Anti-Parkinson's Drugs Class PDF

Drugs for Parkinson Disease Chapter 24 Objectives Recognize the features of Parkinson’s disease Identify the agents used to treat Parkinson’s disease and describe how these drugs work Describe side effects, precautions, contraindications, interactions and adverse reactions for the...

Drugs for Parkinson Disease Chapter 24 Objectives Recognize the features of Parkinson’s disease Identify the agents used to treat Parkinson’s disease and describe how these drugs work Describe side effects, precautions, contraindications, interactions and adverse reactions for these classifications and the selected prototypes Describe care of patients receiving these drugs Parkinson’s Disease (PD) Chronic, progressive, degenerative neurological disorder affects the control of body movements other symptoms Parkinson’s Disease Motor symptoms include: Bradykinesia (hypokinesia) Rigidity Rest tremor Postural instability Gait disturbances (manner of walking) Mask-like (expressionless) face Dystonias (eg lower back muscles) Parkinson’s Disease Other Symptoms Sleep disturbances Depression Psychosis Dementia Loss of smell Apathy Autonomic dysfunction orthostatic hypotension, urinary urgency, constipation Parkinson’s Disease (PD) Affects dopamine-producing neurons in the brain Symptoms caused by an imbalance of two neurotransmitters Dopamine (DA) Acetylcholine (ACh)  Str – Striatum Skeletal muscle motor control Parkinson’s Disease Symptoms occur when loss of ~ 70-80% of dopamine neurones in the substantia nigra (SN) of the basal ganglia DA Inhibitory Controlled Movement Excitatory ACh  DA Inhibitory Disturbed Movement Excitatory ACh Parkinson’s Disease Treatments and interventions drugs for movement abnormalities deep brain stimulation - DBS (drug-resistant PD) exercise (balance, mobility, depression, constipation) socialization Parkinson’s Disease Most drug therapy focused on DA pathway Replacement (precursor) drugs Prevent DA metabolism DA receptor agonists Drugs Affecting DA System Direct Indirect DA receptor levodopa-carbidopa agonists selegiline (MAOI) amantidine Drug Therapy for PD Dopamine System Precursor - levodopa-carbidopa Prevent DA metabolism - MAOI DA receptor agonists - pramipexole, ropinirole Anticholinergic agents Benztropine (Cogentin) Diphenhydramine (for anticholinergic effect)  Indirect Therapy Dopamine Precursor - Parkinson’s Disease: Levodopa Therapy Levodopa is a precursor of dopamine Blood-brain barrier does not allow exogenously supplied dopamine to enter but does allow levodopa Levodopa is taken up by dopaminergic terminal converted into dopamine, then released Parkinson’s Disease: Levodopa Therapy Aimed at increasing dopamine release from surviving DA neurones Balances the effects of cholinergic pathways on muscle control Parkinson’s Disease: Levodopa Therapy Therapy maintains functional mobility for years prolongs quality of life prolongs life expectancy Full therapeutic response may take several months to develop Therapy does not cure or stop progression of disease Parkinson’s Disease: Levodopa Therapy As PD progresses, it becomes more and more difficult to control symptoms with levodopa DBS is alternative Parkinson’s Disease: Levodopa Therapy Levodopa metabolism outside of CNS GI liver Most commonly, levodopa not given alone additional drug to reduce peripheral levodopa metabolism Parkinson’s Disease: Levodopa Therapy Combination Therapy Carbidopa is given with levodopa benserazide is alternative Carbidopa does not cross the blood-brain barrier BUT prevents levodopa breakdown in the periphery Lower dosage to achieve desired effects reduced nausea & vomiting Parkinson’s Disease: Levodopa Therapy Combination Therapy Levodopa can also be metabolized to inactive substance by the enzyme COMT Use COMT inhibitors Entacapone, opicapone inhibits COMT more levodopa available to enter brain used to reduce “on-off” phenomenon (see later slide) Entacapone Carbidopa Parkinson’s Disease: Levodopa Therapy Combination Therapy Levodopa + Carbidopa Levodopa + Carbidopa + Entacapone Parkinson’s Disease: Levodopa Therapy “Wearing-off” effect gradual loss - subtherapeutic levels near end of dosing interval “On-off” Phenomenon abrupt loss of drug effect even at high drug levels lasts from minutes to hours unknown reason Levodopa Therapy Adverse Effects Nausea and vomiting CTZ (reduced by carbidopa combination) Dyskinesia - (ironically) involuntary muscle movements eg oral and facial muscles (chewing motion), writhing/flinging movement of arms and legs CV Hypotension and cardiac dysrhythmias Psychosis eg hallucinations, paranoid ideation Other Indirect Dopaminergic Therapies Dopaminergic Therapy Prevent DA metabolism MAO-B inhibitor: selegiline, rasagiline Inhibits DA breakdown in neurones Amantadine promotes DA release from nerve endings Selective Monoamine Oxidase Inhibitor (MAOI) Therapy Selegiline irreversible MAOI that selectively inhibits MAO- B Does not elicit the “cheese effect” of the nonselective MAOIs used to treat depression (cheese, red wine, etc) see MOAI to treat depression Selective MAO-B Therapy: Selegiline Selegiline is a MAO-B inhibitor no effect on NE, 5-HT breakdown NE, 5-HT breakdown by MAO-A Causes an increase in the levels of dopaminergic stimulation in the CNS Selective MAO-B Therapy: Selegiline Milder symptoms (early in disease) Used in combination with levodopa or levodopa-carbidopa Adjunctive agent when response to levodopa is fluctuating (“on-off”) Allows the dose of levodopa to be decreased delays the development of unresponsiveness to levodopa therapy Selective MAO-B Therapy: Selegiline Adverse effects usually mild nausea, abdominal pain, dry mouth lightheadedness, dizziness, insomnia, confusion doses higher than 10 mg/day may cause more severe adverse effects Dopaminergic Therapy Indirect acting: amantadine Causes release of dopamine from the storage sites at the end of nerve cells that are still intact Also blocks the reuptake of dopamine into the nerve endings Does not stimulate dopamine receptors directly May help with levodopa-induced dyskinesias Direct Dopaminergic Therapies Dopaminergic Therapy Direct acting DA receptor agonists Directly stimulate dopamine receptors 1st line treatment for PD younger patients mild/moderate symptoms reduce “wearing off” effect of levodopa less effective than levodopa Dopaminergic Therapy Dopamine Receptor Agonists Older drug (ergot-derived) bromocriptine Newer drugs pramipexole, ropinirole, rotigotine (transdermal patch) replacing older drugs Apomorphine (pen injection) not an opioid! Dopaminergic Therapy Dopamine Receptor Agonists no conversion required no dietary protein restrictions less dyskinesias But.. hallucinations, postural hypotension, drowsiness Impulse control disorders (patient history?) gambling, shopping, hypersexuality  Client Care Implications Inform client not to take other medications with PD drugs before checking with prescriber When starting dopaminergic agents, assist client with walking because of dizziness that may occur Hypotension Levodopa - avoid high protein diets at least around drug administration amino acids reduce GI absorption and transport across blood-brain barrier Client Care Implications Taking levodopa with non-selective MAOIs (antidepressants) may result in hypertensive crisis Levodopa may activate malignant melanoma Important to perform a careful skin assessment of patients Levodopa preparations may darken the client’s urine and sweat harmless Anticholinergic agents  DA Inhibitory Disturbed Movement Excitatory ACh Anticholinergic Therapy With greater influence of cholinergic excitatory pathways on muscle control Muscle tremors Cogwheel rigidity Pill-rolling movement of fingers and head bobbing while at rest Anticholinergic Therapy Anticholinergics block the effects of ACh Used to treat muscle tremors and muscle rigidity associated with PD caused by excessive cholinergic influence when DA is reduced Drugs do not relieve bradykinesia (extremely slow movements) Anticholinergic Drugs Anticholinergic Drugs benztropine (Cogentin) trihexyphenidyl ethopropazine diphenhydramine (traditional antihistamine for anticholinergic effect) Anticholinergic Therapy: Other Indications Also used to treat drug-induced extrapyramidal symptoms (EPS) see drugs for psychosis class Anticholinergic Therapy: Adverse Effects When anticholinergics are administered for any indication, medication effects are the same other uses for anticholinergic drugs Anticholinergic Therapy: Adverse Effects Drowsiness, confusion, disorientation (CNS) Constipation, nausea, vomiting Urinary retention, pain on urination Blurred vision, dilated pupils, photophobia dry skin, fever Decreased salivation = dry mouth (same as Atropine – anticholinergic) Client Care Implications Include questions about client’s: CNS GI and GU tracts Psychological and emotional status Assess for signs and symptoms of PD Masklike expression Speech problems Dysphagia Rigidity of arms, legs, and neck Client Care Implications Monitor for response to drug therapy Improved sense of well-being, mental status Increased appetite Increased ability to perform ADLs, to concentrate, and to think clearly Less intense parkinsonian manifestations, such as less tremor, shuffling gait, muscle rigidity, and involuntary movements