L33. Drugs used in neurological disorders I →↑↓ Flashcards
Mechanism, Contraindication, S/E of Dopamine Precurosr Levo-dopa (L-Dopa)
High Therapetuic index
Mechanism
Readily transported into the CNS and →converted to dopamine in the brain by DOPA decarboxylase
Well absorbed from the GI tract
Extremely short half-life
Contraindication with given L-dopa
Nonselective MAO inhibitors (e.g. phenelzine)
→Resulting in excess dopamine in the periphery, which could lead to a life-
threatening hypertensive crisis
Pyridoxine (Vitamin B6)
→Increasing peripheral breakdown of L-dopa
Antipsychotics
Blocking dopamine receptors and causing parkinsonian-like symptoms
Adverse (side) Effects
Due to the conversion of L-dopa to dopamine in the periphery
→Nausea
→ Vomiting
→ Arrhythmias
→ Postural (orthostatic) hypotension: on standing or sitting up
Due to overstimulation of central dopamine receptors
Dyskinesia: presence of involuntary movements
→ Hallucination
→ Restlessness
→ Confusion
Mechanism, Contraindication, S/E of Carbidopa
peripheral DOPA decarboxylase inhibitor
Administered with L-dopa (L-dopa + carbidopa in 4:1 ratio known
as SINEMET®)
→ To reduce the metabolism of L-dopa in the periphery
→To increase the availability of dopamine to the CNS
Mechanism, Contraindication, S/E of Benserazide
peripheral DOPA decarboxylase inhibitor
Administered with L-dopa (L-dopa + benzerazide in 4:1 ratio
known as MADOPAR®)
→ To reduce the metabolism of L-dopa in the periphery
→ To increase the availability of dopamine to the CNS
Mechanism, Contraindication, S/E of Bromocriptine
Dopamine receptor agonists
MOA
An ergot derivative
→ Acts as a dopamine receptor agonist at D2-like receptors
In conjunction with L-dopa / carbidopa
→To relieve rigidity and tremor
→Minimal effects on bradykinesia
Side (adverse) effects
→Hallucination and delirium
→Nausea and vomiting
→Cardiac arrhythmia, postural hypotension
→Erythromelalgia: a condition characterized by red, painful, and
swollen feet or hands
Mechanism, Contraindication, S/E of Pergolide
MOA
An ergot derivative
→Acts as a dopamine receptor agonist at both D1-like and D2-like receptors
→ In combination with L-dopa / carbidopa and anticholinergic drugs
Side (adverse) effects →Hallucination →Confusion →Postural hypotension →Urinary tract infection
Mechanism, Contraindication, S/E of of Pramipexole and Ropinirole
First-line therapy in young patient
MOA
Non-ergot dopamine receptor agonists at D2-like receptors
Added on to L-dopa / carbidopa treatment in patients with advanced Parkinson’s disease
side (adverse) effects →Dyskinesia →Dizziness →Insomnia or somnolence (drowsiness) →Postural hypotension
Mechanism, Contraindication, S/E of of Rotigotine
MOA
→Non-ergot dopamine D2-like receptor agonist at clinical doses
→Transdermal patches when used in the treatment of Parkinson’s disease
Side (adverse) effects
→Application site reactions including hypersensitivity reactions or skin
problems such as redness, rashes, itching, irritation, burning
sensations etc.
→Dizziness
→Headache
→Nausea
Mechanism, Contraindication, S/E of Selective Monoamine Oxidase B (MAO-
B) Inhibitors
(Selegiline and Rasagiline)
MOA
→by inhibiting the enzyme MAO-B in the brain that metabolizes or breakdown brain dopamine
→Decrease the metabolism of dopamine in the periphery and brain
→ Increase dopamine levels
→ Enhance the effects of L-dopa / carbidopa or L-dopa / benserazide
Side (adverse) effects: →a threat of hypertensive crisis in high dosages →nausea →headache →abdominal pain →dry mouth
Mechanism, Contraindication, S/E of
Catechol-O-methyl Transferase (COMT)
Inhibitors
Entacapone Tolcapone
Mechanism of action:
by blocking COMT for the peripheral conversion of levodopa (L-dopa) to 3-O-methyldopa
Adverse (side) effects →Dyskinesia →Hallucination →Postural hypotension →Diarrhea →Sleep disorders →Hepatic necrosis (for tolcapone only)
Mechanism, Contraindication, S/E of Dopamine Facilitator (Amantadine)
→To enhance the release of dopamine from surviving nigral neurons
→ To inhibit the reuptake of dopamine at synapses
→ More effective than anticholinergic agents in improving bradykinesia and rigidity when used along with L-dopa /
carbidopa or L-dopa / benserazide
Adverse (side) effects →Restlessness, agitation, confusion →Postural hypotension →Peripheral edema →Skin rash
Mechanism, Contraindication, S/E of
Central Anticholinergic Agents
Benztropine, benzhexol and biperidine
MoA
→To reduce cholinergic output of the striatum by blocking the receptors
→To reduce primary symptoms such as tremor, rigidity, and akinesia (NOT bradykinesia) as well as secondary symptom such as drooling
Side (adverse) effects →Sedation → Urinary retention → Dry mouth → Constipation → Mental confusion
Choices of treatment for PD
→L-dopa + carbidopa (SINEMET)
→ L-dopa + benzerazide (MADOPAR) is the best treatment for elderly initially diagnosed with PD
→Addition of a COMT inhibitor or a MAO-B inhibitor to L-dopa / carbidopa can reduce motor fluctuations in patients with
advanced disease
→Anticholinergics can be useful addition to L-dopa / carbidopa
for control of tremor
→ Apomorphine should be available for rescue use in patients
with “off” episodes
Treatment for Huntington’s Disease
Medications for movement disorder
→ Tetrabenazine – “dopamine-depleting” to suppress the involuntary jerking
and writhing movement (chorea)
→ Antipsychotic drugs
→ → Haloperidol and risperidone (newer) – using side effect of this class of drugs to
suppress movements
Medications for psychiatric disorder
→ Antidepressants
→ → Fluoxetine (SSRI) – to treat depression
→ Mood-stabilizing drugs
→ → Carbamazepine – to treat irritability
Mechanism, Contraindication, S/E of
Acetylcholinesterase inhibitors
Galantamine Rivastigmine Donepezil
To increase the amount of acetylcholine (ACh) available by preventing its breakdown within the synaptic cleft
Side (adverse) effects ─ Nausea, vomiting ─ Diarrhea ─ Abdominal cramps ─ Anorexia (appetite and weight loss) ─ Agitation ─ Dizziness ─ Urine incontinence
Mechanism, Contraindication, S/E of
NMDA receptor antagonists (uncompetitive)
Memantine
MoA
─An uncompetitive NMDA receptor antagonist (Block open channel )
─To improve cognitive ability by protecting CNS neurons
from the excitotoxic effects of glutamate
Adverse (side) effects ─Headache ─Dizziness ─Confusion ─Constipation
