AY 2024 Sem 2 A477 IS05 Lecture Notes - student PDF

A477 Clinical Skills in Pharmacy Practice Lesson 5: Epilepsy Interactive Seminar Module Chair: Jin Mengqi Updated on 22nd Oct 2024...

A477 Clinical Skills in Pharmacy Practice Lesson 5: Epilepsy Interactive Seminar Module Chair: Jin Mengqi Updated on 22nd Oct 2024 COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 1  OFFICIAL (CLOSED) \ NON- SENSITIVE Learning Outcomes 1. Explain what epilepsy is Describe the pathophysiology of epilepsy (competent) Distinguish between partial and generalized seizures based on their definitions and the associated signs and symptoms (competent) List the risk factors for epilepsy (competent) List the signs and symptoms of status epilepticus (competent) Describe the complications of epilepsy (proficient) 2. Propose pharmacological treatment for epilepsy Define the goal of treatment in epilepsy (competent) Explain the rationale and types of pharmacological treatment for epilepsy (proficient) List the common side effects of medications used in epilepsy. (competent) COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 2  OFFICIAL (CLOSED) \ NON- SENSITIVE Learning Outcomes 2. Propose pharmacological treatment for epilepsy (continued) Demonstrate skills in educating patient to identify rare medication side effects of antiepileptics and when to seek medical attention (proficient) Evaluate prescription orders for drug-related problems, including drug-drug, drug-food interactions, inappropriate use of formulation/dosage with anti-epileptic medications (proficient) Assess patient’s profile to recommend appropriate pharmacological treatment, including special population of child-bearing age woman (advanced) Demonstrate patient counselling skills related to the medications used in epilepsy (proficient) COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 3  OFFICIAL (CLOSED) \ NON- SENSITIVE Watch this video: Reference: https://www.youtube.com/watch?v=PG12JfJJW9U COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 4  OFFICIAL (CLOSED) \ NON- SENSITIVE What is Epilepsy? Epilepsy is a common neurological disorder characterised by recurring seizures with or without convulsions. A seizure is a sudden, uncontrolled electrical disturbance in the brain that can lead to changes in behaviour, movements or feelings, and in levels of consciousness. A convulsion describes the involuntary action of jerking and contraction. If the patient has two or more seizures or a tendency to have recurrent seizures, the patient has epilepsy. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 5  OFFICIAL (CLOSED) \ NON- SENSITIVE Risks factors for epilepsy  Babies who are born small for their age. More common  Babies who have seizures in the first month  Seizures occurring within days after head of their lives. injury (“early posttraumatic seizures”).  Babies who are born with abnormal areas in  Family history of epilepsy or fever-related their brains. seizures.  Cerebral palsy.  Abnormal blood vessels in the brain.  Conditions with intellectual and  Serious brain injury or lack of oxygen to the developmental disabilities. brain.  Alzheimer’s disease (late in the illness).  Brain tumors.  Autism spectrum disorder.  Infections of the brain: abscess, meningitis,  Use of illegal drugs, such as cocaine. or encephalitis.  Stroke resulting from blockage of arteries. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 6  OFFICIAL (CLOSED) \ NON- SENSITIVE Pathophysiology A seizure results when a sudden imbalance occurs between the excitatory and inhibitory forces within the network of cortical neurons in favour of a sudden-onset net excitation. Normal Inhibition Excitation Epilepsy Excitation Glutamate GABA Aspartate Inhibition COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 7  OFFICIAL (CLOSED) \ NON- SENSITIVE Epilepsy: Clinical Presentation Classification of epileptic seizure Partial Seizure Generalized Seizure Status Unclassifie (bilaterally symmetrical (local onset) epilepticus d seizures without local onset) Simple partial Simple Partial Seizures Myoclonic Seizures Sudden onset of muscle contractions that may Mayseizure be motor, sensory, Myoclonic occur throughout the body psychic and/or autonomic Onset may be so sudden that the patient falls to Medical emergency in the ground, or so subtle that the seizure looks like which seizures recur a tremor without the patient Complex Partial Seizures regaining consciousness Complex Loss of consciousness Tonic Clonic Seizures (Grand mal) between events partial Tonic phase: fall, loss of consciousness, extension seizure Automatisms may occur during unconsciousness Tonic-clonic of arms & legs, fingers & jaw clenched Clonic phase: muscles relax, resulting in rhythmic jerking of the body & head Secondarily generalized Absence Seizures Rapid onset and characterized by automatisms: This condition may Absence licking lips, chewing, grimacing, scratching, fumbling develop in any type of seizure, but it is most with clothes, blank staring, change in facial common in tonic-clonic expression seizures Lack of awareness, responsiveness, memory Status epilepticus may cause brain damage or cognitive dysfunction and may be fatal 8 COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE  OFFICIAL (CLOSED) \ NON- SENSITIVE Defining Different Seizure Types PARTIAL SEIZURES GENERALIZED SEIZURES Seizures that initially affect one specific Seizures that affect both hemispheres of area in one hemisphere of the brain. the brain. May or may not cause an alteration of Result in a loss of consciousness. consciousness. Symptoms can include blank stares, Symptoms can include muscle falling to the floor, sudden muscle jerks, twitching, repetitive motions, and the and repetitive stiffening and relaxing of appearance of “daydreaming”. muscles. Partial seizures can become generalized seizures. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 9  OFFICIAL (CLOSED) \ NON- SENSITIVE Tonic Clonic Seizure: The most common type of seizure Tonic phase: cause stiff muscles and may cause loss of consciousness. These seizures usually affect muscles in the back, arms and legs and may cause patient to fall to the ground. Clonic phase: associated with repeated or rhythmic, jerking muscle movements. These seizures usually affect the neck, face and arms. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 10  OFFICIAL (CLOSED) \ NON- SENSITIVE Epilepsy complication: Sudden Unexplained Death in Epilepsy (SUDEP) It occurs in a small percentage of persons with epilepsy. Persons with symptomatic epilepsy have a much greater risk. Autopsies have not uncovered a physical cause of SUDEP. It is possible that pulmonary oedema, suffocation, or cardiac arrhythmias may be responsible. Some people appear to be at a higher risk than others, such as young adults with generalized tonic-clonic seizures that are not fully controlled with medication and those who abuse alcohol and illicit drugs. Patients using two or more anticonvulsants may be at increased risk for SUDEP. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 11  OFFICIAL (CLOSED) \ NON- SENSITIVE Activity 1: Fill in the blanks 1. A person with has seizures. 2. When a seizure occurs in one part of the brain and not in the whole brain, it is called a seizure. 3. A causes a person’s body to involuntarily jerk and contract. 4. ________ is a medical emergency in which seizures recur without the patient regaining consciousness between events. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 12  OFFICIAL (CLOSED) \ NON- SENSITIVE Guidelines for Antiepileptic Drug Therapy First single agent from 1st line treatment Goal of treatment: Start low and increase slowly to effective control of Help person with epilepsy lead full and seizure or patient cannot tolerate side effect further. productive life. Eliminate seizures without producing side effects. If failed, try second single agent Tailor treatment to needs of individuals / & increase slowly while withdrawing first agent. special populations. Principles of Antiepileptic Drug Selection: Depends on the type of epilepsy If failed, try third single agent Select the best drug to fit the patient’s & increase slowly while withdrawing second agent. profile subsidy status  NDF Use the least expensive antiepileptic drug Antiepileptic drugs which can be taken If failed, start combination. OD preferred over BD/TDS Don’t exceed 3 agents on combination. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 13  OFFICIAL (CLOSED) \ NON- SENSITIVE Antiepileptic drugs: Patient education You may not experience any benefits immediately after starting the medication as it may take up to a few weeks before this medication can exert its full effects. You should continue to take your medication regularly as instructed by your doctor even if you feel well. Stopping your medication without informing your healthcare professional may cause your condition to worsen quickly. Do not stop taking or adjust the dose of this medication without consulting your healthcare professional. Do not change the medication that was dispensed to you without informing your healthcare professional Avoid drinking alcohol while taking this medication. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 14  OFFICIAL (CLOSED) \ NON- SENSITIVE 1st generation of antiepileptic drugs Drug name Indication Dosing Carbamazepine Complex or simple partial seizures (with Start with 100-200mg OD-BD or without loss of consciousness) with or Max: 2g/day in divided doses without secondary generalization. Usual dose: 800mg to 1200mg daily in Generalized tonic-clonic seizures. Mixed divided doses. forms of seizures. Phenytoin Oral dosage form is indicated for control PO: Start with 300mg daily in divided dose 3 of tonic-clonic (grand mal) and doses. Max: 600mg/day psychomotor (temporal lobe) seizures. Usual dose: 300-400mg daily in 2-4 divided dose Injection is indicated for status IV: loading dose: 10 to 15 mg/kg, followed by epilepticus. maintenance doses of 100 mg orally or *Phenytoin has narrow therapeutic index, intravenously every 6 to 8 hours. need careful monitoring Sodium All forms of epilepsy Start at 600mg daily in 2-3 divided doses. Valproate Max:2.5g/day Usual dose: 1-2g daily COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 15  OFFICIAL (CLOSED) \ NON- SENSITIVE Activity 2 Use Mediview to help you find common preparations available for the following antiepileptics. Drug name Preparations available in SG Carbamazepine Phenytoin Sodium Valproate COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 16  OFFICIAL (CLOSED) \ NON- SENSITIVE 1st generation of antiepileptic drugs Common side effects: Dizziness, feeling lightheaded, Drowsiness, GI discomfort: N/V, diarrhoea, constipation Drug name Additional drug specific side effects Carbamazepine Headache, loss of appetite, hyponatremia Phenytoin Headache, decrease in folic acid level in the body Long term use: Growing of hair around the face Thickening of the lips, swollen gums  maintain good oral hygiene and using a soft- bristled toothbrush. Sodium Valproate Change in hair texture to finer at the beginning when you start to use the medication Increase in appetite, weight gain Slight and fine tremors of fingers and hands at the beginning of using the medication. Irregular and/or painful menstruation COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 17  OFFICIAL (CLOSED) \ NON- SENSITIVE 1st generation of antiepileptic drugs Universal rare and serious side effects require immediate medical Drug specific rare SEs: attention Blistering, peeling, red skin rash due to Stevens-Johnson syndrome (SJS) Carbamazepine: and Toxic Epidermal Necrolysis (TEN)  carbamazepine requires testing for Chest pain or fast, pounding or irregular heartbeat specific gene (HLA-B*1502) before initiation Carbamazepine/phenytoin: Blood disorders such as prolonged fever, chills, sore throat, mouth ulcers or Changes in how much and sores or unusual bleeding/bruising how often you urinate Unstable/unsteady Liver problems: Dark colored urine or light-colored stools, yellowing of your movements (Ataxia) eyes or skin, severe loss of appetite, stomach pain, nausea, vomiting that Sodium Valproate: does not go away Severe weakness or dizziness Double vision In rare cases, they may cause the following changes to a person’s mental condition (suicidal ideation and suicidal tendencies), especially in the first few weeks of treatment or during dose changes: Worsening agitation, restlessness, violent behavior New or worsening thoughts of harming yourself or ending your life Other changes in mood or behavior COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 18  OFFICIAL (CLOSED) \ NON- SENSITIVE 1st generation of antiepileptic drugs Drug name Drug metabolism Important note for administration Carbamazepine Substrate of Take after food to avoid stomach upset. CYP2C8 (minor), Cat D drug-drug interaction with hormonal contraceptive and CYP3A4 (major) antibiotics like macrolides. CYP3A4 inducer Avoid grapefruit juice (as it increases the concentration of (strong) carbamazepine). Phenytoin Substrate of Take this medication with or after food. Take phenytoin two hours CYP2C19 (major), apart from a high-protein meal (e.g. with milk or meat), antacids or CYP2C9 (major), enteral feedings, otherwise its efficacy may be reduced. CYP3A4 inducer Cat D drug-drug interaction with hormonal contraceptives. (strong) Sodium Substrate of Take this medication with or after food. Valproate CYP2C19 (minor), CYP2C9 (minor), etc. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 19  OFFICIAL (CLOSED) \ NON- SENSITIVE Activity 3 Use UpToDate drug information to help you complete the following table. Drug name Reproductive consideration (Child-bearing potential woman with or without family planning) Carbamazepine Phenytoin Sodium Valproate COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 20  OFFICIAL (CLOSED) \ NON- SENSITIVE Levetiracetam Dose adjustment in renally impaired MOA (FYI): Synaptic vessel protein SV2A binding in the brain. Indications Dosing Monotherapy and adjunct therapy for partial Initial: 500mg BD seizures with or without secondary Max dose 1.5g BD generalisation Adjunct therapy in primary generalised tonic- clonic seizures and myoclonic seizure COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 21  OFFICIAL (CLOSED) \ NON- SENSITIVE Levetiracetam: Counselling points Take this medication with or without food Common side effects: Dizziness or feeling lightheaded Drowsiness GI SEs: Nausea, vomiting, diarrhea; loss of appetite Pain: Neck pain, tingling or prickling sensation on skin Rare and serious side effects are similar to 1 st generation antiepileptic universal side effects, but It may cause hallucinations (seeing or hearing things that are not there), depression, aggression, irritability It may cause problems in balance/ coordination, unsteadiness in movement It does not cause hepatotoxicity Monotherapy with the lowest effective dose is recommended during pregnancy COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 22  OFFICIAL (CLOSED) \ NON- SENSITIVE Lamotrigine MOA (FYI): Fast Na+ channel blockade; inhibits glutamate. Indications Dosing Adjunct or monotherapy in the treatment of Initial: 25 mg OD epilepsy, for partial seizures and generalized seizures Maintenance: 100-200mg daily in 1-2 divided doses, increased if necessary up to 500mg daily Drug interactions: Not a CYP450 inducer or inhibitor COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 23  OFFICIAL (CLOSED) \ NON- SENSITIVE Lamotrigine: Counselling points Take this medication with or without food Common side effects: Dizziness or feeling lightheaded Drowsiness, fatigue, headache GI SEs: Nausea, vomiting, constipation; loss of appetite and weight loss Blurred or double vision or uncontrollable eye jerking Pain: Joint pain, neck pain, numbness in the hands and feet; Painful menstruation Swelling of hands or legs from water retention - to inform doctor if bothersome or persistent Rare and serious side effects are similar to 1 st generation antiepileptic universal side effects Lamotrigine lowers the efficacy of oral contraceptives significantly, child-bearing woman should use alternate or back-up methods of contraception if not planning for family. Monotherapy with the lowest effective dose is recommended during pregnancy COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 24  OFFICIAL (CLOSED) \ NON- SENSITIVE Gabapentin Max dose MOA (FYI): Blocks Ca2+ channels. adjustment in renally impaired Indications Dosing Monotherapy for partial seizures with or without Initial: 300mg OD-TDS secondary generalisation Usual dose: 900mg to 3.6g daily in 3 divided doses. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 25  OFFICIAL (CLOSED) \ NON- SENSITIVE Gabapentin: Counselling points May be taken with or without food Take antacids at least two hours apart from gabapentin, as they may reduce the amount of medication being taken up by your body. Common side effects: Nausea Drowsiness Dizziness Swelling of hands or legs Fatigue (Feeling of tiredness), muscle weakness Rare and serious side effects include: Blurring of your vision or loss of vision Worsening agitation, restlessness or violent behaviour COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 26  OFFICIAL (CLOSED) \ NON- SENSITIVE Activity 4 What is the implication for this special pharmacokinetics property? UpToDate: Gabapentin Drug Information COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 27  OFFICIAL (CLOSED) \ NON- SENSITIVE Clonazepam Indications Dosing All forms of epilepsy, myoclonus Initial: 0.5 to 1.5 mg/day in 1 to 3 divided doses *Only recommended by specialist after all the other antiepileptic drugs fail to work Maintenance: 2–8 mg daily; may be given in 1–2 divided doses if necessary Counseling points: This medicine may cause dizziness, muscle weakness, fatigue, confusion, vomiting, constipation and changes in appetite. These may eventually decrease or disappear. Drowsiness may persist into the following day. If affected by dizziness or drowsiness, do not drive or operate machinery. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 28  OFFICIAL (CLOSED) \ NON- SENSITIVE Recall: Status epilepticus is a medical emergency in which seizures recur without the patient regaining consciousness between events. Status epilepticus: Management  Give immediate emergency care and treatment to children, young people and adults who have prolonged (lasting 5 minutes or more) or repeated (≥3 in an hour) convulsive seizures.  Administer rectal diazepam in the community or IV lorazepam in the hospital.  Monitor the person for obstruction in airway, respiratory and cardiac function.  In the community, call an ambulance if seizure continues 5 minutes after administering the emergency medication. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 29  OFFICIAL (CLOSED) \ NON- SENSITIVE Use of Diazepam / Lorazepam in status epilepticus MOA(FYI): Enhance GABA-A receptor responses Drug Dosing Diazepam (rectal) By rectum as rectal solution, (adult and child > 12yo): 10-20mg, repeated once after 10-15 minutes if necessary. Reference on how to use rectal diazepam: https://www.singhealth.com.sg/sites/shcommonassets/Assets/Medication /pdf/diazepam-rectal-administration-english.pdf Lorazepam(IV) 4 mg for 1 dose, then 4 mg after 10 minutes if required for 1 dose, to be administered into a large vein COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 30  OFFICIAL (CLOSED) \ NON- What can you do for someone having a SENSITIVE seizure? (FYI) 1.Should you hold the person to stop the movement? 2.Should you put anything in patient’s mouth to prevent biting his/her tongue? 3.Should you do mouth-to-mouth breaths (like CPR? COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 31  OFFICIAL (CLOSED) \ NON- SENSITIVE Things to do at the end of lesson Revise today’s topic and attempt LEO cluster quiz (SDL) Asynchronous E-learning for week 6. No pre-readings for week 6 in Mc Graw Hill smartbook. COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE 32  OFFICIAL (CLOSED) \ NON- SENSITIVE Next week’s topics Renal and hepatic impairment 33 COPYRIGHT © REPUBLIC POLYTECHNIC, SINGAPORE