Central Nervous System Part 1 Flashcards
1
Q
How is dementia caused?
A
when the brain is damaged by disease such as Alzheimer’s, strokes or Parkinson’s
2
Q
What are the Cognitive symptoms of Dementia
A
- Memory Loss
- difficulties thinking/concentrating
- difficulties finding the right word
- Losing track of date
3
Q
What are the Non-cognitive symptoms of dementia
A
- psychiatric and behavioural problems
- difficulty with daily activities
4
Q
Management of cognitive symptoms
(mild-moderate Alzheimer’s symptoms)
A
Acetylcholinesterase Inhibitors
- Donepazil
- Galantamine
- Rivastigmine
5
Q
Donepazil interactions in Dementia
A
Concomitant use with Antiphycotics increased risk of Neuroleptic Malignant Syndrome
6
Q
What is Neuroleptic Malignant Syndrome
A
fever, altered mental status, muscle rigidity, and autonomic dysfunction.
7
Q
Galantamine cautions
A
Stop at first sight of skin rash or skin reactions
8
Q
Rivastigmine forms
A
Rivastigmine causes GI symptoms, withhold until solved
Transdermal Patches cause less GI Disturbances
9
Q
Management of cognitive symptoms
(moderate to severe Alzheimer’s symptoms)
A
NMDA Glutamate Receptor Antagonists
Memantine
10
Q
Cholinergic Effects Anagram
A
DUMB BELLS
11
Q
Cholinergic Effects Anagram D
A
Diarrhoea
12
Q
Cholinergic Effects Anagram U
A
Urination
13
Q
Cholinergic Effects Anagram M
A
Muscle weekness, cramps and Miosis
14
Q
Cholinergic Effects Anagram B
A
Bronchospasm
Bradycardia
15
Q
Cholinergic Effects Anagram E
A
Emesis (vomiting)
16
Q
Cholinergic Effects Anagram L
A
Lacrimation (teary eyes)
17
Q
Cholinergic Effects Anagram S
A
Salivation and sweating
18
Q
Management of Non-cognitive symptoms in Dementia
A
Antipsychotic Drugs
(Severe)
19
Q
Antipsychotics in elderly Dementia patients cautions
A
increased risk of stroke and death
assess benefits taking into account patient history of stroke/heart attack, diabetes and smoking
20
Q
Non-Cognitive symptom treatment in Dementia (extreme violent behaviour)
A
Oral Benzodiazepines
or…
Antipsychotics
If intramuscular needed, use: (haloperidol, olanzapine, lorazepam)
21
Q
Non-Cognitive symptom treatment in Dementia treatment (Dementia with Lewy bodies)
A
Lewy bodies are clumps of protein forming inside brain cells
(also found in parkinson’s disease)
Treatment:
Acetylcholinesterase Inhibitors (rivastigmine)
22
Q
What is Epilepsy
A
a sudden surge of electrical activity of neurons in the brain
23
Q
What are the 2 types of Non-epileptic seizures
A
Organic: hypoglycaemia / fever
Psychogenic:
mental processes (distressing thoughts)
24
Q
Drug dose of most anti-epileptic dugs
A
twice daily
25
Drugs used to treat seizures Part 1
- Barbiturates (phenobarbital long half life ON)
- Benzodiazepines (clobazam, clonazapam, lorazepam, Midazolam)
- Carbamazepine
- Gabapentin, Pregabalin
- Lamotrigine (long half life ON)
26
Drugs used to treat seizures Part 2
- Levetiracetam
- Phenytoin (long half life ON)
- Sodium Valproate
- Topiramate
27
Drugs used to treat seizures Part 3
- Lacosamide
- Perampanel
- Rufinamide
- Tiagabine
- Vigabatrin
- Zonisamide
28
Types of Epileptic Seizures
- Focal partial seizures with / without secondary generalisation
- Tonic-clonic seizures
- Absence Seizures
- Myoclonic Seizures
- Atonic / Tonic Seizures
29
Focal Partial Seizures treatment (with/without secondary generalisation)
1st Line:
Lamotrigine or Carbamazepine
Alternative:
Levetiracetam, Valproate or Oxcarbazepine
30
Tonic-Clonic Seizures treatments (generalised)
1st Line:
Valproate or Carbamazepine
Alternative:
Lamotrigine
31
Absence Seizures treatments (generalised)
1st Line:
Ethosuximide or Valproate
Alternative:
Lamotrigine
32
Myoclonic Seizures (generalised)
1st Line:
Valproate
Alternative:
Topiramate, Levetiracetam
33
Atonic/Tonic Seizures (generalised)
1st Line:
Valproate
34
Some Anti-epileptic Drugs caution
potential harm when switching between different brands for epilepsy CATEGORY 3
35
Epilepsy Drug Categories
Category 1:
advised to stay on same product
Category 2:
Based on clinical judgement and patient consultation
Category 3:
Do not need to stay on same product
36
Epilepsy Drugs Category 1 Examples
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
37
Epilepsy Drugs Category 2 Examples
- Valproate
- Lamotrigine
- Clonazepam
- Topiramate
38
Epilepsy Drugs Category 3 Examples
- Levetiracetam
- Gabapentin
- Pregabalin
- Ethosuximide
39
Anti-epileptic drug withdrawal cautions
- Gradually withdraw under specialist supervision
- If done abruptly, sever rebound seizures can occur
- If on combination therapy, withdraw 1 drug at a time
40
Epilepsy and Driving:
Your license will be taken away if you have
- epileptic seizures while awake and lost consciousness
41
Anti-epileptic Drugs and Pregnancy
- increased risk of teratogenicity
- reduces effectiveness of hormonal contraception (Carbamazepine)
42
Anti-epileptic drugs and pregnancy high risk drugs.
Highest Risk
- valproate
- valproic acid
Increased Risk
- Carbimazapine
- Phenytoin
- Phenobarbital
- Lamotrigine
Increased chance of Cleft Palate (lip not joined properly)
- Topiramate in first trimester
43
What do anti-epileptic drugs have a risk of causing during pregnancy
Minor and major congenital malformations and long term development disorders
44
Which anti-epileptic drugs need to be dose adjusted due to changing drug plasma concentrations during pregnancy
Phenytoin
Carbamazepine
Lamotrigine
45
Which anti-epileptic drugs do you need to monitor foetal growth with
Topiramate
Levetiracetam
46
Refer to specialist when planning a pregnancy whilst taking anti-epileptic drugs, what are the options
- Withdraw then resume after 1st trimester pregnancy
or...
- Use mono therapy only
47
What is neural tube defect
occurs when the neural tube does not close properly
48
Which drug and dose reduces the risk of neural tube defect when taking anti-epileptic medication and when to take it
Folic Acid 5mg OD
taken before contraception up until 12 weeks after pregnancy
49
What must you do if you are a woman planning on getting pregnant while on epilepsy medication
Notify the uk epilepsy and pregnancy register
50
What is neonatal haemorrhage
a bleeding problem that occurs in a baby during the first few days of life
51
What reduces the risk of neonatal haemorrhage
Vitamin K injection in newborn
52
Which anti-epileptic medication can cause withdrawal effects in newborns
Benzodiazepines and phenobarbital
53
What to monitor on a baby during anti-epileptic drugs and breastfeeding
Drowsiness, weight gain, feeding difficulty, adverse effect, developmental milestones
54
Which anti-epileptic medication is present in high concentrations in breast milk
Lamotrigine
Zosinamide
Ethosuximide
Primidone
55
What anti-epileptic drug accumulates due to baby slow metabolism
Phenobarbital
Lamotrigine
56
What anti-epileptic drug inhibits sucking reflex
Phenobarbital
Primidone
57
What anti-epileptic drug increases risk of drowsiness in infants
Benzodiazepines
Phenobarbital
Primidone
58
What anti-epileptic drug should you avoid abrupt withdrawal of breastfeeding with
Phenobarbital
Primidone
59
Anti-epileptic drug side effects:
Anti-epileptic Hypersensitivity Syndrome
Rash, Fever, Lymphadenopathy (lymph node swelling)
Carbamazepine, Phenytoin, Phenobarbital, Primodine and Lamotrigine
Increased risk in concomitant use:
Phenytoin and Carbamazepine
60
Anti-epileptic drug side effects:
Suicidal Behaviour
report any mood changes, distressing thoughts or feelings of suicide
61
Anti-epileptic drug side effects:
Skin Rashes
Lamotrigine
Steven-Johnson syndrome and Epidermal Necrosis
If Lamotrigine is high initial dose, rapid dose increase or taken with valproate
62
What is Toxic Epidermal Necrosis
extensive exfoliation of the epidermis and mucous membrane, which may result in sepsis and death
63
What is Steven-Johnson syndrome
blistering and peeling of the skin and surfaces of the eyes, mouth and throat
64
What is Blood Dycrasias
any condition that affects the blood, bone marrow, or lymph tissue.
65
Anti-epileptic drug side effects:
Blood Dycrasias
C Vet Plz Acronym
Ethosuximide, Valproate, Carbamazepine, Phenytoin, Lamotrigine, Topiramate,
Zonisamide
66
Anti-epileptic drug side effects:
Eye Problems
Vigabatrin:
visual field deflects
Topiramate:
Acute myopia with secondary angle closure glaucoma
67
Anti-epileptic drug side effects:
Encephalopathic Symptoms
Vigabatrin
Marked sedation, stupor and confusion
withdraw or reduce dose
68
Anti-epileptic drug side effects:
Severe Respiratory Depression
Gabapentin
69
Patients at higher risk of Severe Respiratory Depression while using Gabapentin include...
- Compromised respiratory function
- Respiratory/neurological disease
- Elderly
- Renal impairment
- concomitant use with CNS depressants
70
Anti-epileptic enzyme inducers (Carbamazepine, Phenytoin, Phenobarbital) interaction with interaction with oral contraceptives and warfarin...
decreases drug plasma concentration
71
Phenytoin (high risk drug as narrow therapeutic index) mode of action
binds to neuronal sodium channels in their inactive state; prolonging inactivity
72
What is phenytoin used for...
focal seizures and generalised tonic-clonic seizures. Exacerbates absence and myoclonic seizures (avoid)
73
Phenytoin therapeutic ranges...
10-20mg/L
or
40-80mcg/L
74
Neonate Phenytoin therapeutic ranges...
(below 3 months)
6-15mg/L
or
25-60mcg/L
75
Phenytoin has non-linear relationship between doses and drug plasma concentration, which means
Small change in dose/drug absorption
=
Large change in plasma concentration
76
Phenytoin high protein binding monitoring
During states of lowered protein binding in the body, plasma conc of phenytoin is increased.
Because phenytoin is a highly protein-bound drug
therefore plasma conc will increase
77
States of low protein binding in people
- pregnancy
- children (neonates)
- elderly
- liver failure
78
Symptoms of Phenytoin toxicity
- Slurred Speech
- Nystagmus (uncontrolled repetitive eye movements)
- Ataxia
- Confusion
- Hyperglycaemia
- Diplopia (double vision)
79
Phenytoin brand cautions
- Phenytoin is risk 1 category epileptic drug
--- Different oral formulations vary in bioavailability
80
Switching between phenytoin products
Phenytoin sodium is not the sane bioavailability as phenytoin base
100mg Phenytoin Sodium = 92mg Phenytoin base
81
Side effects of Phenytoin Part 1
- changes in appearance
(coarsening of facial features) (gingival swelling)
- Blood Dyscrasias (blood infections)
(report signs of infection)
if leucopenia is severe: immediately withdraw drug
82
Side effects of Phenytoin Part 2
- Hypersensitive reactions
(report fever, rash, swollen lymph nodes)
- Rashes (report them)
(discontinue if rashes reappear)
Han Chinese and Thia Patients with HLA*1502 allele
have increased risk of Steven-Johnson syndrome
83
Side effects of Phenytoin Part 3
- Low vitamin D
(phenytoin induces vitamin D metabolism) (use vitamin D supplement)
- Hepatotoxicity
(discontinue immediately)
--- dark urine, nausea, abdominal pain, itching and jaundice
- Suicidal Ideation
(small increase with all anti-epileptic)
84
Side effects of Phenytoin Part 4
- Bradycardia, Hypotension (IV Phenytoin) (prescribing dose needs to be accurate as risk of severe harm)
(monitor ECG and BP)
- IV Fosphenytoin
(cardiovascular reactions)
--- Asystole, ventricular fibrillation, cardiac arrest, heart block
(monitor cardio function)
85
Phenytoin Sodium and Fosphenytoin dose equals
Fosphenytoin 1.5mg
=
Phenytoin Sodium 1mg
give fesphenytoin only IV and IM
86
Drugs that interact with Phenytoin to increase plasma concentration
Amiodarone, Cimetidine, miconazole, fluconazole, chloramphenicol,
Diltiazem,
Valproate, trimethirprom
87
Drugs that interact with Phenytoin to reduce its drug concentration
Therapeutic failure
St John's Wort,
Rifampicin
88
Drugs that interact with Phenytoin to antagonise its anticonvulsant effects
- Quinolones
- Tramadol
- Mefloquine
- SSRI's
- Antipsychotics
89
Carbamazepine (narrow therapeutic drug) mode of action
Inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability
90
What is Carbamazepine used for
First line in focal seizures, generalised tonic-clonic seizures. Exacerbates atonic, clonic and myoclonic seizure
91
Carbamazepine dose therapeutic range
4-12mg/L
or
20-50mcg/L
(monitor plasma conc after 1 to 2 weeks)
92
Symptoms of Carbamazepine Toxicity
- Incoordination
- Hyponatraemia
- Ataxia (lack of voluntary muscle movement)
- Nystamus
- Drowsiness
- Blurred vision
- Arrhythmias
- Gastro-intestinal disturbances
93
Side Effects of Carbamazepine Part 1
- blood diseases
(report signs of infection, fever, sore throat)
- Hepatotoxicity
(report signs of liver toxicity, dark urine, jaundice)
94
Side Effects of Carbamazepine Part 2
- Hypersensitivity reactions
(antiepileptic hypersensitivity syndrome)(report fever, rash, swollen lymph nodes)
- Rashes (report rashes)
(THIA AND CHINESE ALLELE)
- Hyponatraemia
95
Dose Limiting or Dose Related side effects of Carbamazepine
- Headaches
- Ataxia
- Drowsiness
- Nausea
- Vomiting
- Blurred vision
- Allergic skin reactions
(M/R forms reduce side effects)
96
What drugs interact with Carbamazepine to increase plasma concentration
- Cimetidine
- Macrolides
- Miconazole
97
What drugs interact with Carbamazepine reduce plasma conc
St John's Wort
Phenytoin
98
What drugs interact with Carbamazepine to reduce anticonvolsant effect
Quinolones
SSRI's
Antipsychotics
99
What drugs interact with Carbamazepine to increase risk of hypontraemia
- Aldosterone Antagonists (spironolactone, Eplerenone)
- SSRI's
- Diuretics
- NSAID's
100
What drugs interact with Carbamazepine to increase risk of hepatotoxicity
- tetracyclines
- sulfasalazine
- sodium valproate
- methotrexate
- fluconazole
- alcohol
101
Carbamazepine reduces the effects of ..
- Warfarin
- HRT and hormonal contraceptives
102
Sodium Valproate mode of action
weak inhibitor of neuronal sodium channels, stabilises resting membrane potentials and reduces neuronal excitability
103
Sodium Valproate indications
first line in all types of generalised seizures
104
Sodium Valproate and pregnancy caution
Valproate medicines contra-indicated in females of child bearing potential
Unless they are in Pregnancy Prevention Programme or no other alternative
105
Pregnancy Prevention Programme
- for females with child bearing potential, when other treatments are not tolerated
- Fully informed of risks associated with pregnancy and valproate
- Patients must table highly effective contraception
106
Pregnancy Prevention Programme contraception
- Implants, IUDs, Sterilisation
- 2 complementary forms of contraception:
pill + barrier method + regular pregnancy tests
107
Pharmacist dispensing actions when dispensing valproate related products
- provide valproate PATIENT CARD
- Remind patient of risks and use of good contraception
- Try to use whole pack. Must include PIL and warning labels (sticker or box)
- Ensure they have received patient guide
108
Side Effects of Sodium Valproate
- Hepatotoxicity
(potentially fatal) (report signs of liver toxicity)
(Discontinue if abnormally prolonged Prothrombin time
- Blood disease
(report signs of infection)
- Pancreatitis
(report signs of pancreatitis- abdominal pain, nausea, vomiting)
109
Sodium valproate reaction with these drugs to reduce its anticonvulsant effects
Quinolones, SSRIs, Mefloquine
110
Sodium valproate reaction with these drugs to increase risk of hepatotoxicity
Statins, Carbamazepine, Tetracylines, fluconazole, itraconazole, methotrexate, sulfasalazine
111
Sodium valproate reaction with these drugs, increasing its plasma conc
lamotrigine, phenobarbital (other anti-epileptic)
112
What is status epilepticus
Epileptic fits follow one after the other without regaining consciousness
113
Convulsive status epilepticus treatment
IV Lorazepam
(avoid IV Diazepam as it causes thrombophlebitis)
114
Non-Convulsive status epilepticus treatment
If not loss of awareness:
- use normal oral antiepilpetic drugs
if loss of awareness or failed to respond to oral antiepilpetic drugs:
- IV Lorazepam
115
What is a Febrile convulsion
Convulsion in child with high temp of 38'C or higher
116
Febrile convulsion treatment
if < 5 mins:
- Paracetamol
if >5 mins:
- IV Lorazepam
117
Febrile or normal convulsive seizures emergency in community treatment
- Diazepam rectal solution
or...
- Midazolam Oromucosal Solution
repeat once after 10 to 15 mins if necessary
118
Anxiety Psychological Symptoms
- Restlessness
- Worry
- Fear
- Difficulty concentrating
- Irritability
119
Anxiety Physical Symptoms
- Palpitations
- muscle aches and tension
- trembling
- sweating
- shortness of breath
- insomnia
120
Anxiety treatment
- Benzodiazepines
(short acting benzodiazepines are better for elderly and for liver impairment, but greater withdraw effects)
- Beta-Blockers (for autonomic symptoms: Palpitations)
- Buspirone (5HT1a Agonist)
(low dependance and abuse, but takes 2 weeks to work)
121
Other medication to treat Anxiety
- Antidepressants
- Antiphycotics
- Meprobamate (license cancelled as serious CNS damage)
122
Benzodiazepines (Schedule 4 Part 1) mode of action
Facilitates and enhances the binding of GABA to the GABAa receptor to cause widespread depressant effect on synaptic neurotransmission
123
Benzodiazepines examples
- Clobazam (long acting)
- Diazepam (long)
- Lorazepam (short)
- Oxazepam (short)
- Alprazolam (long)
124
Benzodiazepines side effects
- Paradoxical increase in hostility aggression
(range form increased talking to aggression)
- Overdose can cause:
Ataxia, Drowsiness, Dysarthria, Nystagmus, Respiratory depression or coma
- Sedation (avoid alcohol)
125
Benzodiazepine dependance
- Avoid long term use, and abrupt withdrawal
126
Benzodiazepine long term use and abrupt withdrawal symptoms
- Toxic psychosis
- Confusion
- Delirium
127
Benzodiazepine withdrawal symptoms
increased anxiety, insomnia, weight loss, tremors, sweating, loss of appetite, tinnitus, perceptual disorders
128
Benzodiazepine withdrawal symptoms occurrence timing
Stopping Short Acting Benzodiazepine
- occurs within a day of stopping
Stopping Long acting Benzodiazepines
- occurs within 3 weeks of stopping
129
Drugs that interact with Benzodiazepines which increase sedation and CNS depressant effects
Alcohol, Opioids, antihistamines, antidepressants, barbiturates, antipsychotics
130
Drugs that interact with Benzodiazepines that increase its plasma conc
Amiodarone, diltiazem, macrolides, fluconazole
131
ADHD symptoms
- hyperactivity
- impulsivity
- inattention
132
ADHD treatment for children (5 years and over)
1st Line:
- Methylphenidate
2nd Line:
- Lisdexamfetamine (dexamfetamine for patients intolerable to longer effect profile)
133
ADHD treatment for adults
1st Line:
- Methylphenidate
2nd Line:
- Lisdexamfetamine (dexamfetamine for patients intolerable to longer effect profile)
Alternative:
- Atomoxetine
134
Methylphenidate mode of action
Potent CND stimulant, increasing dopamine and noradrenaline levels in the brain
135
Methylphenidate side effects
- Appetite loss
- weight loss
- insomnia
- tachycardia
- raised BP
- tourette's syndrome
- growth restriction in children
136
Methylphenidate monitoring
Monitor on starting, dose change and every 6 months:
- Pulse
- BP
- Appetite
- Weight/Height
137
Methylphenidate contra-indications
cardiovascular disease , hyperthyroidism, severe hypertension, uncontrolled bipolar, severe depression
138
Methylphenidate prescribing
for M/R preparations prescribe using brand
139
Dexamfetamine and Lisdexamfetamine mode of action
Potent CNS stimulants, increasing dopamine and noradrenaline levels in the brain
140
Dexamfetamine and Lisdexamfetamine side effects
- appetite loss
- anorexia
- tachycardia
- increased BP
- tourette's
- growth restrictions
141
Dexamfetamine and Lisdexamfetamine monitoring
Monitor on starting, dose change and every 6 months:
- pulse
- BP
- appetite
- weight and height
- agression
- depression
allow catch up periods for growth (drug-free periods)
142
Dexamfetamine and Lisdexamfetamine contra-indications
- CVD
- hyperthyroidism
- moderate to severe hypertension
- agitated states
143
Atomoxetine mode of action
Noradrenaline reuptake inhibitor causes increased levels of noradrenaline at synaptic cleft
144
Atomoxetine side effects
- Suicidal thoughts (report this behaviour)
- Haptotoxicity (report signs of liver toxicity)
- QT prolongation (avoid concomitant use of drugs that increase QT)
145
Atomoxetine monitoring
Monitor on starting, dose change and every 6 months:
- Pulse
- BP
- Psychiatric symptoms
- appetite
- weight and height
146
What is bipolar disorder and Mania
Characterised by extreme mood swings. A bipolar episode can last several weeks or months
147
Two types of episodes in Bipolar disorder
Mania-
feeling high and overactive
(less severe called hypomania)
Depression-
feeling low and lethargic
148
Acute episodes of Mania and hypomania treatment
- Benzodiazepines (short term)
- Antipsychotics
(quetiapine, olanzapine, risperidone)
--- Add lithium or Valproic Acid added to antipsychotics if response inadequate
149
Prophylaxis of Bipolar disorder (2 years)
- Lithium salts
- Valproate (sodium valproate or Valproic Acid)
- Olanzapine
- Carbamazepine (if unresponsive to other drugs)
150
Contra-indications in Bipolar Disorder
- Do not give antidepressants
- Rapid cycling Bipolar disorder
- recent history of hypomania
- manic episode
- rapid mood fluctuations
151
Lithium Salts indications
Prophylaxis and treatment of mania, hypomania, and depression in bipolar disorder, resistant depression and aggressive or self harming behaviour.
152
Lithium Therapeutic range for lower end for prophylactic treatment / elderly
0.4mmol/L to 1mmol/L
153
Lithium Therapeutic range for acute manic episode or patients who have previously relapsed or have subsyndromal symptoms
0.8mmol/L to 1mmol/L
154
Plasma Lithium Monitoring
- Blood samples taken 12 hours post dose
- Monitored every 3 months
- Monitor more if signifiant intercurrent illness or significant changes to diet or water intake
155
Lithium caution
avoid abrupt withdrawal, due to high risk of relapse
156
Symptoms of Lithium Toxicity (REVeNGe)
- R enal Disturbances (polyuria, hypernatraemia)
- E xtrapyramidal symptoms
(muscle weakness, fine tremor, ataxia)
- V isual disturbances
- N ervous system disturbances
(confusion, drowsiness, stupor)
- G astro-intestinal effects
157
If lithium plasma levels exceed 2mmol/L complications can include
- renal failure
- arrhythmias
- seizures
- bp changes
- circulatory failure
- coma
- sudden death
158
Side effects of Lithium Part 1
- Thyroid disorders
(monitor thyroid function tests)
(report hypothyroidism symptoms: weight gain fatigue)
- Renal Impairment
(monitor renal function tests)
(lithium is nephrotoxic)
(report renal dysfunction)
159
Side effects of Lithium Part 2
- Benign Intracranial Hypertension
(report persistant headaches and visual disturbances)
- QT Prolongation (cardiac function)
- Lowers Seizures Threshold
160
Lithium prescribing
prescribe by hand
- different preparations vary in bioavailability
161
Lithium toxicity symptoms
hyponatraemia (lower sodium in plasma)
162
Lithium counselling points
- report sings of lithium toxicity
- maintain salt and water intake
- lithium can cause drowsiness, so dont drive. Avoid alcohol
163
What is a lithium treatment pack
contains a PIL, alert card and record book
- patient should always carry alert card
164
Lithium OTC interactions
- Ibuprofen
- Soluble Analgesics
- Antacids
165
Lithium and pregnancy/breast feeding
Lithium is teratogenic
- effective contraception must be used
- toxicity can occur in breastfeeding infants
166
What are extrapyramidal symptoms
increased motor tone, changes in the amount and velocity of movement, and involuntary motor activity.
167
What drugs interact with lithium to increase risk of seizures include
- Ciprofloxacin
- SSRIs
168
What drugs interact with lithium to prolonge the QT interval
- Quinolones
- SSRIs
- Marcolides
- Amiodarone
- Antipsychotics
- Theophylline
- Corticosteroids
- Loop and Thiazide Diuretics
169
What drugs interact with lithium that reduce renal excretion and what is the complication of that
- ACE inhibitors / ARB's
- NSAID's
This is because lower renal excretion allows more drug to stay in the body, increasing risk of toxicity
170
What drugs interact with lithium to cause hyponatraemia
- Diuretics
- Antidepressants
171
What drugs interact with lithium that cause higher risk of extrapyramidal symptoms
- Haloperidol
- Clozapine
- Metoclopramide
172
What drugs interact with lithium that affect salt balance
- Soluble/effervescent analgesics
- Sodium containing antacids
173
What drugs interact with lithium that cause an increased risk of neurotoxicity
- Phenytoin
- Carbamazepine
- Antipsychotics
- Amitriptyline
174
What drugs interact with lithium that increase the risk of serotonin syndrome (too much serotonin in brain)
- Sumatriptan
- SSRI's
- Amfetamines
- St Johns Wort
- Tramadol
175
What are the psychological symptoms of depression
- Low self esteem
- Worry/anxiety
- Suicidal thoughts
176
What are the physical symptoms of depression
- Lack of energy
- changes in weight/appetite
- Insomnia
177
Antidepressant mode of action
Depression is caused by the under activity of monoamine neurotransmitters. Antidepressants increase monoamine levels at the synapse
178
Depression treatment
1st Line:
SSRI's
2nd Line:
Increase SSRI dose / change SSRi
or...
Mirtazepine
3rd Line:
add another antidepressant class
or...
add augmenting agent (lithium / antipsychotic)
179
2nd Line alternative for depression treatment
- Lofepramine
- Reboxetine
- Moclobemide
- Venlafelaxine
180
Severe Refractory depression treatment
Electroconvulsive Therapy
181
Best and most safe antidepressant
SSRI
better tolerated, safer in overdose than other classes.
182
What are SSRI's the least in?
Least...
- Sedating
- Antimuscarinic
- Epileptogenic
- Cardiotoxic
183
How long do antidepressants take to work
- at least 2 weeks to work
- initial worse feeling, increased agitation and anxiety
- Review ever 1-2 weeks at the start
- Wait 4 weeks at least to see if treatment failure
184
How long to take antidepressants for
- continue for at least 6 months (12 months in elderly) after remission
- at least 12 months in anxiety disorder
- 2 years in recurrent depression
185
Side effects of Antidepressants Part 1
- Hyponatraemia (especially SSRI's and in elderly)
causes drowsiness, confusion, convulsions
186
Side effects of Antidepressants Part 2
- Suicidal Ideation and Behaviour
(at risk: children, young adults, history of suicide thoughts)
Monitor:
- for suicidal behaviour / self harm
(especially at start or change of dose)
187
Side effects of Antidepressants Part 3
Seretonin syndrome
- Neuromuscular hyperactivity
(tremors, muscle rigidity)
- Altered mental state
(agitation, confusion and mania)
- Autonomic dysfunciton
(urination, BP changes, diarrhoea, tachycardia, sweating, shivering)
188
Cautions when switching antidepressant brands
washout period required when stopping one antidepressant and starting another class.
This is to avoid serotonin syndrome
189
Washout period for Monoamine Oxidase Inhibitors (MAOIs)
2 weeks before switching
(Moclobemide is reversible so doesn't require washout period)
190
Washout period for Selective Serotonin Reuptake Inhibitors (SSRIs)
1 week before switching
(2 weeks for sertraline)
(5 weeks for Fluoxetine)
191
Washout period for Tricyclic Antidepressants (TCAs)
1 to 2 weeks before switching
(3 weeks if imipramine or Clomipramine)
192
Antidepressant abrupt withdrawal
- withdrawal symptoms occur within 5 days of stopping
- risk of withdrawal symptoms increase if taking for more than 8 weeks
- reduce dose gradually over 4 weeks
193
What two antidepressants have the highest risk of withdrawal reaction
- Paroxetine
- Venlafaxine
194
Selective Serotonin Reuptake Inhibitors (SSRIs) mode of action
selectively inhibits the reuptake of 5-HT from synaptic cleft
195
Examples of SSRIs
- Citalopram
- Escitalopram
- Fluoxetine
- Sertraline
- Fluvoxamine
- Paroxetine
196
Which SSRI is safe in MI and unstable angina
Sertraline
197
Which antidepressant is licensed for children
Fluoxetine
198
Which SSRIs causes QT prolongation
Citalopram/Escitalopram
199
SSRI side effects (GASH)
G astrointestinal disturbances
A ppetite or weight disturbances
S erotonin syndrome
H ypersensitivty reactions (stop if rashes occur)
200
Other SSRI side effects
- bleeding risk increased
- QT interval prolongation
- seizure threshold lowered
- movement disorders
201
SSRI overdose symptoms
- nausea
- vomiting
- agitation
- tremor
- drowsiness
- sinus tachycardia
- convulsions
202
What drugs interact with SSRIs to increase their plasma concentration
Grapefruit Juice (enzyme inhibitor)
203
What drugs interact with SSRIs to increase risk of bleeding
- NSAIDs
- Anticoagulants
- Anti-platelets (warfarin)
204
What drugs interact with SSRIs (especially citalopram/escitalopram) to increase risk of prolonged QT interval
- Erythromycin
- TCAs
- Sotalol
- Amiodarone
- Chloroquine
- Mefloquine
- Lithium
- Quinine
- Antipsychotics
- Theophylline
- Loop/thiazide diuretics
- corticosteroids
205
What drugs interact with SSRIs to increase risk of hyponatraemia
- Diuretics
- Desmopressin
- Carbamazepine
- NSAIDs
206
What drugs interact with SSRIs to increase risk of serotonin syndrome
- St Johns Wart
- Amfetamines
- Sumatriptan
- Selegiline
- Tramadol
- TCAs
- MAOI
- Ondansetron
207
Tricyclic Antidepressants (TCAs) and Tricyclic-Like Antidepressants mode of action
Inhibits the reuptake of 5-HT and noradrenaline. Also blocks a wide range of receptors M, H1, alpha1/2 and D2
208
Usual Dose of Tricyclic Antidepressants
once daily at night (ON)
209
Examples of Tricyclic Antidepressants
- Amitriptyline
- Clopiramine
- Dosulepin (dangerous in overdose)
- Doxepin
- Trimipramine
- Imipramine
- Lofepramine
- Nortriptylline
210
Examples of Tetracycline Antidepressants
- Mianserin
- Trazodone
211
What TCAs are used also for neuropathic pain
- Amitriptyline
- Nortriptylline
212
TCA properties compared to SSRIs
- more sedating
- more epileptogenic
- more cardiotoxic
- more antimuscarinic
213
Side effects of TCAs (TCAS acronym)
- T CAs are more toxic in overdose than SSRIs
- C ardiac side effects
- A ntimuscarinic side effects
- Seizures
214
Other TAC side effects
- hallucinations
- mania
- hypotension
- sexual dysfunction
- breast changes
215
Examples of antimusarinic side effects
- drug mouth
- blurred vision
- constipation
- tachycardia
- urinary retention
- pupil dilation
- raised intra-ocular pressure, angel closure glaucoma
216
What drugs react with TCAs to reduce plasma concentrations
Carbamazepine
217
What drugs react with TCAs to increase plasma concentrations
Cimetidine
218
What drugs react with TCAs to increase risk of
Diuretics, Desmopressin, Carbamazepine
219
What drugs react with TCAs to increase risk of QT interval prolongation
Amiodarone, Sotalol, Antipsychotics, Citalopram/Escitalopram, loop/thiazide diuretics, B2 agonsits, corticosteroids, theophylline
220
What drugs react with TCAs that increases risk of hypotension
Alpha-blockers, beta-blockers, ACEI, CCBs, Antipsychotics, Levodopa, NSAIDs, SGLT2 inhibitors (gliflozin), diuretic, Amfetamines, 5-HT1a agonists, ondansetron
221
Monoamine Oxidase Inhibitors (MAOIs)
Blocks monoamine oxidase enzymes which leads to accumulation of monoamines
222
Why are MAOIs rarely used
due to significant food and drug interactions
223
What are the two types of MAOIs
- Irreversible
- Reversible
224
Examples of Irreversible MAOIs
- Phenelzine (hepatoxicity more likely)
- Isocarboxazid (hepatoxicity more likely)
- Tranylcypromine (greatest stimulant action)
225
Examples of Reversible MAOIs
- Moclobemide (no washout period- short acting)
226
Side Effects of Monoamine Oxidise Inhibitors
- Hepatotoxicity
- Postural hypotension (discontinue if palpitations or frequent headache)
- Hypertensive crisis (stop if with headache)
227
Drugs that react with MAOIs to increase chance of hypertensive crisis
- Pseudoephedrine
- Adrenaline
- Noradrenaline
- Levodopa
- TCAs (potentially lethal)
228
How long can food/drug interactions last after stopping MAOIs
2 weeks
229
MAOIs patient counselling
- Avoid foods containing tyramine
- Eat only fresh food
- Avoid alcohol/low alcohol drinks
230
Which food contain tyramine
- mature cheese
- wine
- pickled herring
- broad bean pods
- meat stocks
- marmite
- fermented soya bean products
231
What is Benperidol used for?
Control of deviant antisocial sexual behaviour
232
What type of drug is Benperidol
Butyrophenone antipsychotic
233
What are the four dopamine pathways for schizophrenia
- Mesocorticol Pathways
- Mesolimbic Pathways
- Nigrostratal Pathway
- Tuberofundiular Pathway
234
What symptoms does under activity in the schizophrenic mesocorticol pathway produce
Negative symptoms
- social withdrawal
- poor hygiene
- apathy
- catatoia
235
What symptoms does over actvity in the schizophrenic mesolimbic pathway produce
Positive Symptoms
- hallucinations
- delusions
- disorganised speech
236
What symptoms does D2 antagonism in the schizophrenic Nigrostratal Pathway produce
Extrapyramidal symptoms
- parkinsonism
- dystonia
- dyskinesia
237
What symptoms does D2 antagonism in the schizophrenic Tuberofundiular Pathway produce
Hyperprolactinaemia
- menstruation disturbances
- galactorrhoea
- breast enlargement
- sexual dysfunction
238
Advice on doses of antipsychotic medication above the BNF upper limit
- consider alternatives
- beware of risk factors (obesity, elderly)
- consider drug interactions
- Do ECG to exclude QT prolongation (regular ECG to see if occurs)
- increase dose once weekly only
- regular BP, pulse and temp
- consider high-dose therapy for short term (stop if no improvement over 3 months)
239
How to administer antipsychotics in emergency antipsychotic episode
- IM route
- IM dose lower than oral dose
240
Prescribing antipsychotics in elderly
- in patients with dementia, increased risk of death and increased risk of stroke
- Susceptible to postural hypotension and hypo/hyper thermia
- Initial dose should be half of adult dose
- not not treat mild-moderate psychotic symptoms
241
Prescribing antipsychotics in patients with learning disabilities. if patient isn't experiencing psychotic symptoms:
- reduce dose or stop long term treatment
- review condition after dose reduced/treatment stopped
- refer to psychiatrist
- Annual documentation for reasons for continuing antipsychotics if dose not changed or stopped
242
1st Generation Antipsychotics mode of action
Blocks post-synaptic Dopamine D2 receptors in the brain
243
What is hyperprolactinaemia
abnormally high levels of the hormone prolactin (which stimulates breast milk production during and after pregnancy) in the blood
antipsychotic mediation can have this side effect
244
Different groups of 1st Generation Antipsychotics
- Phenothiazines
- Butyrophenones
- Thioxanthes
- Other
245
How many group of antipsychotics are there in Phenothiazines
3
246
Group 1 Phenothiazines (1st generation antipsychotics)
Most Sedative
- Chlorpromazoine
- Levomepromazine
- Promazine
247
Group 2 Phenothiazines (1st generation antipsychotics)
Least extrapyramidal side effects
- Pericyazine
248
Group 3 Phenothiazines (1st generation antipsychotics)
Most extrapyramidal side effects
- fluphenazine
- perphenazine
- Prochlorperazine
- Trifuloperazine
249
Examples of Butyrophenones (1st generation antipsychotics)
Most extrapyramidal side effects
- Haloperidol (QV interval prolongation)
250
Examples of Thioxanthenes (1st generation antipsychotics)
- Flupentixol (alerting effect, dont take in evening)
- Zuclopenthixol (used in aggressive patients)
251
Examples of Other 1st generation antipsychotics
- Pimozide (QT interval prolongation)
- Sulpiride
- Loxapine (bronchospasm)
252
2nd generation antipsychotics mode of action
Blocks post-synaptic Dopamine D1-D4 receptors and acts on wide range of other receptors
(produce distinct clinical side effects)
253
2nd generation antipsychotics indications
- more able to treat metabolic side effects
- maybe more effective at treating negative symptoms
254
Examples of 2nd generation antipsychotics
- Amisulpride
- Aripiprazole
- Clozapine
- Lurasidone
- Olanzapine
- Paliperidone
- Quetiapine
- Risperidone
255
Which 2nd generation antipsychotics causes the most hyperprolactinaemia
- Amisulpride
- Risperidone
256
Which 2nd generation antipsychotics does not hyperprolactinaemia
- Aripiprazole
257
Which 2nd generation antipsychotic causes the most weight gain and diabetes
- Olanzapine
- Clozapine
258
Clozapine mode of action
2nd generation antipsychotics and is the most effective
259
Clozapine uses
- resistant schizophrenia
(8 to 10 weeks)
if symptoms do not stop, measure clozapine plasma levels before adding second antipsychotic
260
If more than 2 missed doses of clozapine what needs to happen...
Treatment needs to be reinitiated by specialist
261
What drugs interact with Clozapine that increase agranulocytosis
- Aminosalicylates
- Immunosupressants (methotrexate, cytotoxic drugs)
262
What is agranulocytosis
a condition in which the absolute neutrophil count (ANC) is less than 100 neutrophils per microlitre of blood
263
Side effects of Clozapine (M)
Myocarditis and cardiomyopathy
(stop permanently)
264
What is myocarditis
inflammation of the heart muscle (myocardium). The inflammation can reduce the heart's ability to pump blood.
265
What is Cardiomyopathy
where the walls of the heart chambers have become stretched, thickened or stiff, reduce blood pumping
266
Side effects of Clozapine (A)
Agranulocytosis and neutropenia (low WCC)
Clozapine patient monitoring service = leucocyte and differential blood count
every week for 18 weeks, then every 2 weeks for 1 year, then monthly
- avoid drugs that reduce leucopoiesis
- report influenza like symptoms
267
Side effects of Clozapine (G)
Gastrointestinal obstruction
intestinal peristalsis, constipation, paralytic ileus
treat constipation
patient must report constipation
268
What are antipsychotic depot preparations and why are they used
Slow, long acting injection
(typically end in deconate)
administered every 1 to 4 weeks by IM
they are used as maintenance therapy to aid compliance
269
Aantipsychotic depot preparations considerations
- should give oral antipsychotic concomitant
270
Do not confuse with other injection preparations
IM Haloperidol deconate is used for maintenance
IM Haloperidol is used for rapid control in acute episodes
271
What needs to happen with patients with schizophrenia
physical health monitoring every year (including cardiovascular risk assessment)
272
Antipsychotic extrapyramidal symptoms
- Parkinsonism (tremors) (more common in adults and elderly)
- Akathisia (inner relentlessness (usually after large initial dose)
- Tardive dyskinesia (rhythmic involuntary movements of tongue, face, jaw)
(more common in elderly, and long term treatment or high doses)
stop when worm like tongue movements
273
Hyperprolactinaemia signs
- breast symptoms (enlargement, galactorrheoa)
- reduced bone mineral density
- menstrual irregularities
- sexual dysfunction
274
What is the only antipsychotic without the side effect of Hyperprolactinaemia
Aripiprazole
275
Antipsychotic metabolic side effects
- hyperglycaemia and sometimes diabetes
- weight gain
- Lipid changes
usually with 2nd generation antipsychotics
276
Antipsychotic sexual dysfunciton
mostly with haloperidol and Risperidone
277
Mechanisms of Sexual dysfunction
- Blocking D receptors (low libido)
- Blocking M receptors (arousal disorders)
- Blocking alpha 1 receptors
(erectile dysfunction, ejaculation problems)
278
Antipsychotic Cardiovascular side effects side effects
- Tachycardia
- Arrhythmias
- Hypotension
- QT prolongation (most risky= dose above max and IV)
need to have annual CV risk assessment
279
Antipsychotic side effects, hypotension and interference with temperature control
- elderly are especially at risk of falls, hypothermia, hyperthermia
(initial elderly dose should be half of adult dose
280
What antipsychotics can cause postural hypotension
clozapine
chloropromazine
Lurasidone
Quetiapine
281
Antipsychotic drugs side effects, neuroleptic malignant syndrome
(FATAL)
symptoms of this:
- muscle rigidity
- change in consciousness
- hyperthermia
- tachycardia
- urinary incontinence
(stop drug immediately)
(lasts 5-7 days after stopping)
282
Treatment of neuroleptic malignant syndrome
- Bromocriptine
- Dantrolene
(dopamine receptor agonists)
283
Other side effects of antipsychotic drugs
- Antimuscarinic side effects
(dry mouth, constipation, urinary retention, blurred vision)
- Blood dyscasisas (monitor with blood cell count)
- Photosensitivity (at high doses)
- Sedation
(avoid alcohol)
284
Caution with chlorpromazine (antipsychotic)
avoid direct contact, do not crush tablets and handle solutions with care
285
Pimozide (antipsychotic) caution
- prolongs QT interval
- monitor ECG before treatment and yearly
- if prolonged, stop or reduce dose
286
What drugs to not give with Pimozide
QT prolongation drugs:
- TCAs
- Antipsychotics
- Antiarrhythmics
Electrolyte imbalance causing drugs:
- Diuretics
287
Side effects of Phenothiazine antipsychotics
- Hepatotoxicity
- Acute dystonic reactions (muscle spasms, oculogric crisis (upward deviation of eye ball)
(especially girls and young women)
288
Antipsychotic drug monitoring: every year
- FBC
- Urea/Electrolytes
- LFT
- ECG
(at start then annually)
289
Antipsychotic drug monitoring: at 3 months then yearly
- blood lipids
- weight
(at start, then 3 months, then yearly)
290
Antipsychotic drug monitoring: 4-6 months then yearly
- Fasting BG level
(at start, 4-6 months, then yearly)
291
Antipsychotic drug monitoring: frequently
- BP
(at start and frequently)
292
What medications interact with antipsychotic drugs to increase QT interval
- Amiodarone
- Ciprofloxacin
- Macrolides
- Quinine
- SSRIs
293
What medications interact with antipsychotic drugs that increases risk of extrapyramidal side effects
- Metoclopramide
- Levodopa
294
What medications interact with antipsychotic drugs that increase risk of sedation and CNS depressant effects
- hypnotics (zopiclone)
- benzodiazepines
- opioids
- anti-epileptics
295
What medications interact with antipsychotic drugs to increase risk of hypotension
- anti-hypertensives
- diuretics
- nitrates
296
What medications interact with antipsychotic drugs that increases antimuscarinic effects
- TCAs
- Antihistamines
- Antimuscarinics (hyoscine)
297
What is Parkinson's Disease
Progressive loss of dopaminergic neurones. Means dopamine is deficient in nigrostriatal pathway. This pathway controls body movement
298
Symptoms of Parkinson's Disease
- Motor symtoms
(hypokinesia, bradykinesia, rigidity, postural instability)
- Non motor symptoms
(dementia, depression, sleep disturbances, speech and language change, swallowing problems
(notify DVLA)
299
Parkinson's disease treatment cautions
- Do not abruptly stop treatment
(can cause acute akinesia and Neuroleptic Malignant syndrome)
- to treat nausea and vomiting use Domperidone, not metoclopramide
300
What are the 4 types of Dopaminergic drugs
- Levodopa
- Dopamine Receptor Agonists
- MAO-B Inhibitors
- COMT Inhibitors
301
Which dopaminergic drug is associated with more motor complications
Levodopa (dopamine precursor)
302
Which dopaminergic drugs are ERGOT-derived
Dopamine Receptor Agonists
- Bromocriptine
- Cabergoline
- Pergolide
303
Which dopaminergic drugs are not ERGOT-derived
Dopamine Receptor Agonists
- Pramipexole
- Ropinirole
- Rotigotine
304
Which dopaminergic drug is Adjunct to Levodopa
COMT Inhibitors
305
Treatment of Parkinson's disease with Motor symptoms decreasing quality of life
1st Line:
Levodopa
306
Treatment of Parkinson's disease without Motor symptoms decreasing quality of life
1st Line:
- Levodopa
- Non-ERGOT derived dopamine-receptor agonists
- MAO-B inhibitors
- COMT inhibitors
307
What is dyskinesia?
involuntary, erratic, writhing movements of the face, arms, legs or trunk
308
What is refractory motor fluctuations 'off' episodes in Parkinson's
where motor symptoms are more noticeable
309
Treatment of Advanced Parkinson's Disease (refractory motor fluctuations 'off' episodes)
- Apomorphine
(SC) (intermittent injections/continuous infusion)
310
Treatment of Parkinson's disease (with severe motor fluctuations, hyperkinesia or dyskinesia)
- Levodopa-Carbidopa intestinal gel
311
Treatment of non-responsive Parkinson's disease
Deep Brain Stimulation
312
Levodopa mode of action
Levodopa is the amino acid precursor of dopamine and acts by replenishing depleted dopamine levels in the brain
(1st line parkinsons)
313
What is Co-Careldopa
Levodopa + Carbidopa
314
What is Co-Beneldopa
Levodopa + Benserazide
315
What are Peripheral Dopa-decarboxylase inhibitors
blocks conversion of levodopa to dopamine in plasma, allow more levodopa to move through BBB. Dopamine is unable to go there
- less side effects
- lower dose required for therapeutic effect
316
Side Effects of Levodopa
- Impulse control disorders (gambling, sexual behaviour)
- Excessive sleepiness and sudden onset of sleep
(can't drive)
- Motor complications
(dyskinesia=involuntary muscle movements)
- End of Dose deterioration with shorter length of benefit
(M/R forms may help)
317
Dopamine-Receptor Agonists (DRA) mode of action
Direct action on dopamine D2 receptors in striatum
(usually associated with more side effects)
318
Side effects of Ergot derived Dopamine-Receptor Agonists (DRA)
Fibrotic Reactions
(Pulmonary)
- Dyspnoea (shortness of breath)
- Persistant cough
319
Side effects of Ergot derived Dopamine-Receptor Agonists (DRA)
Fibrotic Reactions
(Retroperitoneal) (abdomen area)
- Abdominal pain
- Tenderness
320
Side effects of Ergot derived Dopamine-Receptor Agonists (DRA)
Fibrotic Reactions
(Pericardial)
- Cardiac failure
321
Side effects of Dopamine-Receptor Agonists (DRA)
overall
- Impulsive control disorders
- Excessive sleepiness
- Psychotic symptoms (hallucinations and delusions)
- Hypotensive reactions in first few days
322
MAO-B inhibitors
Inhibits monoamine oxidase B enzymes which are responsible for the breakdown of monoamines: dopamine
323
Examples of MAO-B inhibitors
- Rasagiline
- Selegiline (metabolises to amfetamine
324
What drugs interact with MAO-B inhibitors that increase risk of hypertensive crisis
- Pseudoephedrine
- Phenylephrine
- Oxymetazoline
- Nasal decongestants
- adrenaline
- noradrenaline
- methylphenidate
- amphetamines
- B2 agonists
325
COMT inhibitors mode of action
Prevents the peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to the brain
(adjunct to Levodopa)
326
Indication of COMT inhibitors
adjunct to levodopa in 'end-of-dose' motor fluctuations
327
Examples of COMT inhibitors
- Entacapone (colours urine red/brown)
- Tolcapone (hepatotoxicity) (report signs of liver toxicity)
328
What drugs interact with COMT inhibitors to increase cardiovascular effects
- Adrenaline
- Noradrenaline
- MAOIs
