adverse reactions of drugs targeting epilepsy, parkinson and alzheimer's disease hamid r....
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Adverse Reactions of Drugs Targeting Epilepsy, Parkinson
and Alzheimer's disease
Hamid R. SadeghniaDepartment of Pharmacology
School of Medicine, MUMS
Outline
Adverse Drug Reactions (ADRs)
ADRs of anti-epileptic drugs
ADRs of anti-parkinsonian drugs
ADRs of drugs targeting Alzheimer's disease
ADRs: any unexpected, unintended, undesired, or excessive response to a medicine that occurs at doses usually used for prophylaxis, diagnosis, or therapy of disease
ADRs
Anticonvulsants• Carbamazepine
(Tegretol)• Clobazam (Urbanyl)• Clonazepam (Klonopin)• Diazepam (Valium)• Ethosuximide (Zarontin)• Gabapentin (Neurontin)• Lamotrigine (Lamictal)• Levetiracetam (Keppra)
• Oxcarbazepine (Trileptal)• Phenobarbital (Luminal)• Phenytoin (Dilantin)• Primidone (Mysoline)• Topiramate (Topamax)• Valproic Acid (Depakene)• Zonisamide (Zonegran)
I. CNS Effects:drowsiness, somnolence, fatigue, ataxia,
headache, restlessness, nystagmus, blurred vision, diplopia, dizziness, vertigo and paresthesia
The most frequently occurring adverse effectsDose relatedMost noticeable during initial therapy
General Statement
II. GI Effects:nausea and vomiting, gastric distress, dysphagia, loss of taste, constipation, diarrhea, anorexia hiccups
General Statement
III. Dermatologic Effects:skin rash, urticaria, exfoliative dermatitis, toxic epidermal necrosis, Stevens-Johnson syndrome, systemic lupus erythematosus (SLE),
Appear to be hypersensitivity reactions
General Statement
IV. Hematologic Effects:folate deficiency and megaloblastic anemiabone marrow depression
aplastic anemia macrocytic anemia, leukopenia, Thrombocytopenia, agranulocytosis
Appear to be idiosyncratic reactions
General Statement
V. Hepatic Effects:Hepatitis and jaundiceHypersensitivity reactions
VI. Renal Effects:fatal nephrotic syndromes (oxazolidinediones,
Succinimides)
VII. hypocalcemia, rickets or osteomalaciasupplemental vitamin D (4000 units/week)
General Statement
Common: drowsiness, dizziness, ataxia, confusion, nausea, vomiting, rash, blurred vision, nystagmus
Hyponatremia and water intoxication– Antidiuretic effects ( Plasma level of ADH)
Idiosyncratic reactions: – Bone marrow depression (aplastic anemia
agranulocytosis, etc.)– Stevens–Johnson syndrome, toxic epidermal necrolysis– hepatitis
Carbamazepin (Tegretol)
Pregnancy: Category D
Common: anterograde amnesia, disorientation, drowsiness, fatigue, incoordination, drug dependence
Serious: respiratory depression, bone marrow depression, hypotension, rigidity, hepatitis
Clobazam (Urbanyl) Clonazepam (Klonopin)Diazepam (Valium)
Pregnancy: Category C
GI distress • pain, nausea, vomiting, anorexia
CNS effects • drowsiness, lethargy, euphoria, dizziness,
headache, and hiccupUrticaria, skin rashes, including Stevens-
Johnson syndrome, SLEblood disorders
• leucopenia, agranulocytosis, thrombocytopenia and aplastic anaemia
Ethosuximide (Zarontin)
Pregnancy: Category C
Commons:Anorexia, weight loss, nausea and vomiting,
rash, insomnia, headache, dizziness, somnolence, and diplopia
Serious:aplastic anemia severe hepatitis
FELBAMATE (Felbatrol)
Pregnancy: Category D
Common: • dizziness (15%), ataxia (12%), fatigue,
somnolence, weight gainSerious:
• depression, leukopenia, bronchospasm, nystagmus, diplopia, personality changes, poor coordination
Gabapentin (Neurontin)
Pregnancy: Category C
Dizziness Ataxia Headache Diplopia, blurred vision Nausea, vomiting Somnolence Skin rash “Stevens-Johnson”, toxic epidermal necrolysis Blood dyscrasias (neutropenia, etc)
Lamotrigine (Lamictal)
Pregnancy: Category C
Asthenia, Dizziness Somnolence Nervousness Ataxia, Headache, Amnesia, Depression, Psychotic adverse reactions
Levetiracetam (Keppra)
Pregnancy: Category C
• Like CBZ with improved toxicity profile:• Hyponatremia (more commonly than CBZ)• Dizziness, ataxia, nystagmus, and diplopia• Less hypersensitivity reactions
(erythematous skin rashes, etc.)• Less idiosyncratic blood dyscrasias (aplastic
anemia, agranulocytosis, etc.)• Less hepatotoxicity
Oxcarbazepine (Trileptal)
Pregnancy: Category C
• Common: lethargy, drowsiness, sedation, CNS excitation
• Serious: – hypoventilation, – apnea, – hypotension, – confusion, – psychiatric disturbance,– arrhythmias
Phenobarbital (Luminal)
Pregnancy: Category D
• Ataxia, confusion, diplopia and nystagmus• Hirsutism • Gingival hyperplasia• Folate deficiency and megaloblastic anemia • Idiosyncratic reactions
• severe dermatitis (skin rash, SLE, SJS, etc.)• bone marrow depression (agranulocytosis, etc.)
Phenytoin (Dilantin)
Pregnancy: Category D
• Common: drowsiness, diplopia, nausea, vomiting, ataxia, sedation, headache, GI problems
• Serious: – leukopenia, – megaloblastic anemia responsive to folate,– lupus-like syndrome
Primidone (Mysoline)
Pregnancy: Category D
• Ataxia • Fatigue• Dizziness• Cognitive slowing• Paresthesias• Confusion• Reduced sweating with hyperthermia • Impaired speech
Topiramate (Topamax)
Pregnancy: Category C
• Common: – Nausea, vomiting, abdominal cramping,
dyspepsia, diarrhea, anorexia.
• Serious: – Hepatotoxicity (fatal), – Thrombocytopenia, – Erythema multiforme,– Pancreatitis
Valproic acid (Depakene)
Pregnancy: Category D
• Atrial fibrillation; ventricular extrasystoles • Agitation; Ataxia; confusion; paresthesia;
depression• Somnolence, speech abnormalities• Agranulocytosis; anemia; thrombocytopenia• Rash; Stevens-Johnson syndrome, toxic
epidermal necrolysis
Zonisamide (Zonegran)
Pregnancy: Category D
Antiparkinson drugs
• Anticholinergics– Biperiden– Trihexyphenidyl– Diphenhydramin
e
• Dopaminergic Agents• Amantadine• Bromocriptine• Levodopa C,
Levodopa B• Pramipexole• Ropirinole• Selegiline
Anticholinergics
• Common: – Dry mouth, blurred vision, constipation,
urinary retention, drowsiness, dry skin, hyperthermia, IOP
• Serious: – forgetfulness, hallucinations, sedation,
depression, anxiety, arrhythmia
Pregnancy: Category C
Amantadine (Symmetrel)
• Common: – dizziness, – insomnia
• Serious: – CHF, – seizures, hallucinations, depression, psychosis,– bone marrow depression,– renal toxicity
Pregnancy: Category C
BROMOCRIPTINE (Parlodel)
• Common: – decreased BP (28%), – headache (10%), dizziness,– Nausea, vomiting
• Serious: – Seizures, CVA, depression, hallucinations – prolonged hypotension, MI– liver toxicity– pulmonary fibrosis
Pregnancy: Category B
Levodopa C (Sinemet) Levodopa B (Madopar)• Common: – Nausea, vomiting, cardiac arrhythmias, postural
hypotension, anxiety, insomnia, somnolence, vivid dreams
• Serious: – Aggression, paranoid delusions, hallucinations,
delirium, severe depression, dyskinesias (involuntary choreiform movements)
end-of-dose “wearing off ” and “peak-dose dyskinesias.”
Pregnancy: Category C
Pramipexole (Sifrol)Ropirinole (Requip)• Common: – nausea, vomiting, confusion, hallucinations,
lightheadedness, postural hypotension, sedation, vivid dreams
• Serious: – compulsive behaviors, psychosis, sleep attacks,
depression– dyskinesias Pregnancy: Category C
Selegiline (L-Deprenyl)
• Common: – nausea (20%), dizziness, abdominal pain (8%),
dry mouth (66%),
• Serious: – arrhythmias, confusion, psychosis, depression,
hallucinations, agitation, tremor, orthostatic hypotension
Pregnancy: Category C
Selegiline (L-Deprenyl)
• Food & drug interactions: – Food containing tyramine– SSRIs– SNRIs– TCAs– Opioid analgesics (Tramadol, etc.)– Sympathomimetic amines (amphetamines, etc.)– Carbamazepine and Oxcarbamazepine
PHARMACOTHERAPY OF COGNITIVE SYMPTOMS
• Cholinesterase inhibitors (In mild–moderate disease)
– Donepezil (Aricept)
– Galantamine (Remenyl)
– Rivastigmine (Excelon)
• Antiglutamatergic agents (In moderate to severe disease)
Memantin (Namenda)
Cholinesterase inhibitors
• GI symptoms (nausea, vomiting, and diarrhea, Peptic ulcers/GI bleeding, anorexia)
• urinary incontinence,• dizziness, headache, insomnia, confusion,
depression, seizures• syncope, bradycardia, • salivation, sweating• Exacerbation of asthma
Pregnancy: Category B
Memantin (Namenda)
Well tolerated• Constipation, • Vomiting,• Somnolence,• Confusion, dizziness, • Hallucinations, headache,• Coughing,• Hypertension
Pregnancy: Category B
Egb 761 (Ginkgo Biloba extract)
Antioxidant, anti-inflammatory and neuroprotective effects
nausea, stomach upset headache insomnia Hemorrhage (effects on platelet
adhesion, anti-PAF activity)
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