Central Nervous System Part 1 Flashcards
How is dementia caused?
when the brain is damaged by disease such as Alzheimer’s, strokes or Parkinson’s
What are the Cognitive symptoms of Dementia
- Memory Loss
- difficulties thinking/concentrating
- difficulties finding the right word
- Losing track of date
What are the Non-cognitive symptoms of dementia
- psychiatric and behavioural problems
- difficulty with daily activities
Management of cognitive symptoms
(mild-moderate Alzheimer’s symptoms)
Acetylcholinesterase Inhibitors
- Donepazil
- Galantamine
- Rivastigmine
Donepazil interactions in Dementia
Concomitant use with Antiphycotics increased risk of Neuroleptic Malignant Syndrome
What is Neuroleptic Malignant Syndrome
fever, altered mental status, muscle rigidity, and autonomic dysfunction.
Galantamine cautions
Stop at first sight of skin rash or skin reactions
Rivastigmine forms
Rivastigmine causes GI symptoms, withhold until solved
Transdermal Patches cause less GI Disturbances
Management of cognitive symptoms
(moderate to severe Alzheimer’s symptoms)
NMDA Glutamate Receptor Antagonists
Memantine
Cholinergic Effects Anagram
DUMB BELLS
Cholinergic Effects Anagram D
Diarrhoea
Cholinergic Effects Anagram U
Urination
Cholinergic Effects Anagram M
Muscle weekness, cramps and Miosis
Cholinergic Effects Anagram B
Bronchospasm
Bradycardia
Cholinergic Effects Anagram E
Emesis (vomiting)
Cholinergic Effects Anagram L
Lacrimation (teary eyes)
Cholinergic Effects Anagram S
Salivation and sweating
Management of Non-cognitive symptoms in Dementia
Antipsychotic Drugs
(Severe)
Antipsychotics in elderly Dementia patients cautions
increased risk of stroke and death
assess benefits taking into account patient history of stroke/heart attack, diabetes and smoking
Non-Cognitive symptom treatment in Dementia (extreme violent behaviour)
Oral Benzodiazepines
or…
Antipsychotics
If intramuscular needed, use: (haloperidol, olanzapine, lorazepam)
Non-Cognitive symptom treatment in Dementia treatment (Dementia with Lewy bodies)
Lewy bodies are clumps of protein forming inside brain cells
(also found in parkinson’s disease)
Treatment:
Acetylcholinesterase Inhibitors (rivastigmine)
What is Epilepsy
a sudden surge of electrical activity of neurons in the brain
What are the 2 types of Non-epileptic seizures
Organic: hypoglycaemia / fever
Psychogenic:
mental processes (distressing thoughts)
Drug dose of most anti-epileptic dugs
twice daily
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)
Drugs used to treat seizures Part 2
- Levetiracetam
- Phenytoin (long half life ON)
- Sodium Valproate
- Topiramate
Drugs used to treat seizures Part 3
- Lacosamide
- Perampanel
- Rufinamide
- Tiagabine
- Vigabatrin
- Zonisamide
Types of Epileptic Seizures
- Focal partial seizures with / without secondary generalisation
- Tonic-clonic seizures
- Absence Seizures
- Myoclonic Seizures
- Atonic / Tonic Seizures
Focal Partial Seizures treatment (with/without secondary generalisation)
1st Line:
Lamotrigine or Carbamazepine
Alternative:
Levetiracetam, Valproate or Oxcarbazepine
Tonic-Clonic Seizures treatments (generalised)
1st Line:
Valproate or Carbamazepine
Alternative:
Lamotrigine
Absence Seizures treatments (generalised)
1st Line:
Ethosuximide or Valproate
Alternative:
Lamotrigine
Myoclonic Seizures (generalised)
1st Line:
Valproate
Alternative:
Topiramate, Levetiracetam
Atonic/Tonic Seizures (generalised)
1st Line:
Valproate
Some Anti-epileptic Drugs caution
potential harm when switching between different brands for epilepsy CATEGORY 3
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
Epilepsy Drugs Category 1 Examples
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
Epilepsy Drugs Category 2 Examples
- Valproate
- Lamotrigine
- Clonazepam
- Topiramate
Epilepsy Drugs Category 3 Examples
- Levetiracetam
- Gabapentin
- Pregabalin
- Ethosuximide
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
Epilepsy and Driving:
Your license will be taken away if you have
- epileptic seizures while awake and lost consciousness
Anti-epileptic Drugs and Pregnancy
- increased risk of teratogenicity
- reduces effectiveness of hormonal contraception (Carbamazepine)
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
What do anti-epileptic drugs have a risk of causing during pregnancy
Minor and major congenital malformations and long term development disorders
Which anti-epileptic drugs need to be dose adjusted due to changing drug plasma concentrations during pregnancy
Phenytoin
Carbamazepine
Lamotrigine
Which anti-epileptic drugs do you need to monitor foetal growth with
Topiramate
Levetiracetam
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
What is neural tube defect
occurs when the neural tube does not close properly
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
What must you do if you are a woman planning on getting pregnant while on epilepsy medication
Notify the uk epilepsy and pregnancy register
What is neonatal haemorrhage
a bleeding problem that occurs in a baby during the first few days of life
What reduces the risk of neonatal haemorrhage
Vitamin K injection in newborn
Which anti-epileptic medication can cause withdrawal effects in newborns
Benzodiazepines and phenobarbital
What to monitor on a baby during anti-epileptic drugs and breastfeeding
Drowsiness, weight gain, feeding difficulty, adverse effect, developmental milestones
Which anti-epileptic medication is present in high concentrations in breast milk
Lamotrigine
Zosinamide
Ethosuximide
Primidone
What anti-epileptic drug accumulates due to baby slow metabolism
Phenobarbital
Lamotrigine
What anti-epileptic drug inhibits sucking reflex
Phenobarbital
Primidone
What anti-epileptic drug increases risk of drowsiness in infants
Benzodiazepines
Phenobarbital
Primidone
What anti-epileptic drug should you avoid abrupt withdrawal of breastfeeding with
Phenobarbital
Primidone
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
Anti-epileptic drug side effects:
Suicidal Behaviour
report any mood changes, distressing thoughts or feelings of suicide
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
What is Toxic Epidermal Necrosis
extensive exfoliation of the epidermis and mucous membrane, which may result in sepsis and death
What is Steven-Johnson syndrome
blistering and peeling of the skin and surfaces of the eyes, mouth and throat
What is Blood Dycrasias
any condition that affects the blood, bone marrow, or lymph tissue.
Anti-epileptic drug side effects:
Blood Dycrasias
C Vet Plz Acronym
Ethosuximide, Valproate, Carbamazepine, Phenytoin, Lamotrigine, Topiramate,
Zonisamide
Anti-epileptic drug side effects:
Eye Problems
Vigabatrin:
visual field deflects
Topiramate:
Acute myopia with secondary angle closure glaucoma
Anti-epileptic drug side effects:
Encephalopathic Symptoms
Vigabatrin
Marked sedation, stupor and confusion
withdraw or reduce dose
Anti-epileptic drug side effects:
Severe Respiratory Depression
Gabapentin
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
Anti-epileptic enzyme inducers (Carbamazepine, Phenytoin, Phenobarbital) interaction with interaction with oral contraceptives and warfarin…
decreases drug plasma concentration
Phenytoin (high risk drug as narrow therapeutic index) mode of action
binds to neuronal sodium channels in their inactive state; prolonging inactivity
What is phenytoin used for…
focal seizures and generalised tonic-clonic seizures. Exacerbates absence and myoclonic seizures (avoid)
Phenytoin therapeutic ranges…
10-20mg/L
or
40-80mcg/L
Neonate Phenytoin therapeutic ranges…
(below 3 months)
6-15mg/L
or
25-60mcg/L
Phenytoin has non-linear relationship between doses and drug plasma concentration, which means
Small change in dose/drug absorption
Large change in plasma concentration
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
States of low protein binding in people
- pregnancy
- children (neonates)
- elderly
- liver failure
Symptoms of Phenytoin toxicity
- Slurred Speech
- Nystagmus (uncontrolled repetitive eye movements)
- Ataxia
- Confusion
- Hyperglycaemia
- Diplopia (double vision)
Phenytoin brand cautions
- Phenytoin is risk 1 category epileptic drug
— Different oral formulations vary in bioavailability
Switching between phenytoin products
Phenytoin sodium is not the sane bioavailability as phenytoin base
100mg Phenytoin Sodium = 92mg Phenytoin base
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
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
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)
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)
Phenytoin Sodium and Fosphenytoin dose equals
Fosphenytoin 1.5mg
Phenytoin Sodium 1mg
give fesphenytoin only IV and IM
Drugs that interact with Phenytoin to increase plasma concentration
Amiodarone, Cimetidine, miconazole, fluconazole, chloramphenicol,
Diltiazem,
Valproate, trimethirprom
Drugs that interact with Phenytoin to reduce its drug concentration
Therapeutic failure
St John’s Wort,
Rifampicin
Drugs that interact with Phenytoin to antagonise its anticonvulsant effects
- Quinolones
- Tramadol
- Mefloquine
- SSRI’s
- Antipsychotics
Carbamazepine (narrow therapeutic drug) mode of action
Inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability
What is Carbamazepine used for
First line in focal seizures, generalised tonic-clonic seizures. Exacerbates atonic, clonic and myoclonic seizure
Carbamazepine dose therapeutic range
4-12mg/L
or
20-50mcg/L
(monitor plasma conc after 1 to 2 weeks)
Symptoms of Carbamazepine Toxicity
- Incoordination
- Hyponatraemia
- Ataxia (lack of voluntary muscle movement)
- Nystamus
- Drowsiness
- Blurred vision
- Arrhythmias
- Gastro-intestinal disturbances
Side Effects of Carbamazepine Part 1
- blood diseases
(report signs of infection, fever, sore throat) - Hepatotoxicity
(report signs of liver toxicity, dark urine, jaundice)
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
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)
What drugs interact with Carbamazepine to increase plasma concentration
- Cimetidine
- Macrolides
- Miconazole
What drugs interact with Carbamazepine reduce plasma conc
St John’s Wort
Phenytoin
What drugs interact with Carbamazepine to reduce anticonvolsant effect
Quinolones
SSRI’s
Antipsychotics
What drugs interact with Carbamazepine to increase risk of hypontraemia
- Aldosterone Antagonists (spironolactone, Eplerenone)
- SSRI’s
- Diuretics
- NSAID’s
What drugs interact with Carbamazepine to increase risk of hepatotoxicity
- tetracyclines
- sulfasalazine
- sodium valproate
- methotrexate
- fluconazole
- alcohol
Carbamazepine reduces the effects of ..
- Warfarin
- HRT and hormonal contraceptives
Sodium Valproate mode of action
weak inhibitor of neuronal sodium channels, stabilises resting membrane potentials and reduces neuronal excitability
Sodium Valproate indications
first line in all types of generalised seizures
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
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
Pregnancy Prevention Programme contraception
- Implants, IUDs, Sterilisation
- 2 complementary forms of contraception:
pill + barrier method + regular pregnancy tests
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
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)
Sodium valproate reaction with these drugs to reduce its anticonvulsant effects
Quinolones, SSRIs, Mefloquine
Sodium valproate reaction with these drugs to increase risk of hepatotoxicity
Statins, Carbamazepine, Tetracylines, fluconazole, itraconazole, methotrexate, sulfasalazine
Sodium valproate reaction with these drugs, increasing its plasma conc
lamotrigine, phenobarbital (other anti-epileptic)
What is status epilepticus
Epileptic fits follow one after the other without regaining consciousness
Convulsive status epilepticus treatment
IV Lorazepam
(avoid IV Diazepam as it causes thrombophlebitis)
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
What is a Febrile convulsion
Convulsion in child with high temp of 38’C or higher
Febrile convulsion treatment
if < 5 mins:
- Paracetamol
if >5 mins:
- IV Lorazepam
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
Anxiety Psychological Symptoms
- Restlessness
- Worry
- Fear
- Difficulty concentrating
- Irritability
Anxiety Physical Symptoms
- Palpitations
- muscle aches and tension
- trembling
- sweating
- shortness of breath
- insomnia
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)
Other medication to treat Anxiety
- Antidepressants
- Antiphycotics
- Meprobamate (license cancelled as serious CNS damage)
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
Benzodiazepines examples
- Clobazam (long acting)
- Diazepam (long)
- Lorazepam (short)
- Oxazepam (short)
- Alprazolam (long)
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)
Benzodiazepine dependance
- Avoid long term use, and abrupt withdrawal
Benzodiazepine long term use and abrupt withdrawal symptoms
- Toxic psychosis
- Confusion
- Delirium
Benzodiazepine withdrawal symptoms
increased anxiety, insomnia, weight loss, tremors, sweating, loss of appetite, tinnitus, perceptual disorders
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
Drugs that interact with Benzodiazepines which increase sedation and CNS depressant effects
Alcohol, Opioids, antihistamines, antidepressants, barbiturates, antipsychotics
Drugs that interact with Benzodiazepines that increase its plasma conc
Amiodarone, diltiazem, macrolides, fluconazole
ADHD symptoms
- hyperactivity
- impulsivity
- inattention