narrated powerpoint on cns drugs & parkinson's (ch 20-21)

Chapter 20: 

Chapter 20 Introduction to Central Nervous System Pharmacology

CNS Drugs: 

CNS Drugs Agents that act on the brain and spinal cord Medical uses Psychiatric disorders, suppression of seizures, pain relief, production of anesthesia Nonmedical uses Stimulant, depressant, euphoriant, and other “ mind-altering ” abilities

Transmitters of the Central Nervous System: 

Transmitters of the Central Nervous System Currently, there are 22 known transmitters. More are likely to be discovered.

The Blood-Brain Barrier (BBB): 

The Blood-Brain Barrier (BBB) Impedes entry of drugs into the brain Passage across the BBB limited to lipid-soluble drugs Protein-bound or highly ionized drugs cannot cross Mixed blessing of BBB

Adaptation of the CNS to Prolonged Drug Exposure: 

Adaptation of the CNS to Prolonged Drug Exposure Different effects possible when drug is taken chronically versus initial use of drug Increased therapeutic effects Decreased side effects Tolerance and physical dependence

Development of New Psychotherapeutic Drugs: 

Development of New Psychotherapeutic Drugs Complexity of mental health Lack of adequate animal models of mental illness Mentally healthy individuals cannot be used as subjects No effect or paradoxical effects Psychopharmacology accidental discoveries

Approaching the Study of CNS Drugs: 

Approaching the Study of CNS Drugs Key points for study – recognize that: There are numerous neurotransmitters. Their precise functional roles are not clear. Their complexity makes it difficult to know with certainty just how CNS drugs produce their effects.

Chapter 21: 

Chapter 21 Drugs for Parkinson ’ s Disease

Parkinson’s Disease (PD): 

Parkinson’s Disease (PD) PD is a neurodegenerative disorder of the extrapyramidal system associated with disruption of neurotransmission in the striatum Characterized by dyskinesias and akinesia Proper function of the striatum requires a balance between the neurotransmitters dopamine and acetylcholine (ACh) Imbalance between dopamine and ACh results from degeneration of the neurons that supply dopamine to the striatum

Parkinson’s Disease (PD): 

Parkinson’s Disease (PD) Affects over 1 million Americans Second only to Alzheimer’s disease as the most common degenerative disease of neurons Symptoms generally appear in middle age and progress No cure for motor symptoms Drug therapy can maintain functional mobility for years (prolongs/improves quality of life)

Slide 12: 

Footer Text 12

Cardinal Symptoms of PD: 

Cardinal Symptoms of PD Dyskinesias Tremor at rest Rigidity Postural instability Bradykinesia (slowed movement) Tremor In addition to motor symptoms Autonomic disturbances Depression Psychosis and dementia

Slide 14: 

Fig. 21-1. A model of neurotransmission in the healthy striatum and parkinsonian striatum. A, In the healthy striatum, dopamine (DA) released from neurons originating in the substantia nigra inhibits the firing of neurons in the striatum that release gamma-aminobutyric acid (GABA). Conversely, neurons located within the striatum, which release acetylcholine (ACh), excite the GABAergic neurons. Hence, under normal conditions, the inhibitory actions of DA are balanced by the excitatory actions of ACh, and controlled movement results. B, In Parkinson ’ s disease, the neurons that supply DA to the striatum degenerate. In the absence of sufficient DA, the exci-tatory effects of ACh go unopposed, and disturbed movement results.

Parkinson’s Disease (PD): 

Parkinson’s Disease (PD) Therapeutic goals Ideal treatment (reverse neuronal degeneration or prevent further degeneration) does not exist Goal is to improve patient’s ability to carry out activities of daily life Drug selection and dosages are determined by extent to which PD interferes with work, dressing, eating, bathing, etc.

Drug Therapy for Parkinson’s Disease: 

Drug Therapy for Parkinson’s Disease Two major categories Dopaminergic agents By far the most commonly used drugs for PD Promote activation of dopamine receptors Levodopa (Dopar) Anticholinergic agents Prevent activation of cholinergic receptors Benztropine (Cogentin)

Drug Therapy for Parkinson’s Disease: 

Drug Therapy for Parkinson’s Disease Levodopa (drug “ holidays ” recommended) Levodopa/carbidopa Dopamine agonists Pramipexole (Mirapex) Entacapone (Comtan) Amantadine (Symmetrel) Selegiline (Eldepryl, Carbex)

Drug Selection: Initial Treatment: 

Drug Selection: Initial Treatment Mild symptoms: MAO-B inhibitor Selegiline or rasagiline More severe symptoms: levodopa or a dopamine agonist Levodopa more effective than dopamine agonists, but long-term use carries a higher risk for disabling dyskinesias Management of motor fluctuations “ Off ” times (can be reduced with dopamine agonists, COMT inhibitors, and MAO-B inhibitors) Drug-induced dyskinesias

Levodopa: 

Levodopa Highly effective, but benefits diminish over time Most effective in first 2 years – by end of 5 years, symptoms may return to pretreatment level Acute loss of effect and on-off phenomenon Orally administered, rapid absorption from small intestine Food delays absorption Neutral amino acids compete with levodopa for intestinal absorption and for transport across blood-brain barrier High-protein foods will reduce therapeutic effects

Levodopa: 

Levodopa Adverse effects Nausea and vomiting Dyskinesias Cardiovascular effects Psychosis May darken sweat and urine Can activate malignant melanoma Drug “ holidays ” Drug interactions: first-generation antipsychotics, MAOIs, anticholinergics, pyridoxine Food interactions: protein and vitamins with pyridoxine

Carbidopa: 

Carbidopa Advantages No adverse effects of its own Increases the available levodopa in the CNS and allows for 75% decrease of levodopa dosage; therefore reduces cardiovascular and GI adverse effects Effects come mainly from levodopa when given in combination Levodopa/ carbidopa ( Sinemet , Paracopa )