Neurodegnerative Diseases Flashcards
Which drugs cause Parkinson like symptoms
Haloperidol
Metoclopramide
Valproate
Chlorpromazine
What is the first line drug for Parkinson’s disease
L-DOPA
What converts L DOPA to dopamine in the substantia nigra
It gets decarboxylated by DOPA decarboxylase
L DOPA side effects
Nausea, vomiting, cardiac arrhythmias, hypotension
CNS: anxiety confusion and hallucinations
What is wearing off syndrome
Happens in chronic use of LDOPA and can cause dyskaniesia and akaniesia
What happens over time with L DOPA use
The therapeutic window narrows leading to on and off phenomenon
Who is L DOPA contraindicated in
Psychotic patients
How to improve bioavailability of L DOPA
we administer it with Carbidopa -> drops peripheral side effects
What’s the % of L dopa reaching the brain with and without Carbidopa
Without 1-3%
With 5-10%
What’s the major peripheral pathway of L DOPA breakdown after
COMT
What are the COMT inhibitors
Tolcapone and entacapone
Which COMT inhibitor enters the CNS
tolcapone
Which COMT INHIBITR has long half life
Tolcapone
What are the adverse effects of tolcapone
Hepatotoxic
What are the MAO B inhibitors
selegiline and rasagiline
Extra safinamide
Which MAO B inhibitor is more potent
Rasagiline
What happens when selegiline is metabolised
It is converted to amphetamines
What is the initiation therapy for Parkinson’s disease
Dopamine receptor agonist
What’s the drug combination in advanced Parkinson’s
Carbidopa/LDOPA + D2 agonist
Which D2 agonist isn’t used any more
Bromocriptine as it has a lot of side effects
Which D2 agonist is used for restless leg syndrome
Ropinirole
Long term use of bromocriptine side effects
Vasospasm in patients with peripheral vascular disease
Pulmonary and retroperitoneal fibrosis
Which anti muscarinic agents are used in the treatment of Parkinson’s
Benztropine and trihexphnidyl
What are Benztropine and trihexphnidyl contraindications
BPH and GLUCOMA
What’s the mechanism of action of amantadine
Enhances effects of endogenous dopamine and inhibits cholinergic receptors
When is LDOPA TAKEN
30 mins before food to avoid food competing with L DOPA. Absorption
L DOPA drug interactions
With Vitamin B6 it increases peripheral breakdown
What happens in Alzheimer’s disease
Neuronal loss in the temporal lobe including entraorhinal cortex and hippocampus
What ACHE inhibitors are used in Alzheimer’s
Donepezil
Galantamine
Rivastigmine
Which ACHE inhibitor is given oral and indicated for Parkinson’s dementia
Rivastigmine (only one not metabolised by CYP 450)
Which ACHE inhibitor is given as a transdermal patch for people who can’t with the side effects
Rivastigmine
ACHE inhibitors side effects
Bradycardia and bronchoconstriction
Nause, vomiting and diarrhoea
Mechanism of action of NMDA antagonist
Prevent NMDA receptors excite toxicity
Which NMDA inhibitor is used for Alzheimer’s
MEMANTINE
MEMANTINE mechanism of action
Non competitive NMDA type glutamate receptor antagonist blocking Ca2+ influx into neurons
NMDA antagonist can it be used as monotherapy
Yes or with ACHE Inhibitors
What is Huntington’s disease
It’s an inherited neurological disorder
-Movement disorder due to defect in basal ganglia
What happens in Huntington’s disease
Over activity of dopamine due to imbalance decrease of ACH and GABA which antagonise DOPAMINE
Drugs that deplete the central dopamine store by blocking entry to neurone storage vesicles
Roseripine and tetrabanzine
Drugs that block dopaminergic receptors
Phenothiazines and butyrophenones and haloperidol
AE : Parkinsonism and restlessness
What is bipolar disorder
Mood shift between two extremes depression and mania (euphoria)
What’s used in the treatment of bipolar disorder
Mood stabilisers mainly LITHIUM
What anticonvulsants are used to treat bipolar disorder
Carbamazepine
Valproate
Gabapentin
Lamotrigine
When are anticonvulsants used instead of lithium
When lithium does not work or is not sutiable
Lithium onset of action
7-10 days
Is lithium eliminated by the liver
No it’s not
What is mediated lithium effect
IP3 and DAG
Lithium indications
Acute mania
Prophylaxis of BPD
mania/hypo mania- depression
Lithium therapeutic index
Narrow
Can cause goiter (hypothyroidism) edema, teratogenic
What’s an alternative to lithium
Carbamazepine-P450 inducer
Carbamazepine side effects
Can cause agranulocytosis leukopenia
What’s the most sedating antidepressant
Doxepin
