Antiparkinsonian Drugs PDF

Preview

Summary

Antiparkinsonian Drug Notes...

Description

HLSC 3P19: Pharmacology Chapter 16: Antiparkinsonian Drugs: Parkinson’s Disease: •

Parkinson’s Disease (PD): chronic, progressive, neurodegenerative disorder affecting the dopamine producing neurons in the brain.

•

PD results from an imbalance in 2 neurotransmitters – dopamine & acetylcholine – in basal ganglia. o Balance between dopamine and acetylcholine is needed for proper regulation of posture, muscle tone, and voluntary movement. o Dopamine acts in basal ganglia to control movements.

•

Classic symptoms of PD include: o Bradykinesia: slowness of movement o Postural instability: decrease or change in motor or muscle movement leads to unsteadiness and hesitation in movement in gait when individual starts or stops walking, or causes leaning to one side when sitting o Rigidity: resistance of the muscles to passive movement o Tremors: shakiness of the extremities, seen at rest. o Akinesia (manifesting as bradykinesia): absence or poverty of movement resulting in mask like facial expression and impaired postural reflexes.

•

PD is a progressive condition o As disease progresses there’s degeneration of surviving dopaminergic terminals that take up pharmacologically administered levodopa.

•

Motor complications include: o On-off phenomenon: swings in response to levodopa o Wearing-off phenomenon: occurs when antiparkinsonian medications begin to lose their progresses. o Dyskinesia: difficulty in performing voluntary movements ▪ Two types: •

Chorea: irregular, spasmodic, involuntary movements of the limbs or facial muscles.

•

Dystonia: movement of disorder involves the head, neck, and tongue and symptom common in patients with PD

o Dementia (may result) Treatment of Parkinson’s Disease: •

Treatment of the disease is primarily drug therapy

•

Physical activity is a priority for patients with PD.

•

For severe cases, surgical technique of deep brain stimulation of dopamine-deficient brain tissues o helps to reduce Parkinson-associated dyskinesia.

Drug Therapy: •

drug therapy is aimed at: o increasing the levels of dopamine or antagonizing the effects of acetylcholine.

•

Both direct acting and indirect acting drugs are available to treat PD.

Direct Acting Dopamine Receptor Agonists: •

Directing acting dopamine receptor agonists: used to treat PD, first line agents used upon diagnosis.

•

These drugs include: o Nondopamine dopamine receptor agonists ▪ Ergot derivative: •

Bromocriptine

▪ Nonergot drugs: •

Pramipexole dihydrochloride monohydrate (Mirapex ®)

•

Ropinirole (Requip ®)

o Dopamine replacement drugs Non-dopamine Dopamine Receptor Agonists: •

Mechanism of Action: o All of the non-dopamine dopamine receptor agonists work by direct stimulation of presynaptic and postsynaptic dopamine receptors in the brain.

o These drugs are used in early and late stages of the disease. •

Indication: o These drugs are used to treat various stages of PD. o There is less risk of motor complications with ergot/nonergot nondopamine receptor agonist monotherapy. o Bromocriptine: inhibits production of hormone prolactin, stimulating normal lactation

•

Contraindications: o Known allergy o Not used concurrently with adrenergic drugs

•

Adverse Effects: o Dizziness o Fatigue o Syncope o Drowsiness o GI upset o Edema

Dopamine Replacement therapy: •

Levodopa: biological precursor of dopamine required by the brain for dopamine synthesis o Works presynaptically to increase brain levels of dopamine o Carbidopa must be used alongside with levodopa

•

Levodopa-carbidopa: provides exogenous sources of dopamine that directly replaces dopamine in basal ganglia.

•

Mechanism of Action: o Dopamine replacement drug stimulate presynaptic dopamine receptors to increase brain levels of dopamine. o Levodopa is able to cross the blood-brain barrier, and it’s converted to dopamine.

o Large oral doses of levodopa required – since broken down outside CNS by an enzyme ▪ Large doses result in high peripheral levels of dopamine and lead to many unwanted adverse effects. ▪ These problems avoid when administered with carbidopa o Carbidopa: doesn’t cross the blood-brain barrier and inhibits the breakdown of levodopa – allows more levodopa to enter the brain (basal ganglia) and converted to dopamine ▪ Carbidopa used alone has no effect on Parkinson’s Disease •

Indications: o Dopamine replacement drugs used to directly restore dopaminergic activity in PD. ▪ Gold standard in treating PD – they work Presynaptically o As PD progresses, become more difficult to control it with levodopa ▪ Ultimately, levodopa no longer controls the PD, and the patient is seriously debilitated. ▪ This generally occurs between 5 and 10 years after the start of levodopa therapy

•

Contraindications: o Angle closure glaucoma – raise intraocular pressure o Undiagnosed skin condition

•

Adverse effects: o Cardiac dysrhythmias o Hypotension o Chorea o Muscle cramps o Depression o Anxiety o GI distress – N/V/diarrhea

•

Interactions:

o Vitamin B6 (pyridoxine) Indirect Acting Dopaminergic Drug: Monoamine Oxidase Inhibitors: •

MAO causes breakdown of catecholamines dopamine, norepinephrine, and epinephrine in the body.

•

MAO-B inhibitor drug example includes: o Selegiline o Rasagiline

•

Mechanism of action: o Most MAO-B Inhibitors occurs in CNS o Primary role of MAO enzymes is breakdown of catecholamines – dopamine, norepinephrine, and epinephrine and serotonin ▪ Helps to counter the dopaminergic deficiency seen in PD

•

Indications: o Selegiline & Rasagiline used in combination with levodopa-carbidopa o These drugs are adjunctive drugs – used when patient’s response to levodopa is fluctuating. ▪ They can prolong the effects of levodopa and reduce fluctuations in motor control. ▪ May delay the need for taking levodopa when used as monotherapy in early stages of the disease.

•

Contraindications: o Known drug allergy o Concurrent use of opioid drug meperidine hydrochloride

•

Adverse effects: o CNS effects: ▪ Dizziness, insomnia, hallucinations, agitations, ataxia, depression , paresthesia, headache, o Cardiovascular effects:

▪ Hypotension, hypertension, chest pain o GI effects: ▪ Nausea, diarrhea o Other effects: ▪ Dyskinesia ▪ Weight loss ▪ Dermatological reactions ▪ Rhinitis ▪ Pharyngitis Dopamine Modulator: •

Dopamine modulator drug example: o Amantadine

•

Mechanism of action: o Amantadine works by causing the release of dopamine and other catecholamines from their storage sites, vesicles, in presynaptic fibre within basal ganglia. o Amantadine blocks the reuptake of dopamine int nerve fibres ▪ Resulting in higher levels of dopamine and improved dopamine neurotransmission.

•

Indications: o Amantadine indicated in early stages of PD, while some intact neurons in basal ganglia. ▪ Usually only effective for only 6-12 months, after it fails

•

Contraindications: o Known drug allergy

•

Adverse effects: o Dizziness o Insomnia o Nausea

Catechol Ortho-Methyltransferase Inhibitors: •

COMT inhibitor drug example: o Entacapone (Comtan®)

•

Mechanism of action: o Entacapone: works presynaptically and blocks COMT (which catalyzes the breakdown of body’s catecholamines) o Can’t cross the blood brain barrier and can act only peripherally o This drug prolongs the effect of levodopa

•

Indications: o COMT inhibitors indicated for treatment of PD.

•

Contraindications: o Known drug allergy

•

Adverse effects: o GI upset o Urine discolouration o Worsen dyskinesia

Anticholinergic Therapy: •

Anticholinergics: block the effects of ACh – used to treat muscle tremors and muscle rigidity associated with PD o These two symptoms are caused by excessive cholinergic activity

•

Anticholinergics do not relieve bradykinesia (extremely slow movements).

•

Anticholinergic drug examples: o Benztropine: anticholinergic drug used for PD and extrapyramidal symptoms from antipsychotic drugs ▪ Caution during hot weather or exercise because it may cause hyperthermia ▪ Adverse effects: •

Tachycardia, confusion, disorientation, toxic, psychosis, urinary retention, dry throat, constipation, nausea, vomiting

▪ Anticholinergic syndrome ▪ Avoid alcohol o Trihexyphenidyl •

Mechanism of action/ Drug Effects: o Block the effects of neurotransmitter ACh at cholinergic receptors in the brain o Anticholinergics used as adjunct therapy in PD due to anti-tremor o Purpose of use is to reduce excessive cholinergic activity in the brain. o Anticholinergic drugs help alleviate bothersome and debilitating symptoms o Acetylcholine is responsible for SLUDGE: ▪ S – salivation ▪ L – lacrimation (tearing of the eyes) ▪ U – urination ▪ D – diarrhea ▪ G – increased GI motility ▪ E – emesis (vomiting) o Anticholinergics have the opposite and experience the adverse effects. o Antihistamines can be used to manage cholinergic symptoms in PD ▪ Antihistamine drug examples include: •

•

Diphenhydramine hydrochloride

Adverse effects: o Dry mouth & decreased salivation o Urinary retention o Blurred vision o Decreased GI motility (constipation) o Dilated pupils (mydriasis o Smooth muscle relaxation

Nursing Process:

Nursing Assessment: •

Before medication is given, assess and document vital signs and ABCs

•

Obtains thorough physical assessment and complete nursing history o CNS assessment: ▪ Inquire about headaches, fatigue, weakness, paralysis, dizziness, syncope. ▪ Question about any changes in baseline levels of alertness ▪ Assess response to stimuli, assess pupils ▪ Assess deep tendon reflexes ▪ Observe patients ability to walk o GI & GU: ▪ Determine daily urinary and bowel patterns with attention to changes in or loss of control of bladder or bowel ▪ Inquire about patients needing assistance with daily functions. ▪ Assess for nutrition imbalances o Skin and Oral mucous membranes: ▪ Assess skin and document colour and moisture o Respiratory system: ▪ RR rate, rhythm, depth, effort, breath sounds o Psychological & emotional status: ▪ Assess recent or changes in mood, affect, or personality. o Functional abilities: ▪ Inquire about everyday function in personal and professional life

Nursing Implementation: •

Levodopa-carbidopa: o Oral doses given with food to help minimize GI upset o Amino acids from dietary protein interfere with the uptake of levodopa in the brain.

o While taking levodopa-carbidopa to continue to eat high protein foods but use portion control o Teach about the importance of well balanced meals o Teach the importance of drinking water – 3000mL/day o Teach that sucking on hard candies or lozenges may be helpful in reducing dry mouth •

Anticholinergics: o Take medication after meals or at bedtime and not at the same time as other medications o Teach that the medication takes a few days to several weeks to show effectiveness o Teach about measures to prevent or treat dry mouth o Teach to report any adverse effects immediately

•

MAO-B inhibitors: o Orthostatic hypotension is transient problem, patient must move and change position slowly

•

COMT inhibitors: o The onset of COMT inhibitors have rapid therapeutic effects o Drugs taken without regard to meals or food o Teach that these drugs to never discontinue abruptly and require a gradual weaning period o Teach to change positions slowly and with positions to avoid syncope dur to orthostatic hypotension. o Teach entacapone turns their urine brownish orange...