DEMENTIA & ALZHEIMERS
OVERVIEW:
- Alzheimer’s disease (AD) is the most common cause of dementia
- DEMENTIA: a group of neurological symptoms:
o Memory impairment: e.g. forgetting names, faces, recent events
o Becoming easily confused: esp in unfamiliar environments
o Tasks requiring planning become increasingly more difficult
o Becoming more withdrawn/anxious
o Having difficulty thinking: e.g. hard to find the right word
All these symptoms make it difficult for pts to function INDEPENDENTLY – pts with severe
dementia need help w/ daily tasks e.g. dressing & shopping
ALZHEIMERS:
- AD is a neurodegenerative disease: loss of CNS neurons – this is progressive AND
irreversible (but this is NOT a normal part of ageing) – can progress to DEATH
- AD characterised by a lack of ACh in CNS
Alzheimer’s Disease = Acetylcholine Down
ACETYLCHOLINESTERASE INHIBITORS (AChEis) – Donepezil, Galantamine,
Rivastigmine
OVERVIEW:
- 1st line drugs in MILD-MODERATE AD
- MOA: Inhibit AChE in the CNS increased conc. & duration of action of ACh
- SIDE EFFECTS: Pro-cholinergic effects:
o Increased fluid production: e.g. lacrimation, saliva, sweat
o Bronchospasm: cautionary use in asthma/COPD
o Bradycardia: due to increased PS activity in heart
o Urinary incontinence: due to increased PS activity in bladder
o Muscle cramping: XS ACh activates/contracts skeletal muscles (at
neuromuscular junction) muscle weakness
As AD progresses, the amount of ACh available in CNS DECLINES, so the efficacy of the
AChEis also DECLINES (as there’s less ACh for the AChE enzyme to degrade)
NMDA RECEPTOR ANTAGONISTS – Memantine, Ketamine
OVERVIEW:
- 2nd line drug used in MODERATE-SEVERE AD – or where 1st line is CI/not tolerated
- MOA: antagonises the NMDA receptor (a glutamate-receptor subtype) to reduce
glutamate activity in CNS – memantine also has effects on ACh)
Anti-dementia drugs do NOT treat the disease – but simply slow the progression of
neurodegeneration (since it’s irreversible)
, EPILEPSY AND SEIZURE DISORDERS
OVERVIEW:
- Monotherapy is preferred method of treatment – using multiple AEDs increases
interaction risk and ADR risk
- When switching from one AED to another – ensure the old AED is GRADUALLY
WITHDRAWN and the new AED is GRADUALLY INTRODUCED
EPILEPSY VS SEIZURES:
- Seizure: a SINGLE occurrence of synchronised overexcitation in the CNS (can often
be PROVOKED e.g. by drug overdose, drug interactions, tumours)
- Epilepsy: pt is termed ‘epileptic’ when they have 2 OR MORE UNPROVOKED seizures
i.e. the underlying cause of that overexcitation was unknown
TYPES OF GENERALISED SEIZURES (GS)
DEFINITIONS:
- GS: involves overexcitation in the ENTIRE BRAIN (in contrast to focal seizures – only
involves part of the brain) – always leads to the pt. becoming UNCONSCIOUS
- TONIC: sudden stiffening of muscles
- CLONIC: rhythmic jerking/spasming of muscles
GS SEIZURE TYPES (In order of how common they are)
1- Tonic-Clonic: Initial tonic phase followed by clonic phase (lasts few mins)
2- Absence: loss of awareness of surroundings (staring blankly into space) – 15 seconds
3- Clonic: rhythmic spasming WITHOUT tonic
4- Tonic: PROLONGED contraction of all muscles WITHOUT clonic
5- Myoclonic: a very SUDDEN spasm of a single muscle/group of muscles
6- Atonic: complete LOSS of all muscle control fall
RISK-BASED CATEGORIES OF AEDs:
- AEDs can be classified into 3 categories to determine whether the SAME BRAND
needs to be prescribed/dispensed
- This only applies to AEDs being used in epilepsy (NOT for other indications e.g.
neuropathic pain, migraine prophylaxis, BPD)
THREE CATEGORIES:
- CATEGORY 1 (C3P)– Maintain SAME brand (alternatively prescribers can prescribe
generic and write the manufacturer’s name beside it)
Carbamazepine, Phenytoin, Phenobarbital, Primidone
- CATEGORY 2 – Use PRESCRIBER’S clinical judgment & patient consultation to assess
need to maintain same brand
Valproate, Lamotrigine, Topiramate, Zonisamide (can cause fatal
HEAT STROKE – adequate hydration), Clobazam, Clonazepam
- CATEGORY 3 – Do NOT NEED to maintain same brand
Levetiracetam, Lacosamide, Ethosuximide, Pregabalin, Gabapentin
,TREATMENT CESSATION:
- Cessation must be GRADUAL (over about 6 months) and NOT ABRUPT
- Abruptly stopping treatment MORE SEIZURES (esp true of BARBTURATES e.g.
phenobarbital & BENZOS e.g. clobazam)
- If combination therapy needs to be stopped, gradually stop 1 DRUG AT A TIME
DRIVING WITH EPILEPSY:
- Epileptics can drive a vehicle (but not a large goods vehicle/LGV) if:
o They’ve been seizure-free for ONE YEAR
o They’ve only had seizures whilst asleep for the last THREE YEARS
- The patient will be banned for SIX MONTHS from driving if:
o They’ve been put on a new AED
o They’ve been put on a new dose of existing AED (including withdrawal)
o They’ve completely stopped taking their AEDs
AEDs & PREGNANCY:
- ALL Category 1 AEDs are TERATOGENIC
- SOME Category 2 AEDs are TERATOGENIC:
o Valproate: MOST teratogenic of ALL AEDs – requires PPP
in women of CBP
o Topiramate: child is 3x more likely to develop CLEFT
LIP/PALATE when mother takes topiramate in 1st trimester
- Just like epilepsy in non-pregnant patients, lowest-effective dose
of MONOTHERAPY is recommended here
- The two safest AEDs in pregnancy: If an epileptic woman wants to get
o Levetiracetam (Category 3 - Keppra) pregnant, offer 5mg folic acid, not
o Lamotrigine (Category 2 - Lamictal) 400mcg (for non-epileptics) due to
higher risk of neural tube defects
AEDs & BREASTFEEDING:
- BF is encouraged if the mother is on monotherapy – always safest to feed BEFORE
dosing (as plasma-concentrations will be at their lowest)
- BF-child monitoring requirements:
o Adequate weight gain
o Developmental milestones (e.g. first steps, emotional expression etc.)
o Sedation
- If the child is experiencing ADRs – then formula feeds should be introduced OR wean
child off breastmilk
The MOST teratogenic AED (Valproate) and LEAST teratogenic AED (Lamotrigine) belong in
the SAME category (2)
ALL AEDs are SAFE to use in BF, but not all are safe in pregnancy
, SODIUM VALPROATE (SV) – Epilim
INDICATIONS:
- 1st line in ALL TYPES of seizures
- Acute & chronic management of bipolar disorder
- 2nd line treatment in STATUS EPILEPTICUS (where benzos haven’t worked)
- Migraine prophylaxis (UNLICENSED)
MOA:
- Inhibitor of VG-Na+ channels Combination of these effects LESS
- Increases GABA activity in CNS uncontrolled excitation in CNS
SIDE EFFECTS: ‘vALPrOate - AL PrO’
- Anaemia & Agranulocytosis (bleeding, infection risk)
- Liver toxicity (jaundice, dark urine, abdominal pain)
- Pancreatitis (jaundice, weight-loss, steatorrhea)
- rO = Spina bifida: a defect of the neural tube (the structure
that develops into the baby’s brain & spinal cord) – results in
a hOle in the spinal cord – occurs when mother takes SV
during pregnancy
IMPORTANT POINTS:
- Generally, SV is 1st Line AED in most seizure types, but NOT in WOCBP
- If SV must be used in WOCBP, then she must adhere to the PPP
PHENYTOIN
INDICATIONS:
- ALMOST ALL TYPES of seizure
- Do NOT use in Absence or Myoclonic seizures (makes them worse)
- 2nd line treatment in STATUS EPILEPTICUS (where benzos haven’t worked)
MOA: Inhibits VG-Na+ ion channels (SAME as SV – but NO GABA action)
SIDE EFFECTS: ‘HOT MA’
- Hypertrophy of gums AND Hirsutism
- Osteomalacia (AKA rickets in children) – softening of bones deformities
- Teratogenicity
- Megaloblastic anaemia (e.g. B12 or folate-deficiency)
- Ataxia – lack of skeletal muscle control speech and gait abnormalities
PHARMACOKINETICS:
- Unlike most drugs (which follow 1st order kinetics),
phenytoin follows ZERO-ORDER KINETICS:
- Rate of elimination remains constant regardless of
the dose/[plasma-drug]
Thus, phenytoin is a NTI drug, as small changes in dose can have a large impact on
plasma levels TOXICITY (so requires STRICT MONITORING of plasma levels)
OVERVIEW:
- Alzheimer’s disease (AD) is the most common cause of dementia
- DEMENTIA: a group of neurological symptoms:
o Memory impairment: e.g. forgetting names, faces, recent events
o Becoming easily confused: esp in unfamiliar environments
o Tasks requiring planning become increasingly more difficult
o Becoming more withdrawn/anxious
o Having difficulty thinking: e.g. hard to find the right word
All these symptoms make it difficult for pts to function INDEPENDENTLY – pts with severe
dementia need help w/ daily tasks e.g. dressing & shopping
ALZHEIMERS:
- AD is a neurodegenerative disease: loss of CNS neurons – this is progressive AND
irreversible (but this is NOT a normal part of ageing) – can progress to DEATH
- AD characterised by a lack of ACh in CNS
Alzheimer’s Disease = Acetylcholine Down
ACETYLCHOLINESTERASE INHIBITORS (AChEis) – Donepezil, Galantamine,
Rivastigmine
OVERVIEW:
- 1st line drugs in MILD-MODERATE AD
- MOA: Inhibit AChE in the CNS increased conc. & duration of action of ACh
- SIDE EFFECTS: Pro-cholinergic effects:
o Increased fluid production: e.g. lacrimation, saliva, sweat
o Bronchospasm: cautionary use in asthma/COPD
o Bradycardia: due to increased PS activity in heart
o Urinary incontinence: due to increased PS activity in bladder
o Muscle cramping: XS ACh activates/contracts skeletal muscles (at
neuromuscular junction) muscle weakness
As AD progresses, the amount of ACh available in CNS DECLINES, so the efficacy of the
AChEis also DECLINES (as there’s less ACh for the AChE enzyme to degrade)
NMDA RECEPTOR ANTAGONISTS – Memantine, Ketamine
OVERVIEW:
- 2nd line drug used in MODERATE-SEVERE AD – or where 1st line is CI/not tolerated
- MOA: antagonises the NMDA receptor (a glutamate-receptor subtype) to reduce
glutamate activity in CNS – memantine also has effects on ACh)
Anti-dementia drugs do NOT treat the disease – but simply slow the progression of
neurodegeneration (since it’s irreversible)
, EPILEPSY AND SEIZURE DISORDERS
OVERVIEW:
- Monotherapy is preferred method of treatment – using multiple AEDs increases
interaction risk and ADR risk
- When switching from one AED to another – ensure the old AED is GRADUALLY
WITHDRAWN and the new AED is GRADUALLY INTRODUCED
EPILEPSY VS SEIZURES:
- Seizure: a SINGLE occurrence of synchronised overexcitation in the CNS (can often
be PROVOKED e.g. by drug overdose, drug interactions, tumours)
- Epilepsy: pt is termed ‘epileptic’ when they have 2 OR MORE UNPROVOKED seizures
i.e. the underlying cause of that overexcitation was unknown
TYPES OF GENERALISED SEIZURES (GS)
DEFINITIONS:
- GS: involves overexcitation in the ENTIRE BRAIN (in contrast to focal seizures – only
involves part of the brain) – always leads to the pt. becoming UNCONSCIOUS
- TONIC: sudden stiffening of muscles
- CLONIC: rhythmic jerking/spasming of muscles
GS SEIZURE TYPES (In order of how common they are)
1- Tonic-Clonic: Initial tonic phase followed by clonic phase (lasts few mins)
2- Absence: loss of awareness of surroundings (staring blankly into space) – 15 seconds
3- Clonic: rhythmic spasming WITHOUT tonic
4- Tonic: PROLONGED contraction of all muscles WITHOUT clonic
5- Myoclonic: a very SUDDEN spasm of a single muscle/group of muscles
6- Atonic: complete LOSS of all muscle control fall
RISK-BASED CATEGORIES OF AEDs:
- AEDs can be classified into 3 categories to determine whether the SAME BRAND
needs to be prescribed/dispensed
- This only applies to AEDs being used in epilepsy (NOT for other indications e.g.
neuropathic pain, migraine prophylaxis, BPD)
THREE CATEGORIES:
- CATEGORY 1 (C3P)– Maintain SAME brand (alternatively prescribers can prescribe
generic and write the manufacturer’s name beside it)
Carbamazepine, Phenytoin, Phenobarbital, Primidone
- CATEGORY 2 – Use PRESCRIBER’S clinical judgment & patient consultation to assess
need to maintain same brand
Valproate, Lamotrigine, Topiramate, Zonisamide (can cause fatal
HEAT STROKE – adequate hydration), Clobazam, Clonazepam
- CATEGORY 3 – Do NOT NEED to maintain same brand
Levetiracetam, Lacosamide, Ethosuximide, Pregabalin, Gabapentin
,TREATMENT CESSATION:
- Cessation must be GRADUAL (over about 6 months) and NOT ABRUPT
- Abruptly stopping treatment MORE SEIZURES (esp true of BARBTURATES e.g.
phenobarbital & BENZOS e.g. clobazam)
- If combination therapy needs to be stopped, gradually stop 1 DRUG AT A TIME
DRIVING WITH EPILEPSY:
- Epileptics can drive a vehicle (but not a large goods vehicle/LGV) if:
o They’ve been seizure-free for ONE YEAR
o They’ve only had seizures whilst asleep for the last THREE YEARS
- The patient will be banned for SIX MONTHS from driving if:
o They’ve been put on a new AED
o They’ve been put on a new dose of existing AED (including withdrawal)
o They’ve completely stopped taking their AEDs
AEDs & PREGNANCY:
- ALL Category 1 AEDs are TERATOGENIC
- SOME Category 2 AEDs are TERATOGENIC:
o Valproate: MOST teratogenic of ALL AEDs – requires PPP
in women of CBP
o Topiramate: child is 3x more likely to develop CLEFT
LIP/PALATE when mother takes topiramate in 1st trimester
- Just like epilepsy in non-pregnant patients, lowest-effective dose
of MONOTHERAPY is recommended here
- The two safest AEDs in pregnancy: If an epileptic woman wants to get
o Levetiracetam (Category 3 - Keppra) pregnant, offer 5mg folic acid, not
o Lamotrigine (Category 2 - Lamictal) 400mcg (for non-epileptics) due to
higher risk of neural tube defects
AEDs & BREASTFEEDING:
- BF is encouraged if the mother is on monotherapy – always safest to feed BEFORE
dosing (as plasma-concentrations will be at their lowest)
- BF-child monitoring requirements:
o Adequate weight gain
o Developmental milestones (e.g. first steps, emotional expression etc.)
o Sedation
- If the child is experiencing ADRs – then formula feeds should be introduced OR wean
child off breastmilk
The MOST teratogenic AED (Valproate) and LEAST teratogenic AED (Lamotrigine) belong in
the SAME category (2)
ALL AEDs are SAFE to use in BF, but not all are safe in pregnancy
, SODIUM VALPROATE (SV) – Epilim
INDICATIONS:
- 1st line in ALL TYPES of seizures
- Acute & chronic management of bipolar disorder
- 2nd line treatment in STATUS EPILEPTICUS (where benzos haven’t worked)
- Migraine prophylaxis (UNLICENSED)
MOA:
- Inhibitor of VG-Na+ channels Combination of these effects LESS
- Increases GABA activity in CNS uncontrolled excitation in CNS
SIDE EFFECTS: ‘vALPrOate - AL PrO’
- Anaemia & Agranulocytosis (bleeding, infection risk)
- Liver toxicity (jaundice, dark urine, abdominal pain)
- Pancreatitis (jaundice, weight-loss, steatorrhea)
- rO = Spina bifida: a defect of the neural tube (the structure
that develops into the baby’s brain & spinal cord) – results in
a hOle in the spinal cord – occurs when mother takes SV
during pregnancy
IMPORTANT POINTS:
- Generally, SV is 1st Line AED in most seizure types, but NOT in WOCBP
- If SV must be used in WOCBP, then she must adhere to the PPP
PHENYTOIN
INDICATIONS:
- ALMOST ALL TYPES of seizure
- Do NOT use in Absence or Myoclonic seizures (makes them worse)
- 2nd line treatment in STATUS EPILEPTICUS (where benzos haven’t worked)
MOA: Inhibits VG-Na+ ion channels (SAME as SV – but NO GABA action)
SIDE EFFECTS: ‘HOT MA’
- Hypertrophy of gums AND Hirsutism
- Osteomalacia (AKA rickets in children) – softening of bones deformities
- Teratogenicity
- Megaloblastic anaemia (e.g. B12 or folate-deficiency)
- Ataxia – lack of skeletal muscle control speech and gait abnormalities
PHARMACOKINETICS:
- Unlike most drugs (which follow 1st order kinetics),
phenytoin follows ZERO-ORDER KINETICS:
- Rate of elimination remains constant regardless of
the dose/[plasma-drug]
Thus, phenytoin is a NTI drug, as small changes in dose can have a large impact on
plasma levels TOXICITY (so requires STRICT MONITORING of plasma levels)
