**THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** DENT 3005:Introduction to Pharmacology **Neurological drugs** Dr Thuy Linh Truong thuy.truong@uwa.edu.au A slide title page with the university logo and text over a background of various pills and capsules. # **DENT 3005: Introduction to Pharmacology** ## **Neurological drugs** Dr Thuy Linh Truong thuy.truong@uwa.edu.au THE UNIVERSITY OF WESTERN AUSTRALIA **Acknowledgement** of **country** 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 A black and white aboriginal-style artwork is displayed next to the text. # **Acknowledgement of country** 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 Outcomes** **Learning objectives** 1) Understand the different types of neurological drugs and their mechanism of action 1) Drugs for epilepsy 2) Drugs for Parkinson's 3) Drugs for migraines 4) Drugs for Alzheimer's 5) Drugs for MS 6) Drugs for Myasthenia Gravis 7) Other 2) Recognise oral and dental side effects of these drugs 3) Understand drugs interactions with dental medications 4) Applied knowledge to clinical scenarios <img /> # **Learning Outcomes** ## **Learning objectives** 1) Understand the different types of neurological drugs and their mechanism of action - 1) Drugs for epilepsy - 2) Drugs for Parkinson's - 3) Drugs for migraines - 4) Drugs for Alzheimer's - 5) Drugs for MS - 6) Drugs for Myasthenia Gravis - 7) Other 2) Recognise oral and dental side effects of these drugs 3) Understand drugs interactions with dental medications 4) Applied knowledge to clinical scenarios Neurological drugs • Epilepsy • Parkinson's disease • Migraine • Alzheimer's disease • Multiple sclerosis # **Neurological drugs** - Epilepsy - Parkinson's disease - Migraine - Alzheimer's disease - Multiple sclerosis Epilepsy - **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** - **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 | 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 | ## **Epilepsy Seizure Characteristics** | 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 | **Antiepileptics** | 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$^3$, | clobazam, clonazepam, lamotrigine | | valproate | | | **Myoclonic seizures** | | | valproate | clobazam, clonazepam, levetiracetam, phenobarbital | | **Infantile spasms** | | | prednisolone, | vigabatrin$^4$, clonazepam, valproate | | tetracosactide | | $^1$ 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 # **Antiepileptics** | | 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 # Barbiturates * **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| ## **Barbiturates** - **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| # Benzodiazepines * **[Neurology]** – also in *psychotropics* * **MOA:** potentiate inhibitory effect of GABA * **Drug interactions** * Other CNS depressants: monitor sedation * Alprazolam: itraconazole, ketoconazole $\rightarrow$ enhance sedation & respiratory depression * Diazepam + fluconazole $\rightarrow$ increase adverse effect * Midazolam + [CYP3A4 inh] $\rightarrow$ enhance sedation & respiratory depression * **ADR:** fatigue, drowsiness, muscle weakness, ataxia, dry mouth, hypersalivation $\text{\copyright}$ 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. ## **Benzodiazepines** - **[Neurology]** – also in *psychotropics* - **MOA:** potentiate inhibitory effect of GABA - **Drug interactions** - Other CNS depressants: monitor sedation - Alprazolam: itraconazole, ketoconazole $\rightarrow$ enhance sedation & respiratory depression - Diazepam + fluconazole $\rightarrow$ increase adverse effect - Midazolam + [CYP3A4 inh] $\rightarrow$ enhance sedation & respiratory depression - **ADR:** fatigue, drowsiness, muscle weakness, ataxia, dry mouth, hypersalivation $\text{\copyright}$ 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. # Gabapentinoids * **MOA**: bind to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels $\rightarrow$ 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 | ## **Gabapentinoids** - **MOA**: bind to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels $\rightarrow$ 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 antiepileptics** | Selected drug (brand) | Selected ADR | |---|---| | Acetazolamide | | | Brivaracetam | | | Cannabidiol | | | Carbamazepine | | | Ethosuximide | | | Lacosamide | | | Lamotrigine | | | Levetiracetam | | | Oxcarbazepine | | | Perampanel | | | Phenytoin | | | Rufinamide | | | Stiripentol | | | Sulthiame | | | Tiagabine | | | Topiramate | | | Valproate | | | Vigabatrin | | | Zonisamide | | | Selected drug (brand) | Selected ADR | |---|---| | Carbamazepine (Tegretol) | [common]: drowsiness, ataxia, dizziness, dry mouth<br>[rare]: severe skin reactions, orofacial dyskinesia | | Ethosuximide (Zarontin) | [common]: dizziness, drowsiness, ataxia<br>[rare]: Steven Johnson's | | Lamotrigine (Lamictal) | [common]: dizziness, ataxia, hyperkinesia<br>[rare]: severe skin reactions | | Levetiracetam (Keppra) | [common]: drowsiness, dizziness, vertigo, ataxia<br>[rare]: severe skin reactions | | Oxcarbazepine (Trileptal) | [common]: dizziness, tremor, ataxia, nystagmus<br>[rare]: severe skin reactions | | Phenytoin (Dilantin) | [common]: sedation, ataxia, nystagmus, vertigo, gingival hyperplasia<br>[rare]: severe skin reactions | | Topiramate (Topamax) | [common]: dizziness, nervousness, agitation, speech disorder<br>[infrequent]: aphasia, nystagmus, taste disturbance | | Valproate (Epilim) | [common]: ataxia, dizziness, tremor, | ## **Other antiepileptics** | Selected drug (brand) | Selected ADR | |---|---| | Acetazolamide | | | Brivaracetam | | | Cannabidiol | | | Carbamazepine (Tegretol) | [common]: drowsiness, ataxia, dizziness, dry mouth<br>[rare]: severe skin reactions, orofacial dyskinesia | | Ethosuximide (Zarontin) | [common]: dizziness, drowsiness, ataxia<br>[rare]: Steven Johnson's | | Lacosamide | | | Lamotrigine (Lamictal) | [common]: dizziness, ataxia, hyperkinesia<br>[rare]: severe skin reactions | | Levetiracetam (Keppra) | [common]: drowsiness, dizziness, vertigo, ataxia<br>[rare]: severe skin reactions | | Oxcarbazepine (Trileptal) | [common]: dizziness, tremor, ataxia, nystagmus<br>[rare]: severe skin reactions | | Perampanel | | | Phenytoin (Dilantin) | [common]: sedation, ataxia, nystagmus, vertigo, gingival hyperplasia<br>[rare]: severe skin reactions | | Rufinamide | | | Stiripentol | | | Sulthiame | | | Tiagabine | | | Topiramate (Topamax) | [common]: dizziness, nervousness, agitation, speech disorder<br>[infrequent]: aphasia, nystagmus, taste disturbance | | Valproate (Epilim) | [common]: ataxia, dizziness, tremor, | | Vigabatrin | | | Zonisamide | | **Serious skin reactions** Two images showing severe skin reactions on a person's face. ## **Serious skin reactions** **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 ## **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** **implications** * 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 ## **Epilepsy: Dental implications** - **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 Disease * 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 # **Parkinson's Disease** - 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 agonists * **MOA**: stimulate dopamine receptor * **Drug interactions** * Apomorphine: clarithromycin, erythromycin, fluconazole $\rightarrow$ 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 | ## **Dopamine agonists** - **MOA**: stimulate dopamine receptor - **Drug interactions** - Apomorphine: clarithromycin, erythromycin, fluconazole $\rightarrow$ 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 | **Anticholinergics** * **MOA:** block muscarinic actions of acetylcholine * **Drug interactions** * Benzatropine, trihexyphenidyl: nil dental interactions * **ADR** * Dizziness, drowsiness * Orthostatic hypotension * Dyskinesia * Dry mouth <table> <thead> <tr> <th>Generic name</th> <th>Brand Name</th> </tr> </thead> <tbody> <tr> <td>Benzatropine</td> <td>Benztrop</td> </tr> <tr> <td>Trihexyphenidyl</td> <td>Artane</td> </tr> </tbody> </table> **Tertiary amines** * Atropine, Atropine (antidote) * Benzatropine * Darifenacin * Hyoscine hydrobromide * Orphenadrine * Oxybutynin * Solifenacin * Tolterodine * Trihexyphenidyl **Quaternary amines** * Glycopyrronium (anaesthesia) * Hyoscine butylbromide * Propantheline ## **Anticholinergics** - **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 B** - 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 | ## **Monoamine oxidase inH type B** - 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 Parkinson** * 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 | ## **Other drugs for Parkinson** - **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 implications** * Drug interactions * QT prolongation drugs * CYP3A4 * ADR * [common]: Dizziness, drowsiness, orthostatic hypotension, dyskinesia, impulse control disorders, dry mouth ## **Drugs for PD: Dental implications** - **Drug interactions** - QT prolongation drugs - CYP3A4 - **ADR** - [common]: Dizziness, drowsiness, orthostatic hypotension, dyskinesia, impulse control disorders, dry mouth **PD** **Dental** **implications** * 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 ## **PD: Dental implications** - 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 **Migraines** * 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 # **Migraines** - **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 **Triptans** * **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 | ## **Triptans** - **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 | Calcitonin gene related peptide antagonist * 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 | ## **Calcitonin gene related peptide antagonist** - 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 migraine** * MOA: $5HT_2$ antagonist * Drug interactions * Other CNS depressants * ADR * [common]: sedation * [infrequent]: dry mouth, dizziness <table> <thead> <tr> <th>Generic name</th> <th>Brand Name</th> </tr> </thead> <tbody> <tr> <td>Botulinum toxins</td> <td>Botox, Xeomin, Dysport</td> </tr> <tr> <td>Pizotifen</td> <td>Sandomigran</td> </tr> </tbody> </table> ## **Other drugs to prevent migraine** - **MOA**: $5HT_2$ antagonist - **Drug interactions** - Other CNS depressants - **ADR** - [common]: sedation - [infrequent]: dry mouth, dizziness | Generic name | Brand Name | | :--- | :--- | | Botulinum toxins | Botox, Xeomin, Dysport | | Pizotifen | Sandomigran | **Drugs for migraine Dental implications** - 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 ## **Drugs for migraine: Dental implications** - **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 Disease** * 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 # **Alzheimer's Disease** - 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 **Anticholinesterases** * **MOA:** decrease breakdown of acetylcholine * **Drug interactions [Galantamine]** * QT prolongation: clarithromycin, erythromycin, fluconazole * **[CYP3A4 inh]** * **ADR** * Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting <table> <thead> <tr> <th>Generic name</th> <th>Brand Name</th> </tr> </thead> <tbody> <tr> <td>Donepezil</td> <td>Arazil, Aricept</td> </tr> <tr> <td>Galantamine</td> <td>Galantyl, Reminyl</td> </tr> <tr> <td>Rivastigmine</td> <td>Exelon</td> </tr> </tbody> </table> ## **Anticholinesterases** - **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's * **MOA**: N-methyl-D-aspartate (NMDA) antagonist * **Drug interactions**: limited information * **ADR** * [common]: confusion, dizziness, drowsiness, headache, agitation, hallucinations, dyspnoea * [infrequent]: anxiety | Generic name | Brand Name | | :--- | :--- | | **Memantine** | **Ebixa, Memanxa** | ## **Other drugs for Alzheimer's** - **MOA**: N-methyl-D-aspartate (NMDA) antagonist - **Drug interactions**: limited information - **ADR** - [common]: confusion, dizziness, drowsiness, headache, agitation, hallucinations, dyspnoea - [infrequent]: anxiety | Generic name | Brand Name | | :--- | :--- | | **Memantine** | **Ebixa, Memanxa** | **Drugs for AD** **Dental** **implications** - **Drug interactions** - QT prolongation drugs - CYP3A4 - **ADR** - [common]: Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting, confusion, headache, agitation, hallucinations, dyspnoea - [infrequent]: anxiety ## **Drugs for AD: Dental implications** - **Drug interactions** - QT prolongation drugs - CYP3A4 - **ADR** - [common]: Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting, confusion, headache, agitation, hallucinations, dyspnoea - [infrequent]: anxiety ## **Multiple sclerosis** * **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 | # **Multiple sclerosis** - **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 modulator** * **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** | ## **Sphingosine 1-phosphate receptor modulator** - **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** | Fumarates **• MOA:** exact mode of action unknown **• Drug interactions** • Limited information **• ADR** • [common]: flushing • [rare]: serious opportunistic infections | Generic name | Brand Name | |---|---| | Dimethyl fumarate | Tecfidera | | Diroximel fumarate | Vumerity | ## **Fumarates** - **MOA:** exact mode of action unknown - **Drug interactions** - Limited information - **ADR** - [common]: flushing - [rare]: serious opportunistic infections | Generic name | Brand Name | |---|---| | Dimethyl fumarate | Tecfidera | | Diroximel fumarate | Vumerity | **Other drugs for MS** * 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 | | ## **Other drugs for MS** - 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** **implications** - Drug interactions - CYP3A4 - ADR - [common]: Hypertension, infection, basal cell carcinoma, flushing, infection ## **Drugs for MS: Dental implications** - **Drug interactions** - CYP3A4 - **ADR** - [common]: Hypertension, infection, basal cell carcinoma, flushing, infection **Myasthenia gravis** * **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 $\rightarrow$ muscle weakness (e.g. limbs, speech, chewing) * **Treatment**: cholinesterase inhibitors increase acetylcholine availability * Overdosage $\rightarrow$ cholinergic crisis * **Goal**: enhance neuromuscular transmission, improve muscle strength # **Myasthenia gravis** - **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 $\rightarrow$ muscle weakness (e.g. limbs, speech, chewing) - **Treatment**: cholinesterase inhibitors increase acetylcholine availability - Overdosage $\rightarrow$ cholinergic crisis - **Goal**: enhance neuromuscular transmission, improve muscle strength Anticholinesterases in MG * 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 <table><thead><tr><th>Generic name</th><th>Brand Name</th></tr></thead><tbody><tr><td>Edrophonium</td><td>Not marketed AUS</td></tr><tr><td>Neostigmine</td><td>Neostigmine inj</td></tr><tr><td>Pyridostigmine</td><td>Mestinon</td></tr></tbody></table> ## **Anticholinesterases in MG** - **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 implications** * Drug interactions * No dental implication * ADR * [common]: increase salivation * Monitor cholinergic crisis ## **Drugs for MG: Dental implications** - **Drug interactions** - No dental implication - **ADR** - [common]: increase salivation - Monitor cholinergic crisis ## **Other neurological drugs** | **Generic name (brand)** | **MOA** | **Selected ADR** | **Selected drug interaction** | | :--- | :--- | :--- | :--- | | Baclofen (Clofen) Chronic spasticity associated with MS | $\text{GABA}_\text{B}$ 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 | # **Other neurological drugs** | **Generic name (brand)** | **MOA** | **Selected ADR** | **Selected drug interaction** | | :--- | :--- | :--- | :--- | | Baclofen (Clofen) Chronic spasticity associated with MS | $\text{GABA}_\text{B}$ 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 | **References** * 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 Illustration of a person sneezing/blowing their nose surrounded by medication, and a separate illustration of pill bottles with scattered pills. # **References** - 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]. 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