Chapter 4: Nervous System Flashcards
1
Q
What kind of drugs should be minimised in patients with cognitive impairment, such as dementia?
A
Antimuscarinics
e.g. amitriptyline, paroxetine, solifenacin, antipsychotics
Can result in cognitive impariment
2
Q
What is first line treatment options for patients with mild to moderate Alzheimer’s?
A
Monotherapy with one of the following Ach inhibitors:
Donezipil
Rivastigmine
Galantamine
Drug tx should only be initiated under a specialist (however can then be managed in primary care)
3
Q
What is 1st line for patients with SEVERE Alzheimer’s in someone who is not on any medication for the condition?
A
Memantine
4
Q
If a patient is on an Ach inhibitor for their mild/moderate Alzheimer’s, however their condition gets more severe, what should be done?
A
Consider adding memantine. In this case, it can be initiated in primary care without the advice from a specialist
5
Q
In patients with moderate Alzheimer’s, what is the risk of stopping Ach inhibitor treatment?
A
Can cause a substantial worsening in cognitive function
6
Q
What is the MHRA warning regarding prescribing antipsychotics in elderly patients with dementia?
A
^ risk of stroke and a small increased risk of death.
If needed, use the lowest effective dose and for the shortest time
Review every 6 weeks
7
Q
What is the risk of prescribing antipsychotics in patients with Lewy body/Parkinson’s Disease dementia?
A
Antipsychotic drugs can worsen motor features of the condition, and in some cases cause severe antipsychotic sensitivity reactions
8
Q
What patient advice is needed for galantamine?
A
Risk of serious skin reaction including Stevens-Johnson Syndrome
Stop taking if reaction occurs
9
Q
What is the MHRA advice surrounding switching between different manufacturers’ products in epilepsy?
A
Category 1: ENSURE BRAND
Carbamazepine, phenobarbital, phenytoin, primidone.
Category 2: Brand clinical judgement
Clobazam, clonazepam, eslicarbazepine acetate, lamotrigine, oxcarbazepine, perampanel, rufinamide, topiramate, valproate, zonisamide.
Category 3: Brand unnecessary
Brivaracetam, ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin, tiagabine, vigabatrin.
10
Q
What is antiepileptic hypersensitivity syndrome?
A
Rare but potentially fatal syndrome
The symptoms usually start between 1 and 8 weeks of exposure; fever, rash, and lymphadenopathy are most commonly seen.
11
Q
What is the MHRA advice regarding antiepileptic drugs and psychological side effects?
A
Associated with a small increased risk of suicidal thoughts and behaviour (can occur as early as one week after starting treatment)
Seek medical advice if they develop mood changes
12
Q
True or false:
Routine injection of vitamin K at birth minimises the risk of neonatal haemorrhage associated with antiepileptics.
A
True
13
Q
What is 1st line for newly diagnosed focal seizures?
A
Carbamazepine or Lamotrigine
14
Q
What is 1st line for tonic-clonic seizures?
What would be an alternative if this is unsuitable? What is the problem with this?
A
Sodium valproate
Lamotrigine, carbamazepine is an alternative however may exacerbate myoclonic seizures
15
Q
What is 1st line for absence seizures?
What would be an alternative?
A
Ethosuximide or sodium valproate
Lamtorogine is an alternative
16
Q
What is 1st line for myoclonic seizures?
What would be alternative options?
A
Sodium valproate
Topiramate or levetiracetam
17
Q
Atonic and clonic seizures are usually seen in which patient group?
What is the drug of choice for this?
A
Childhood or associated with cerebral damage or mental retardation
Sodium valproate
Lamotrigine can be added
18
Q
Which benzodiazepines can be used in epilepsy management (not status epilepticus)?
A
Clobazam
Clonazepam
19
Q
Seizures lasting longer than 5 minutes should be treated with what benzodiazepine?
What should you monitor?
A
IV lorazepam - can repeat once after 10 minutes if response fails
Monitor for hypotension and respiratory depression
20
Q
IV diazepam is effective in seizures but carries a high risk of what?
A
Thrombophlebitis
21
Q
True or false:
Diazepam IM or suppositories should be used for status epilepticus
A
False- absorption is too slow
22
Q
If after initial treatment of IV lorazepam and there is no response after 25 mins, what should be used?
A
Phenytoin/phenobarbital/fosphenytoin
If this does not work- anaesthesia
23
Q
Do brief febrile convulsions need any treatment?
A
No, may give paracetamol to reduce fever
However, if prolonged (>5 mins) or recurrent, treat as epileptic seizure.
24
Q
Is long term anticonvulsant prophylaxis recommended?
A
Rarely indicated
25
If an epileptic patient becomes pregnant, what supplement is recommended alongside their pregnancy, especially in the first trimester?
Folate supplementation to prevent neural tube defects
High dose 5mg OD
26
Pregnant patients who are taking what antiepileptics should have fetal growth monitoring?
Topiramate or levetiracetam
27
What conditions can lamotrigine exacerbate?
Parkinson's Disease
| Myoclonic seizures
28
What is a main side effect of lamotrigine?
What are the risk factors of this?
Hypersensitivity syndrome.
Serious skin rxns: SJS, TEN have developed (ESP in children); most rashes occur in first 8 weeks.
Risk factors include concomitant use of valproate, too high dose or too rapid dose increase
29
What is the patient advice surrounding lamotrigine?
- Don't suddenly stop treatment as needs to be tapered off gradually
- Contact doctor immediately if any rash or signs of hypersensitivity
- Rare - be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection.
30
What vitamin supplementation should you consider if a patient is on carbamazepine?
Vitamin D
| Especially if immobilised for long periods, or who have inadequate sun exposure/dietary intake of calcium
31
What are the main side effects to look out for if a patient is on carbamazepine?
Blood or skin disorders
Antiepileptic hypersensitivity syndrome
Seek medical help if fever, rash, mouth ulcers etc occur
ALSO can cause hepatotoxicity so report signs of dark urine, nausea, vomiting
32
What is an important side effect to look out for with ethosuximide?
Blood disorders (fever, mouth ulcers, or bleeding develops)
33
What severe side effect is associated with fosphenytoin (used for status epilepticus)?
Associated with severe cardiovascular reactions- asystole, ventricular fibrillation. Observe patient for at least 30 minutes after infusion
34
What is the MHRA advice regarding gabapentin?
Risk of severe respiratory depression
35
What are the serious side effects of lamotrigine?
Skin rxns: within 1-8 weeks. They include serious skin reactions i.e. SJS TEN
Blood disorders - signs such as anaemia, bruising, or infection
36
What antiepileptic is licensed for migraine prophylaxis?
Topiramate
37
What vitamin supplementation should you consider if a patient is on sodium valproate?
Consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
38
What types of toxicity is associated with sodium valproate?
Blood disorders
Hepatic failure
Pancreatitis
39
What is the safety alert associated with injectable phenytoin?
Risk of death and severe harm from error with the prescribing/preparation/administration
40
What vitamin supplementation should you consider if a patient is on phenytoin?
Consider vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium.
41
What are the symptoms of phenytoin toxicity?
Nystagmus (involuntary eye movement), diplopia (double vision), slurred speech, ataxia, confusion, and hyperglycaemia
42
What is nystagmus?
| What is diplopia?
Involuntary eye movement = nystagmus
| Diplopia = Double vision
43
What is the patient advice surrounding phenytoin?
Can cause agranulocytosis- Recognise signs of blood or skin disorders- report if mouth ulcer, bruising, bleeding develops
Antiepileptic sensitivity syndrome
44
What are specific side effects with topiramate? Hint - eyes
```
Acute myopia (near sightedness) with secondary angle-closure glaucoma
Encephalopathic symptoms - sedation, confusion
```
Patients should report signs of raised intra-ocular pressure
45
What is primidone used for?
Essential tremor
| Epilepsy
46
What are specific side effects of IV phenytoin?
Bradycardia
| Hypotension
47
What is buspirone used for?
Acute anxiety
48
What is a risk with IV diazepam?
Venous thrombophlebitis
49
How long should bipolar therapy be for?
For at least two years from the last manic episode and up to five years if the patient has risk factors for relapse.
50
Can lithium lower seizure threshold?
Yes
51
Long term use of lithium has been associated with what?
Thyroid disorders
| Mild cognitive and memory impairment
52
What are the signs of lithium toxicity?
```
GI disturbances- n+v, diarrhoea
Visual disturbances, nystagmus
Tremor. Restlessness.
CNS - confusion, drowsy, lack of coordination
Hypernatraemia
Cardiac arrhythmias. Circulatory failure
Renal failure
Increased thirst. Polyuria.
Memory impairment. Coma
```
53
When should lithium samples be taken?
12 hours post dose
54
How often should serum lithium monitoring take place in the initial and continuous treatment phase?
Weekly initially
Weekly after every dose change
3 months thereafter
55
What should you test/measure before starting lithium treatment?
```
Cardiac- ECG - can prolong QT
Renal function
Thyroid function
Blood count - can cause leukocytosis
Body weight - dosing for Priadel is based on weight
```
56
Once initiated on lithium therapy, how often should you measure BMI, electrolytes, eGFR and thyroid function?
Every 6 months
57
What is lithium used for?
```
Treatment and prophylaxis of:
Mania
Bipolar disorder
Recurrent depression
Aggressive/self harming behaviour
```
58
What class of drug is first line in depression?
SSRI
59
In patients with a history of unstable angina or recent MI, what is the most appropriate antidepressant?
Sertraline
60
Are SSRIs or TCAs more sedating?
TCAs are more sedating
| Also have more antimuscarinic and cardiotoxic side effects
61
How often should patients be reviewed at the start of antidepressant treatment?
Every 1-2 weeks
62
Antidepressant treatment should be continued for at least how many weeks before you consider switching?
How many weeks is this in the elderly?
4 weeks
6 weeks in the elderly as they may take longer to respond
63
Following first remission, how long should antidepressant treatment be continued for?
How long in the elderly?
At least 6 months
12 months in the elderly
64
Patients with recurrent depression should receive maintenance treatment for how long?
At least 2 years
65
How long should antidepressant treatment be continued for in generalised anxiety disorder?
At least 12 months as risk of relapse is high
66
What electrolyte imbalance is associated with antidepressants?
Which class of antidepressant is this the most common in?
Low sodium
SSRIs
Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.
67
True or false:
The use of antidepressants has been linked with suicidal thoughts and behaviour
True
68
What are the symptoms of serotonin syndrome?
Neuromuscular hyperactivity (such as tremor, hyperreflexia, clonus, myoclonus, rigidity), autonomic dysfunction (tachycardia, blood pressure changes, hyperthermia, diaphoresis, shivering, diarrhoea), and altered mental state (agitation, confusion, mania).
69
If a patient fails to respond to their first line SSRI treatment for depression, what would be the options?
Increasing the dose
Switching to a different SSRI or mirtazapine
Other 2nd line options:
Lofepramine (TCA), moclobemide (reversible MAOI), and reboxetine (NRI)
70
Management of acute anxiety involves the use of what drug class options?
Benzodiazepine or buspirone
71
For chronic anxiety, what is used?
Antidepressant - SSRI
If patient cannot tolerate SSRI, pregabalin can be considered
Benzodiazepine may be needed until the antidepressant starts to work
72
After how many weeks is anxiety classed as chronic?
4 weeks
73
Panic disorder, OCD, PTSD and phobic states such as social anxiety disorder are treated with what drug class?
SSRIs
74
What are the less sedating TCAs?
Imipramine hydrochloride, lofepramine, and nortriptyline.
75
If a pt is on an antidepressant and is going to be changed to an MAOI, what time period should they have stopped the previous antidepressant?
2 weeks
3 weeks if starting clomipramine or imipramine (TCAs)
76
What is the patient advice surrounding MAOIs?
Advised to only eat fresh foods and avoid "going off" or stale food (meat, fish)
Avoid alcohol
Avoid large amounts of tyramine-rich foods e.g. mature cheese - hypertensive reaction
77
MAOI interactions can persist for how long after discontinuing MAOI?
2 weeks
78
Can SSRIs cause QT prolongation?
Yes
79
What type of drug is duloxetine?
| What type of drug is venlafaxine?
SNRI
80
What type of drug is trazadone and what is it used for?
Serotonin uptake inhibitor
Depression particularly when sedation is required
81
What are SSRIs cautioned in?
Cardiac disease
Bleeding- especially GI
Epilepsy as they can cause seizures
82
Can mirtazapine cause QT prolongation?
| Can TCAs cause QT prolongation?
Yes
83
What is the patient advice regarding mirtazapine?
Blood disorders- report fever, sore throat etc
84
Which antidepressant class is associated with a high rate of fatality?
TCAs
Cardiovascular and epileptogenic effects
Cautioned in those with a high risk of suicide- consider reduced supply on prescription so there are more regular reviews
85
What class of drug is dosulepin?
TCA
86
What are the symptoms of TCA overdose?
```
Hypotension
Hypothermia
Convulsions
Respiratory failure
Dilated pupils
Urinary retention
```
87
What do you need to consider in terms of the dose in patients on oral antipsychotics that require a change to IM?
IM bypasses first pass metabolism so consider a lower dose than that of the oral
88
In schizophrenia, are antipsychotics more effective on the negative or positive symptoms?
More effective on the positive symptoms
89
What are the main side effects of antipsychotics?
- Extrapyramidal - parkinsonism, dystonia, tardive dyskinesia
- Hyperprolactinaemia
- Sexual dysfunction
- CVS: QT prolong., hypotension, arrhythmias
- Hyperglycaemia, DB, weight gain
- Hypo/hyperthermia
- Neuroleptic malignant syndrome
- Blood dyscrasias
- Photosensitisation
90
What is dystonia?
Abnormal face/body movements
91
Which antipsychotic is least likely to cause hyperprolactinaemia?
Aripiprazole
92
Which antipsychotics are most likely to cause hyperprolactinaemia?
Risperidone, amisulpride, first generation antipsychotics
93
Which antipsychotics carry the highest risk of QT prolongation?
Haloperidol
| Pimozide
94
Which antipsychotics commonly cause weight gain?
Clozapine
| Olanzipine
95
Which antipsychotics commonly cause hyperglycaemia and diabetes?
Clozapine
Olanzipine
Risperidone
Quetiapine
96
Are first or second generation antipsychotics better at treating negative symptoms of schizophrenia?
Second generation
97
If extra-pyramidal side effects are a concern, should first or second generation antipsychotics be prescribed?
Second generation
98
Which antipsychotic is least likely to cause QT prolongation?
Aripriprazole
99
Are first or second generation antipsychotics more likely to cause insulin resistance and diabetes?
Second generation is more likely
100
Which antipsychotics are least likely to cause weight gain?
Aripiprazole
Haloperidol
Amisulpride
101
Patients should receive an antipsychotic for how many weeks before it is deemed ineffective?
4-6 weeks
102
When should clozapine be used in schizophrenia?
When 2 or more antipsychotics have not worked
One of the antipsychotics tried must have been a second generation
All the tried antipsychotics must have been tried each for at least 6-8 weeks
103
True or false:
| Clozapine patients must be registered with a clozapine patient monitoring service
True
104
What monitoring is required at the start of antipsychotic treatment?
Full blood count, urea and electrolytes, and liver function test monitoring
Blood lipids
Weight
Fasting blood glucose and blood pressure
ECG if history of cardiovascular risk factors present
105
What is the MHRA advice regarding clozapine?
Potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus
- seek immediate medical advice
106
What are the specific side effects with clozapine?
- Agranulocytosis
- Cardiomyopathy
- Intestinal obstruction
- Hypersalivation
107
How does clozapine interact with smoking?
Smoking breaks down clozapine so a higher dose may be needed
108
Is haloperidol a first or second generation antipsychotic?
First
109
Is olanzapine a first or second generation antipsychotic?
Second
110
Is clozapine a first or second generation antipsychotic?
Second
111
What is the important safety information associated with dopamine-receptor antagonists e.g. levodopa?
Impulse control disorders e.g. gambling, binge eating
112
What is the patient advice regarding co-benelodopa?
Sudden onset of sleep
| Caution when driving/operating machinery
113
Madopar contains which drug?
Co-beneldopa
114
Sinemet contains which drug?
Co-careldopa
115
Stalevo contains which drug combination?
Levodopa, carbidopa, entacapone
116
What neurological condition is amantadine used in?
Parkinson's Disease
117
What is apomorphine used for?
How do you manage the associated nausea and vomiting side effect?
Advanced Parkinson's Disease - "off" episodes (loevodopa stops working)
To combat the associated nausea and vomiting side effects, you can use domperidone but only short term (due to QT prolongation risk with domperidone and apomorphine used together)
118
What is the important safety information regarding bromocriptine and cabergoline?
Associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions.
Impulse control disorders
119
What would be first line in the following condition:
A patient with Parkinson's whose motor symptoms are decreasing their quality of life
Co-carelopda or co-benelopda
120
What would be first line in the following condition:
A patient with Parkinson's whose motor symptoms are NOT affecting their quality of life
Could be prescribed a choice of levodopa, non-ergot-derived dopamine-receptor agonists (pramipexole, ropinirole or rotigotine) or monoamine-oxidase-B inhibitors (rasagiline or selegiline hydrochloride).
121
Levodopa is associated with what side effect?
Motor complications, incl. response fluctuations (on / off periods) and dyskinesias
Take at specific times of the day to avoid "off" periods
However, the overall motor improvement is more noticeable with levodopa
122
Patients who develop dyskinesia or motor fluctuations despite optimal levodopa therapy should be offered what?
A choice of non-ergotic dopamine-receptor agonists (pramipexole, ropinirole, rotigotine), monoamine oxidase B inhibitors (rasagiline or selegiline hydrochloride) or COMT inhibitors (entacapone or tolcapone) as an adjunct to levodopa
If these do not work, then bromocriptine/cabergoline/pergolide could be considered
123
If drug therapy is required for a Parkinson's Disease patient who develops postural hypotension, what is considered as first line?
Midodrine
124
What is an advantage of domperidone over metoclopramide?
Less readily crosses the BBB so less likely to cause sedation and dystonic reactions
125
What is aprepitant used for?
Nausea and vomiting in chemotherapy
126
If vomiting during the first trimester of pregnancy is severe and requires drug therapy, what is used?
Short term antihistamine e.g. promethazine
127
What is Hyperemesis gravidarum?
Severe vomiting in pregnancy
128
In Hyperemesis gravidarum what vitamin supplementation should be considered?
Thiamine to reduce the risk of Wernicke's
129
What is the MHRA warning associated with domperidone?
Risk of cardiac side effects
QT prolongation
Max treatment duration should not normally exceed 1 week
130
What is the MHRA warning associated with metoclopramide?
Risk of neurological side effects
Extrapyramidal disorders and tardive dyskinesia
Recommended that it should only be prescribed for up to 5 days
Especially in young adults <20 years
131
Can ondansetron cause QT prolongation?
Yes
132
What is the problem with enteric coated aspirin in acute pain?
Slow onset of action
133
What are the weak opioids?
Codeine
Dihydrocodeine
Meptazinol
134
At what body weight should IV paracetamol be adjusted and what dose should you use?
<50kg
| 15mg/kg
135
What are the side effects of opioid analgesics?
- Constipation
- Nausea
- Respiratory depression
- Drowsiness
- Dependence and withdrawal
- Overdose - pinpoint pupils, coma
136
What is the MHRA warning regarding codeine?
Restricted use in children due to reports of morphine toxicity.
Codeine = only used to relieve acute moderate pain in children > 12 yrs only if it cannot be relieved by other painkillers.
Serious life-threatening ADR in children with obstructive sleep apnoea who received codeine after tonsillectomy or adenoidectomy
137
What is a potential side effect of IV fentanyl?
Muscle rigidity (may involve thoracic muscles)
138
Why should you monitor patients using fentanyl patches if they have a fever?
Increased absorption of drug
139
Why mustn't you expose fentanyl patches to heat e.g. baths and saunas?
May increase absorption
140
True or false:
Pethidine has multiple strengths in tablet form
False- only has 50mg strength so do not legally need to state the strength on the prescription
141
What is the difference between oxynorm and oxycontin?
Oxynorm- immediate release oxycodone
| Oxycontin- modified release oxycodone
142
What is the difference between Shortec and Longtec
Shortec- immediate release oxycodone
| Longtec- modified release oxycodone
143
True or false:
For migraine relief, if a patient does not respond to one 5HT1-receptor agonist, an alternative 5HT1-receptor agonist should be tried.
True
144
In what situations would you consider migraine prophylaxis?
- suffer at least two attacks a month;
- suffer an increasing frequency of headaches;
- suffer significant disability despite suitable treatment for migraine attacks;
- cannot take suitable treatment for migraine attacks
145
What is the most commonly used beta blocker for migraine prophylaxis?
Propranolol
146
A self adhesive capsaicin patch 8% is licensed in what?
Treatment of peripheral neuropathic pain in non-diabetic patients
147
Capsaicin cream 0.075% is licensed in what?
Post herpetic neuralgia
Painful diabetic neuropathy
Osteoarthritis
148
Is withdrawal is more common with the short or long acting benzodiazepines?
Short acting
149
Is diazepam short or long acting?
Long acting - good for if insomnia is associated with daytime anxiety
150
Is lorazepam short or long acting?
Short acting - little or no hangover effect
151
What kind of effect can happen as a result of taking benzodiazepines?
Paradoxical effects
| A paradoxical increase in hostility and aggression may be reported by patients taking benzodiazepines
152
Why are benzodiazepines cautioned in hepatic impairment?
If they are needed, are short or long acting ones recommended?
Can precipitate coma
Short acting
(However, in alcohol withdrawal, a long acting e.g. chordiazepoxide or diazepam is used via fixed dosed regimen)
153
For patients on opioid maintenance therapy, what should happen if they miss:
1) 3 or more days
2) 5 or more days
1) In community pharmacy, refer back to the prescriber. They should consider reducing the dose
2) An assessment of illicit drug use is also recommended before restarting substitution therapy
154
For opioid addiction, what can be used for opioid maintenance therapy?
Buprenorphine or methadone
155
Is buprenorphine or methadone more sedating?
Methadone
For this reason, buprenorphine may be more suitable for employed patients or those who drive, and is also safer to use if prescribed other sedating drugs
However, those who experience increased anxiety during opioid withdrawal may prefer methadone
156
What is first line for alcohol dependence?
What would be an alternative?
Acamprosate / naltrexone with a psychological intervention
| Alternative- disulfiram if the others are not suitable or if the patient wants this but understands the associated risks
157
What should be given to alcohol dependent patients who are at risk of Wernicke's encephalopathy?
Thiamine
158
What is the patient advice regarding disulfiram?
Counselled on the disulfiram-alcohol reaction—rxns may occur following exposure to small amounts of alcohol found in perfume, aerosol sprays, or low alcohol and "non-alcohol" beers and wines; symptoms may be severe and life-threatening and can include nausea, flushing, palpitations, arrhythmias, hypotension, respiratory depression, and coma.
Patients and their carers should be counselled on the signs of hepatotoxicity— discontinue tx and seek immediate medical attention if they feel unwell or symptoms such as fever or jaundice develop.
159
What is varenicline used for?
Smoking cessation
| Brand name= Champix
160
What is the MHRA advice regarding varenicline?
Suicidal behaviour
Patients are advised to discontinue treatment and seek prompt medical advice if they develop agitation, depressed mood, or suicidal thoughts. Patients with a history of psychiatric illness should be monitored closely while taking varenicline.
161
What monitoring does clozapine require?
Monitor leucocyte and differential blood counts. Clozapine requires differential WBC monitoring weekly for 18 weeks, then fortnightly for up to 1 year, and then monthly
Blood lipids and weight at baseline
FASTING blood glucose baseline
Baseline prolactin
162
If it does need diluting, IV phenytoin should be administered in what fluid via what and why?
Sodium chloride
| Via large vein, in line phenytoin filter is needed as it precipitates easily
163
When should lithium be stopped before major surgery?
24 hours
164
Ethosuximide is used for what type of seizures?
Absence
| Myoclonic
165
Hair loss with regrowth of curly hair is a rare effect of which drug?
Valproate
Phenytoin
Carbamazepine
Lamotrigine
Valproate
166
Taking trimethoprim with phenytoin primarily increases the risk of what?
Hyperkalaemia
Megaloblastic anaemia
Bleeding
Low sodium
Megaloblastic anaemia
Trimethoprim inhibits folate synthesis
Phenytoin increases folate metabolism
(Same with trimethoprim and methotrexate)
167
Purple glove syndrome is a rare side effect of which epilepsy drug?
Phenytoin
168
What is the ideal level range for lithium?
For acute episodes of mania, what would the target level range be?
0. 4–1 mmol/litre -lower end for elderly and for maintenance therapy
0. 8–1 mmol/litre is recommended for acute episodes of mania
169
What is the risk of abrupt lithium withdrawal?
How should it be withdrawn?
Increases the risk of relapse
| The dose should be reduced gradually over a period of at least 4 weeks (preferably of up to 3 months).
170
What is the patient advice regarding diet and fluid intake if on lithium therapy?
Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake.
171
How does lithium interact with ACEis?
Risk of lithium toxicity
Excretion of lithum reduced by ACEi
172
How does lithium interact with NSAIDs?
Risk of lithium toxicity
Excretion of lithium probably reduced by NSAIDs
173
How does lithium interact with loop and thiazide diuretics?
Excretion of lithium reduced by Loop and Thiazide – Sodium depletion
174
How does lithium interact with amiodarone?
Risk of ventricular arrhythmias
175
What is the desired total serum concentration for phenytoin?
What can be a disadvantage of measuring total concentration?
10-20mg/L
However, need to be careful as there are certain conditions where protein binding may be reduced e.g. elderly
There is also reduced protein binding in the first 3 months of life
It may be more appropriate to measure free plasma phenytoin concentration
176
Are preparations containing phenytoin sodium and phenytoin base bioequivalent?
No
177
Why is it important to maintain good oral hygiene if taking phenytoin?
Can cause gingival hyperplasia
178
How does phenytoin interact with NSAIDs?
Effect of phenytoin enhanced by NSAIDs
179
How does phenytoin interact with amiodarone?
Amiodarone inhibits metabolism of phenytoin
180
How does phenytoin interact with warfarin?
Phenytoin accelerates metabolism of warfarin
181
How does phenytoin interact with cimetidine?
Cimetidine inhibits the metabolism of phenytoin
182
How does phenytoin interact with fluoxetine?
Phenytoin concentration increased by fluoxetine
183
How does phenytoin interact with St John's Wort?
St. Johns Wort (an enzyme inducer) reduces plasma conc. of phenytoin
184
Is lithium use associated with hyper or hypothyroidism?
Hypothyroidism
185
```
Which of these side effects is not associated with lithium?
Hyperthyroidism
Tremors
Increased urination/thirst
Leukocytosis
```
Hyperthyroidism
Associated with hypothyroidism
186
Which of these side effects is not associated with phenytoin?
Skin coarsening
Gum hypertrophy
Hair loss
Osteomalacia
Hair loss
Associated with substantial hair growth (hypertrichosis)
187
Has diazepam got a short or long half life?
Long half life
188
Sinemet absorption is reduced when taken with foods high in what nutrient?
Protein
Fat
Carbohydrates
Protein as it competes with levodopa for absorption
189
Are typical antipsychotics first or second generation antipsychotics?
First generation
190
Are atypical antipsychotics first or second generation antipsychotics?
Second generation
191
What antibiotic class can result in carbamazepine toxicity?
Macrolides
192
What antidepressant can be used for smoking cessation?
Bupropion
193
Carbamazepine commonly causes what electrolyte imbalance?
Hyponatraemia
194
True or false:
| Phenytoin is not known to cause skin pigmentation
False
| Causes yellow-brown pigmentation
195
What is the advice surrounding antipsychotics and sunlight?
As photosensitisation may occur with higher dosages, patients should avoid direct sunlight.
196
What is the general advice regarding monitoring patients on antipsychotics?
ECG may be required before tx
Monitor prolactin concentration at the start of therapy, at 6 months, and then yearly.
Patients with schizophrenia should have physical health monitoring (including cardiovascular disease risk assessment) at least once per year.
197
What is the advice regarding treatment cessation of antipsychotic drugs?
^risk of relapse if medication is stopped after 1–2 years. Withdrawal after long-term therapy should always be gradual and closely monitored. Patients should be monitored for 2 years after withdrawal of antipsychotic medication for signs and symptoms of relapse.
198
What is the NICE 2017 guidance surrounding choice of Donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease?
The three acetylcholinesterase (AChE) inhibitors donepezil, galantamine, and rivastigmine as monotherapies are recommended as options for managing mild to moderate Alzheimer's disease
Tx should normally be started with the drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once shared care has started). However, an alternative AChE inhibitor could be prescribed if it is considered appropriate
199
What is ergotamine used for?
In what patient groups would this not be appropriate for?
Cluster headaches - unlincensed
coronary heart disease; hyperthyroidism; inadequately controlled hypertension; obliterative vascular disease; peripheral vascular disease; Raynaud’s syndrome; sepsis; severe hypertension; temporal arteritis
200
What are the contraindications for benzodiazepines?
Acute pulmonary insufficiency; marked neuromuscular respiratory weakness; sleep apnoea syndrome; unstable myasthenia gravis
201
Selegiline is what type of drug?
Monoamine oxidase B inhibitor
202
What is used as adjunct to co-beneldopa or co-careldopa to reduce 'end of dose' deterioration?
Selegiline - can be used alone
Enatcapone
Tolcapone
203
What parkinsons disease drug colours your urine reddish brown?
Entacapone
204
What Parkinson's Disease medicine can exacerbate oedema and cautioned in congestive heart failure?,
Amantadine
205
Hair loss is a common side effect of what Parkinsons Medicine?
Selegiline
206
How do you manage status epilepticus?
- IV lorazepam if seizure > 5 minutes
- Must have resuscitation facilities available (if not, use rectal diazepam or buccal midazolam although absorption is slower)
- Can administer lorazepam again after 10 mins if no response
- If after 25 minutes after onset and no response, give phenytoin (slow IV)/fosphenytoin (can be given more rapidly) /phenobarbital
- If after 45 minutes after onset and no response, sedate patient
207
Treatment with domperidone should not exceed how many days?
| Treatment with metoclopramide should not exceed how many days?
7 days - Domperidone
| 5 days - Metoclopramide
208
A withdrawal regimen after stabilisation with methadone hydrochloride or buprenorphine should be attempted only after careful consideration.
How long does complete opioid withdrawal usually take in:
i) an inpatient setting
ii) community setting
Inpatient setting is usually 4 weeks
Community setting is usually 12 weeks
209
If a patient is on an opioid withdrawal regime but starts to use illicit drugs again, what should happen?
The withdrawal regimen should be stopped and maintenance therapy should be resumed at the optimal dose.
210
Following successful opioid withdrawal treatment in the management of addiction, how long should the patient be followed up for?
6 months at least
211
True or false:
| For opioid addiction replacement therapy, buprenorphine has to be given every day
False
| Can be given on alternate days in higher doses
212
Does buprenorphine or methadone require a shorter drug-free period (before naltrexone is needed for relapse prevention)?
Buprenorphine
213
Which of the following can you titrate faster:
Methadone
Buprenoprhine
Buprenoprhine - can titrate within 1 week
Methadone can take several weeks
214
After how many hours of heroin use can you administer:
Methadone
Buprenoprhine
Why does there need to be a gap?
At least 8 hours after for methadone
6-12 hours after for Buprenoprhine
This is to reduce the risk of precipitated withdrawal
215
What is the recommendation of opioid withdrawal in pregnancy during:
i) 1st trimester
ii) 2nd trimester
iii) 3rd trimester
1st trimester- avoid as increased risk of spontaneous miscarriage
2nd trimester - can do withdrawal however needs to be slow (dose reduction every 3-5 days)
3rd trimester - avoid as increased risk of stillbirth and foetal distress
216
What is the only trimester that you can do opioid withdrawal therapy?
2nd
217
If a patient on methadone becomes pregnant, should they stop the methadone?
No
Therapy should be continued
Drug metabolism can be increased in the third trimester; it may be necessary to either increase the dose of methadone hydrochloride or change to twice-daily consumption (or a combination of both strategies) to prevent withdrawal symptoms from developing.
218
What do you need to consider in the third trimester in terms of methadone and drug metabolism?
Drug metabolism can be increased in 3rd trimester; it may be necessary to either ^ dose of methadone or change to BD consumption (or a comb of both strategies) to prevent withdrawal symptoms from developing.
219
What is the advice regarding opioid substitution during breastfeeding?
What red flag symptoms should you look out for?
Doses of methadone and buprenorphine should be kept as low as possible in breast-feeding mothers. Increased sleepiness, breathing difficulties, or limpness in breast-fed babies of mothers taking opioid substitutes should be reported urgently
220
What is lofexidine used for?
Management of symptoms of opioid withdrawal
Can be prescribed as an adjuvant to opioid substitution therapy
221
What are the most effective drug treatments for smoking cessation?
Varenicline
or
Combination of long acting NRT (patch) AND short acting NRT (gum, lozenge etc)
222
How long are nicotine patches generally applied for?
In what group of patients would this be longer?
16 hours a day, patch removed overnight
24 hours a day is the patient experiences strong nicotine cravings upon waking
223
Can varenicline be used alongside NRT?
No
224
Can varenicline be used alongside bupropion for smoking cessation?
No
225
For smoking cessation, how much treatment should be prescribed for the patient?
2 weeks with an assessment just before their supply finishes
226
Can e-cigarettes be supplied by smoking cessation services?
No
227
When should NRT be used in smoking pregnant patients?
Only if non-drug treatment options have failed
228
What drugs do cigarettes interact with and require higher doses as metabolism is increased?
```
Theophylline
Clozapine
Olanzapine
Haloperidol
Chlorpromazine
Ropinerole
Cinacalcet
```
229
What are the side effects of nicotine containing preparations?
```
Local irritation
GI disturbances
Dry mouth if spray, lozenge
Palpitations - rarely with patches and oral spray
Hot flushes
```
230
Abnormal dreams can occur with which NRT preparation?
Patch- this is reduced if removed before bed
231
Where should you apply an NRT patch?
Do you have to rotate sites of application?
Trunk, upper arm, hip
Yes- Avoid using the same site for several days
232
How long before the target smoking quit date should varenicline and bupropion be started?
7-14 days before
233
Are e-cigs licensed is smoking cessation?
No - aways recommend a licensed treatment if asked e.g. NRT patch
234
A CO level of what suggests the person has stopped smoking or is a non-smoker?
10 ppm or less
235
How long after starting varenicline or bupropion should the person be followed up?
How does this compare with NRT?
3-4 weeks
2 weeks for NRT
236
How many weeks is a course of varenicline?
12 weeks
237
Capsaicin 0.025% cream is licensed for what?
Symptomatic relief in osteoarthritis
238
Using antipsychotics and what drug for dementia can increase the risk of neuroleptic malignant syndrome?
Donepezil
239
What Acetylcholinerase inhibitor is licensed for dementia in Parkinson's Disease (Lewy body)?
Rivastigmine
240
For rivastigmine patches, you should avoid using the same area on the body for how many days?
14 days
241
What are the side effects of cholinergic drugs?
| DUMB BELS
Diarrhoea
Urination
Muscle weakness/cramps
Bronchospasm
Bradycardia
Emesis
Lacrimation (teary eyes)
Salivation/sweating
242
Does the following have a short or long half life?
Lamotrigine
Phenytoin
Phenobarbital
Long, allows for OD dosing
243
Does levetiracetam need to be prescribed by brand?
No - Category 3
244
Does lamotrigine need to be prescribed by brand?
Based on clinical judgement - Category 2
245
Does valproate need to be prescribed by brand?
Based on clinical judgement - Category 2
246
Does ethosuximide need to be prescribed by brand?
No- Category 3
247
Does topimarate need to be prescribed by brand?
Based on clinical judgement - Category 2
248
With antiepileptic carries the risk of cleft palate following exposure in the first trimester?
Topiramate
249
What antiepileptics are present in high amounts in breast milk? (ZELP)
Zonisamide
Ethosuximide
Lamotrigine
Primidone
250
What antiepileptics accumulate in breast feeding children due to a slower metabolism?
Phenobarbital
| Lamotrigine
251
What antiepileptics inhibit sucking reflex in breast feeding?
Phenobarbital
| Primidone
252
What antiepileptics have an established risk of drowsiness in babies?
Benzodiazepines
Phenobarbital
Primidone
253
What antiepileptics carry a high risk of withdrawal symptoms?
Phenobarbital
| Primidone
254
What antiepileptics are mainly associated with antiepileptic hypersensivitiy syndrome?(CP3L)
```
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Lamotrigine
```
In first 8 weeks of starting discontinue immediately
255
What antiepileptics can cause blood dyscrasias?
```
Carbamazepine
Valproate
Ethosuximide
Topiramate
Phenytoin
Lamotrigine
Zonisamide
```
256
What are the signs of phenytoin toxicity? (SNACHD)
```
Slurred speech
Nystagmus
Ataxia
Confusion
Hyperglycaemia
Diplopia
```
257
What pre-treatment screening is needed in Chinese and Thai patients when starting phenytoin and carbamazepine- why?
HLB-B*1502 allele - have an increased risk of Steven-Johnson syndrome
258
True or false:
| Phenytoin inhibits Vitamin D metabolism
False
It induces Vitamin D metabolism- consider supplementation in immobilised patients/inadequate sun exposure or dietary intake of calcium
259
Why is phenytoin cautioned in hepatic impairment?
Decreased protein binding so increased risk of toxicity
260
How does phenytoin and levothyroxine interact?
Phenytoin= enzyme inducer so reduces drug concentration
| Increased risk of hypothyroidism
261
What are the symptoms of carbamazepine toxicity (I HANDBAG)?
In co-cordination
```
Hyponatraemia
Ataxia (drunk)
Nystagmus
Drowsiness
Blurred vision, diplopia
Arrhythmias
GI disturbances
```
262
If a whole pack of sodium valproate cannot be dispensed, what must be put on the part pack?
Warning sticker
263
If a patient on sodium valproate is experiencing nausea, vomiting, abo pain, what should you do?
Refer
Could be hepatotoxicity or pancreatitis
264
Is lorazepam short or long acting?
Short acting
265
What groups of patients are short acting benzodiazepines more suitable for?
```
Elderly
Hepatic impairment (however in acute alcoholic withdrawal a longer benzodiazepine is used)
```
266
What is a disadvantage of short acting benzodiazepines?
Carries greater risk of withdrawal symptoms
267
Withdrawal symptoms can occur without how much time of stopping a short acting benzodiazepine?
Within 1 day
268
Withdrawal symptoms can occur without how much time of stopping a long acting benzodiazepine?
Within 3 weeks
269
How would you reduce someone's diazepam dose if on long term therapy to prevent withdrawal?
If on high doses, how is this done?
Reduce diazepam dose, usually by 1–2 mg every 2– 4 weeks
For high doses- reduce by up to one tenth every 1-2 weeks
270
What schedule is methylphenidate (Concerta)?
CD2
271
What are the side effects of methylphenidate and dexamfetamine?
- Appetite loss, insomnia, weight loss
- Increased HR and BP
- Tics, Tourette's
- Growth restriction in children- monitor height and weight, allow drug free periods to grow
- Psychiatric disorders
Monitor the above after a dose change and then every 6 months
272
What is dexamfetamine used for?
Narcolepsy
| Refractory ADHD
273
How would you treat an acute episode of mania?
Benzodiazepines
Antipsychotics- quetiapine, olanzapine, risperidone
Lithium or valproic acid can be added if inadequate response
274
What can you use for prophylaxis of bipolar disorder?
Lithium salts
Sodium valproate / valproic acid
Olanzapine
275
What should you not give in patients with bipolar?
Antidepressants
276
What are the signs of lithium toxicity? (REVNG)
```
Renal disturbances
Extrapyramidal symptoms
Visual disturbances
Nervous system disturbances
GI side effects
```
277
If a patient has persistent headaches and on lithium, what should you do?
Refer
| Lithium can cause benign intracranial hypertension
278
A deficiency in what electrolyte can lead to lithium toxicity?
Sodium (hyponatraemia)
Therefore, be careful if on drugs that cause low sodium e.g. diuretics
279
What is the only antidepressant licensed in children?
Fluoxetine
280
Can SSRIs lower seizure threshold?
Yes
281
Can TCAs cause seizures?
Yes
282
What is the interaction between TCAs and antihypertensives?
Increased risk of hypotension
283
Is moclobemide a reversible or irreversible MAOI?
Reversible - no washout period needed as it is short acting
284
With what MAOIs are hepatotoxicty more likely?
Phenelzine
| Isocarboxazid
285
What is the advice surrounding clozapine and missed doses?
If 2 or more doses missed, then need to re-titrate dose
286
Sexual dysfunction is most common with what antipsychotics?
Haloperidol and risperidone
287
Can antipsychotics interfere with your temperature regulation?
Can antipsychotics cause neuroleptic malignant syndrome?
Yes
288
What are the advantages of using peripheral dopa-decarboxylase inhibitors for Parkinson's?
Lower dose needed for therapeutic effect
Fewer side effects - nausea, vomiting, cardiovascular events
289
```
What class of drug is pramipexole?
What class of drug is ropinerole?
What class of drug is rotigotine?
```
Non ergot derived dopamine agonist
290
What are the side effects of ergot derived dopamine agonists?
Fibrotic reactions
Pulmonary- look out for SOB, cough
Retroperitoneal - look out for abdominal pain and tenderness
Pericardial- look out for cardiac failure
291
Is COMT inhibitor monotherapy licensed in Parkinson's?
No
| Used as an adjunct to levodopa
292
What kind of toxicity is caused by tolcapone?
Hepatotoxicty
| Look out for vomiting, dark urine, abdominal pain
293
What is the antisickness choice of drug in Parkinson's?
Domperidone
294
What two electrolyte imbalances should be corrected before using 5HT3 antagonists e.g. ondansetron?
Hypokalaemia and hypomagnesaemia
295
True or false:
Naloxone only partially reverses the effects of buprenorphine
True
296
In what situations is it advised for patients to immediately remove a fentanyl patch?
Breathing difficulties
Drowsiness, impaired speech
Signs of opioid toxicity
297
Can tramadol lower the seizure threshold?
Yes
298
True or false:
You can take two doses of sumatriptan for the same attack 2 hours later?
True but symptoms must have been improved after taking the first tablet
299
How would you treat trigeminal neuralgia (facial pain with electric shocks in the jaw)?
Carbamazepine or phenytoin
300
Transient insomnia is caused by what?
Shift work
| Jet lag
301
Is zopiclone a long or short acting hypnotic?
Short acting
302
For short term insomnia, hypnotics should not be used for longer than what?
3 weeks max
Ideally 1 week
303
Can methadone cause QT prolongation?
Yes
304
For short term relief of anxiety, hypnotics should not be used for longer than what?
2-4 weeks
305
What are the signs of benzodiazepine withdrawal?
It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances
306
During benzodiazepine withdrawal, what 3 classes of drugs should be avoided if possible (in the case of additional therapy to help with withdrawal symptoms)?
Beta blockers
Antidepressants
Antipsychotics
307
In terms of insomnia, in what cases are short acting hypnotics preferred?
Sleep onset insomnia
Where sedation the following day is not desirable
Elderly
Short term insomnia
308
In terms of insomnia, in what cases are long acting hypnotics preferred?
Poor sleep maintenance e.g. early morning awakening that causes daytime effects
If an anxiolytic effect is needed during the day
Diazepam
309
How should transient insomnia be managed?
Usually self-limiting and short term e.g. jet lag
If a hypnotic is indicated one that is rapidly eliminated should be chosen, and only one or two doses should be given
310
How can chronic insomnia be managed?
What are the common causes of chronic insomnia?
Rarely benefited by hypnotics and is sometimes due to mild dependence caused by injudicious prescribing of hypnotics
The underlying psychiatric complaint should be treated, adapting the drug regimen to alleviate insomnia.
Anxiety, depression, and abuse of drugs and alcohol are common causes
311
What is the risk of long term benziodiazepine therapy in the management of insomnia?
Can cause rebound insomnia and a withdrawal syndrome.
312
Is withdrawal more common with short or long acting benzodiazepines?
Short acting
313
Is temazepam long or short acting?
Short acting
314
What would be an appropriate benzodiazepine for someone suffering from insomnia with daytime anxiety?
Diazepam - long acting
| Single dose at night
315
What role do beta blockers play in anxiety?
Can help with the autonomic physical symptoms e.g. tremor and palpitations
They do not reduce non-autonomic symptoms, such as muscle tension
They do not help with psychological symptoms
316
True or false:
A benzodiazepine may be used as short-term adjunctive therapy at the start of antidepressant treatment to prevent the initial worsening of symptoms.
True
317
What is 1st line for mild depression if a patient is presenting for the first time?
Psychological therapy should be considered initially
If history of moderate or severe depression, consider antidepressant therapy
318
What class of drug is mirtazapine?
TETRAcycline antidepressant
319
Venlafaxine is generally reserved for what type of depression?
More severe
320
What is classed as chronic anxiety?
>4 weeks duration
321
Is generalised anxiety disorder a form of acute or chronic anxiety?
Chronic
322
What class of drug is duloxetine?
SNRI
323
If changing from fluoxetine to MAOI, what is the period of time you can start this after fluoxetine has been stopped?
What about starting an MAOI from other SSRIs?
At least 5 weeks
With other SSRIs, it is only 1 week
324
How long should a patient not drive through after an unprovoked seizure?
6 months
325
How long should a patient not drive through after a seizure in established epilepsy?
How about if the seizure was whilst the patient was asleep?
12 months even if the patient was asleep
unless:
- Established pattern of only having seizures when the patient is asleep over one year
- If had seizures in the past awake, need to have 3 years of only having seizures asleep
326
If an epileptic patient has had a seizure whilst asleep, the patient should not drive for 12 months. What are the exceptions?
UNLESS:
- Established pattern of only having seizures when the patient is asleep over one year
- If had seizures in the past awake, need to have 3 years of only having seizures asleep
327
Should an epileptic person drive during medication changes?
No
328
If withdrawn from an epilepsy med, how long should a patient not drive for?
6 months
329
What is the MHRA warning associated with the sedating antihistamine hydroxyzine?
QT prolongation
330
What is the therapeutic range for carbamazepine?
4-12 mg/L
331
Has pregabalin got an MHRA warning on the risk of severe respiratory depression?
No - Gabapentin does
332
What is amitriptyline used for?
Major depressive disorder- not recommended
Migraine prophyaxis
Neuropathic pain
333
What would be the starting dose of amitriptyline for neuropathic pain?
10-25mg ON
| Max of 75mg
334
What is pregabalin used for in terms of pain?
Peripheral AND central neuropathic pain
335
What is the max dose of pregabalin a day?
600mg
336
What would be the starting dose of pregabalin for neuropathic pain?
150mg daily in divided doses
337
What is the max dose of gabapentin a day?
3.6g
338
What is gabapentin used for in terms of pain?
Only peripheral neuropathic pain
339
What would be the dosing regimen of gabapentin in neuropathic pain?
Day 1 - 300mg OD
Day 2 - 300mg BD
Day 3 -300mg TDS
340
Examples of antimuscarinic drugs
```
Atropine
Scopolamine
Ipratropium
Tiotropium
Toleterodine
Solifenacin
Benztropine
Trihexyphenidyl
```
341
Effects of Atropine as antimuscarinic drug
Eye - relaxation ciliary muscle = dilation of pupil, not responsive to light, can be used prior to eye surgery but due to long duration of action (lasting days) cyclopentolate or tropicamide is preferred (lasting hours)
GI - blocks M3 Rec reducing gut motility, prolonging transit time and gastric emptying
Heart - blocks M2 receptors on SA/AV => tachycardia (^30-40bpm)
Salivary/sweat/lacrimal glands = dry mouth, dry skin and ultimately increase in body temperature
342
3 types oc holinergic antagonists
1 antimuscarinics
2 Ganglionic blockers
3 Neuromuscular blockers
343
Scopolamine
unlike atropine has greater CNS effect and longer duration of action
- prevent motion sickness
- post op n+v
patch formulation effect lasting up to 3 days
344
Ipratropium and Tiotropium
MOA
Indication
Difference?
Block muscarinic Acetylcholine receptors without specificity for subtypes
M3 block results in decreased contractility of smooth muscle in lungs = bronchodilation =& reduction of mucus secretion
Both administered as inhalation treatment for maintenance bronchospasms for pt in COPD
Ipratropium <= nasal spray = rhinorrea = runny nose
Tiotropium long acting agent dosed once daily
Ipratropium short acting dosed up to qds
tiotropium bromide is electrically charged, not absorbed by the GI tract and does not pass the BBB
345
Antimuscarinics USE
Prior to eye operation = atropine
Motion sickness = scopolamine
COPD maintenance of bronchospasms = ipratropium/tiotropium
Bladder problems = Tolterodine / solifenacin/ oxybutynin/ fesoterodine
Parkinson like disorders = Benztropine / Trihexyphenidyl
346
Antimuscarinics for bladder conditions
Tolterodine
Solifenacin
Oxybutynin
Fesoterodine
M3 receptor. overall efficacy similar.
347
Trihexyphenydil
Trihexyphenidyl exerts its effects by reducing the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.
348
Anticholinergic adverse effects
```
ABCDs
A - agitation
B - blurred vision
C - constipation/ confusion
D - dry mouth
S - stasis of urine and sweating
```
349
Ganglionic blockers' main agent?
main agent is nicotine - cig smoke; stimulates and later represses autonomic ganglia. Cholinergic agonist but also functional antagonist as it can stimulate and block cholinergic function.
Acts on nicotinic rec or parasympathetic and sympathetic autonomic ganglion, ^release of neurotransmitters such as dopamine, norepinehprine and serotonin.
350
Neurotransmitters and effects
| on Mood and Cognitive function
NE - alertness, concentration, energy
==> ATTENTION
Dopamine - pleasure, reward, motivation/drive
==> APPETITE + SEX + AGGRESSION
Serotonin - obsessions, compulsions, memory
==> ANXIETY + IMPULSE + IRRITABILITY
NE
351
SE of NICOTINE
Apart from smoking cessation nicotine is not very useful in clinical practice
CNS stimulation ^doses => convulsions
depresses CNS => respiratory paralysis
stimulating adrenal medulla and sympathtic ganglia => ^BP and HR but higher doses can cause BP to fall
GI system: increases motility => nausea and vomiting
Use of nicotine in any form can cause addiction due to CNS stimulation but also alertness and feeling of wellbeing
352
Neuromuscular blockers MOA
Block cholinergic transmission between motor nerve endings and nicotinic receptors on the skeletal muscle
```
Action Potential (AP) => release Acetylcholine at axon of motor neuron
Acetylcholine binds to Nicotinic receptors => opens Na ion channels letting Na ions enter muscle fibre
AP along sarcoplasmic reticulum => Ca release => leading to muscle contraction.
```
353
What are non depolarizing neuromuscular blockers? Clinical uses?
Non-depolarizing: competitive antagonists, bind to Acetylcholine receptors but do not induce ion channel (Na) opening. Prevent depolarization of the muscle cell membrane.
Clinical practice: aid mechanical ventilation and tracheal intubation, muscle relaxation during surgery allowing for lower doses of general anaesthetics. Cannot be absorbed from GI and must usually be injected IV onset 2 min. Paralyze small fast contracting muscles first e.g. eyes, fingers, then larger muscles of neck and limbs (recover in reverse)
Cisatracurium, Pancuronium, Atracurium
354
What are depolarizing neuromuscular blockers? Clinical uses?
Acetylcholine receptor agonists
Resistant to degradation by acetylcholinesterase => persistent depolarization
succinylcholine binds to nic. rec. => Na channel to open and stay open. Prolonged depolarization => transicent fasciculations => flaccid paralysis 'Phase 1 block'
Eventually channels close and membrane repolarizes but continued stimulation causes receptor to desensitize to acetylcholine = preventing formation of further action potentials 'Phase 2 block'
RAPID ONSET (1min lasting 10min) used to facilitate rapid sequence endotracheal intubation in critically ill patients. Muscle relaxation in electroconvulsive therapy.
SE: apnea, hyperkalaemia, systole, malignant hypothermia
355
```
Least likely to cause dry mouth (xerostomia)
A. amitriptyline
B. clozapine
C. oxybutynin
D. procyclidine
```
A. amitriptyline - SSRI
B. clozapine - atypical antipsychotic
C. oxybutynin - anticholinergic/antimuscarinic
D. procyclidine - anticholinergic
All can cause anticholinergic SE but clozapine can cause hypersalivation
