1. Parkinson’s Disease A degenerative and progressive disorder Associated with neurological consequences of decreased dopamine levels produced by the basal ganglia (substantia nigra) Dopamine is a neurotransmitter found in the neural synapses in the brain Balance, posture, muscle tone and involuntary movement depends on the roles of dopamine (inhibitory) and acetylcholine (Ach: excitatory)

2. If dopamine missing, Ach produces more of an effect on muscles Pharmacological basis of anti-parkinson drugs: –Restore dopamine function –Inhibit Ach within corpus striatum

3. Medication Rational Replace depleted levels of dopamine Stimulate the nerve receptors enabling neurotransmission Increase the effect of dopamine on nerve receptors (agonist) Counteract the imbalance of Ach and Dopamine

4. The Drugs –Dopaminergic drugs (improving dopamine functioning) Levodopa Dopamine receptor agonists Amantadine Selective monoamine oxidase B inhibitors Catechol-O-methyltransferase inhibitors –Antimuscarinic drugs (Ach inhibitors)

5. Levodopa (Madopar & Sinemet) Can not administer dopamine directly, as it does not cross the blood brain barrier A natural amino acid that the brain converts into dopamine (replacement therapy) used since the 1960’s. Levodopa is combined with Carbidopa, which is a dopamine decarboxylase inhibitor that does not cross the blood brain barriers

6. Source: Adams et al (2006). Pharmacology for Nurses – A Pathophysiologic Approach. Prentice Hall Publishers

7. Adverse effects: –As a result of the amount of peripheral dopamine levels Nausea, vomiting Postural hypotension –As a result of the amount of CNS dopamine levels Dyskinetic involuntary movements (face & neck) Hallucinations and confusion

8. Dental Parkinsonian tremors of the orofacial musculature and the use of levodopa-containing medications may cause bruxism; therefore, the dentist should examine the dentition of a patient with PD for excessive loss of tooth structure.

9. Dopamine receptor agonists Bromocriptine ; Pergolide; cabergoline ; Ropinirole. Direct agonists of dopamine receptors in the brain. cabergoline has been implicated in damaging heart valves and possibly predisposing patients to endocarditis. (Another ergot-derived dopamine agonist, pergolide, has been removed from the market.) People who have bacterial endocarditis or a prosthetic cardiac valve meet the American Heart Association criteria requiring an antibiotic prophylaxis regimen during dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa

10. Selective monoamine oxidase B –MoA: prolongs the effects of levodopa as MAO-B degrades dopamine –Patients being treated with the monoamine oxidase inhibitor (MAOI) rasagiline can receive local anesthetic solutions containing levonordefrin or epinephrine because MAOIs do not potentiate the pressor or cardiac effects of these direct-acting catecholamines. –However, the MAOI selegiline is unique in that it undergoes extensive first-pass metabolism to l- methamphetamine and l-amphetamine, and interactions with levonordefrin or epinephrine may result in severe hypertension

11. Dentists should not prescribe meperidine hydrochloride to patients being treated with the MAOIs selegiline and rasagiline because of a potentially toxic interaction in which severe hyperthermia, hypertension and tachycardia may develop. MAOIs also increase the potency of other narcotic analgesic agents, so the dentist would be prudent to prescribe only one-half the usual dosage of the narcotic agent.

12. Antimuscarinic/Anticholinergic Drugs: –Trihexyphenidyl, Benztropine; Orphanadrine. –Less common drugs but they affect Ach based interactions –MoA: blocking cholingeric (Ach) receptors to restore balance –Pharmacokinetics: fairly well absorbed, extensive hepatic metabolism, intermediate to long half-lifes –Adverse effects: dry mouth and confusion

13. Catechol-O-methltransferase inhibitors - COMT Entacapone MoA: inhibits the breakdown of levodopa –Pharmacokinetics: variability of absorption, extensive first-pass metabolism, short half-life –Adverse effects: dyskinesias, hallucinations; N, V, Dia and abdominal pain –New combination – Levodopa/carbidopa/entacapone (Stalevo) as 1 tablet (50, 100, 150mg)

14. Practitioners must take precautions when administering local anesthetic agents containing epinephrine in patients being treated with levodopa-containing medications and medications containing entacapone, because these patients may experience an exaggerated effect on blood pressure and heart rate. Therefore, it is prudent to administer no more than 0.05 milligrams of epinephrine—as is found in three cartridges of 2 percent lidocaine with 1:100,000 epinephrine—per 30-minute period, with careful aspiration to avoid intravascular administration. Entacapone is excreted via bile, so the dentist should be cautious when prescribing erythromycin and ampicillin, both medications known to interfere with biliary excretion.

15. Dentals Oral-rinse topical agents such as chlorhexidine gluconate may not be appropriate, because many patients with PD may not be able to swish and expectorate to minimize ingestion. Lastly, artificial salivary products should be prescribed for patients showing signs of xerostomia.

16. Drugs used to treat Alzheimer disease Pharmacological intervention for Alzheimer disease is only palliative (calming) and provides modest short-term benefit. None of the current therapeutic agents alter the underlying neurodegenerative process. Current therapeutics are aimed at either (1) improving cholinergic transmission within the CNS or (2) preventing the excitotoxicity actions of NMDA glutamate receptors in selected brain areas.

17. Acetylcholinesterase inhibitors Many studies have linked the progressive loss of cholinergic neuron and, presumably cholinergic transmission within the cortex, to the memory loss that hallmark (trademark ) symptoms of Alzheimer disease. Inhibition of Acetylcholinesterase within CNS will improve cholinergic transmission, Examples on this group are Donepezil, and Galantamine. At best these agents provide a modest reduction in the rate of loss of cognitive functioning in Alzheimer disease. Common adverse effect include anorexia, muscles gramps, and diarrhea

18. ChEI is nonspecific to the brain and has a generalized systemic effect, which increases cholinergic activity such as salivation, peristalsis, and vascular muscle relaxation. These patients may have increased nausea, vomiting, abdominal pain, and diarrhea. Increased salivation may make it more challenging to maintain a dry field during dental treatment as well as increase choking sensation and pose some difficulty for the patient to maintain a removable prosthesis. As mentioned above, donepezil and galantamine are metabolized through the liver microsomal pathway, and the use of antimicrobial drugs such as erythromycin and ketoconozole may decrease their metabolism.78 A.H. Friedlander, D.C. Norman, M.E. Mahler, K.M. Norman and J.A. Yagiela, Alzheimer's disease: psychopathology, medical management and dental implications, J Am Dent Assoc 137 (2006), pp. 1240–1251. View Record in Scopus | Cited By in Scopus (8) 78 Excitation, agitation, bradycardia, loss of consciousness, and digestive disorders may be seen as a result of hypercholinergic effects.78View Record in ScopusCited By in Scopus (8) 78

19. NDMA receptors antagonist Over stimulation of glutamine receptors, particularly of the NMDA type, has been shown to result in excitotoxic effects on neurons, and is suggested as a mechanism for neurodegenerative processes. Antagonist of NDMA glutamine receptors are often neuroprotective, preventing the loss of neurons following ischemic and other injuries. Memantine is an example and has shown to prevent or slow the rate of memory loss in Alzheimer dementia, even in patient with moderate to sever cognitive losses. Memantine is well tolerated, with few dose related adverse effects, which include confusion and restlessness.