Pharmacology Exam 2

Generalized seizures:

Convulsive or nonconvulsive Produce immediate loss of consciousness

Baclofen (Lioresal): Adverse effects

o Nausea o Constipation o Urinary retention o Drowsiness o Dizziness o Weakness o Fatigue o CNS depression can be minimized with doses that are small initially and then gradually increased. - Overdose can produce coma and respiratory depression. - No antidote for overdose - treatment is supportive

Generalized seizures: Atonic

· Atonic - sudden loss of muscle tone o If seizure activity is limited to the muscles of the neck, "head drop" occurs. o However, if the muscles of the limbs and trunk are involved, a "drop attack" can occur, causing the patient to suddenly collapse, occur mainly in children.

Generalized seizures: Febrile

· Febrile - Fever-associated seizures are common among children ages 6 months to 5 years. o Febrile seizures typically manifest as generalized tonic-clonic convulsions of short duration (1 minute or less) o Children who experience these seizures are not at high risk of developing epilepsy later in life. o Children usually outgrow these

Generalized seizures: Myoclonic

· Myoclonic - sudden muscle contraction that lasts for just 1 second o Seizure activity may be limited to one limb (focal myoclonus) or it may involve the entire body (massive myoclonus).

Generalized seizures: Status epilepticus

· Status epilepticus - seizure that persists for 15 to 30 minutes or longer or a series of recurrent seizures during which the patient does not regain consciousness. o Can interfere with breathing o High risk for harm

Generalized seizures: Tonic-clonic

· Tonic-clonic - (formerly known as grand mal seizures) o Neuronal discharge spreads throughout both hemispheres of the cerebral cortex o You have major convulsions o Characterized by a period of muscle rigidity (tonic phase) followed by synchronous muscle jerks (clonic phase) o Often see urination, but not defecation o May be preceded by a loud cry, caused by forceful expiration of air across the vocal cords o Usually accompanied by marked impairment of consciousness and after the seizure it's followed by a period of central nervous system (CNS) depression, referred to as the postictal state. o Seizure typically lasts 90 seconds or less.

Definition of Muscle Spasm and Spasticity

• Muscle spasm is defined as involuntary contraction of a muscle or muscle group. Muscle spasm is often painful and reduces the ability to function.

Epilepsy: Promoting patient adherence

• Promoting patient adherence: seizure control is highly dependent on patient adherence. It is estimated that nonadherence accounts for about 50% of all treatment failures.

Antiepileptic Drugs: Goals of Treatment

• Reduce seizures to a level that allows the patient to live as normal a life as possible • Balance the desire for complete seizure control with an acceptable level of side effects

Mixed Seizures: Lennox - Gastaut Syndrome

• Severe form of epilepsy that usually develops during the preschool years • Involves developmental delay and a mixture of partial and generalized seizures • Seizure types include partial, atonic, tonic, generalized tonic-clonic, and atypical absence. • In children with Lennox-Gastaut syndrome, seizures can be very difficult to manage • It is a chronic condition that requires a lot of experimentation with a lot of seizure drugs to get the seizures under control

Epilepsy: Suicide risk

• Suicide risk: Antiepileptic drugs: In 2008, the U.S. Food and Drug Administration (FDA) warned that all AEDs can increase suicidal thoughts and behavior.

Gabapentin (Neurontin, Gralise):

• Therapeutic use: Adjunctive therapy of partial seizures • Off-label use: Neuropathic pain, prophylaxis of migraine, treatment of fibromyalgia, and relief of postmenopausal hot flashes

Newer Antiepileptic Drugs

• Total of 14 - are prescribed less frequently than traditional AEDs (except for oxcarbamazapine & lamotrigine) • Thought to be as effective as traditional AEDs • Better tolerated - fewer adverse effects • Thought to pose less of a risk to growing fetus • Little to no interaction with liver enzymes (except for oxcarbamazapine) • Approval process - FDA originally approved newer AEDs for adjunctive therapy not monotherapy. There's a push to expand FDA approved indications.

Classification of Antiepileptic Drugs

• Traditional AEDs: more established, more affordable • Newer AEDs: safer during pregnancy, less drug interactions, usually better tolerated

2 groups of Drugs for Muscle Spasm and Spasticity

• Two groups of drugs that cause skeletal muscle relaxation - One group for localized muscle spasm - One group for spasticity • Most drugs (except dantrolene) produce their effects through actions on the central nervous system (CNS) and NOT locally on the muscle

Zonisamide (Zonegran): MOA

• Underlying mechanism appears to be blockade of neuronal sodium channels and calcium channels. Is sometimes used off-label for management of bipolar disorder, migraine prophylaxis, and Parkinson's disease.

Levetiracetam (Keppra): Therapeutic uses ( FDA approved & unlabeled)

• Unique agent that is chemically and pharmacologically different from all other AEDs In the United States, the drug is approved for adjunctive therapy of 1. Myoclonic seizures in adults and adolescents age 12 years and older 2. Partial-onset seizures in adults and children age 4 years and older 3. Primary generalized tonic-clonic seizures in adults and children age 6 years and older • Unlabeled uses include migraine, bipolar disorder, and new-onset pediatric epilepsy. In Europe, the drug is approved for monotherapy of partial seizures, for which it is highly effective.

Phenytoin (Dilantin) Traditional AEDs

• Used to treat partial and tonic-clonic seizures • Mechanism of action: Selective inhibition of sodium channels • Varied oral absorption • Half-life: 8 to 60 hours (pharmacokinetics is variable from person to person)

Epilepsy: Withdrawing antiepileptic drugs:

• Withdrawing antiepileptic drugs: AEDs be withdrawn slowly (over a period of 6 weeks to several months) o Failure to gradually reduce dosage is a frequent cause of SE (status epilepticus) o If the patient is taking two drugs to control seizures, they should be withdrawn sequentially, not simultaneously.

Contraction rates

SA :60-100bpm AV: 40-60bpm Ventricles: 20-40bpm

Topiramate (Topamax): MOA

Seizure reduction occurs by four mechanisms: 1. Potentiation of GABA-mediated inhibition 2. Blockade of voltage-dependent sodium channels 3. Blockade of calcium channels 4. Blockade of receptors for glutamate, an excitatory neurotransmitter.

Gabapentin (Neurontin, Gralise): Adverse reactions

Adverse reactions - Very well tolerated - Most common side effects: o Somnolence (sleepiness) o Dizziness o Ataxia o Fatigue o Nystagmus o Peripheral edema

Phenytoin (Dilantin) : Therapeutic levels

10 to 20 mcg/mL (micrograms per milliliter)

Arteries vs. Veins

Arteries: are always vessels that carry blood away from the heart - arteries are carrying deoxygenated blood in the pulmonary circulation Veins: are always vessels that carry blood to the heart - veins are carrying oxygenated blood in the systemic circulation - even though we are used to seeing systemic circulation veins carrying deoxygenated blood arteries carry oxygenated (keep in mind)

Diazepam (Valium) (Full card)

• Member of the benzodiazepine family - The only one labeled to treat spasticity Mechanism - Acts in the CNS - Mimics action of GABA - No direct action of skeletal muscle so, like Baclofen, will not cause muscle weakness Adverse effect - Sedation

Baclofen (Lioresal): MOA

- Acts on the spinal cord - Suppresses hyperactive reflexes - Precise mechanism unknown - May mimic the action of GABA (inhibitory transmitter) on spinal neurons

Causes of Muscle Spasm and Spasticity

- Epilepsy - Hypocalcemia (calcium levels are decreased) - Pain syndromes: Adult and chronic Trauma: Localized skeletal muscle injury

Topiramate (Topamax): Therapeutic use ( FDA approved & unlabeled)

- FDA approved for: 1. Adjunctive treatment of adults and children 2 years and older with partial seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome 2. Monotherapy of adults and children 10 years and older with partial seizures or primary generalized tonic-clonic seizures 3. Prophylaxis of migraine in adults - Unlabeled uses include: bipolar disorder, cluster headaches, neuropathic pain (including the pain of diabetic neuropathy), infantile spasms, essential tremor, binge-eating disorder, bulimia nervosa, and weight loss. Studies also show promise for management of alcohol and cocaine dependence.

Gingival Hyperplasia

- Gingival hyperplasia: Swelling, tenderness, and bleeding of the gums - Gingivectomy (removal of some of the gum line) - Folic acid (0.5 mg/day) may prevent gum overgrowth - Risk can be minimized by good oral hygiene, including dental flossing and gum massage

Centrally Acting Muscle Relaxants: Adverse effects (Continued)

- Hepatic toxicity o Tizanidine [Zanaflex] and metaxalone [Skelaxin] can cause liver damage o Chlorzoxazone [Lorzone, Parafon Forte DSC] can cause hepatitis and potentially fatal hepatic necrosis. (patients will get liver enzymes checked frequently) - Physical dependence - Chronic, high-dose therapy can cause physical dependence, manifesting as a potentially life-threatening abstinence syndrome if these drugs are abruptly withdrawn. • Other adverse effects - o Cyclobenzaprine and orphenadrine have significant anticholinergic (atropine-like) properties, and hence may cause dry mouth, blurred vision, photophobia, urinary retention, and constipation. o Methocarbamol may turn urine brown, black, or dark green; patients should be forewarned of this harmless effect. o Tizanidine can cause dry mouth, hypotension, hallucinations, and psychotic symptoms. o Carisoprodol can be hazardous to patients predisposed to intermittent porphyria (decreased ability to sweat)

Baclofen (Lioresal): Therapeutic uses

- Multiple sclerosis, spinal cord injury, and cerebral palsy - NOT used with stroke (because their injury is a little more complex and can include parts of the brain where we don't want to have inhibition) - Decreases flexor and extensor spasms - Suppresses resistance to passive movement - No direct effect on skeletal muscle - Because baclofen has no direct muscle-relaxant action, it does not decrease muscle strength, therefore baclofen is preferred to dantrolene when spasticity is associated with significant muscle weakness

Fosphenytoin (Cerebyx): Adverse effects

- Nystagmus - repetitive oculomotor movements - Sedation (all AED drugs fall under the category of CNS depressants) - Ataxia - loss of coordinated muscle movements - Diplopia - double vision - Cognitive impairment - Gingival hyperplasia (gums) - Skin rash - Effects in pregnancy - increased risk for congenital anomalies - Cardiovascular effects - arrhythmia, hypotension risk - Temporary paresthesia's and itching, especially in the groin area

Centrally Acting Muscle Relaxants: Therapeutic use

- Relief of localized spasm caused by muscle injury - Can decrease local pain and tenderness - Can increase range of motion - Frequently causes sedation - With the exception of baclofen and diazepam, the central muscle relaxants are not useful for treating spasticity or other muscle disorders resulting from CNS pathology.

Antiepileptic Drugs: Mechanisms of action

- Some drugs will suppress sodium influx (movement into the cell) o Going to help block action potentials - Suppression of calcium influx o Going to help block the release of neurotransmitters - Antagonism of glutamate (antagonists to glutamate) o Going to help block stimulation of synapses - Potentiation of gamma-aminobutyric acid (GABA) - ubiquitous inhibitory neurotransmitter o Going to help turn up the volume on inhibition of synapses

Antiepileptic Drugs: Effects

- Suppress discharge of neurons within a seizure focus - Suppress propagation of seizure activity from the focus to other areas of the brain - They are going to affect components of the neurons that are needed to fire action potentials and to generate synaptic transmission

Therapeutic level of digoxin?

0.5-2

Blood flow through the heart

1-Superior & Inferior Vena Cava, 2-Rt Atrium, 3-Tricuspid Valve, 4- Rt Ventricle, 5-Pulmonary Valve, 6-Pulmonary Artery, 7- Lungs-pick up oxygen, 8-Pulmonary Veins, 9- Lt Atrium, 10- Mitral Valve (Bicuspid), 11-Lt Ventricle, 12- Aortic Valve, 13-Aorta, 14- Body

Risk factors for digoxin toxicity?

Hypokalemia Renal or liver failure Large loading dose Large maintenance doses Infants & aged Hypothyroidism Hypoxia

Oxcarbazepine (Oxtellar XR, Trileptal): Indication

Indicated for monotherapy and adjunctive therapy of partial seizures in adults and children

Heart pumps how much per minute?

5-6L

Secondary to being a positive inotrpoe, digoxin functions are also?

A negative dromotrope = slows conduction, and negative chronotrope = slows HR, antiarrhythmic and indirect diuretic.

Phenytoin (Dilantin) :Drug interactions

Inhibitor & Inducer: - Decreases the effects of oral contraceptives, warfarin, and glucocorticoids - Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid - Dosing: Highly individualized - Administration: With food (will enhance absorption)

Tiagabine (Gabitril): Action and use

Action and use - Adjunctive therapy for partial seizures in patients at least 12 years old - Blocks reuptake of GABA by neurons and glia; inhibitory influence of GABA is intensified, and seizures are suppressed

Phenobarbital: Actions Traditional AEDs

Actions - Reduces seizures without causing sedation - Anticonvulsant barbiturate - Potentiates the effects of GABA

Lamotrigine (Lamictal): Adverse effects

Adverse effects - Dizziness, diplopia, blurred vision, nausea, vomiting, and headache - Severe skin reactions - Aseptic meningitis (a meningitis - inflammation of the meninges of the brain that is not caused by a bacterial infection) Signs & Symptoms = fever, headache, rigidity in back of the neck - Risk for suicide

Valproic Acid (Depakene, Depakote, Depacon): Adverse effects

Adverse effects - Gastrointestinal effects - Hepatotoxicity: Liver failure - Pancreatitis - Teratogenic effects - Hyperammonemia (Ammonia level of the blood stream rises = the liver is responsible for neutralizing ammonia so valproic acid may be causing this elevation

Tiagabine (Gabitril): Adverse effects

Adverse effects - Generally, well tolerated o Dizziness o Somnolence o Asthenia o Nausea o Nervousness o Tremor o Confusion o Abnormal thinking o Trouble concentrating

Phenobarbital: Adverse effects

Adverse effects - Neuropsychologic effects (drowsiness and sedation) - Dependency - Rickets and Osteomalacia - Nystagmus - Ataxia

Primidone (Mysoline): Adverse effects

Adverse effects similar to phenobarbital: o Neuropsychologic effects (drowsiness and sedation) o Dependency o Rickets and Osteomalacia o Nystagmus o Ataxia

Carbamazepine (Tegretol): Adverse effects

Adverse effects: - Neurologic effects: Nystagmus and ataxia - Hematologic effects: Leukopenia, anemia, and thrombocytopenia - Causes birth defects - Hypo-osmolarity (Blocks the excretion of water) - Dermatologic effects: Rash and photosensitivity reactions

Phenytoin (Dilantin) : Adverse effects

Adverse effects: - Nystagmus - repetitive oculomotor movements - Sedation (all AED drugs fall under the category of CNS depressants) - Ataxia - loss of coordinated muscle movements - Diplopia - double vision - Cognitive impairment - Gingival hyperplasia (gums) - Skin rash - Effects in pregnancy - increased risk for congenital anomalies - Cardiovascular effects - arrhythmia, hypotension risk Gingival Hyperplasia - Gingival hyperplasia: Swelling, tenderness, and bleeding of the gums - Gingivectomy (removal of some of the gum line) - Folic acid (0.5 mg/day) may prevent gum overgrowth - Risk can be minimized by good oral hygiene, including dental flossing and gum massage

Oxcarbazepine (Oxtellar XR, Trileptal): Adverse effects

Adverse effects: o Dizziness o Drowsiness o Double vision o Nystagmus o Headache o Nausea o Vomiting o Ataxia • Clinically significant hyponatremia (sodium concentration below 125 mmol/L) • Stevens-Johnson syndrome • Toxic epidermal necrolysis (dying off of skin cells and it appears like significant burns over a large portion of the body)

Digoxin used for the treatment of?

CHF Atrial arrythmias Sinus tachycardia Increases quality of life and "exercise" tolerance

Oxcarbazepine (Oxtellar XR, Trileptal): Drug interactions

Drug interactions (oral contraception, phenytoin)

Phenobarbital: Drug interactions

Drug interactions - Oral contraceptives (enhanced metabolism) - Warfarin (enhanced metabolism) - Central nervous system depressants - Valproic acid (increased levels of phenobarbital) Drug withdrawal (must be done very carefully and slowly)

Valproic Acid (Depakene, Depakote, Depacon): Drug interactions

Drug interactions - Phenobarbital (decreases levels of phenobarbital) - Phenytoin (increased levels of phenytoin) - Topiramate (increased risk of hyperammonemia) - Meropenem (reduced levels of valproic acid) - Imipenem/cilastatin (reduced levels of valproic acid)

Gabapentin (Neurontin, Gralise): Drug interactions

Drug interactions - unlike many AEDs there's no significant drug interactions

Primidone (Mysoline): Drug interactions

Drug interactions similar to phenobarbital o Oral contraceptives (enhanced metabolism) o Warfarin (enhanced metabolism) o Central nervous system depressants Valproic acid (increased levels of phenobarbital)

Carbamazepine (Tegretol): Drug-drug and drug-food interactions

Drug-drug and drug-food interactions - Hepatic drug-metabolizing enzymes - Warfarin (enhances metabolism of warfarin) - Oral contraceptives (enhanced metabolism of OC) - Phenytoin (increased blood levels of phenytoin) - Phenobarbital (enhanced metabolism of phenobarbital) - Grapefruit juice (enhances absorption and inhibits metabolism of carbamazepine)

Drugs for muscle spasm

Drugs used to treat muscle spasm are not used to treat muscle spasticity EXCEPT for Baclofen and Diazepam (these two are used to treat muscle spasticity)

What needs to be stable to prevent digoxin toxicity?

Electrolyte levels, especially K+, Ca++ and Mg+. In hypokalemia, hypercalcemia, hypomagnesia risk systemic digoxin toxicity.

ADEs of digoxin?

GI: N/V, anorexia CNS: Blurred vision, diplopia, halos CV: Bradycardia, tachycardia, PVCs (premature ventricular contractions) Serious ADE: Ventricular fibrillation

What is the process of starting a patient on digoxin?

Give a loading dose to get blood levels up quickly = digitalize Means give .75-1 mg divided over three doses

MAP

MAP is proportional to: MAP = CO X TPR

Oxcarbazepine (Oxtellar XR, Trileptal): MOA

MOA: Antiseizure effects: Voltage-sensitive sodium channels in neuronal membranes blocked (critical in order to activate action potentials), hyperexcitable neurons stabilized, and seizures suppressed

Dantrolene (Dantrium) (Full card)

Mechanism - Acts directly on skeletal muscle - Suppresses the release of calcium from the sarcoplasmic reticulum - Therapeutic doses have only minimal effects on contraction of smooth muscle and cardiac muscle. Therapeutic uses - Spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury - Malignant hyperthermia • Potentially fatal condition caused by succinylcholine and general anesthetics • The heat of malignant hyperthermia is generated by muscle contraction occurring secondary to massive release of calcium from the SR. • Dantrolene relieves symptoms by acting on the SR (sarcoplasm reticulum) to block calcium release. Adverse effects o Muscle weakness (because it acts on skeletal muscle) o Drowsiness o Diarrhea - Hepatic toxicity - should be given in the lowest effective dose - Acne-like rash (less common)

Carbamazepine (Tegretol): MOA

Mechanism of action - Suppresses high-frequency neuronal discharge in and around seizure foci

Valproic Acid (Depakene, Depakote, Depacon): Mechanism of action Traditional AEDs

Mechanism of action - Suppresses high-frequency neuronal firing through the blockade of sodium channels - Suppresses calcium influx through T-type calcium channels - May augment the inhibitory influence of GABA

How does the body get rid of digoxin?

Metabolized in liver, but vast majority is secreted by kidneys = must have normal kidney function

Signs and symptoms of digoxin toxicity

N/V, confusion, blurred vision Bradycardia, PVCs

Digoxin administered via?

PO or IV

Which digoxin dose will be larger and why?

PO will be larger than IV because of large first pass effect

Fosphenytoin (Cerebyx) Traditional AEDs

Prodrug that is converted to phenytoin when metabolized (done by the liver)

Treatment for digoxin toxicity?

Stop Dig Tx symptomatically: - KCL (potassium chloride) to correct hypokalemia - Anti-arrhythmics - Atropine for bradycardia - Digibind in severe cases, binds and allows to be secreted

Lamotrigine (Lamictal): Therapeutic use

Therapeutic use - Broad spectrum of antiseizure activity - Bipolar disorder

Valproic Acid (Depakene, Depakote, Depacon): Therapeutic uses

Therapeutic uses - Seizure disorders - Bipolar disorder - Migraine

Phenytoin (Dilantin) : Therapeutic uses

Therapeutic uses: - Epilepsy - Cardiac dysrhythmias

Phenobarbital: Uses

Uses - Epilepsy (partial and generalized tonic-clonic seizures) - Sedation - Induction of sleep

Carbamazepine (Tegretol): Uses Traditional AEDs

Uses: - Epilepsy - Bipolar disorder - Trigeminal and glossopharyngeal neuralgias (chronic nerve pain)

Contraindications for digoxin?

V tack V fib 2nd or 3rd degree heart block (impulse from SA node doesn't arrive at ventricles)

Centrally Acting Muscle Relaxants: 2 drugs

diazepam and tizanidine— are thought to relieve spasm by enhancing presynaptic inhibition of motor neurons in the CNS. - Diazepam: promotes presynaptic inhibition by enhancing the effects of gamma-aminobutyric acid (GABA) - Tizanidine: promotes inhibition by acting as an agonist at presynaptic alpha2 receptors.

positive inotropic prototype

digoxin - increases strength of myocardial contraction

Centrally Acting Muscle Relaxants: Adverse effects

o Generalized CNS depression o Drowsiness o Dizziness o Lightheadedness is common o Should be advised to avoid alcohol and all other CNS depressants

Zonisamide (Zonegran): Adverse effects

o Drowsiness o Dizziness o Anorexia o Headache o Nausea o Metabolic acidosis o Impaired speech o Concentration o Other cognitive processes • Severe psychiatric effects - effects. During clinical trials, 2.2% of patients either discontinued treatment or were hospitalized because of severe depression; 1.1% attempted suicide

Topiramate (Topamax): Adverse effects

o Somnolence o Dizziness o Ataxia o Nervousness o Diplopia o Nausea o Anorexia o Weight loss o Cognitive effects (confusion, memory difficulties, altered thinking, reduced concentration, difficulty finding words) can occur, but the incidence is low at recommended dosages. o Kidney stones and paresthesia's occur rarely. o Can cause metabolic acidosis (inhibition of carbonic anhydrase) o Can cause hyperhidrosis (reduced sweating) posing a risk of hyperthermia. o Have been case reports of angle-closure glaucoma. Left untreated, this rapidly leads to blindness. o When taken during the first trimester of pregnancy, topiramate increases the risk of cleft lip and cleft palate. Category D o Risk for suicide may be greater than with most other AEDs.

Generalized seizures: Absence (petit mal)

· Absence (petit mal) - loss of consciousness for a brief time (10 to 30 seconds) o Usually involve mild, symmetric motor activity (eye blinking) or no motor activity at all. o The patient may experience hundreds of absences attacks a day o Absence seizures occur primarily in children and usually cease during the early teen years.

Epilepsy: Monitoring plasma drug levels:

• Monitoring plasma drug levels: In addition to serving as a guide for dosage adjustment, knowledge of plasma drug levels can help determine if: 1. Monitoring patient adherence (if the patient is taking the drug) 2. Determining the cause of lost seizure control (is the patient having seizures again because they truly have developed a tolerance? Or is it because the blood levels of the drug are going down) 3. Identifying causes of toxicity, especially in patients taking more than one drug.

Pregabalin (Lyrica): Abuse potential / dependency

• Abuse potential - In clinical trials, 4% to 12% of patients reported euphoria as a side effect. • Physical dependency - Abrupt discontinuation can cause insomnia, nausea, headache, diarrhea, and other symptoms that suggest physical dependence.

Primidone (Mysoline) Traditional AEDs

• Active against all major seizure disorders except absence seizures • Nearly identical in structure to phenobarbital

Zonisamide (Zonegran): Therapeutic uses

• Adjunctive therapy of partial seizures in adults

Pregabalin (Lyrica): Adverse Reactions

• Adverse effects: o Dizziness o Somnolence o Blurred vision o Significant weight gain o Difficulty thinking o Headache o Peripheral edema o Dry mouth • Hypersensitivity reactions: Life-threatening angioedema - swelling of the face, tongue, lip, gums, throat, and larynx. • Rhabdomyolysis - Severe muscle injury syndrome - muscle starts to break down In clinical trials, three patients developed rhabdomyolysis (muscle breakdown). However, it is not clear that pregabalin was the cause. Nonetheless, patients should be instructed to report signs of muscle injury (pain, tenderness, weakness). If rhabdomyolysis is diagnosed, or even suspected, pregabalin should be withdrawn

Pregabalin (Lyrica): Therapeutic uses

• Analog of GABA (mimics the actions of GABA) • Neuropathic pain associated with diabetic neuropathy • Postherpetic neuralgia • Adjunctive therapy of partial seizures • Fibromyalgia

Epilepsy: Therapeutic Considerations

• Drug evaluation - Antiepileptic drug (AED) trial period - Dosage adjustment - Seizure frequency chart - We are trying to get the patient on the lowest drug dose that will help control their seizures to a point that is acceptable. - Requires a lot of individualized dosing and seizure tracking

Pregabalin (Lyrica): Drug interactions

• Drug interactions - Alcohol, opioids, benzodiazepines, and other CNS depressants may intensify the depressant effects of pregabalin. No interactions with liver enzymes.

Tiagabine (Gabitril):Drug interactions

• Drug interactions - levels of tiagabine can be decreased by phenytoin, phenobarbital, and carbamazepine— all

Ethosuximide (Zarontin) Traditional AEDs

• Drug of choice for absence seizures • Suppresses neurons in the thalamus that are responsible for generating absence seizures • Generally devoid of significant adverse effects and interactions Initially may cause drowsiness, dizziness, and lethargy

Felbamate (Felbatol): (full card)

• Effective AED with a broad spectrum of antiseizure activity • Potentially fatal adverse effects: Aplastic anemia and liver failure • Restricted to patients with severe epilepsy that is refractory to all other therapy

Centrally Acting Muscle Relaxants

• For most centrally acting muscle relaxants, the mechanism of spasm relief is unclear. • Many investigators believe that relaxation of spasm results primarily from the sedative properties of these drugs, and not from specific actions exerted on CNS pathways that control muscle tone

Levetiracetam (Keppra): MOA, Adverse effects, Drug interactions

• Mechanism of action: Unknown • Adverse effects: Mild to moderate - The most common are drowsiness and asthenia (lack of strength= weakness) • Drug interaction: Does not interact with other AEDs