Drugs for Parkinson_27s 2

Drugs for Parkinsonism and Parkinson’s Disease I. Parkinsonism  group of disorders that share four main symptoms: 1. tremors 2. rigidity 3. slowness of movement (bradykinesia) 4. poor balance and coordination. Idiopathic Parkinson’s Disease  loss of dopamine- secreting neurons in substantia nigra  cause unknown (idiopathic)  causal theories:  viral infection  head trauma  atherosclerosis Pseudoparkinsonism/ Drug –induced Parkinsonism  causes:  antipsychotics (phenothiazines)  poisons (carbon monoxide, manganese) Basal ganglia cells INHIBITION Type 1 drugs Dopaminergics A. Dopaminergics STIMULATION Type 2 drugs Anticholinergics  Levodopa*  Carbidopa- levodopa (Sinemet) B. MAO –B inhibitor  Selegiline C. COMT inhibitors  tolcapone  entacapone D. Dopamine Agonists  amantadine  ropinirole  bromocriptine A. biperiden (Akineton) B. benztropine(Cogentin) C. diphenhydramine (Benadryl) D. procyclidine E. trihexyphenidyl (Artane) pramipexole pergolide A. Dopaminergics MOA: increase dopamine concentration 1. Levodopa Indic: DOC for idiopathic parkinson’s dse SE/ adverse effect:: (high dose)  N&V  dyskinesia  psychosis  Increase libido  orthostatic hypotension, cardiac dysrhythmias  assoc. melanoma formation  “ on – off” fluctuations 2. Carbidopa – Levodopa (Sinemet)  Advantages:  more dopamine reaches basal ganglia  smaller dose of dopamine required  single dosaging Indic: Idiopathic parkinson’s dse SE:  more severe -in high doses B. Dopamine agonists 1. Amantadine (Symmetrel) MOA: increases dopamine release Indic: 1. early onset idiopathic parkinson’s disease 2. early onset drug- induced parkinsonism 3. influenza A respiratory virus 2. Bromocriptine (Parlodel) Pergolide Pramipexole Ropinirole MOA: stimulate dopamine receptors S/E of Dopaminergics & dopamine agonists: 1. 2. 3. 4. 5. 6. 7. 8.  dyskinesia involuntary body movements tachycardia N&V urinary retention constipation dizziness & orthostatic hypotension psychosis Contraindications to dopaminergics & dopamine agonists: 1. narrow angle glaucoma 2. suspicious skin lesions 3. lactation 4. severe cardiac dse 5. severe renal problem 6. severe psychiatric problem Drug interactions:  pyridoxine (Vit B6 ) decrease effect of levodopa  antipsychotic drugs  phenytoin  MAO inhibitors & TCA ---> hypertensive crisis if taken with levodopa  C. MAO - B inhibitor  selegiline MOA: inhibits monoamine oxidase (MAO) –B ---> prolongs action of levodopa Indic: 1. early onset parkinsonism 2. decrease “on –off” fluctuation of levodopa SE; Dopaminergics/ Dopa agonists + MAOI Tyramine + MAOI --> hypertensive crisis D. COMT inhibitors MOA: inhibit COMT ---> incease levodopa concentration in brain 1.Tolcapone 2.Entacapone Indication: 1. adjunct to levodopa / sinemet therapry SE;  severe liver damage  dark yellow to orange urine E. Anticholinergics MOA: block stimulating effects of Ach --> reduce tremors & rigidity, minimal effect on bradykinesia 1. Benztropine (Cogentin) 2. Biperiden (Akineton) 3. Trihexyphenidyl (Artane) Indic: 1. drug –induced parkinsonism 2. Parkinson’s disease SE: same as Atropine  BLOCK SLUDS  disorientation & confusion, memory loss  hypotension, tachycardia Drug interactions:  phenothiazines, antihistamines, TCA ---> increasese anticholinergic properties  Antipsychotics --> decrease effect of anticholinergics CI:  Narrow- angle glaucoma  Intestinal & urinary obstruction  BPH  Myasthenia gravis  COPD  Severe memory loss/dementia Patient: Doctor, I have a split personality. Psychiatrist: Nurse, bring in another chair. Drugs for Myasthenia Gravis Myasthenia Gravis  autoimmune disease  lack of acetylcholine (Ach) reaching cholinergic receptors in skeletal muscle  s/sx: o ptosis & diplopia o weaknes & fatigue of skeletal muscles o dysphagia o dysarthria o respiratory muscle weakness Drug Therapy: A. Acetylchoinesterase Inhibitors/ Cholinesterase Inhibitors (AChE inhibitors) MOA: inhibit cholinesterase --> more Ach activates cholinergic receptors ---> promote muscle contraction 1. Ultra-shorting  Edrophonium (Tensilon)  Myasthenia Crisis Sx: Cause: : Tensilon test : Tx : muscle weakness underdose of AChE inhibitors positive pyridostigmine vs Cholinergic crisis muscle weakness overdose of AChE inhibitors negative atropine sulfate 2. Short- acting  Neostigmine (Prostigmin) 3. Intermediate- acting  Pyridostigmine (Mestinon)* 4. Long- acting  Ambenonium SE;  INCREASE SLUDS  hypertension B. Glucocorticoid  Prednisone Indic: decreases MG sxs & promotes remission SE: increase blood sugar, abnormal fat deposits, muscle wasting C. Immunosuppressive agent  Azathioprine (imuran) SE: leucopenia, hepatotoxicity Drugs for Mutiple Sclerosis Multiple Sclerosis  autoimmune disease  attacks myelin sheath of nerves in brain & spinal cord  s/sx:  diplopia  weakness in extremities  spasticity of extremities Drug therapy: Phase of MS 1. Acute Attack: S/Sxs fatigue, optic neuritis motor weakness Treatment prednisone ACTH 2. Remission-exacerbation recurrence of MS sxs spasticity betaseron - interferon- beta azathioprine immunosuppressants cyclophosphamide 3. Chronic Progressive progressive MS sxs (wheel-chair bound) cyclophosphamide (Cytoxan) ACTH Drugs to avoid in MS: 1. antihistamine / histamine (H2) blockers – ranitidine, cimetidine 2. NSAID - indomethacin 3. beta blocker - propanolol Drugs for Alzheimer’s Disease Alzheimer’s disease  chronic, progressive neural degeneration in cortex  s/sx; o confusion o marked memory loss ---> dementia o Loss of judgement & time disorientation o Inability to perform ADL  cause unknown  causal theories: o progressive loss of Ach-producing neurons & deficiency in Ach o neuritic plaques o apolipoprotein E4 (apo E4) o beta- amyloid protein o neurofibrillary tangles inside neurons Stage 1 Mild (early confusion) early cognitive decline  memory loss  recall difficulties  some decrease in social functioning unable to perform complex tasks unable to concentrate no knowledge of current events needs assistance for survival disoriented to time & events needs assistance for survival forget spouse & family members unaware of surroundings fecal & urinary incontinence increase CNS disturbances limited speech, scream unable to ambulate, sit up or feed self May slip into stupor / coma Stage 2 Moderate stage 3 Moderately severe (Early dementia) Severe stage 4 stage 5 Very severe (Late dementia) Drug therapy: A. Acetylcholinesterase (AChE) inhibitors / Cholinesterase (ChE) inhibitors MOA: block Ache ----> allow more Ach to stimulate cholinergic receptors     Tacrine (Cognex)* Donezepil (Aricept) Rivastigmine (Exelon) Memantine SE/adverse effects: (increase SLUDS)  Increase GI activity & secretions  cardiodepression  miosis, BOV  dizziness & drowsiness  weight loss Drug interactions: NSAIDS – increase GI secretions Theophylline – increased 2x with tacrine B. Investigational drugs for alzheimer’s:  NSAIDS  Calcium blockers  MAO- B inhibitors  ACE inhbiibitors Until you value yourself, you won't value your time. Until you value your time, you will not do anything with it. M. Scott Peck