Dizziness Pharmacotherapy Overview PDF

**Dizziness: Pharmacotherapy Overview** **Background:** Dizziness is a common symptom with many potential causes. It refers to a range of sensations including lightheadedness, vertigo, disequilibrium, and presyncope. It is important to distinguish between vertigo (a specific type of dizziness assoc...

**Dizziness: Pharmacotherapy Overview** **Background:** Dizziness is a common symptom with many potential causes. It refers to a range of sensations including lightheadedness, vertigo, disequilibrium, and presyncope. It is important to distinguish between vertigo (a specific type of dizziness associated with a spinning sensation) and other forms of dizziness like presyncope (feeling faint), disequilibrium (unsteadiness), and lightheadedness. **Pathophysiology & Etiology:** Dizziness can be categorized into **central** or **peripheral** causes: 1. **Peripheral causes**: - **Benign paroxysmal positional vertigo (BPPV)**: Most common cause of vertigo. Caused by displaced otoliths in the semicircular canals. - **Meniere's disease**: Characterized by episodic vertigo, tinnitus, and hearing loss due to excess fluid in the inner ear. - **Vestibular neuritis/labyrinthitis**: Viral infections causing inflammation of the vestibular system, resulting in vertigo. 2. **Central causes**: - **Stroke/TIA**: Can cause dizziness and imbalance due to impaired blood flow to the brain. - **Multiple sclerosis (MS)**: Neurological disease that can affect coordination and balance. - **Migrainous vertigo**: Dizziness associated with migraines, often accompanied by headache and photophobia. **Risk Factors:** - Age (older adults) - History of head trauma - Neurological disorders (e.g., MS, stroke) - Cardiovascular conditions (e.g., orthostatic hypotension) - Diabetes (may affect inner ear function) - Medication use (e.g., antihypertensives, benzodiazepines) **Non-Pharmacological Therapy:** 1. **Vestibular rehabilitation**: Used primarily for conditions like BPPV and vestibular neuritis to help retrain the brain to compensate for balance issues. 2. **Epley maneuver**: A physical therapy technique used for BPPV to reposition displaced otoliths. 3. **Dietary changes for Meniere's disease**: Low-salt diet to reduce fluid retention in the inner ear. 4. **Hydration and avoiding triggers**: Particularly important in orthostatic hypotension and dehydration-induced dizziness. **Pharmacological Therapy:** **First-line Treatments:** 1. **Benign Paroxysmal Positional Vertigo (BPPV)**: - **Non-pharmacological**: Epley maneuver. - **Pharmacological**: Usually, no drugs are required for BPPV unless symptoms are severe. 2. **Vestibular Neuritis/Labyrinthitis**: - **Corticosteroids (e.g., prednisone)**: Can be used in acute vestibular neuritis to reduce inflammation (though not always first-line). - **Antiemetics (e.g., meclizine, dimenhydrinate)**: Used for symptom relief in acute episodes. 3. **Meniere's Disease**: - **Diuretics (e.g., hydrochlorothiazide)**: To reduce fluid buildup. - **Antihistamines (e.g., meclizine)** or **benzodiazepines (e.g., diazepam)**: For acute vertigo attacks. 4. **Migrainous Vertigo**: - **Triptans (e.g., sumatriptan)**: Used for acute attacks associated with migraines. - **Beta-blockers (e.g., propranolol)** or **anticonvulsants (e.g., topiramate)**: Used for migraine prevention. **Second-line Treatments:** 1. **Vertigo of Unknown Cause**: - **Anticholinergics (e.g., scopolamine)**: For motion sickness-related dizziness. 2. **Benzodiazepines** (e.g., lorazepam): In cases of acute anxiety-induced dizziness. 3. **Antihistamines (e.g., diphenhydramine)**: Can be used for dizziness associated with vestibular disorders but should be used cautiously due to sedation. **Side Effects of Common Medications:** 1. **Antihistamines (e.g., meclizine, dimenhydrinate)**: - **Drowsiness** and sedation. - **Anticholinergic effects**: Dry mouth, constipation, blurred vision. 2. **Benzodiazepines (e.g., lorazepam, diazepam)**: - **Sedation**. - **Dependence** and withdrawal symptoms if used long-term. 3. **Corticosteroids**: - **Weight gain**, **hyperglycemia**, **osteoporosis** (with long-term use). 4. **Diuretics (e.g., hydrochlorothiazide)**: - **Electrolyte imbalances** (e.g., hypokalemia). - **Dehydration** and **orthostatic hypotension**. **Monitoring and Follow-up:** - **For vestibular disorders**: Monitor for improvement in balance, dizziness, and vertigo with non-pharmacological therapies (e.g., Epley maneuver). - **For Meniere's disease**: Regular monitoring of renal function and electrolytes if diuretics are used. - **For corticosteroids**: Monitor blood glucose levels, weight, and signs of infection. - **For antihistamines and benzodiazepines**: Assess for signs of sedation, fall risk, and tolerance/dependence if used long-term. - **For diuretics**: Regular monitoring of electrolytes and kidney function to avoid complications. **Important Points for Pharmacists:** - **Accurate diagnosis** is crucial as treatment strategies differ greatly depending on the etiology. - **Counsel patients** on the potential sedative effects of antihistamines, benzodiazepines, and other vertigo treatments. - **Monitor for drug interactions**, especially in elderly patients, who are at higher risk of polypharmacy. - Encourage **lifestyle modifications** such as fall prevention strategies in older adults. **Movement Disorders: Pharmacotherapy Overview** **Background:** Movement disorders refer to a group of neurological conditions that cause abnormal voluntary or involuntary movements. Common types include **Parkinson's Disease (PD)**, **Essential Tremor (ET)**, **Dystonia**, **Huntington's Disease (HD)**, and **Tourette Syndrome**. These conditions vary in terms of their pathophysiology, symptoms, and treatment options. **Pathophysiology & Etiology:** 1. **Parkinson's Disease (PD)**: - PD is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing neurons in the **substantia nigra**. - **Classic symptoms**: Tremor at rest, rigidity, bradykinesia (slowness of movement), and postural instability. - **Etiology**: Idiopathic, though genetic mutations (e.g., PARK2) and environmental factors (e.g., pesticides) may play a role. 2. **Essential Tremor (ET)**: - ET is a common, often hereditary condition characterized by rhythmic, involuntary shaking, typically of the hands. - The tremor is often exacerbated by stress or movement. - **Etiology**: Genetic mutations (e.g., LINGO1) or idiopathic. **Risk Factors:** - **Age**: Most movement disorders (e.g., PD, HD) become more prevalent with age. - **Family history**: Genetic components play a significant role in conditions like PD, ET, and HD. - **Environmental exposures**: Pesticides, toxins, and certain medications (e.g., neuroleptics) can increase the risk of movement disorders. - **Head trauma**: Can contribute to certain movement disorders, including PD and dystonia. **Non-Pharmacological Therapy:** 1. **Parkinson's Disease**: - **Physical therapy**: Helps improve mobility and reduce rigidity. - **Speech therapy**: Addresses speech and swallowing difficulties. - **Deep Brain Stimulation (DBS)**: Surgical option for patients with PD who do not respond to medication. 2. **Essential Tremor**: - **Physical therapy**: Can help with tremor management in severe cases. - **Surgical options**: DBS or thalamotomy in refractory cases. **Pharmacological Therapy:** **Parkinson's Disease:** - **First-line**: 1. **Levodopa/Carbidopa**: Most effective treatment for motor symptoms. Levodopa is converted to dopamine in the brain. - **Side effects**: Nausea, dyskinesias (involuntary movements), wearing-off effect. 2. **Dopamine Agonists (e.g., pramipexole, ropinirole)**: Mimic dopamine in the brain. - **Side effects**: Drowsiness, hallucinations, impulse control disorders. 3. **MAO-B Inhibitors (e.g., selegiline, rasagiline)**: Prevent dopamine breakdown. - **Side effects**: Insomnia, nausea. - **Second-line**: 4. **COMT Inhibitors (e.g., entacapone)**: Extend the effect of levodopa. - **Side effects**: Diarrhea, urine discoloration. 5. **Amantadine**: Used for dyskinesia in advanced PD. - **Side effects**: Livedo reticularis (skin discoloration), edema. **Essential Tremor:** - **First-line**: 1. **Beta-blockers (e.g., propranolol)**: Reduce tremor intensity. - **Side effects**: Bradycardia, hypotension, fatigue. 2. **Primidone (anticonvulsant)**: Effective for tremor reduction. - **Side effects**: Sedation, ataxia. - **Second-line**: 3. **Gabapentin or Topiramate**: For tremor unresponsive to first-line therapy. - **Side effects**: Dizziness, somnolence. **Monitoring and Follow-up:** 1. **Parkinson's Disease**: - Regular monitoring for motor complications (e.g., dyskinesias) with long-term levodopa therapy. - Monitor for psychiatric side effects (e.g., hallucinations, impulse control disorders) with dopamine agonists. 2. **Essential Tremor**: - Monitor for efficacy of beta-blockers and anticonvulsants. - Regularly assess for side effects such as fatigue or dizziness with propranolol. **Important Points for Pharmacists:** - Ensure **patient adherence** to therapy, particularly with PD, where motor symptoms fluctuate. - Counsel patients on potential **side effects**, especially in older adults who may be more sensitive to antipsychotic drugs or dopamine agonists. - Emphasize the importance of **monitoring** and **dose adjustments** to manage motor symptoms and side effects. Here's a table that highlights the key differences between **Parkinson's Disease (PD)** and **Essential Tremor (ET)**: **Feature** **Parkinson's Disease (PD)** **Essential Tremor (ET)** ------------------------------------ -------------------------------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------- **Pathophysiology** Degeneration of dopamine-producing neurons in the **substantia nigra**, leading to decreased dopamine in the brain. Genetic or idiopathic disorder causing abnormal motor control in the cerebellum or basal ganglia. **Main Symptoms** **Resting tremor**, bradykinesia (slowness of movement), rigidity, postural instability. **Action tremor** (occurs during movement), often affects the hands, head, or voice. **Tremor Characteristics** **Resting tremor** (typically occurs when limbs are relaxed), often asymmetrical. **Postural tremor** or **kinetic tremor** (occurs during voluntary movement), usually bilateral. **Onset** Gradual onset, usually after age 60. Typically begins in early adulthood or middle age, but can occur at any age. **Etiology** Primarily idiopathic, though genetic and environmental factors (e.g., toxins) may contribute. Often hereditary, though it can be idiopathic. **Progression** Progressive, with worsening symptoms over time, including cognitive decline. Generally stable or slowly progressive, without cognitive decline. **Response to Medication** **Levodopa/Carbidopa** is the most effective treatment, but over time, **dyskinesias** may develop. **Beta-blockers** (e.g., propranolol) and **primidone** are first-line treatments. **Treatment Goals** To manage motor symptoms (tremor, bradykinesia, rigidity), improve quality of life. Primarily to reduce tremor intensity and improve function. **Non-Pharmacological Treatments** Physical therapy, speech therapy, deep brain stimulation (DBS) for advanced stages. Physical therapy, deep brain stimulation (DBS) for refractory cases. **Associated Conditions** Cognitive decline, depression, autonomic dysfunction (e.g., orthostatic hypotension). Rarely associated with other neurological conditions. **Family History** Less commonly familial, though genetic mutations (e.g., PARK2) have been identified in some cases. Often has a family history of ET, suggesting a genetic component. **Medication Side Effects** Levodopa: **Dyskinesias**, **nausea**, **motor fluctuations**. Dopamine agonists: **Hallucinations**, **impulse control disorders**. Beta-blockers: **Bradycardia**, **fatigue**, **hypotension**. Primidone: **Sedation**, **ataxia**. **Seizures and Epilepsy: Pharmacotherapy Overview** **Background:** - **Seizures** are transient disturbances in brain function due to abnormal electrical activity. They can manifest as a variety of symptoms, depending on the area of the brain affected. - **Epilepsy** is a chronic neurological disorder characterized by a predisposition to recurrent, unprovoked seizures. - Seizures may be categorized into **focal** (originating from one part of the brain) or **generalized** (involving both hemispheres of the brain). **Status epilepticus** refers to a continuous seizure lasting more than 5 minutes or recurrent seizures without recovery of consciousness between them. **Pathophysiology & Etiology:** 1. **Epilepsy**: Results from an imbalance between excitatory and inhibitory neurotransmission in the brain, often involving neurotransmitters like **glutamate** (excitatory) and **GABA** (inhibitory). 2. **Seizure Triggers**: - **Genetic mutations** can cause inherited epilepsy syndromes. - **Brain injury**, **stroke**, **brain tumors**, and **infection** (e.g., meningitis) can lead to secondary epilepsy. - **Alcohol withdrawal**, **sleep deprivation**, or **flashing lights** can trigger seizures in predisposed individuals. 3. **Types of Seizures**: - **Focal (partial) seizures**: Originates in a specific area of the brain and can evolve into generalized seizures (secondary generalization). - Subtypes: Focal onset aware, focal onset impaired awareness. - **Generalized seizures**: Involves both brain hemispheres from the onset. - Subtypes include **tonic-clonic**, **absence**, **myoclonic**, **atonic**, and **tonic** seizures. **Risk Factors:** - **Genetic factors**: Family history of epilepsy increases risk. - **Age**: Seizures are common in children and older adults. - **Head trauma**, **stroke**, or **brain tumors** can increase the risk of developing epilepsy. - **Infections** (e.g., meningitis, encephalitis) and **fever** in children. - **Drug use**: Recreational drugs (e.g., cocaine, amphetamines) and withdrawal from alcohol or benzodiazepines. - **Metabolic disturbances**: Hyponatremia, hypoglycemia. **Non-Pharmacological Therapy:** 1. **Lifestyle Modifications**: - **Sleep hygiene**: Ensuring adequate sleep to avoid seizure triggers. - **Avoidance of triggers**: Reducing exposure to flashing lights, excessive alcohol, or known seizure triggers. - **Stress management**: Techniques like mindfulness or relaxation. 2. **Surgical Therapy**: - **Resection surgery**: For refractory focal seizures, surgery to remove the seizure focus may be considered. - **Vagus nerve stimulation (VNS)**: For refractory epilepsy, a device that stimulates the vagus nerve to reduce seizure frequency. - **Responsive neurostimulation (RNS)**: A device that detects abnormal brain activity and delivers electrical pulses to prevent seizures. 3. **Dietary Therapy**: - **Ketogenic diet**: High-fat, low-carbohydrate diet often used in pediatric epilepsy. - **Modified Atkins diet**: Less restrictive than ketogenic diet, also used for refractory seizures. **Pharmacological Therapy:** **First-Line Pharmacological Treatments:** 1. **Focal Seizures**: - **Carbamazepine**: Preferred in focal seizures. - **Side effects**: Dizziness, diplopia, hyponatremia, leukopenia, rash (Stevens-Johnson syndrome). - **Lamotrigine**: Effective for focal and generalized seizures, with fewer side effects. - **Side effects**: Rash (including life-threatening Stevens-Johnson syndrome), dizziness, ataxia. - **Levetiracetam**: Frequently used in both focal and generalized seizures. - **Side effects**: Irritability, fatigue, behavioral changes. - **Valproic acid (VPA)**: Effective for focal and generalized seizures, particularly absence seizures. - **Side effects**: Hepatotoxicity, teratogenicity (contraindicated in pregnancy), weight gain, thrombocytopenia. 2. **Generalized Seizures**: - **Valproic acid**: First-line for generalized tonic-clonic seizures, myoclonic, and absence seizures. - **Side effects**: Hepatotoxicity, teratogenicity (contraindicated in pregnancy), weight gain. - **Lamotrigine**: Also effective in generalized seizures. - **Side effects**: Rash (Stevens-Johnson syndrome), dizziness, ataxia. 3. **Absence Seizures**: - **Ethosuximide**: First-line therapy for absence seizures. - **Side effects**: Nausea, vomiting, lethargy. - **Valproic acid**: Can also be used for absence seizures, but less preferred in children due to side effect profile. **Second-Line Therapy:** - **Topiramate**: Used for both focal and generalized seizures, especially in drug-resistant cases. - **Side effects**: Cognitive impairment, weight loss, kidney stones, metabolic acidosis. - **Phenytoin**: For generalized tonic-clonic and focal seizures, used less frequently due to adverse effects. - **Side effects**: Gingival hyperplasia, hirsutism, megaloblastic anemia, rash, ataxia. - **Clonazepam (Benzodiazepine)**: Can be used for status epilepticus or acute seizure control. - **Side effects**: Sedation, tolerance, and dependence with long-term use. **Status Epilepticus Management:** - **First-line**: Benzodiazepines (e.g., lorazepam, diazepam). - **Second-line**: Phenytoin, fosphenytoin, or levetiracetam if seizures persist. - **Third-line**: General anesthetics (e.g., propofol) may be considered in refractory status epilepticus. **Monitoring and Follow-Up:** - **Therapeutic drug monitoring (TDM)**: Important for drugs like **phenytoin**, **valproic acid**, and **carbamazepine** to ensure appropriate drug levels and avoid toxicity. - **Renal and hepatic function**: Regular monitoring for drugs like **valproic acid** and **carbamazepine** due to hepatotoxicity and potential liver enzyme induction/inhibition. - **Complete blood counts (CBC)**: For drugs like **carbamazepine** (risk of leukopenia) and **phenytoin** (risk of megaloblastic anemia). - **Weight and metabolic monitoring**: For drugs like **valproic acid** (weight gain) and **topiramate** (weight loss, kidney stones). - **Pregnancy testing and counseling**: Many antiepileptic drugs (e.g., **valproic acid**) are teratogenic, so regular pregnancy testing and counseling are essential for women of childbearing age. **Important Considerations for Pharmacists:** - **Drug interactions**: Many AEDs (e.g., **phenytoin**, **carbamazepine**) are inducers of hepatic enzymes and can lower levels of other drugs (e.g., oral contraceptives). Similarly, enzyme inhibitors (e.g., **valproic acid**) can increase the levels of other drugs. - **Adherence**: Seizure control relies heavily on consistent medication adherence. Pharmacists should educate patients on the importance of taking medications regularly. - **Reassess treatment**: If seizures are not controlled, pharmacists should be proactive in discussing alternative treatments or referral for specialized care (e.g., epilepsy centers). **Drug** **Concentration-Dependent AEs** **Idiosyncratic AEs** **Chronic AEs** ------------------- ---------------------------------------------------------- ------------------------------------- ------------------------------------------------------------- **Phenytoin** Cerebellar toxicity (dizziness, unsteady gait, sedation) Rash, blood dyscrasias Gingival hyperplasia, hirsutism, acne, cognitive impairment **Valproic acid** Thrombocytopenia, CNS depression Acute hepatic failure, pancreatitis Hyperammonemia, weight gain **Carbamazepine** Lethargy, decreased WBC Rash, blood dyscrasias Hyponatremia **Phenobarbital** Respiratory depression Osteomalacia, mood changes **Lacosamide** PR interval prolongation (CV effects) **Lamotrigine** Rash **Levetiracetam** Behavioral AEs, psychosis **Gabapentin** Weight gain, CNS AEs **Pregabalin** Weight gain, CNS AEs **Topiramate** Weight loss, cognitive AEs **Oxcarbazepine** Hyponatremia **Vigabatrin** Permanent vision loss **Key Highlights:** - **Phenytoin**: Acute treatment; watch for cerebellar toxicity and potential chronic effects like cognitive impairment and gingival hyperplasia. - **Valproic acid**: Risk of liver failure (idiosyncratic), thrombocytopenia (concentration-dependent), and chronic effects like weight gain. - **Carbamazepine**: May cause hyponatremia with prolonged use; caution with potential for serious rash. - **Lamotrigine**: Major risk for life-threatening rash (SJS). - **Topiramate**: Associated with weight loss and cognitive side effects, especially when used chronically. **\ Seizures and Epilepsy Summary** **Definitions:** - **Epileptic Seizures**: Result from excessive synchronous neuronal activity. - **Epilepsy**: Defined by 2 unprovoked seizures \>24 hours apart or 1 unprovoked seizure with \>60% risk of recurrence in 10 years. - **Resolved Epilepsy**: Seizure-free for 10 years, no ASMs in the last 5 years. **Seizure Types:** - **Focal Seizures**: - *Focal Aware*: No impaired consciousness, lasts \90 mmHg and oxygen saturation \>90%. - Mechanical ventilation as needed. **Pharmacological Therapy** 1. **ICP Control**: - **First-line**: Mannitol or hypertonic saline. - Mannitol: Monitor serum sodium, osmolality, and renal function. - Hypertonic saline: Often used as bolus; superior in some cases. - Sedatives: Propofol (rapid onset, neuroprotective but monitor for infusion syndrome). - Avoid corticosteroids (associated with higher mortality). 2. **Seizure Prophylaxis**: - Indications: GCS \60 mmHg). - Adverse drug reactions (e.g., sedation, hypotension). - Electrolyte imbalances. - Seizure activity and secondary complications (infection, thromboembolism). - Pharmacists\' role: - Ensure appropriate medication therapy. - Monitor for drug-related problems, including renal drug clearance changes in critically ill patients. **Background and Pathophysiology** - **Cognitive impairment** encompasses a spectrum from mild cognitive impairment (MCI) to severe dementia, including Alzheimer's Disease (AD). - **Pathophysiology of AD**: - Extracellular beta-amyloid plaques and intracellular neurofibrillary tangles lead to: - Neuronal death. - Synaptic dysfunction. - Dysregulation of neurotransmitters, especially acetylcholine and glutamate. **Risk Factors** - **Modifiable**: - Hypertension, diabetes, smoking, obesity, depression, physical inactivity, low educational attainment. - **Non-modifiable**: - Age, APOE4 genotype, family history. **Non-Pharmacological Therapy** - Structured routines and environmental modifications: - Calendars, clocks, photos, and adequate lighting. - Cognitive stimulation: - Activities like puzzles, memory exercises. - Lifestyle interventions: - Regular physical activity, balanced diet (Mediterranean diet), smoking cessation. - Behavioral interventions for agitation: - Music or pet therapy, distraction techniques, sensory stimulation. **Pharmacological Therapy** 1. **Symptomatic Management**: - **Cholinesterase inhibitors (CI)**: - **Donepezil, Rivastigmine, Galantamine**. - Indications: Mild to moderate AD. - Side effects: Nausea, diarrhea, insomnia, vivid dreams, bradycardia. - Monitoring: Heart rate, GI symptoms, weight loss. - **Memantine (NMDA receptor antagonist)**: - Indication: Moderate to severe AD (monotherapy or adjunct with CI). - Side effects: Dizziness, confusion, GI symptoms. - Monitoring: Blood pressure, renal function. 2. **Disease-Modifying Therapies**: - **Lecanemab (FDA-approved)**: - Targets amyloid-beta aggregates. - Requires regular MRI monitoring for amyloid-related imaging abnormalities (ARIA). - **Aducanumab** (withdrawn in Canada): - High cost, limited evidence of clinical benefit. 3. **Behavioral and Psychological Symptoms of Dementia (BPSD)**: - Antipsychotics: **Risperidone** (FDA/Health Canada-approved for aggression in dementia). - Side effects: Increased risk of stroke, mortality. - Others: SSRI (e.g., citalopram), mood stabilizers (e.g., carbamazepine), or memantine. - **Not recommended**: Benzodiazepines, valproate. **Monitoring and Follow-Up** - **Regular assessments**: - Cognitive function (MMSE, MoCA). - Behavioral symptoms. - Medication adherence and side effects. - **Safety considerations**: - Fall risk, wandering, driving capability. - **Support caregivers**: - Provide education on disease progression and non-pharmacologic strategies. **Pharmacist's Role** - **Optimize therapy**: - Ensure correct dosing and monitor for contraindications (e.g., bradycardia, GI bleeding with CI). - **Prevent polypharmacy issues**: - Identify and reduce inappropriate medications, especially those with anticholinergic effects. - **Educate caregivers**: - On non-drug interventions and realistic treatment expectations.