit K should be administered after delivery if used
114
valproate and pregnancy
avoid
highest risk of teratogenicity
115
benzo mechanism
GABA agonists
potentiate GABA inhibitory effect on CNS by increasing number and frequency of chloride channels opened
116
lipid solubility of benzos, poor to good
temazepam
lorazepam
diazepam
flurazepam
midazolam
taylor lautner didnt find me
117
benzos to use in hepatic impairment
temazepam
oxazepam
Lorazepam
Tired old liver
118
common benzo side effects
drowsiness
ataxia
impaired new learning
anterograde amnesia
119
benzo withdrawal effects
anxiety
irritability
dizziness
depersonalisation/derealisation
increased sensory perception
abnormal perception
120
benzo reversal
flumazenil
121
benzo half lives - chlordiazepoxide
5-30 hours
122
benzo half lives - lorazepam
10-20 hours
123
benzo half lives - temazepam
8-22 hours
124
benzo half lives - nitrazepam
15-38 hours
125
benzo half lives - diazepam
20-100 hours
126
zolpidem half life
2 hours
127
zopiclone half life
5-6 hours
128
zaleplon half life
2 hours
129
chemical make up of clozapine
dibenzodiazepine
130
active placebo
drug that produces noticeable effects, but none for the condition for which it is being given
131
nocebo effect
when patient experience adverse effects when treated with a placebo
132
placebo - natural remission theory
proposes that the improvement that occurs in a placebo group is by chance nadwould have happened anyway
133
placebo - psychological factors
patients expectations when given the placebo are very important
134
placebo - classical conditioning
patients who have got better in the past with an active treatment may be habituated to expect improvement by any subsequent treatment, even if it is a placebo
135
factors that affect medication adherence
cognitive deficits
substance misuse
clinician access
side effects
high frequency of doses
homelessness
poor family support
lack of insight
chronic illness
polypharmacy
136
4 categories considered before taking medication in the health belief model
benefits
costs
susceptibility
secondary benefits of medication and adherence
137
cognitive approaches to improving adherence (4)
behaviour modification intervention
motivational interviewing
compliance theory
psychoeducation
138
placebo rates in depression
up to 60%
139
principles of rational prescribing (10)
1 clear reasons for prescribing
2 awareness of pts medication history
3 consider other factors that might influence the prescription
4 take into account the patients ideas concerns expectations
5 choose effective, save and cost effective medications
6 adhere to national guidelines and local formularies
7 legible writing of prescriptions
8 monitor for benefits and adverse effects
9 communicate and document prescribing decisions
10 prescribe within the limitations of your knowledge, skills and experience
140
Type A adverse drug reactions
augmented / dose related reactions
- predictable from the known drug properties
- related to dose
- mostly reversible by stopping/decreasing dose
eg oversedation, EPSEs
141
Type B adverse drug reactions
bizarre or idiosyncratic/immunological reactions
cannot be predicted from drugs known properties, and not dose dependent
- immunological eg SJS
- other idiosyncratic reactions eg agranulocytosis with clozapine
142
hyperprolactinaemia pathway
tuberoinfundibular
143
increased negative symptoms pathway
mesocortical
144
reduced positive symptoms pathway
mesolimbic pathway
145
antipsychotics with highest risk of metabolic ADRs
olanzapine
clozapine
146
antipsychotics with lowest risk metabolic ADRs
aripiprazole
amisulpride
haloperidol
sulpride
147
Type c adverse drug reactions
chronic eg diabetes secondary to second gen antipsychotics
148
Type D adverse drug reactions
delayed
eg tardive dyskinesia secondary to antipsychotics
149
type E adverse drug reactions
end of use
eg SSRI discontinuation symptoms
150
type F adverse drug reactions
failure of therapy
eg SSRIs that dont treat depression
151
factors influencing likelihood and nature of ADRs (7)
drug pharmacology
dose and therapeutic window
route of administration
route of metabolism and elimination
interactions with other pharmacology
patient factors including variance in pharmacokinetics
excipients in different generic forms of the drug
152
patient factors influencing ADRs (7)
age
weight
gender
pregnancy
cormorbid illness and physical functioning
genetic factors including ethnicity
use of other drugs including alcohol and smoking
153
managing type A ADRs (6)
1. stop the drug
2. reduce the dose
3. switch to drug less likely to cause the effect
4. treat the symptoms
5. change timing to help tolerability of the ADR
6. may be appropriate to continue and monitor the ADR
154
D2 antagonism related ADRs
hyperprolactinaemia
EPSEs
negative sx eg apathy, flat affect
155
EPSE pathway
nigrostriatal
156
antipsychotics with highest risk sedation as ADR
quetiapine
olanzapine
clozapine
chlorpromazine
zuclopenthixol
157
antipsychotics with lowest risk sedation as ADR
amisulpride
aripiprazole
risperidone
paliperidone
sulpride
158
antipsychotics highest risk long QT
haloperidol
chlorpromazine
quetiapine
159
antipsychotics lowest risk long QT
aripiprazole
160
antipsychotics highest risk parkinsonian symptoms
haloperidol
trifluoperazine
161
antipsychotics lowest risk parkinsonian symptoms
aripiprazole
olanzapine
quetiapine
clozapine
162
antipsychotics highest risk akathisia
aripiprazole
haloperidol
trifluoperazine
163
antipsychotics lowest risk akathisia
quetiapine
clozapine
164
antipsychotics highest risk dystonia
haloperidol
trifluoperazine
165
antipsychotics lowest risk dystonia
aripiprazole
olanzapine
quetiapine
clozapine
166
antipsychotics highest risk tardive dyskinesia
FGAs
167
antipsychotics lowest risk tardive dyskinesia
clozapine
quetiapine
olanzapine
168
antipsychotics highest risk hyperprolactinaemia
risperidone
paliperidone
FGAs
169
antipsychotics lowest risk hyperprolactinaemia
aripiprazole
quetiapine
clozapine
170
antipsychotics highest risk postural hypotension
chlorpromazine
clozapine
171
antipsychotics lowest risk postural hypotension
amisulpride
sulpride
aripiprazole
172
antipsychotics highest risk sexual dysfunction
risperidone
paliperidone
FGAs
173
antipsychotics lowest risk sexual dysfunction
aripiprazole
quetiapine
clozapine
174
antipsychotics highest risk anticholinergic ADRs
clozapine
flupentixol
zuclopentixol
quetiapine
175
antipsychotics lowest risk anticholinergic ADRs
amisulpride
aripiprazole
sulpride
176
NICE recommended antipsychotic monitoring
metabolic: activity, diet, weight, waist, BM, HbA1c, lipids
CVS: HR, BP, ECG
prolactin
movement disorder assessment
177
agranulocytosis
severe reduction in production of granulocytes (WBCs)
178
risk of agranulocytosis with cloapine
0.8%
179
neutropenia
reduction in production of neutrophils
180
risk of neutropenia with clozapine
2.7%
181
lithium common ADRs (9)
nausea, diarrhoea
fine tremor
polyuria and polydipsia
ankle oedema
reduced eGFR
hypothyroidism
worsening psoriasis and acne
metallic taste
weight gain
182
semisodium valproate common ADRs (7)
diarrhoea
gastric irritation
nausea
thrombocytopenia
hyperammonemia
transient hair loss with curly regrowth
weight gain
183
carbamazepine common ADRs (10)
nausea and vomiting
ataxia
blurred vision
dizziness
drowsiness and fatigue
hyponatraemia
oedema
allergic skin reactions
dermatitis
dry mouth
184
lamotrigine common ADRs (14)
dairrhoea
nausea
vomiting
blurred vision
dizziness
drowsiness
aggression headache
insomnia
nystagmus
tremor
arthralgia
back pain
rash
dry mouth
185
symptoms of lithium toxicity
anorexia, nausea, diarrhoea
course tremor
muscle weakness and twitching
ataxia
drowsiness, disorientation
coma
seizures
186
thiazide diuretic effect lithium. examples of these
metolazone
hydrochlorothiazide
chlorthalidone
indapamide
chlorothiazide
methylclothiazide
187
5-HT1A types of ADRs
antidepressant action
188
5-HT2 receptor ADR types
sexual dysfunction
vivid dreams
189
5-HT3 receptor ADR types
nausea
increased intestinal motility
190
5-HT4 receptor ADR types
positive chronotropic effects (arrhythmia)
increased intestinal motility
191
5-HT6 receptor ADR types
possible role in memory function
192
5-HT7 receptor ADR types
possible role in insomnia
193
mirtazapine more likley and less likely SEs
more likely: sedation
less likely: sexual dysfunction, nausea, anorexia
194
allosteric modulator
cause a change in a receptor that alters how responsive it is when an agonist binds
195
reversal of opioids
naloxone
naltrexone
196
what does disulfiram do
inhibits acetaldehyde dehydrogenase which breaks down acetaldehyde - unpleasant reaction
197
dementia drug lease likely to cause nausea/vomiting/diarrhoea
memantine
198
dementia drug most likely to cause constipation
memantine
199
dementia drug least likely to cause anorexia
memantine
200
antidementia drugs most likely to cause agitation
rivastigmine, donepezil
201
benzo reversal agent
flumazenil
202
4 types of drug interaction
pharmaceutical - one substance interacts with another BEFORE administration
pharmacokinetic - one substance alters the bioavailability of another
pharmacodynamic - one substance alters the effect of another, leading to additive or opposing effects
behavioural - one substance alters a persons behaviour to enhance or reduce compliance to another substance
203
mechanism different between serotonin syndrome and NMS
serotonin syndrome - excess serotonergic excitation
NMS - too little dopaminergic neurotransmission
204
serotonin syndrome symptoms
hypertonia
tremor
myoclonus
hyperreflexia
delirium
tachycardia
HTN
205
NMS symptoms
muscle rigidity
tremor
hyporeflexia
ataxia
delirium
tachycardia
hyperthermia
206
green clozapine result
continue clozapine prescription
207
amber clozapine result
blood monitoring should increase to twice weekly until a green result is achieved
208
red clozapine result
- stop clozapine immediately
- daily blood monitoring required
- monitor patient for signs of infection
- patient may require hospital admission
209
clozapine tachycardia management
beta blockers eg atenolol are first line after myocarditis is excluded
should be started after patient has been on cloz for few months as tolerance may develop and tachycardia may resolve
consider cardiology referral if tachycardia persists of if there are concerning features
210
managing hypertension in clozapine
slow titration
antihypertensives eg ACE inhibitors and beta blockers
211
managing hypotension in clozapine
tolerance tends to develop over 4-6 weeks
stand slowly etc
increase dietary salt and fluid intake
is persists, fludrocortisone may be used - but risk of CCF so gradual dose reduction
212
myocarditis symptoms
chest pain
palpitations
breathlessness
fatigue
213
myocarditis physical examination
fever
arrhythmia
tachycardia
signs of acute heart failure
214
myocarditis investigations
CRP and trop elevated
ECG - diffused TWI and saddle ST segments
215
myocarditis monitoring
baseline - trop, CRG, echo
weekly - CRG, trop
every other day for 28 days - HR, BP, temp, RR
216
myocarditis management
suspected: continue clozapine, daily trop and CRP, monitor for signs of illness
top 2 times normal limit or CRP >100: stop clozapine immediately, echo, refer to cardiology
217
management of clozapine hypersalivation
optimising dose and timing, consider split dose
watch and wait if tolerable
meds:
hyoscine hydrobromide
pirenzepine
amisulpride, sulpride, glycopyrrolate, propantheline
218
why does clozapine cause nausea
anticholinergic effects leading to delayed gastric emptying
hypersalivation, increased appetite and effects on the hypothalamus may also contribute to nausea
especially problematic in first 6 weeks, often improves
if intolerable - antiemetics
219
clozapine constipation non pharmacological management
dietary fibre increase
adequate hydration
exercise
220
clozapine constipation laxatives
stimulants eg senna
can add other classes if stimulants alone ineffective
221
pharmacological options for clozapine weight gain
metformin
aripiprazole
topiramate
222
pharmacological options for dyslipidaemia in clozapine
statins
if only triglycerides raised - fish oils, fibrates
223
clozapine hepatic effects
elevated LFTs in up to 50% of patients
most cases clinically insignificant and resolve by 13 weeks
however, cases of hepatitis and liver failure are reported
224
in context of hepatic effects, clozapine should be discontinued if... (3)
LFT raised more than 3 times upper normal
bilirubin is raised
hepatitis or jaundice develops
225
management of clozapine sedation
usually improves over few months
start low and go slow
reduce/stop other sedating medications
gradually reduce to minimal effective dose
asymmetric dose splitting - largest dose in the evening
aripiprazole can help if other methods fail
226
rate of seizures in clozapine
5% of those on doses >600mg develop seizures
EEG frequently abnormal, even in absence of seizures
effect is dose related
myoclonic jerks can indicated increased seizure risk
227
prevention of clozapine seizures
monitor blood levels
use minimum effective dose
consider prophylactic anticonvulsants if plasma levels >0.5 or doses >600mg
228
following clozapine seizure
withhold clozapine for 24 hours
check plasma levels
restart at dose 25-50% lower
add an anticonvulsant
229
anticonvulsant choice in clozapine
sodium valproate - useful if mood stabilising effect also desirable
lamotrigine - also augments antipsychotic effect of clozapine but can exacerbate myoclonic jerks
topiramate - less commonly used, may aid weight loss
AVOID carbamazepine and phenytoin - impact on clozapine metabolism, increasing clearance and reducing levels. may also be increased risk of agranulocytosis.
230
benign transient pyrexia clozapine
reasonably common in first 3 weeks of treatment
around 1:20 patients
can be managed by simple measures eg paracetamol
however, investigate in case of more serious cause eg myocarditis, agranulocytosis, NMS
231
clozapine management of fever >37.5 degrees
urgent FBC, trop and CK
physical examination
consider echo, CXR, urinalysis, blood cultures
slow titration
232
clozapine management of fever >38.5 degrees
same as fever >37.5 but also WITHHOLD CLOZAPINE
233
clozapine eneuresis
1:5 may suffer eneuresis
under reported - need to ask specifically
may be persistent
234
clozapine enuresis non pharmacological management
limit evening fluid intake and void before bed
avoid diuretic substances eg caffeine, alcohol
try waking to void at night - enuresis alarms
235
clozapine enuresis pharmacological management
minimal effective clozapine dose
asymmetric dose splitting, smaller evening dose
desmopressin
anticholinergics eg oxybutinin, solfenacin, trihexiphenidyl
alpha 1 agonists eg ephedrine
amitriptyline
236
OCD symptoms with clozapine
up to 10% of patients
can be delayed or insidious onset
frequently under reported
can be transient ~3 weeks, but may persist in some cases
could be relieved by higher doses at night
237
management of OCD symptoms with clozapine
lowest effective cloz dose
CBT tried before pharm rx
antidepressants:
SSRIs
clomipramine
caution as antidepressants can elevate clozapine, esp fluvoxamine
sulpride/amisulpride
aripiprazole
238
parotid swelling in clozapine
occasionally reported
sometimes spontaneously resolved, sometimes persists
management:
cessation of clozapine
minimal effective dose
combination of benzatropine and terazosin
239
withdrawal of clozapine
should be done gradually over at least 1-2 weeks to avoid withdrawal effects including
- rebound psychosis
- cholinergic rebound
if needs to be stopped suddenly (eg myocarditis, agranulocytosis) - closely monitor and support symptomatically including benzos if needed
240
cardiovascular adverse effects of clozapine
tachycardia - very common
hypertension - common
hypotension - common
myocarditis - very rare
cardiomyopathy - very rare
241
GI adverse effects of clozapine
sialorrhoea - very common
nausea - very common
constipation - common
242
metabolic adverse effects of clozapine
dyslipidaemia - very common
weight gain - very common
impaired glucose tolerance - very common
243
CNS adverse effects of clozapine
sedation - very common
seizures - common
myoclonic jerks - common
244
haematological adverse effects of clozapine
neutropenia - common
agranulocytosis - uncommon
245
other adverse effects of clozapine
urinary incontinence - very common
fever - very common
OCD symptoms - common
