DENT 3005: Introduction to Pharmacology¹

Neurological drugs

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Acknowledgement of country²

The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.

Artist: Dr Richard Barry Walley OAM

Learning Outcomes³

Learning objectives

Understand the different types of neurological drugs and their mechanism of action
- 1. Drugs for epilepsy
- 1. Drugs for Parkinson’s
- 1. Drugs for migraines
- 1. Drugs for Alzheimer’s
- 1. Drugs for MS
- 1. Drugs for Myasthenia Gravis
- 1. Other
Recognise oral and dental side effects of these drugs
Understand drugs interactions with dental medications
Applied knowledge to clinical scenarios

Neurological drugs⁴

Epilepsy
Parkinson’s disease
Migraine
Alzheimer’s disease
Multiple sclerosis

Epilepsy⁵

Seizures: transient uncontrolled electrical discharges
- Causes: biochemical imbalance, structural
- Partial Vs generalized
Epilepsy: recurrent, unprovoked seizure, different types
Pharmacological targets
- Inhibitory GABA Vs excitatory glutamatergic pathways
- Voltage gated membrane channels

Epilepsy Seizure Characteristics⁶

Seizure	Characteristics
Absence (generalized)	Sudden transient loss of consciousness
Myoclonic (generalized)	Convulsive movements of body
Tonic (generalized)	Muscle contractions forcing body into rigid & fixed positions
Tonic-clonic (generalized)	Collapse, followed by rigidity then violent convulsions, and deep seep postictally, unresponsiveness, deep confusion
Aura (simple partial)	Usually experiencing sedation (e.g. olfactory, visual or aural) w/ no stimulus present
Jacksonian (simple partial)	Muscle spasms characterized by sequential involvement of body parts
Psychomotor (complex partial)	Transient aberrant behavior such as mood alteration, psychotic behavior or apparent drunkenness

Antiepileptics⁷

	First line	Second line
Focal (partial) seizures	carbamazepine	lamotrigine $^{1}$ , clobazam, gabapentin, lacosamide, levetiracetam $^{1}$ , oxcarbazepine, phenobarbital, phenytoin, pregabalin, tiagabine, topiramate, valproate, zonisamide
Generalised tonic-clonic seizures	valproate	carbamazepine $^{2}$ , clobazam, lamotrigine $^{1}$ , levetiracetam $^{1}$ , oxcarbazepine $^{2}$ , phenobarbital, phenytoin $^{2}$ , topiramate
Absence seizures	ethosuximide $^{3}$ , valproate	clobazam, clonazepam, lamotrigine
Myoclonic seizures	valproate	clobazam, clonazepam, levetiracetam, phenobarbital
Infantile spasms	prednisolone, tetracosactide	vigabatrin $^{4}$ , clonazepam, valproate

$^{1}$ may be first line in females of child-bearing potential $^{2}$ do not use if juvenile myoclonic epilepsy is suspected (often presents with a tonic-clonic seizure) as it may be ineffective or worsen seizures $^{3}$ does not prevent generalised tonic-clonic seizures which often coexist in juvenile absence epilepsy $^{4}$ use only if no safer alternative

Barbiturates⁸

MOA: Prolong inhibitory postsynaptic potential
Drug interactions
- Phenobarbital + metronidazole
- Other CNS depressants: monitor sedation
- CYP3A4 substrates: clarithromycin, codeine, erythromycin, azoles, oxycodone, tramadol…
ADR
- Sedation, cognitive impairment, altered mood and behaviour
- [Rare]: exfoliative dermatitis

Generic Name	Brand Name
Phenobarbital	Phenobarb
Primidone	Mysoline

Benzodiazepines⁹

[Neurology] – also in psychotropics
MOA: potentiate inhibitory effect of GABA
Drug interactions
- Other CNS depressants: monitor sedation
- Alprazolam: itraconazole, ketoconazole $\to$ enhance sedation & respiratory depression
- Diazepam + fluconazole $\to$ increase adverse effect
- Midazolam + [CYP3A4 inh] $\to$ enhance sedation & respiratory depression
ADR: fatigue, drowsiness, muscle weakness, ataxia, dry mouth, hypersalivation $\overset{◯}{c}$ and many more

Generic name	Brand Name
Clobazam	Frisium
Clonazepam	Rivotril
Diazepam	Valium
Lorazepam	Lorazepam inj
Midazolam	Hypnovel inj

Ataxia refers to a loss of coordination and balance, resulting in clumsy or awkward movements, often affecting walking, speech, and fine motor skills.

Gabapentinoids¹⁰

MOA: bind to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels $\to$ reduce calcium influx & neurotransmitter release
Drug interactions: other CNS depressants
ADR
- Drowsiness, sedation, dizziness, vertigo
- Dysarthria
- Ataxia
- Tremor
- Dry mouth
- [Rare]: Steven Johnson’s syndrome

Generic name	Brand Name
Gapapentin	Neurontin
Pregabalin	Lyrica

Other antiepileptics¹¹

Selected drug (brand)	Selected ADR
Acetazolamide
Brivaracetam
Cannabidiol
Carbamazepine (Tegretol)	common: drowsiness, ataxia, dizziness, dry mouth [rare]: severe skin reactions, orofacial dyskinesia
Ethosuximide (Zarontin)	common: dizziness, drowsiness, ataxia [rare]: Steven Johnson’s
Lacosamide
Lamotrigine (Lamictal)	common: dizziness, ataxia, hyperkinesia [rare]: severe skin reactions
Levetiracetam (Keppra)	common: drowsiness, dizziness, vertigo, ataxia [rare]: severe skin reactions
Oxcarbazepine (Trileptal)	common: dizziness, tremor, ataxia, nystagmus [rare]: severe skin reactions
Perampanel
Phenytoin (Dilantin)	common: sedation, ataxia, nystagmus, vertigo, gingival hyperplasia [rare]: severe skin reactions
Rufinamide
Stiripentol
Sulthiame
Tiagabine
Topiramate (Topamax)	common: dizziness, nervousness, agitation, speech disorder infrequent: aphasia, nystagmus, taste disturbance
Valproate (Epilim)	common: ataxia, dizziness, tremor,
Vigabatrin
Zonisamide

Serious skin reactions¹²¹³

Anti-epileptics drugs: Dental implications

Drug interactions
- CNS depressants
- CYP3A4
ADR
- common: drowsiness, oversedation, cognitive impairment, altered mood and behaviour, lightheadedness, hypersalivation, ataxia, dizziness, vertigo, dysarthria, tremor, dry mouth, nystagmus, taste disturbances
- [rare]: serious skin reactions
- Phenytoin: gingival hyperplasia

Epilepsy: Dental implications¹⁴

Patient management
Appointment when the concentration of the antiepileptic medication is the most optimal
Avoid potential triggers
Know first aid protocols
- DRSABCD
- Clear AW
- Supine position
- Remove dangerous equipment
- Protect patient: injury & falls
- No attempt should be made to open the patient’s mouth
- Call medical services

Parkinson’s Disease¹⁵

Usually older population
Characteristics: tremor, difficulty coordinating fine movements, hypokinesia, shuffling gait, skeletal muscle rigidity
Normal muscle movement: balance muscarinic cholinergic and dopaminergic activities
Parkinson’s disease: dopaminergic fibres and/or dopamine receptor degenerate
Rationale tx: provide sx relief
Pharmacological: dopamine agonists, anticholinergics, MAO-B, others

Dopamine agonists¹⁶

MOA: stimulate dopamine receptor
Drug interactions
- Apomorphine: clarithromycin, erythromycin, fluconazole $\to$ prolong QT
- Bromocriptine + erythromycin: increase ADR
- Cabergoline + clarithromycin, itraconazole: increase ADR
ADR
- Dizziness, drowsiness
- Orthostatic hypotension
- Dyskinesia
- Impulse control disorders

Generic name	Brand Name
Apomorphine	Movapo inj
Pramipexole	Sifrol
Rotigotine	Neupro
Ergot derivative
Bromocriptine	Parlodel
Cabergoline	Dostinex

Anticholinergics¹⁷

MOA: block muscarinic actions of acetylcholine
Drug interactions
- Benzatropine, trihexyphenidyl: nil dental interactions
ADR
- Dizziness, drowsiness
- Orthostatic hypotension
- Dyskinesia
- Dry mouth

Generic name	Brand Name
Benzatropine	Benztrop
Trihexyphenidyl	Artane

Tertiary amines

Atropine, Atropine (antidote)
Benzatropine
Darifenacin
Hyoscine hydrobromide
Orphenadrine
Oxybutynin
Solifenacin
Tolterodine
Trihexyphenidyl

Quaternary amines

Glycopyrronium (anaesthesia)
Hyoscine butylbromide
Propantheline

Monoamine oxidase inH type B¹⁸

Aka MAOB inH
MOA: inH MAOB, reduce breakdown of dopamine, may block dopamine re-uptake
Drug interactions: nil dental interactions
ADR
- Orthostatic hypotension
- Dyskinesia

Generic name	Brand Name
Rasagiline	Azilect
Safinamide	Xadago
Selegiline	Eldepryl

Other drugs for Parkinson¹⁹

Drug interactions: Entacapone + adrenaline: dental relevance?
Amantadine [ADR]: Orthostatic hypotension, dizziness, dry mouth
Entacapone [ADR]: Orthostatic hypotension, dry mouth, dyskinesia
Opicapone [ADR]: Dry mouth, dizziness, dyskinesia
Combination [ADR]: orthostatic hypotension, dyskinesia, drowsiness, impulse control disorder

Generic name	Brand Name
Amantadine	Symmetrel
Entacapone	Comtan
Levodopa + benserazide + carbidopa	Madopar Kinson, Sinemet
Levodopa + carbidopa & entacapone	Carlevent, Lecteva
Opicapone	Ongentys

Drugs for PD: Dental implications²⁰

Drug interactions
- QT prolongation drugs
- CYP3A4
ADR
- common: Dizziness, drowsiness, orthostatic hypotension, dyskinesia, impulse control disorders, dry mouth

PD: Dental implications²¹

Orthostatic hypotension
Fatigue and exhaustion due to disturbed sleep patterns
Impaired executive functions which leads to distraction and inattention
Short appointments if possible
Patient should take levodopa and symptomatic medication 1 hour prior to planned procedure!
Minimise muscle tone resting jaw opening or possible uncontrolled tremor
Side-effects from medications

Migraines²²

Headache: mod-severe throbbing/pulsing pain
- Other accompanying sx: nausea, vomiting, photosensitivity, phono sensitivity, aura…
Tx rationale
- Relief headache and assoc sx
- Prevent recurrent migraine
- Improve QOL
Treatment
- Non-pharmacological
- Pharmacological: sx relief, acute & preventative

Triptans²³

MOA: action at 5HT1B/1D receptors appears to reduce calcitonin gene-related peptide levels and modulate nociception
Drug interactions
- Eletriptan [CYP3A4 inh]: erythromycin, fluconazole
ADR
- Sensations (tingling, heat, pain, heaviness, tightness)
- Dizziness, drowsiness
- Dry mouth

Generic name	Brand Name
Eletriptan	Relpax
Naratriptan	Naramig
Rizatriptan	Rixalt, Maxalt
Sumatriptan	Imigran
Zolmitriptan	Zoltrip, Zomig

AKA CGRP antagonists
MOA: inH CGRP vasodilation
- Erenumab blocks CGRP receptors
Drug interactions
- Limited information available
ADR: not dentally related

Generic name	Brand Name
Eptinezumab	Vyepti inj
Erenumab	Aivomig
Fremanezumab	Ajovy inj
Galcanezumab	Emgality

Other drugs to prevent migraine²⁵

MOA: $5 H T_{2}$ antagonist
Drug interactions
- Other CNS depressants
ADR
- infrequent: dry mouth, dizziness

Generic name	Brand Name
Botulinum toxins	Botox, Xeomin, Dysport
Pizotifen	Sandomigran

Drugs for migraine: Dental implications²⁶

Drug interactions
- CNS depressants
- CYP3A4
ADR
- common: Sensations (tingling, heat, pain, heaviness, tightness), dizziness, drowsiness, dry mouth
Migraine triggers: avoid
- Ensure patient have acute relief medications

Alzheimer’s Disease²⁷

A form of dementia
Characteristics: neuronal cell loss, brain shrinkage, enlarged ventricles, significant histological changes in brain tissue
Progressive deterioration
Pathophysiology: neuronal cell death, B-amyloid plaques, neurofibrillary tangles
Reduction in Ach and raised glutamate?
Pharmacological: inH acetylcholinesterase, glutamate receptor antagonists

Anticholinesterases²⁸

MOA: decrease breakdown of acetylcholine
Drug interactions [Galantamine]
- QT prolongation: clarithromycin, erythromycin, fluconazole
- [CYP3A4 inh]
ADR
- Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting

Generic name	Brand Name
Donepezil	Arazil, Aricept
Galantamine	Galantyl, Reminyl
Rivastigmine	Exelon

Other drugs for Alzheimer’s²⁹

MOA: N-methyl-D-aspartate (NMDA) antagonist
Drug interactions: limited information
ADR
- common: confusion, dizziness, drowsiness, headache, agitation, hallucinations, dyspnoea

Generic name	Brand Name
Memantine	Ebixa, Memanxa

Drugs for AD: Dental implications³⁰

Drug interactions
- QT prolongation drugs
- CYP3A4
ADR
- common: Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting, confusion, headache, agitation, hallucinations, dyspnoea

Multiple sclerosis³¹

Disease of nervous system
- Demyelination $\to$ [slowed, distorted, blocked] neural transmission
- Plaques: scar tissue
Unpredictable course
- Progressive Vs Relapsing-Remitting forms
Four common syndromes
- Spinal syndrome: most common
- Other syndrome [brainstem, cerebral, cerebella]
Pharmacological
- Immunosuppressants
- Sx relief

Symptom	Drug
Depression/pain	TCAs
Incomplete bladder emptying	A-blockers
Infections	ABs
Neuralgia	Carbamazepine
Spasm/spasticity	Diazepam/ baclofen

Sphingosine 1-phosphate receptor modulator³²

MOA: preventing lymphocytes leaving lymph nodes
Drug interactions
- Fingolimod & Siponimod: CYP3A4 inH
ADR
- Hypertension, infection
- Basal cell carcinoma: check patients for skin cancer

Generic name	Brand Name
Fingolimod	Gilenya
Ozanimod	Zeposia
Siponimod	Mayzent

Fumarates³³

MOA: exact mode of action unknown
Drug interactions
- Limited information
ADR
- [rare]: serious opportunistic infections

Generic name	Brand Name
Dimethyl fumarate	Tecfidera
Diroximel fumarate	Vumerity

Other drugs for MS³⁴

Additional reading on MOA
Most don’t have detailed drug interactions
ADR: related to immunosuppressant effects
- Infections

Drug	Notes
Alemtuzumab	(neurology)
Cladribine	(neurology)
Fampridine
Glatiramer
Interferon beta
Nabiximols
Natalizumab
Ocrelizumab
Ofatumumab
Teriflunomide

Drugs for MS: Dental implications³⁵

Drug interactions
- CYP3A4
ADR
- common: Hypertension, infection, basal cell carcinoma, flushing, infection

Myasthenia gravis³⁶

Autoimmune neuromuscular disorder causing weakness and fatigue of voluntary muscles
Cause: antibodies destroy acetylcholine receptors (AChRs) at neuromuscular junction
Effect: impaired nerve-to-muscle communication $\to$ muscle weakness (e.g. limbs, speech, chewing)
Treatment: cholinesterase inhibitors increase acetylcholine availability
- Overdosage $\to$ cholinergic crisis
Goal: enhance neuromuscular transmission, improve muscle strength

Anticholinesterases in MG³⁷

MOA: inH cholinesterase
Drug interactions: no dental implication
ADR
- common: increase salivation
Monitor Cholinergic crisis
- Excessive sweating, involuntary defecation and urination, miosis, nystagmus, bradycardia, hypotension, increased muscle weakness

Generic name	Brand Name
Edrophonium	Not marketed AUS
Neostigmine	Neostigmine inj
Pyridostigmine	Mestinon

Drugs for MG: Dental implications³⁸

Drug interactions
- No dental implication
ADR
- common: increase salivation
Monitor cholinergic crisis

Other neurological drugs³⁹

Generic name (brand)	MOA	Selected ADR	Selected drug interaction
Baclofen (Clofen) Chronic spasticity associated with MS	$GABA_{B}$ agonist	Hypotension, drowsiness, dizziness, seizures, ataxia, tremor, nystagmus	Drugs causing CNS and respiratory depression
Dantrolene (Dantrium) Chronic spasticity associated with spinal cord injury	A direct acting skeletal muscle relaxant	Drowsiness, dizziness, nervousness, seizures	Drugs causing CNS depression
Riluzole (Rilutek) Amyotrophic lateral sclerosis (ALS)	May act by inhibiting glutamate neurotransmission	Drowsiness, dizziness,	Drugs causing CNS depression
Tetrabenazine (Tetrabenazine) Some dystonic syndromes	Depletes levels of dopamine in the CNS	Drowsiness, parkinsonism, akathisia, agitation, anxiety, confusion, orthostatic hypotension, dysphagia, choking	Drugs causing CNS depression Drug causing QT prolongation

References⁴⁰

Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. Rang & Dale’s pharmacology. 10th ed. Edinburgh: Elsevier; 2023
Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Psychotropics; [updated 2025; cited 2025]. Available from: UWA Onesearch
Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
Bullock S, Manias E. Fundamentals of pharmacology. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
MIMS Australia. eMIMSelite: Consumer medicine information, specific clinical monograph [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch

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L15 Neurology 2025_formatted_text

DENT 3005: Introduction to Pharmacology1

Neurological drugs

Acknowledgement of country2

Learning Outcomes3

Learning objectives

Neurological drugs4

Epilepsy5

Epilepsy Seizure Characteristics6

Antiepileptics7

Barbiturates8

Benzodiazepines9

Gabapentinoids10

Other antiepileptics11

Serious skin reactions1213

Anti-epileptics drugs: Dental implications

Epilepsy: Dental implications14

Parkinson’s Disease15

Dopamine agonists16

Anticholinergics17

Tertiary amines

Quaternary amines

Monoamine oxidase inH type B18

Other drugs for Parkinson19

Drugs for PD: Dental implications20

PD: Dental implications21

Migraines22

Triptans23

Calcitonin gene related peptide antagonist24

Other drugs to prevent migraine25

Drugs for migraine: Dental implications26

Alzheimer’s Disease27

Anticholinesterases28

Other drugs for Alzheimer’s29

Drugs for AD: Dental implications30

Multiple sclerosis31

Sphingosine 1-phosphate receptor modulator32

Fumarates33

Other drugs for MS34

Drugs for MS: Dental implications35

Myasthenia gravis36

Anticholinesterases in MG37

Drugs for MG: Dental implications38

Other neurological drugs39

References40

Footnotes

Graph View

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