Neurology and Mental Health 2 (PDF)

**Important notes** - Akathisia = inability to remain still, motor restlessness (i.e. a type of extrapyramidal side effect and symptom of serotonergic toxicity) - Akinesia: inability to perform a predictable movement +-----------------------------------+-------------------------------...

**Important notes** - Akathisia = inability to remain still, motor restlessness (i.e. a type of extrapyramidal side effect and symptom of serotonergic toxicity) - Akinesia: inability to perform a predictable movement +-----------------------------------+-----------------------------------+ | Outcomes | Serotonin -- Migraine and | | | depression | +===================================+===================================+ | Describe serotonin synthesis, | **Serotonin synthesis** | | storage, release, receptor | | | action, reuptake and degradation | **L-tryptophan** -- derived from | | | food | | | | | | - 5-Hydroxytryptophan via | | | tryptophan hydroxylase (rate | | | limiting) | | | | | | - 5-hydroxytryptamine | | | (serotonin) via L-aromatic | | | acid decarboxylase (AKA dopa | | | decarboxylase) | | | | | | Tryptophan crosses BBB (to make | | | 5-HT), but peripheral 5-HT cannot | | | enter - brain regulates | | | production. | | | | | | **Storage** | | | | | | - Active transport into | | | vesicles (\~1.1M) via | | | vesicular transport -- | | | prevents vesicular leakage | | | into the cytoplasm | | | | | | - Driven by H+ electrochemical | | | gradient across vesicular | | | membrane, generated by ATP | | | dependant H+ pump (active!) | | | | | | **Release** | | | | | | - Action potential | | | depolarisation Ca2+ channels | | | open = influx | | | | | | - Ca2+ entry promotes fusion of | | | vesicles to terminal membrane | | | | | | - Calcium dependant exocytosis | | | of monoamine from the | | | vesicles | | | | | | [Diffuse projection ] | | | | | | - 5HT can be released from | | | varicosities and traditional | | | synapses | | | | | | - Vari | | | cosities: | | | buds that come off axons, | | | and branch onto different | | | areas of the brain | | | | | | [Spontaneous firing ] | | | | | | - Slow tonic firing allows | | | integration of information | | | over a long period of time -- | | | baseline 5HT | | | | | | - Specific stimuli elicits | | | rapid bursts -- superimposes | | | on baseline tone | | | | | | **Pathways** | | | | | | - Synthesis in raphe nuclei | | | transported to terminals of | | | cells | | | | | | - Raphe nuclei project axons | | | to: | | | | | | - Frontal cortex -- impulse | | | control, mood and | | | cognition | | | | | | - Amygdala and hippocampus | | | -- emotion and mood | | | processing | | | | | | - Cerebellum -- muscle | | | control and movement | | | | | | - Thalamus | | | | | | - Hypothalamus | | | | | |  | | | | | | **Reuptake** | | | | | | - Active transport into neurons | | | via high affinity Na+ | | | dependant membrane bound | | | transporter proteins main | | | mechanism | | | | | | **Degradation** | | | | | | Metabolites used to be measured | | | in disease states to test for | | | perturbation of neurotransmitters | | | in disease. | | | | | |  | | | | | | ***[Monoamines ]*** | | | | | | *Catecholamines derived from | | | phenylalanine*: NAd, Ad, Da | | | | | | *Indoleamine derived from | | | tryptophan*: serotonin | | | | | | - Indole ring and amine side | | | chain | +-----------------------------------+-----------------------------------+ | Outcomes | Headaches and migraines | +-----------------------------------+-----------------------------------+ | Be familiar with the diagnostic | **Primary headaches**: caused by | | nosology of the International | chemical activity in the nerves | | Headache Society | around the head and neck, not a | | | symptom of underlying disease. | | | | | | **Secondary headaches**: headache | | | attributed to trauma, or | | | head/related disorder which have | | | a clear underlying cause and | | | require referral. | | | | | | - *Exposures*: dehydration, CO | | | poisoning | | | | | | - *Infection*: acute sinusitis, | | | ear infection, encephalitis, | | | meningitis | | | | | | - *Brain* *related*: blood | | | clot, brain tumour, | | | concussion, stroke | | | | | | - *Other*: glaucoma, high BP | | | | | | **Neuralgias**: cranial | | | neuralgias, central and primary | | | facial pain, and other. Shock | | | like pain in one or more | | | divisions of the trigeminal nerve | | | which arise due to compression or | | | nerve demyelination. | +-----------------------------------+-----------------------------------+ | Recognise possible underlying | **Location and differentiation** | | conditions associated with | | | headaches | ***Most likely***: tension | | | | | | ***Likely***: migraine, | | | sinusitis, eye strain | | | | | | ***Unlikely***: cluster, MOH, | | | temporal arteritis, trigeminal | | | neuralgia, depression | | | | | | ***Very unlikely***: glaucoma, | | | meningitis, subarachnoid | | | haemorrhage, raised intracranial | | | pressure. | | | | | | +--------------+--------------+ | | | | **Sinus** | Pain is | | | | | | behind the | | | | | | forehead, | | | | | | and/or | | | | | | cheekbones | | | | | | | | | | | | - Nasal | | | | | | congesti | | | | | | on | | | | | | | | | | | | - Worsens | | | | | | when | | | | | | bending | | | | | | forward | | | | | | or lying | | | | | | down | | | | | | | +==============+==============+ | | | | **Cluster** | Pain around | | | | | | the eye / | | | | | | one eye -- | | | | | | red eye on | | | | | | affected | | | | | | side | | | | | | | | | | | | - Agitatio | | | | | | n | | | | | | and | | | | | | pacing | | | | | | to | | | | | | relieve | | | | | | pain | | | | | | | | | | | | - Patients | | | | | | are | | | | | | **unable | | | | | | to lie | | | | | | down** | | | | | | | | | | | | - \/=2 | | | following features: | | | | | | - Pain affecting one side of | | | the head | | | | | | - Pulsating or throbbing pain | | | | | | - Aggravated by exertion | | | | | | - Nausea +/- vomiting | | | | | | - Sensitivity to light and | | | sound | | | | | | - Aura: light flashes, blind | | | spots, central or spotty | | | scotoma, zig zag lines | | | | | | [Triggers for migraines | | | ] | | | | | | Triggers will be heterogenous -- | | | keep a diary to track relevant | | | triggers. | | | | | | - Environmental: hot winds, | | | changes in barometric | | | pressure | | | | | | - Stress: emotions, loud | | | noises, flashing lights, | | | glare | | | | | | - Hormonal levels: puberty, pre | | | and during menstruation | | | (declining E) | | | | | | - Drugs: estrogens, | | | vasodilators, caffeine | | | | | | - Food: chocolate, cheese, | | | oranges, preserves, alcohol | | | | | | - Dehydration: sunstroke, | | | general inadequate water | | | intake | | | | | | - Changes in sleep patterns: | | | inadequate sleep, REM sleep | | | | | | [Pathophysiology ] | | | | | | Syndrome of unstable cerebral | | | blood vessels, mediated by 5-HT. | | | | | | Changes in activity by excitable | | | brain cells change 5-HT cerebral | | | blood flow changes contributing | | | to phases of migraine. | | | | | | *Prodrome*: hours or days before | | | headache | | | | | | - High 5-HT causing | | | vasoconstriction of | | | intracranial vessels | | | | | | - Impaired blood flow starting | | | at the visual cortex - | | | hypoperfusion | | | | | | - Symptoms of flashing lights, | | | sensitivity to light, smell | | | and noise | | | | | | *Aura*: immediately precedes | | | headache, for 5-60 minutes | | | | | | - Abnormal cortical and brain | | | stem activity | | | | | | *Headache/pain*: 4-72 hours | | | | | | - Low 5-HT protective | | | intracranial vasodilation 20% | | | increase in cerebral blood | | | flow causing unilateral | | | pulsating pain | | | | | | *Postdrome*: 24-48 hours with | | | follow-on effects at the end of | | | attack | | | | | | - Activation of brainstem | | | nucleus (locus coeruleus) -- | | | *manages residual pain | | | modulation, sensory input, | | | fatigue and recovers | | | autonomic function* | | | | | | - Widespread vasoconstriction | | | mediated by an **alpha-2 | | | adrenoceptor** | | | | | | *Treatment will depend on which | | | phase of the migraine is being | | | treated.* | | | | | |  | | | | | | **Neurogenic inflammation theory | | | of migraine** | | | | | | **The trigemino cerebrovascular | | | system consists of:** | | | | | | - Trigeminal nerves and ganglia | | | -- C fibres nociceptive | | | pathway | | | | | | - Major vessels regulating | | | cerebral blood flow | | | | | | - Smaller vessels in meninges | | | | | | **Trigeminal ganglion cells | | | innervate:** | | | | | | - Large cranial vessels | | | | | | - Meninges and smaller | | | meningeal vessels | | | | | | - Trigeminal nucleus caudalis | | | and spinal cord | | | trigeminocervical complex | | | | | | [Pathway for nociception | | | ] | | | | | | Noxious stimulus *BK, 5-HT, PGs, | | | histamine* C-fibre activity | | | excitation. | | | | | | - Intracranial blood vessels | | | constriction ophthalmic | | | division of trigeminal nerve | | | releases *CGRP, SP, NO, NKA* | | | | | | - *These vasodilatory | | | substances cause:* | | | | | | - **1)** Intracranial and | | | meningeal vasodilation | | | plasma protein leakage | | | and inflammation | | | | | | - **2)** Mast cell | | | degranulation secretion | | | of serotonin, bradykinin, | | | histamine, and | | | prostaglandins | | | inflammation | | | | | | - **Positive feedback | | | perpetuates this neurogenic | | | inflammation and peripheral | | | sensitisation** | | | | | | - Usually, these stimuli are | | | non-noxious reduced stimulus | | | threshold = migraine | | | susceptibility and initial | | | trigger for intracranial | | | vasoconstriction | | | | | | **Further | | | CGRP release triggers the | | | descending pain pathway**: | | | | | | **Role of serotonin in | | | migraines** | | | | | | - Sharp increase in urinary | | | 5-HIAA during attack | | | | | | - Platelet concentration of | | | 5-HT falls | | | | | | - 5-HT1b and 5-HT2 receptors | | | found on intracranial blood | | | vessels | | | | | | - 5-HT1b vasoconstriction | | | | | | - 5-HT2 indirect | | | vasodilation, of | | | intracranial meningeal | | | blood vessels which | | | contribute to neurogenic | | | inflammation | +-----------------------------------+-----------------------------------+ | Recognise alarm symptoms and | **Triggers for referral** | | referral triggers for tension | | | headaches and migraines | - Patient \>50 with the first | | | episode and sudden onset | | | | | | - Onset after head trauma | | | | | | - Frequency and severity of | | | headaches increases from | | | weeks-months | | | | | | - New onset in patients with | | | HIV, cancer or | | | immunosuppression | | | | | | - Signs of systemic illness -- | | | fever, rash, neck stiffness | | | | | | - Papilledema secondary to | | | cranial pressure elevation, | | | bilateral | | | | | | - Confusion and reduced mental | | | abilities | | | | | | - Suspected cluster headache or | | | positional headache | | | | | | - Cough headache which is | | | prolonged | | | | | | **WHAT-STOP-GO protocol** | | | | | | *WHAT is wrong? Assess the | | | patients current medications and | | | health status.* | | | | | | - *Who is the patient, timeline | | | of sx, actual sx, tx for this | | | / other conds.* | | | | | | *STOP and assess the situation.* | | | | | | - *Sx or SEs caused by other | | | conds. or meds., totally | | | sure, overuse and abuse, | | | pharmacist only* | | | | | | *GO supply medicines if | | | appropriate and provide advice.* | | | | | | - *Ask the patient if they have | | | any other questions or would | | | like a CMI* | | | | | | [Questions] | | | | | | - Age | | | | | | - Onset, frequency, duration | | | and timing | | | | | | - Location, severity and nature | | | of pain | | | | | | - Recent injury or trigger -- | | | cluster headaches trigger of | | | laying down? | | | | | | - History of medication use -- | | | medication over use headache | +-----------------------------------+-----------------------------------+ | Make suitable non-pharmacological | **Tension type headaches** -- | | and pharmacological management | [Non-pharmacological | | recommendations for tension | treatment] | | headaches and migraines | | | | - CBT: reduce headache related | | | psychological distress | | | | | | - Mental relaxation: guided | | | imagery exercises | | | | | | - Biofeedback: recognise and | | | control muscle tension from | | | the neck and shoulders, most | | | often combined with | | | relaxation | | | | | | - Physical relaxation: heat pad | | | on neck and shoulders | | | | | | - Acupuncture: \>/=6 sessions | | | effective for pain and | | | tension | | | | | | - Physiotherapy: neck muscle | | | stretching, endurance to | | | relieve tension | | | | | | [Pharmacological treatment | | | ] | | | | | | Wait 4-6 hours before repeating | | | the dose if needed. | | | | | | \*Note that **paracetamol**, | | | **Aspirin** and **NSAIDs** are | | | **all first line** for TTH. | | | | | | [Prophylactic | | | treatment] | | | | | | The efficacy of simple analgesics | | | reduces over time with increasing | | | headache frequency. Consider | | | prophylaxis to reduce analgesic | | | use. | | | | | |  | | | | | | **Migraine** | | | | | | [Acute **non-pharmacological** | | | approaches ] | | | | | | - Cold pack on forehead/back of | | | skull supraorbital and | | | greater occipital nerves | | | | | | - Hot packs over the neck and | | | shoulders nerves innervating | | | scalp | | | | | | - Neck stretches and | | | self-mobilisation | | | | | | - Resting in a quiet room | | | | | | - Physio: postural problems, | | | neck muscle tightness, | | | limited motion | | | | | | [Acute **pharmacological** | | | treatment ] | | | | | | *\*Antiemetics increase GI | | | motility increasing drug | | | absorption of simple analgesics | | | making treatment more effective | | | (with/without nausea).* | | | | | | *\***NSAIDs and Aspirin are | | | generally 1^st^ line, and | | | paracetamol 2^nd^ line*** | | | | | | ***\*Metoclopramide is the first | | | line antiemetic*** | | | | | | *Pharmacology of **triptans*** | | | | | | *MOA*: selective agonist at | | | **5HT1b/1d/1f** receptors to | | | inhibit abnormal activation of | | | trigeminal nociceptors by | | | reducing calcitonin related | | | peptide levels from meningeal | | | vessels: | | | | | | - Constrict cranial vessels and | | | reduce cerebral blood flow | | | via 1B | | | | | | - Inhibit peripheral | | | nociceptors (in the ganglia) | | | and pain transmission to the | | | CNS (through the trigeminal | | | nucleus caudalis) | | | | | | - Overall, reduce pain and are | | | useful in the headache phase | | | of migraine | | | | | |  | | | | | | *Precautions*: | | | | | | - Cerebrovascular/CVD: C/I in | | | uncontrolled HT and | | | peripheral vascular disease, | | | coronary vascular disease, | | | transient ischaemic attack | | | | | | - Elderly: potential increased | | | risk of CV effects | | | | | | - Pregnancy/bf: avoid if | | | possible, **sumatriptan** is | | | the agent of choice | | | | | | *ADEs*: | | | | | | - Common: tinging, heat, pain, | | | heaviness, tightness, | | | drowsiness, weakness, fatigue | | | | | | - Rare: angina, MI, arrythmia, | | | bradycardia, stroke, | | | seizures, ischaemic colitis, | | | hypersensitivity including | | | angioedema and anaphylaxis | | | | | | *Practice points* | | | | | | - Taken when headache is | | | beginning -- not aura or | | | severe headache | | | | | | - Do not repeat dose for same | | | migraine -- 2-4hrs before | | | repeating dose | | | | | | - Do not give triptan within 24 | | | hours of ergometrine or | | | ergometrine within 6 hours of | | | triptan due to risk of | | | vasospasm / vasoconstriction | | | | | | - Same triptan can be used for | | | future attacks | | | | | | - SNRI and SSRI users can take | | | triptans -- caution of | | | serotonin toxicity | | | | | | - Trial and error combine with | | | non-opioid analgesic | | | | | | *Comparative information* | | | | | | No evidence of safety difference | | | -- choice depends on patient. | | | | | | - **Naratriptan**: fewer ADEs | | | and slower onset BUT longer | | | duration of activity useful | | | for patients with extended | | | migraine attacks | | | | | | - **Non-oral formulations | | | (wafers)** useful during | | | nausea and cannot swallow | | | tablets during attack | | | | | | - **C/I for MAOIs (riz, sum, | | | zol)**: increased risk of | | | vasoconstriction and cannot | | | be used with MAOIs | | | | | | **Ergotamines** -- *Ergotamine, | | | dihydroergotamine* | | | | | | - **MOA**: partially activate | | | 5-HT1, and act on 5-HT2, D1, | | | D2, a1, a2 | | | | | | - **Effect**: cause | | | vasoconstriction and block | | | trigeminal nerve transmission | | | -- including coronary | | | vasoconstriction | | | | | | - **ADEs**: nausea and | | | vomiting, do not use with | | | cardiac disease | | | | | | [Migraine **prophylaxis** | | | ] | | | | | | 2 or 3 severe migraine attacks | | | monthly, with significantly | | | impaired QOL: | | | | | | - Acute treatment \>2-4 days / | | | month | | | | | | - Poor response to treatment | | | taken at the start of | | | migraine attack | | | | | | ONE agent at a time at lowest | | | effective dose 8-12 weeks and | | | assess efficacy 3-6 months then | | | review. | | | | | | - **TCAs** -- increase 5HT and | | | NA to inhibit spinothalamic | | | neurons | | | | | | - Pxs only reduces frequency | | | and severity -- still need | | | acute treatment | | | | | | *Comorbidities and migraine | | | prophylaxis* | | | | | | +---------+---------+---------+ | | | | **Comor | **Use** | **Avoid | | | | | bidity* | | ** | | | | | * | | | | | | +=========+=========+=========+ | | | | Insomni | TCA, | - | | | | | a | pregaba | | | | | | | lin, | | | | | | | gabapen | | | | | | | tin | | | | | +---------+---------+---------+ | | | | Anxiety | Propran | - | | | | | , | olol | | | | | | postura | | | | | | | l | | | | | | | tachyca | | | | | | | rdia | | | | | | +---------+---------+---------+ | | | | Obesity | Candesa | Sodium | | | | | or | rtan, | valproa | | | | | diabete | topiram | te | | | | | s | ate | | | | | | | | Pizotif | | | | | | | en | | | | +---------+---------+---------+ | | | | Fibromy | TCA, | - | | | | | algia | pregaba | | | | | | | lin | | | | | +---------+---------+---------+ | | | | Neck | TCA | - | | | | | tension | | | | | | | , | | | | | | | bruxism | | | | | | +---------+---------+---------+ | | | | Asthma | - | Beta | | | | | | | blocker | | | | +---------+---------+---------+ | | | | History | - | Topiram | | | | | of | | ate | | | | | renal | | | | | | | calculi | | | | | | +---------+---------+---------+ | | | | Current | SNRI, | Caution | | | | | /histor | SSRI, | with | | | | | y | TCA | topiram | | | | | of | | ate, | | | | | depress | | BBs or | | | | | ion | | flunari | | | | | | | zine | | | | +---------+---------+---------+ | | | | Un/inad | Propran | - | | | | | equatel | olol, | | | | | | y | gabapen | | | | | | treated | tin, | | | | | | menopau | SSRI | | | | | | se | | | | | | +---------+---------+---------+ | | | | | | [Supplements and migraines | | | ] | | | | | | 3-month trial recommended (harm | | | is low), can be used in | | | combination. | | | | | | +---------+---------+---------+ | | | | Magnesi | **Aura* | 400-650 | | | | | um | * | mg | | | | | | -- | d | | | | | | stops | | | | | | | cortica | | | | | | | l | | | | | | | spreadi | | | | | | | ng | | | | | | | depress | | | | | | | ion. | | | | | | | | | | | | | | Prevent | | | | | | | s | | | | | | | blood | | | | | | | vessel | | | | | | | narrowi | | | | | | | ng. | | | | | +=========+=========+=========+ | | | | Ribofla | **Preve | 200mg | | | | | vin | nts | bd | | | | | (B2) | migrain | | | | | | | e** | | | | | | | and | | | | | | | improve | | | | | | | brain | | | | | | | mitocho | | | | | | | ndrial | | | | | | | functio | | | | | | | n. | | | | | | | | | | | | | | - Mit | | | | | | | ochondr | | | | | | | ial | | | | | | | dys | | | | | | | functio | | | | | | | n | | | | | | | may | | | | | | | be | | | | | | | a | | | | | | | mec | | | | | | | hanism | | | | | | | whi | | | | | | | ch | | | | | | | lea | | | | | | | ds | | | | | | | to | | | | | | | mig | | | | | | | raines | | | | | +---------+---------+---------+ | | | | Co-enzy | **Preve | 150-300 | | | | | me | nt | mg | | | | | Q10 | migrain | d | | | | | | e** | | | | | | | and | | | | | | | improve | | | | | | | brain | | | | | | | mitocho | | | | | | | ndrial | | | | | | | functio | | | | | | | n. | | | | | +---------+---------+---------+ | | | | | | **Lifestyle approaches -- for TTH | | | and migraine** | | | | | | - Regular sleep schedule | | | | | | - Minimal variation in BG -- | | | regular meals, avoid excess | | | simple CHO | | | | | | - Adequate dehydration -- | | | 1.5-2L per day | | | | | | - Limited caffeinated beverages | | | -- 1-2 cups daily | | | | | | - Regular exercise -- 30-40 | | | mins 3-4 times/week, walking | | | avoids excessive motions | | | which could trigger migraine | | | | | | - Workplace ergonomics (esp | | | with computer), regular | | | breaks (rest eyes) | | | | | | - Regular relaxation techniques | | | especially if stress is | | | trigger | | | | | | - Avoid known triggers -- | | | alcohol, monosodium | | | glutamate, citrus, fruit, | | | chocolate, preserved meats, | | | perfume | +-----------------------------------+-----------------------------------+ | Explain the underlying cause of | **Medication overuse headache** | | medication over-use headaches | | | | - Increased risk **of migraine | | | headache** and **tension | | | headaches** | | | | | | - Initially taking medication | | | for episodic headaches as | | | headache frequency increases | | | patients *switch to | | | pre-emptive use in | | | anticipation* | | | | | | - Pathophysiology is unknown | | | common neurobiological | | | pathways with substance | | | abuse, conceptualised as a | | | behavioural disorder | | | | | | [Definition of MOH] | | | | | | Headaches \>15 days / month for | | | \>3 months and: | | | | | | - Opioid, triptan and | | | ergot \>10 days / month -- | | | more potent in inducing MOH, | | | so threshold for use is lower | | | | | | - Simple analgesics \> 15 days | | | / month | | | | | | **Management** | | | | | | MOH typically resolves after | | | overuse is stropped (number of | | | weeks). | | | | | | - Naproxen and prednisolone | | | supress symptoms during | | | bridge therapy | | | | | |  | +-----------------------------------+-----------------------------------+ | Outcomes | EBCM in migraine | +-----------------------------------+-----------------------------------+ | Provide evidence-based advice on | **Food as a trigger** | | the potential role of selected | | | CMs in the prevention of migraine | - Skipping meals is a trigger | | headaches | for migraines -- | | | hypoglycaemia, reactive | | Dietary Triggers | hypoglycaemia and stress | | | response | | | | | | - Food and headache diary | | | helpful to identify dietary | | | triggers | | | | | | - Phenylethylamine, | | | **tyramine**, aspartame, | | | monosodium glutamate (flavour | | | enhancer), nitrate, nitrates, | | | alcohol, caffeine (also tx) | | | | | | - Tyramine: metabolite of | | | tyrosine in aged cheese | | | and ferments | | | | | | - Paediatric headache disorder: | | | caffeine, MSG, coca - most | | | identified | | | | | | **Modifiable risk factors** | | | | | | - Food groups and chemical | | | constituents | | | | | | - Stress | | | | | | - Excessive amounts of caffeine | | | and alcohol | | | | | | - Poor sleep and insomnia | +-----------------------------------+-----------------------------------+ | Feverfew, Magnesium, Riboflavin | **Level A evidence**: Petasites | | and CoQ10 | | | | - Should be offered to patients | | Explain significant known | requiring migraine | | interactions of drug-nutrient and | prophylaxis | | drug-herb interactions | | | | - Some products contain toxic | | | alkaloid pyrrolizidine | | | alkaloids -- unknown quality | | | of source and potential | | | toxicity so avoid this med | | | | | | **Level B**: feverfew, magnesium, | | | riboflavin | | | | | | - Could be considered for | | | patients requiring migraine | | | pxs | | | | | | **Level C**: co-enzyme Q10 | | | | | | - May be considered for | | | patients requiring migraine | | | pxs | | | | | | **Feverfew** -- Tanacetum | | | parthenium (chrysanthemum family) | | | | | | - Herb rich in sesquiterpene | | | lactones - parthenolide | | | | | | - Actions: | | | | | | - Inhibits 5-HT release | | | from platelets | | | | | | - Potential COX and LOX | | | inhibition = | | | anti-inflammatory action | | | | | | - Cochrane: difference | | | between feverfew and | | | placebo of 0.6 migraines | | | per month, finding that | | | this is probably | | | effective at **reducing | | | the number of migraines** | | | | | | - **Dose**: most products | | | contain 0-2-0.35% | | | pathenolide, observed | | | benefits from 50-150mg | | | powdered leaves daily for up | | | to 4 months | | | | | | - **ADEs**: long term use \>4 | | | months may cause moth | | | ulceration, GI sx | | | | | | - **Contact dermatitis**: mouth | | | sores + lip swelling when | | | chewing leaves | | | | | | - **Other**: nervousness, | | | dizziness, headache, | | | insomnia, joint stiffness, | | | tiredness, menstrual changes, | | | weight gain | | | | | | - **Allergy** or | | | hypersensitivity to | | | Compositae family should be | | | avoided | | | | | | - **Interactions**: | | | | | | - Suggested inhibition of | | | 1A1, 2C8, 2C9, 2C19, 2D6 | | | and 3A4 | | | | | | - Cease two weeks before | | | surgery and avoid with | | | anti-coagulants or | | | anti-platelets -- | | | warfarin, heparin, | | | aspirin, nsaids | | | | | | - **Cis**: not recommended in P | | | and BF, or | | | children/adolescents \ 350/day, | | | overuse of hydroxide and | | | sulphate forms can cause | | | other deficiencies | | | | | | - **Cis**: heart block, renal | | | failure | | | | | | - **P****adolescence** | | | : | | | genetic syndrome, CNS | | | infection | | | | | | - **Young adult**: head trauma | | | | | | - **Older adult**: stroke, | | | brain tumour | | | | | | [Epidemiology] | | | | | | - 5% will have a seizure: 1/3 | | | neonate febrile convulsions, | | | 1/3 single seizure, and 1/3 | | | epilepsy | | | | | | - Highest incidence in neonates | | | and elderly | | | | | | - 2-3x the standardised | | | mortality rate | | | | | | [Prognosis ] | | | | | | - 60% achieve seizure control | | | with monotherapy -- some | | | remain seizure free post drug | | | withdrawal | | | | | | - If seizure control is | | | achieved, titrate | | | downwards after 2 years | | | seizure free over several | | | months | | | | | | - Cannot drive until three | | | months drug free | | | | | | [Diagnosis] | | | | | | - Primarily via patient / eye | | | witness history | | | | | | - EEG -- difficult to capture | | | at the correct time | | | | | | - MRI -- difficult to capture | | | at the correct time | | | | | | [Mechanisms by which seizures | | | occur ] | | | | | | *Excitatory and inhibitory | | | neurotransmitter imbalance, and | | | excessive Ach, NAd and 5HT can | | | precipitate seizures, as can | | | changes in:* | | | | | | - Ion channel conduction | | | | | | - Membrane receptor response | | | | | | - Messenger systems | | | | | | - Gene transcription | +-----------------------------------+-----------------------------------+ | Describe: 1. Different types of | **Epilepsy classifications** | | seizures and epilepsy syndromes | | | 2. The mechanism of action of | **Focal onset -- partial: begins | | antiepileptic drugs including | in one hemisphere of the brain** | | examples of those that decrease | | | excitation and increase | - No definite sx, including | | inhibition | motor, sensory or behaviour | | | | | | - Aware, impaired awareness or | | | secondary generalised LOC | | | | | | **Generalised: both hemispheres | | | of the brain are involved** | | | | | | - LOC and bilateral motor | | | **symptoms** include: | | | | | | - Absence or vacant stare | | | | | | - Tonic muscle rigidity | | | | | | - Clonic rhythmic movements | | | | | | - Myoclonic jerking | | | | | | - Tonic-clonic | | | | | | - Atonic with muscle | | | flaccidity | | | | | | - [Idiopathic] | | | | | | - Childhood / juvenile | | | absence epilepsy | | | | | | - Juvenile myoclonic | | | epilepsy -- commonest in | | | adults | | | | | | - Epilepsy with | | | tonic-clonic seizures on | | | awakening | | | | | | - [Symptomatic / secondary | | | ] | | | | | | - Lennox gastaut syndrome | | | | | | **Seizure classifications** | | | | | | - [Focal seizures:] | | | begin in one area of the | | | brain | | | | | | - [Generalised | | | seizures]: all | | | brain areas are | | | hyperexcitable | | | | | | - [Tonic-clonic]: | | | initially tonic stiffening, | | | then clonic rhythmic jerking | | | | | | - [Absence] | | | seizures: blanking out | | | | | | - [Myoclonic]: | | | jerking and twitching of | | | muscles | | | | | | - [Infantile | | | spasms]: | | | stiffening + movement of head | | | and limbs back/forth | | | | | | **Pharmacotherapy for epilepsy** | | | | | | [Broad guidance ] | | | | | | Titrate to therapeutic dose | | | (phenytoin excepted) -- starting | | | low and going slow to achieve | | | lowest effective dose. | | | | | | - Caution with narrow | | | therapeutic index | | | | | | - TDM: phenytoin, lamotrigine | | | (drugs in pregnancy) | | | | | | - Partial carbamazepine | | | | | | - Generalised sodium valproate | | | | | | +--------------+--------------+ | | | | **First line | | | | | | agents** | | | | | +==============+==============+ | | | | *Carbamazepi | - **Adult* | | | | | ne* | *: | | | | | | 100mg n | | | | | *Blocking | increasi | | | | | voltage | ng | | | | | gated and | by | | | | | use | 100-200m | | | | | dependant | g | | | | | sodium | weekly | | | | | channels.* | to | | | | | | 200mg-60 | | | | | | 0mg | | | | | | bd. | | | | | | | | | | | | - **Child* | | | | | | *: | | | | | | 2.5mg/kg | | | | | | bd | | | | | | increasi | | | | | | ng | | | | | | to | | | | | | 5-10mg/k | | | | | | g | | | | | | bd. | | | | | | | | | | | | - **PK**: | | | | | | carbamaz | | | | | | epine | | | | | | auto | | | | | | induces | | | | | | own | | | | | | metaboli | | | | | | sm | | | | | | | | | | | | - **ADRs** | | | | | | : | | | | | | diplopia | | | | | | - | | | | | | earliest | | | | | | sign of | | | | | | toxicity | | | | | | , | | | | | | morbilli | | | | | | form | | | | | | rash | | | | | | Asian, | | | | | | HLA-B\*1 | | | | | | 502 | | | | | | test | | | | +--------------+--------------+ | | | | *Sodium | Adult gender | | | | | valproate* | dependant | | | | | | dosing: | | | | | *Prevent | | | | | | voltage and | - **Female | | | | | use | ** | | | | | dependant | of | | | | | sodium | **childb | | | | | channels.* | earing | | | | | | potentia | | | | | - \+ | l** | | | | | enhance | **w/o | | | | | GABA, | contrace | | | | | inhibit | ption:** | | | | | glutamat | max | | | | | e | 600mg/d, | | | | | and | 400mg d | | | | | inhibit | for 1 | | | | | Ca+ | week | | | | | channels | then | | | | | | 200mg m | | | | | | and | | | | | | 400mg n | | | | | | | | | | | | - **Male** | | | | | | and | | | | | | **female | | | | | | ** | | | | | | who d/n | | | | | | meet | | | | | | above | | | | | | criteria | | | | | | : | | | | | | 500mg d | | | | | | for 1 | | | | | | week | | | | | | then | | | | | | 500mg bd | | | | | | with | | | | | | maximum | | | | | | of | | | | | | 1500mg d | | | | | | | | | | | | - **Child* | | | | | | *: | | | | | | 5mg/kg | | | | | | bd to | | | | | | 10-20mg/ | | | | | | kg | | | | | | bd | | | | | | | | | | | | - **ADRs** | | | | | | : | | | | | | sedation | | | | | | , | | | | | | hair | | | | | | loss, | | | | | | weight | | | | | | gain | | | | | | | | | | | | - Unpredic | | | | | | table | | | | | | drug-dru | | | | | | g | | | | | | interact | | | | | | ions | | | | | | | | | | | | - **Terato | | | | | | genicity**: | | | | | | dose | | | | | | relat