Nervous System Flashcards
1
Q
Who should use short acting benzodiazepines?
A
Elderly
Liver impairment
2
Q
What’s the risk of short acting benzodiazepines?
A
Carries greater risk of withdrawal symptoms
3
Q
Overdose symptoms of benzodiazepines?
A
Drowsiness, ataxia, dysarhtia, nystagmus
Worst case Respiratory depression and coma
4
Q
Other than benzodiazepines, what other drugs are used?
A
BBs for autonomic symptoms like palpitations Serotonin agonist buspirone Antidepressants Antipsychotics Anti epileptic like gabapentin
5
Q
Advantage of using buspirone?
A
Low potential for abuse and dependence but takes 2wks to work
6
Q
How does benzodiazepines work?
A
Increase GABA binding to its receptor
7
Q
What’s the indication of benzodiazepines in anxiety?
A
Short term 2-4wks relief of anxiety that is severe, disabling or causing pt unacceptable distress
8
Q
Side effects of benzodiazepines?
A
Paradoxical increase in hostility aggression - range from talkative news’s and excitement to aggression and antisocial acts. Increased anxiety and perceptual disorders also occur
Sedation = avoid alcohol
Dependence
9
Q
How to avoid dependence to benzodiazepines?
A
Avoid long term use
Avoid abrupt withdrawal
10
Q
What happens in abrupt withdrawal?
A
Toxic psychosis, confusion, convulsions and delirium like symptoms
11
Q
Benzodiazepines withdrawal syndrome symptoms?
A
Increased anxiety, insomnia, weight loss, tremors, sweating, loss of appetite, perceptual disorders, tinnitus
12
Q
When does withdrawal happen after using short term benzodiazepines?
A
Occurs within 3days of stopping
13
Q
When does withdrawal happen after using long term benzodiazepines?
A
Occurs within 3wks of stopping a long acting benzodiazepines
14
Q
How to withdraw benzodiazepines?
A
- Gradually covert over 1wk to equivalent diazepam dose ON
- Reduce diazepam dose by 1-2mg increments every 2-4wks (up to 1/10th every 1-2wks for high doses)
- Reduce diazepam dose further
Can reduce in smaller steps of 500mcg towards the end
15
Q
Which drugs will interact with diazepam to increase sedation and CNS depressant effects
A
Alcohol Opioids Antihistamines Antidepressants Barbiturates Antipyschotics Z-drugs
16
Q
Which drugs increase diazepam’s plasma conc?
A
Amiodarone Diltiazem Macrolides Fluconazole Enzyme inhibitors
17
Q
How long should long term treatment of bipolar disorder continue?
A
At least 2yrs from the last manic episode and up to 5yrs if the pt has risk factors for relapse
18
Q
When should antidepressants be avoided in Co treatment of bipolar and depression?
A
Pts has rapid cycling bipolar disorder
A recent history of hypomania
Rapid mood fluctuations
19
Q
What drug is used in initial stages of treatment for behavioural disturbance or agitation in BPD?
A
Benzodiazepines
20
Q
What drugs are used in acute episodes of mania and hypomania?
A
Antipyschotics
Quetiapine
Olanzapine
Risperidone
21
Q
What can be added to acute episodes of mania and hypomania if response is inadequate with Antipsychotics or if acute severe mania?
A
Lithium or sodium Valproate can be added
22
Q
Drugs used for prophylaxis of BPD?
A
Lithium
Valproate (specialist)
Olanzapine (if there was response in manic epi)
Carbamazepine (specialist in pts unresponsive to other drugs and combo and for rapid cycling BPD)
23
Q
What drug is licensed for the treatment of moderate to severe manic episodes associated with BPD?
A
Asenapine
A 2nd gen Antipsychotic
24
Q
What’s a good combo of drug for pts with frequent relapses of mania and continuing functional impairment?
A
Lithium or Olanzapine as mono or additn either to Valproate
25
How long does it take for lithium to exert its full Prophylactic effect
6-12months after the initiation of therapy
26
Therapeutic range of lithium when used for prophylaxis or for elderly?
0.4-1mmol/L
27
Therapeutic range of lithium when used for treatment of acute manic episodes? Or pts who have previously relapsed
0.8-1mmol/L
28
When should blood sample be taken for plasma lithium monitoring?
12hrs post dose
29
How often should monitoring of plasma lithium level be taken place?
Every 3 months
| Additional monitoring required if significant intercurrent illness or changes to diet or water intake
30
Why should lithium abrupt withdrawal should be avoided?
Higher risk of relapse
31
Signs and symptoms of lithium toxicity?
Revenge
R=renal disturbances (polyuria, incontinence, hypernatraemia)
E=extrapyrimidal symptoms (fine tremor, ataxia, nystagmus and muscle weakness)
V=visual disturbances
N=Nervous system disturbances (confusion and drowsiness, restlessness and in coordination)
G=GI effects (Diarrhoea and vomiting)
32
At what serum lithium conc. Does severe overdose symptoms start appearing?
```
Over 2mmol/L
Revenge symptoms +
Renal failurr
Arrhythmia
Seizures
BP changes
Circulatory failure
Coma and sudden death
```
33
Lithium side effects?
Mild cognitive memory impairment
Thyroid disorder
Renal impairment
Benign intracranial hyoertention
QT prolongation
Lowers seizure threshold
34
Dispensing caution on lithium?
Prescribe by brand
35
What electrolyte imbalance predisposed lithium toxicity?
Hyponatraemia
36
Counselling points on lithium?
Maintain constant adequate salt and water intake esp in intercurrent infection, diarrhoea or vomiting dehydration
Give lithium treatment pack
Affected driving - avoid alcohol
OTC interaction like ibuprofen, soluble analgesics and antacids
37
What does the lithium treatment pack contain?
Contains a PIL, alert card and record book
| Given when initiating treatment and mush always carry the alert card
38
Other than lithium serum conc. What should be monitored as well?
Renal, cardiac (ECG) and Thyroid function, BW/BMI, serum electrolytes and FBC before treatment initiation
BW/BMI, serum ELECTROLYTE, eGGR and Thyroid every 6 months
39
Is lithium safe in preg?
No as teratogenic
Effective contraception
Toxicity cab occur in BF infants as well
40
What drugs will increase risk of seizures if taken with lithium?
Quinolobes
SSRIs
Epilepsy
41
What electrolyte imbalance predisposed QT prolongation?
Hypokalaemia
42
What drugs when taken with lithium increases risk of extrapyrimidal symptoms?
```
Haloperidol
Clozaoine
Phenothiazines
PD
Metoclopramide
```
43
What drugs when taken with lithium increases risk of neurotoxicity?
Phenytoin
Carbamazepine
Antiosychotics
Amitriptyline
44
What drugs when taken with lithium increases risk of Serotonin syndrome?
```
Sumatriptan
SSRIS
MAOIs
Amfetamines
St John's wort
Tramadol
Granisetron
```
45
Which SSRIs case QT prolongation?
Citalopram and escitalopram
46
Which SSRIs has the greatest risk of withdrawal reactions?
Paroxetine
47
Which SSRIs is safe to use after MI and unstable angina?
Sertraline
48
Why are SSRIs first line as antidepressants?
Better tolerated and safer in overdose than other classes
TCAs have similar efficacy to SSRIs but SSRIs are Less sedating, less antimuscarnics and less cardio toxic than TCAs
49
How long does it take for SSRIs to work?
At least 2wks
| But wait at least 4wks (6wks in elderly) before deeming it effective
50
Initial reaction to SSRIs?
Feel worse, increased agitation, anxiety and suicidal ideation
51
How often should you review SSRIs effectiveness at the beginning of treatment?
Review every 1-2wks at start of treatment
52
How long should you taken your antidepressants?
Continue for at least 6months (12 months in elderly) after remission
12months in generalised anxiety as has high risk of disorder
2yrs in recurrent depression
53
Second line for depression treatment?
```
Increase SSRIs
Or
Use different SSRI
Or
Use mirtazepine
```
Other choices include lofepramine (TCA), moclobemide (reversible MAOI)
Or
Venlafaxine or other TCAs for more severe depression
Irreversible MAOIs under specialist
54
Third line treatment for depression?
```
Add another antidepressant class
Or
Lithium or Antipyschotics
Or
Electroconvulsive therapy in severe
```
55
General side effects of antidepressants?
Hyponatraemia esp SSRIs and usually occurs in the elderly
Suicidal ideation and behaviour
Monitor at start of treamtnet or after dose change
Serotonin syndrome
Esp if not well withdrawal, addition of new antidepressants
Can occur within hours or days following changes or initiation
56
Serotonin syndrome symptoms?
Neuromuscular hyperactivity
=tremors, muscle rigidity
Altered mental state
=agitation, confusion and mania
Autonomic dysfunction
=urination, diarrhoea, hyperthermia, tachycardia, pallor, sweating, shivering
57
Washout period for MAOIs after it's stopped?
Wait 2wks before switching
58
Which MAOIs does not require a washout period?
Moclobemide bc short acting and reversible
59
Washout period for SSRIs after it's stopped?
1wk
But
2wks if sertraline
5wks if fluoxetine
60
Washout period for TCAs after its stopped?
1-2wks
But
3wks if imipramine or clomipramine
61
When do antidepressants withdrawal reactions occur?
Within 5 days of stopping
62
The risk of withdrawal reactions is increased if
If antidepressants stopped suddenly after taking for 8wks or morr
63
Higher risk of antidepressants withdrawal reaction with which drugs?
Paroxetine
| Venlafaxine
64
Side effects of SSRIs?
GASH
G=GI disturbances like N&V, diarrhoea
A=appetite or weight disturbance (gain or loss)
S=Serotonin syndrome
H=hypersensitivity reactions = stop if rash occurs
```
Others include
Bleeding risk increased
QT interval prolongation with citalopram and escitalopram
Seizure threshold lowered
Movement disorder and dyskinesia
```
65
Overdose symptoms of SSRIs?
```
N&V
agitation
Tremor
Nystagmus
Drowsiness
Sinus tachycardia
Convulsions
```
66
Juice that increases SSRIs cocn?
Grapefruit juice as an enzyme inhibitor
67
What drugs increase risk of bleeding when given with SSRIs?
NSAIDs /aspirin
Anticoagulant
Antiplatelets
Warfarin
68
Dose of TCAs?
ON
69
When are sedating TCAs given to pts?
Given in anxious agitated pts
70
Sedating TCAs?
```
Amitriptyline
Clomipramine
Dosulepin - dangerous in overdose so specialist use
Doxepin
Trimipramine
```
71
When are Less sedating TCAs given.?
Given in withdrawn apathetic pts
72
Less sedating TCAs?
Imipramine
Lofepramine
Nortriptyline
73
TCA with the most antimuscarnic effect?
Imipramine
74
TCA with the most hepatotoxicity?
Lofepramine
75
Tetracycline antidepressants?
Sedating as well
Mianserim
Trazodone
76
Side effects of TCAs?
TCAS
T=TCAs are more sedating, more epileptogenic, more cardio toxic, more antimuscarnic than SSRIs
C=cardiac side effects like QT prolongation, arrhythmia, heart block and hypertention
A=antimuscarnics
S= seizures
```
Others
Hallucinationsmania
Hypotention
Sexual dysfunction
Breast changes
Extrapyrimidal side effects
```
77
Symptoms of antimuscarnic side effects?
```
Dry mouth
Blurred vision
Constipation
Tachycardia
Urinary retention
Pupil dilation
Raised Intra ocular pressure
Glaucoma
```
78
Drugs of irreversible MAO-B inhibitors?
Only prescribed under specialist = phobic pts and depressed pts with atypical hypochondriacal or hysterical features are said to respond best to MAOIs
Phenelzine
Isocarboxazid
Tranylcypromine
79
MAOIS that are most hepatotoxic?
Phenelzine
| Isocarboxazid
80
Drugs of reversible MAO-A inhibitors
Moclobemide
81
MAOIS with the greatest stimulant effect?
Tranylcypromine
82
MAOIS that are most likely to cause a hypertensive crisis?
Tranylcypromine bc it has the greatest stimulant effect
83
Response time to MAOIS?
3wks or more and may take an additional 1-2wjs to become maximal
84
Side effects of MAOIS?
Hepatotoxicity
Postural hypotention /hypertensive response
=discontinue if palpitations or frequent headaches occur
Hypertensive crisis
=discontinue if throbbing headaches occur
85
Drugs that can cause hypertensive crisis when Co administered with MAOIS?
```
Pseudoephedrine
Adrenaline
Noradrenaljne
Levodopa
Anything dopamine
TCAs esp Tranylcypromine and clomipramine
```
86
Food interactions of MAOIS?
Tyramine rich food
Eat only fresh food and avoid stale
Avoid alcohol
Food and drug interaction can exist 2wks after stopping an irreversible MAOIS
87
Washout periods on MAOIS?
Other antidepressants should not be started for 2wks after MAOIs
3wks if starting clomipramine or imipramine
MAOIs should not be started at least 2wks after previous MAOIS
At least 1-2wks after TCA (3wks in case of clomipramine or imipramine)
At least a week after an SSRIs (5wks in case of fluoxetine)
88
Management of acute anxiety?
Benzodiazepines or buspirone (Serotonin agonist)
| don't use together, withdraw benzo first if wanna use buspirone
89
Treatment for chronic anxiety
Longer than 4wks
| Antidepressant like SSRIs and SNRI (Duloxetine and Venlafaxine)
90
Last resort for anxiety management?
Pregabalin
91
Treatment for panic disorder?
1st line is SSRIs
| 2nd line is clomipramine or imipramine
92
Treatment for OCD?
1st line SSRIs
| 2nd line clomipramine
93
Treatment for Ptsd
SSRIs
94
Treatment for phobia like social anxiety disorder?
1st line SSRIs
| 2nd line for social anxiety disorder is moclobemide
95
Treatment of inappropriate sexual behaviour?
Benperidol an 1st gen Antipsychotics
96
What electrolyte imbalance increases lithium toxicity?
Sodium depletion Hyponatraemia
| So avoid thiazide and loops
97
Schizophrenia has 4 dopamine pathways
| Name each one
Underactivitg in mesicorticol pathway
=negative symotoms (catatonia. Social withdrawal, apathy)
Over activity in mesolimbic oathway
=positive symptoms (hallucinations, delusions)
D2 antagonism in nigrostriatal oathway
=extrapyrimidal symptoms
D2 antagonism in tuberofundibula pathway
=hyperprolactinaemia
(Menstural disturbances, galactirrhoea, gynaecomasta, sexual dysfunction)
98
How to increase Antipsychotics dose?
Slowly and once weekly
99
High dose therapy of Antipsychotics should only continue for?
Limited period only and review regularly
| Stop if there is no improvement after 3 months
100
Important advice on administration of Antipsychotics drugs in an emergency like psychotic episode?
If administered via IM route, dose should be lower than oral dose esp for active pts bc increased blood flow
Prescription should specify dose for each route
Review emergency dose of Antipyschotics at least daily
101
Elderly pts are particularly susceptibile to which side effects?
Postural hypotention and hyper/hypothermia in hot or cold weather
102
Initial dose of Antipsychotics in elderly should be?
Half the adult dose
103
1st generation Antipsychotics mode of action?
Blocks D2 receptors in the brain
| Not selective for any of the 4 dopamine pathways so can cause range of side effects
104
Phenothiazines general side effects?
Hepatotoxic and cause acute dystonic rractions
105
Group 1 of Phenothiazines side effect?
Most sedative
Chlorpromazine
Levomeoromazine
Promazine
106
Chlorpromazine 's specific side effect?
Contact sensitisation
107
Advantage of group 2 Phenothiazines?
Least EPS
| Pericyazine
108
Group 3 Phenothiazines side effecr
```
Most EPS
Fluphenazine
Perphenazine
Prochlorperazine
Trifluoperazibe
```
109
Butyrophenones side effect? And drugs?
Benperidol
| Haloperidol causes QT prolongation and is similar to group 3 Phenothiazines being most EPS
110
Thioxanthenes drug names and side effects?
Flupentixol should not be taken in the evening
Zuclopenthixol has depot preparation and can be used in agitated and aggressive pts and more effective in preventing relapses
111
Other 1st gen antupsychotics?
Pimozide can cause QT prolongatiom
Sulpiride
=both have reduced sedative, antimuscarnic and EPS
Loxapine cause bronchospasm
112
Mode of action of 2nd gen Antipsychotics?
Blocks D1 to D4 receptors
113
Advantage and disadvantage of 2nd gen compared to 1st gen
Maybe more effective at treating negative symptoms
But
More metabolic side effects
114
Side effect of amisulpride
Most hyperprolactinaemia
115
Advantage of aripiorazole?
Does not cause hyperprolactinaemia
116
Side effect of Olanzapine?
Most weight gain and diabetes
117
Side effect of Risperidone?
Most hyperprolactinaemia
118
Which 2nd gen Antipsychotics is the most effective?
Clozapine
119
What anti psychotic is the most effective?
Clozapine
120
Clozapine license?
Licensed for resistant schizophrenia
| Tried 2 or more drugs Inc 2nd gen for at least 6-8wks each
121
How long should clozapine be tried for?
8-10wks
If symptoms do not respond to an optimised dose, measure plasma clozapine levels before augmenting with 2nd anti psychotic drug
122
What to do with clozapine missed dose?
If more than 2, reinitiate by specialist
123
Most important interactions to note with clozapine?
Increased risk of agranulocytosis (blood dyscrasias)
| Aminosalicylate, Immunosuporessants like methotrexate and cytotoxic drugs
124
Side effects of clozapine?
MAG
M=myocarditis and cardiomyopathy
Persistent tachycardia, esp in first 2 months, stop permanently if it occurs
A=agranocytosis and neutropenia
G=GI obstruction
Intestinal peristalsis Impaired so constipation, faecal impaction
125
MHRA warning on clozapine?
Potentially fatal risk of intestinal obstruction, faecal impaction and paralytic ileus
- report constipation before taking next dosr
- take caution with constipation meds e g. Hyoscine used to treat hypersalivation with clozapine
126
Which Antipsychotics most commonly cause EPS?
Pipeazind phenothiazines
The butyrophenones (haloperidol)
1st gen depot preparations
127
What does dystonia mean?
Abnormal face and body movements
128
What does dyskinesia mean?
Involuntary erratic movements of the face, arms, legs or trunk
129
What does akathisia mean?
Restlessness
| Characteristically occurs after large initial doses of Antipsychotics
130
What does tardive dyskinesia mean?
Rhythmic, involuntary movements of tongue, face and jaw
| Which usually develops on long term therapy or with high doses of Antipsychotics
131
Which EPS symptoms is the most serious?
Tardive dyskinesia because it can be irreversible sometimes even on withdraw and treatment is usually ineffective
132
How do both gens of Antipsychotics increase prolactin conc?
Antipsychotics decrease dopamine conc.
| Dopamine inhibits prolactin release so as reduce dopamine, no inhibitions and thus increased prolactin
133
Which Antipyschotics reduces prolactin and why?
Aripiorazole bc it's a dopamine receptor partial agonist
133
Which Antipyschotics reduces prolactin and why?
Aripiorazole bc it's a dopamine receptor partial agonist
134
Which Antipsychotics are most likely to cause hyperprolactinaemia?
1st gen
Risperidone
Amisulpride
135
Symptoms of Hypercholestrrolaemia?
```
Sexual dysfunction
Reduced bone mineral density
Menstural disturbances
Breast enlargement
Galactirrhoea
```
136
Which Antipsychotics commonly cause sexual dysfunction?
Sexual dysfunction
137
CV side effects of Antipsychotics?
Tachycardia, arrhythmia and hypotention
| QT interval prolongation
138
Which Antipsychotics have high probability of causing QT prolongation?
Pimozide and haloperidol
| IV Antipsychotics
139
All Antipsychotics may cause weight gain but which one in particular are a concern?
Clozapine and Olanzapine commonly cause weight gain
| Clozaoine, olanzaoine, Quetiapine and Risperidone may cause hyperglycaemia /diabetes
140
Which Antipsychotics cause postural hypotension? Esp during initial dose titration?
Clozapine, chlorpromazine, lurasidone and Quetiapine
141
Symptoms of neuroleptic malignant syndrome?
```
Hyoerthermia
Fluctuating levels of consciousness
Muscle rigidity
Autonomic dysfunction with pallor
Tachycardia
Labile blood oressure
Sweating
Urinary incontinence
```
142
Neuroleptic malignant syndrome can continue for how long even after drug discontinuation?
5-7days.
| May be unduly prolonged if depot preparations are used
143
Which generation of Antipsychotics are better at treating the negative symptoms of schizophrenia?
Second generation
144
Which Antipsychotics are least likely to cause EPS and thus are used if pts can't tolerate EPS?
2nd gen
| Aripiorazole, clozapine, Olanzapine and Quetiapine
145
Which Antipsychotics are least likely to cause QT prolongation?
Aripiorazole the least
| Amisulpride, clozapine, flupentixol, Fluphenazine, Olanzapine, Perphenazine, Prochlorperazine, Risperidone and Sulpiride
146
Which Antipyschotics has the lowest risk of sexual dysfunction?
Aripiorazole and Quetiapine
| Clozaoine and Olanzapine next bc not significant hyperprolactinaemia
147
Pt should receive an Antipyschotics for how long before deeming it ineffective
4-6wks
148
How long should clozapine used for to assess response?
8-10wks
149
Pt needs to register with what service in order to use clozapine?
Clozapine pt monitoring service
150
What monitoring is required with Antipyschotics at the start of therapy then annually thereafter?
```
FBC
Urea
Electrolytes
LFTs
ECG
```
151
What should be measure when using Antipsychotics at baseline, at 3 months then yearly?
Blood kipids
| Weight
152
What should be measured before using Antipsychotics and frequently during titration?
BP
153
What Antipsychotics can be used for intractable hiccups?
Chlorpromazine and haloperidol
154
Psychomotor agitation should be investigated for an underlying cause but it can be managed with what drugs?
Low doses of chlorpromazine or haloperidol for short term
155
Depot flupentixol dose interval?
2wks
156
Depot Fluphenazine dose interval?
2wks
157
Haloperidol depot dose interval?
4wks
158
Zuclopenthixol depot dose interval?
2wks
159
Dose advice on depot Antipsychotics?
Give a test dose as undesirable effects are prolonged with depots
Give oral Antipyschotics whilst stabilising on depot preparation
Depot preparation typically end in decanoate
160
Important safety info on depot?
Do not confuse with other oreoo
IM haloperidol decanoate is used for maintenance therapy whereas IM haloperidol is used for rapid control in acute episodes
161
Antipsychotics need to be stopped at first sign of tardive dyskinesia which is?
Fine vermicular movement of tongue
162
What needs to be monitored at start, 6monthd and the yearly for antupsychotics?
Prolactin levels
163
There are multiple mechanisms for sexual dysfunction
| What happens if you block D receptors?
Hyperprolactinaemia and low libido
164
There are multiple mechanisms for sexual dysfunction
| What happens if you block M receptors?
Arousal disorder
165
There are multiple mechanisms for sexual dysfunction
| What happens if you block alpha 1 receptors?
Erectile dysfunction and ejaculatory problems
166
Side effects of Antipsychotics apart from the main ones?
```
Antimuscarnics side effects
Blood dyscrasia
Photosensitivity in high doses
Jaundice
Sedation
```
167
Which Antipsychotics prolongs QT interval and cause sudden death?
Pimozide
168
What is labyrinthitis?
Inner ear infection
169
Management of nausea and vomiting in the first trimester?
No drug treatment required bc generally mild
170
Management of severe vomiting in preg?
1st line: Short term treatment with promdthazine
Alternatives: Prochlorperazine or Metoclopramide
If symptoms do not settle in 24 to 48hr, then seek specialist
171
Name of Phenothiazines and how they are used for nausea?
Prophylaxis and treatment of N&V associated with diffuse neoplastic disease, radiation sickness and emesis caused by Opioids and general anaesthetics and cytotoxics
Mainly post operative
Prochlorperazine
Perphenazine
Chlorpromazine
Trifluoperazine
172
Perphenazine and Trifluoperazinr are less what than chlorpromazine？
Less sedating
173
Other than Phenothiazines, what other Antipsychotics are used in nausea and its specific uses?
Haloperidol and Levomeoromazine are used in palliative care
Droperidol for post operative
174
Prophylaxis of motion sickness?
1st line: hyoscine hydrobromide
The sedating antihistamines are less effective but better tolerated
2nd line: promethazine (if sedation required)
Cyclizine or cinnarizine is preferred
Antihistamines are also used in vertigo
175
Metoclopramide's mode of action?
Antagonised D2 receptors in CTZ
Also acts directly on gut to promote gastric emptying and has prokinetic effect so superior compared to Phenothiazines for emesis associated with gastroduodenal, hepatic and biliary diseass
176
MHRA warning on Metoclopramide?
Risk of neurological adverse effects so restricted duration (max 5days), age restrictions (18 plus)
177
Dose of Metoclopramide and max dose?
10mg TDS
| Max 500mcg/kg
178
Side effects of Metoclopramide?
Acute dystonic reactiobs
=facial and skeletal muscle spasms and oculogyric crisis (瞳孔が上を向く)(more common in young, esp girls and young women and in very old)
179
What drug can be used to abort dystonic attacks?
Procyclidine (anti parkinsonian drug)
180
Interactions between Antipyschotics and Metoclopramide?
Increased EPS
181
Parkinsons disease and Metoclopramide interaction?
Metoclopramide exacerbates PD so caution
182
How does domperidone work?
Antagonised D2 receptors in CTZ
| Like metoclooramide, also acts directly in gut to promote gastric emptying, prokinetic effect
183
MHRA warning on domperidone?
Risk of cardiac side effect (QT prolongation, arrhythmia, sudden death)
- so should only be used for N&V
- used at the lowest effective dose of no longer that a week
- contra indicated for use in underlying cardiac disease, drugs that QT prolongation, enzyme inhibitors and severe hepatic imapirment
184
Dose of domperidone?
10mg TDS for adult 12+ and over 35kg
185
Choice of antiemetic in PD?
Domperidone
| Bc doesn't cross the BBB so doesn't cause EPS
186
Drugs of 5HT3 receptor antagonists?
Ondansetron
Granisetron
Palonosetron
187
Use of ondansetron and Granisetron?
For symptomatic relief of post operative N&V
| Chemotherapy induced nausea vomiting
188
Use of Palonosetron?
Prevention of N&V associated with moderately or highly emrtogenic cytotoxic Chemotherapy e.g. Cisplatin based
189
Side effects of 5HT3 receptor antagonists?
QT prolongation
190
Results of interaction between ondansetron and diuretics, steroids, SABA, theophylline, stimulant laxatives abuse, amphiterucin?
Increased risk of torsade de pointes with Hypokalaemia
191
Results of interaction between ondansetron, sumatriptan,MAOIS, SSRIS?
Serotonin syndrome
192
Which steroid has antiemetic effects and is used in vomiting associated with cancer Chemotherapy?
Dexamethasone
193
What synthetic cannabinoid has antiemetic properties and is used for N&V caused by cytotoxic Chemotherapy that is unresponsive to conventional antiemetic?
Nabilone
194
Antiemetic that are used for Chemotherapy and can be combined with dexamethasone and ondansetron?
Aorepitant
Fosapreoitant
Rolapitant
195
Which antiemetic cross the BBB and cause dopamine blockage and thus should not be used in PD?
Metoclopramide, haloperidol, Prochlorperazine
196
What can happen if you abruptly withdraw anti parkinsons drugs?
Acute akinesia
| Neuroleptic malignant syndrome
197
What's the cause of PD?
Death of dopaminergics cells of the substantial nigra in the brain
198
Non drug treatment of PD?
Physiotherapy if balance or motor function problems are present
Speech and language therapy if communication, swallowing or saliva problems
Occupational therapy if difficulties with daily activities
199
What's first line for PD with motor symptoms that decrease their QoL?
Levodopa
200
Levodopa drug combinations?
Co-beneldopa
= benserazide
Co-careldopa
=carbidopa
201
Drugs used for PD with motor symptoms that do Not affect QoL?
```
Levodopa
Or
Non ergot derived dopamine receptor agonists
Or
MAO-B inhibitors
```
202
Drugs of non ergot derived dopamine receptor agonists?
Pramipexole
Ropinirole
Rotigotibe
203
Drugs of MAO-B inhibitors?
Selegiline (metabolised to amphetamine)
| Rasagiline
204
When to start using adjuvant therapy in PD?
Pts who develop dyskinesia or motor fluctuations despite optimal Levodopa therapy
205
Choices of adjuvant therapy?
Non ergot derived dopamine receptor agonists
Or
MAO-B inhibitors
Or COMT inhibitors
206
Drugs of COMT inhibitors?
Entacapone
| Tolcapone
207
Ergot derived dopamine receptor agonists aren't really recommended but when can they be used?
If inadequate response with non ergot derived dopamine receptor agonists
208
If dyskinesia aren't adequately managed by other drugs, what's last resort?
Add amantadine is adjuvant
209
What's amantadine?
A weak dopamine agonist
210
Management off advanced PD?
Apomorohine via SC intermittent injections or continuous infusion
211
How to manage N&V caused by apomorohine?
Start domperidone 2 days before apomorohine treatment and discontinue as soon as possible
212
MHRA advice on domperidone and apomorohine treatment?
Both cause QT interval prolongation and cause serious risk of arrhythmia so assess cardiac risk factors, monitor ECG and ensure benefits outweigh risks when initiating treatment
213
Drug choice for advanced Levodopa responsive PD with severe motor fluctuations, hyperkinesia or dyskinesia
Levodopa carbidopa intestinal gel administered with a portable pump directly into the duodenum or upper jejunum
214
Last resort for advanced PD where drug treatment had failed?
Deep brain stimulation
215
MoA of Levodopa?
Levodopa is the amino acid precursor of dopamine and acts by replenishing depleted dopamine levels in the brain
216
Side effects of Levodopa?
Impulsive control disorders
(gambling, hypersexuality, binge eating, obsessive shopping)
Excessive sleepiness and sudden onset of sleep (so no driving)
```
Motor complications
(dyskinesia=involuntary muscle movements, response fluctuations)
```
End of dose deterioration with shorter length of benefit
So switch to MR?
217
What's the drug group name of carbidopa and benserazide? And its function?
Peripheral dopa decarboxylase inhibitors
They help to reduce side effects like N&V and CV effects
Also reduces dose requirements for therapeutic effect
218
What drugs are considered as dopamine receptor agonsits?
Non ergot derived dopamine receptor
Ergot derived
Apomorohine
Amantadine
219
Disadvantage of dopamine agonists compared to Levodopa?
Associated with more hallucinations, excessive sleepiness and impulse control disorders
220
Side effects of ergot derived dopamine receptor agonists limit their use. What are they?
Fibrotic recations (scarring, thickening tissues)
- pulmonary (dyspnoea, persistent cough)
- retro peritoneal (abdominal pain and tenderness)
- pericardial (cardiac failure)
221
Side effects of dopamine receptor agonists?
Impulsive control disorder
Excessive sleepiness and sudden onset of sleep
Psychotic symptoms like hallucinations and delusions
Hypotensive reactions in the first few days
222
MoA of MAO-B inhibitors?
Inhibit monoamine oxidase B enzymes which are responsible for the breakdown of monoamines=dopamine
223
Important interactions of MAO-B inhibitors?
Hypertensive crisis with pseudoephedrine, phenylephrine, xylometazoline, oxgmetazoljne (OTC nasal decongestants)
Adrenaline, Noradrenaline, amphetamines, B2 agonists
224
MoA of COMT inhibitors?
Preventing the peripheral breakdown if Levodopa by inhibiting catechol-O-methyltransferase, allowing more Levodopa to reach the brain
225
Important interactions of COMT inhibitors?
Increased CV effects with adrenaline, Noradrenaline, MAOIs, Tranylcypromine
226
Side effect of entacapone?
Colours urine reddish brown
227
Side effect of Tolcapone?
Hepatotoxicity
228
Signs of liver toxicity?
```
Anorexia
N&V
Abdominal pain
Dark urine
Pruritus
```
229
What can be used to manage daytime sleepiness caused by PD
Modafinil
| Review treatment at least every 12 months
230
Management of postural hypotention caused by PD
Midodrine is first line
| Fludrocortisone unlicensed alternative
231
Management of psychotic symptoms caused by PD
Quetiapine first line
| Clozapine
232
Management of rapid eye movement sleep behaviour disorder in PD?
Clonazepam
Melatonin
Both unlicensed
233
Management of drooling of saliva in PD?
Glycooyronnium is first line
Botulinum toxin type a is second
Antimuscarnics not recommend because of its cognitive adverse effects
234
What's the important safety info of metoclooramide?
Can cause severe EPS particularly in young adults
235
Different types of insomnia?
Transient insomnia
=caused by environmental factors like noise, shift work, jet lag
Short term insomnia
=related to emotional problem or a serious medical illness
May last a few weeks and may recur
Chronic insomnia
=commonly caused by Psychiatric disorders like anxiety and depression
Other cause include pain, dyspnoea and Pruritus
236
When is it suitable to use short actin hypnotics for insomnia?
When Sedation the following day is not desirable
| Elderly pts
237
When is it suitable to use long a ting hypnosis for insomnia?
Pts with poor sleep maintenance like they wake up early etc
238
Treatment for transient insomnia?
Short acting rapidly eliminated hypnotics
| Only give one or 2 doses
239
management of short term insomnia?
Give no more than 3wks of hypnotics preferably only for 1 wk
Best to take intermittently and omit some doses
240
Management of chronic insomnia
Treat underlying cause
If depression is the cause, could use sedating treatment like mirtazepine or clopipramine
241
Which short term benzodiazepines are used as hypnotics for insomnia?
Nitrazepam
Flurazepam
Diazepam
242
Which benzodiazepines are given as short acting hypnotics?
Lorazolam
Lormetazepam
Temazepam
243
Duration of use with z drugs?
Up to 4wks
2wks if zalepon
For severe insomnia that interferes with daily life
244
Side effects of Z drugs?
Paradoxical effects - adjust dose
Daytime sleepiness - avoid alcohol
245
How long does it take to develop tolerance to z drugs and benzodiazepines?
3_14days of continuous use.
246
What drug used for insomnia is suitable for elderly because no hangover effect?
Clomethiazole
247
What is Melatonin and its license?
A pineal hormone
| Licensed for short term treatment of insomnia in adults over 55
248
What is narcolepsy?
Rare long term brain disorder that causes a person to suddenly fall asleep at inappropriate times
249
Treatment of narcolepsy?
```
Modafinil
Methylphenidate (CD2)
Dexamfetamine (CD2)
Sodium oxybate (CD2)
Pitolisant
```
