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Central Nervous System Diseases
Transcript of Central Nervous System Diseases
BMS - 01
BCAS Parkinson's Disease
Epilepsy PARKINSON'S DISEASE a chronic, progressive disorder that affects nerve cells deep in the brain responsible for planning and controlling body movement. Bodily movements are regulated by a portion of the brain called the ''basal ganglia'' Dopamine works with acetylcholine. These two brain chemicals act to transmit messages between the nerve cells that control the functioning of
muscles throughout the entire body. Acetylcholine sends messages that cause the muscles to contract, dopamine moderates these signals to
proper levels Parkinson's disease, however, there is an imbalance between dopamine and acetylcholine, because there is too much acetylcholine and too little dopamine when the dopamine-producing nerve cells of the substantia nigra begin to die off in some individuals and when 80 percent of dopamine is lost, PD symptoms such as tremor, slowness of movement, stiffness, and balance problems occur In Parkinson's, cells that produce dopamine begin to degenerate As a result, nerves that control muscle contraction send bad signals, causing involuntary tremors and muscle rigidity. Parkinson's disease may also result if the receptors to which dopamine must bind to exert its effects become blocked. •Bradykinesia - slowness of movement, impaired dexterity, decreased blinking, drooling, expressionless face
•Tremor at rest - involuntary shaking that decreases with purposeful movement. Typically starts on one side of the body, usually the hand
•Rigidity - stiffness caused by involuntary increase in muscle tone
•Postural instability - sense of imbalance. Patients often compensate by lowering their center of gravity, which results in a stooped posture. 1.Conserve dopamine in the brain by blocking the breakdown action of MAO-B (Monoamine oxidase) 2.Block the action of the neurotransmitter glutamate, which allows for
an increase in dopamine release. 3.Introduce agents that mimic dopamine and bind to the receptors in
the neuron's synapse. 4.Replace missing dopamine in the brain 5.Reduce activity of the neurotransmitter acetylcholine What are the symptoms? MEDICATIONS
•Levodopa – dopamine replacement therapy
•Dopamine agonists – mimic the action of dopamine
•COMT inhibitors – used along with levodopa. This medication blocks an enzyme known as COMT to prevent levodopa breaking down in the intestine and to allow more of it to reach the brain
•Anticholinergics – block the effect of another brain chemical (a neurotransmitter called acetylcholine) to re-balance its levels with dopamine
•Amantadine – has anticholinergic properties and enhances dopamine transmission
•MAO type B inhibitors – prevents the metabolism of dopamine within the brain. Parkinson's disease Drugs Sometimes a dopamine agonist is used in combination
with levodopa in the later stages of PD. Monoamine oxidase-B inhibitors Catechol-O-methyltransferase (COMT) inhibitors Levodopa The body converts levodopa to dopamine low level of dopamine in the affected part of the brain increases with levodopa. This reduces side-effects and increases the amount that gets to the brain where it is converted to dopamine. Levodopa is always combined with another drug (either benserazide or carbidopa). These prevent levodopa from being converted into dopamine in the bloodstream. Dopamine agonists drugs that act on the same receptors in the brain as dopamine. So, in effect, they act like a substitute for dopamine. Unlike levodopa, they do not need to be converted in the body to become active. There are several types. Ropinirole, pramipexole, or rotigotine are used most commonly. Epilepsy may result from anything that disrupts the brain's natural circuitry, such as:
•Severe head injury
•Brain infection or disease
•Oxygen deprivation MEDICATIONS Epilepsy Epilepsy is a disorder of the brain's electrical system. In epilepsy clusters of nerve cells, or neurons, in the brain sometimes signal abnormally. Neurons normally generate electrochemical impulses that act on other neurons, glands, and muscles to produce human thoughts, feelings, and actions. the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and behavior, or sometimes convulsions, muscle spasms, & loss of consciousness During a seizure, neurons may fire as many as 500 times a second, much faster than
normal. The majority of epileptic seizures are controlled by medication, particularly
anticonvulsant drugs. There are many different AEDs. Generally, they work by changing the levels of the chemicals in the brain that conduct
electrical impulses. This reduces the chance of a seizure. Antiepileptic drugs are the most frequently used treatment of epilepsy. affects sodium channels, and inhibits rapid firing of brain cells. clonazepam (Klonopin): gabapentin (Neurontin): lacosamide (Vimpat): lamotrigine (Lamictal): levetiracetam (Keppra): phenobarbital (Luminal): phenytoin (Dilantin): topiramate (Topamax): valproic acid (Depakote): carbamazepine (Tegretol, Carbatrol): increase the effectiveness of GABA, the brain’s main inhibitory neurotransmitter. works by influencing transport of GABA and effects on calcium channels. It has no drug interactions Vimpat blocks sodium channels (but in a different way from other seizure medicines), and this block reduces brain excitability. A broad-spectrum alternative to VPA, works by several mechanisms including blocking release of glutamate, the brain’s main excitatory neurotransmitter. Levetiracetam is one of the more used medicines in seizure clinics because it probably is effective for a broad-spectrum of seizures types. increases the effect of GABA, the main inhibitory neurotransmitter in the brain. alters brain cell sodium channels, which has the effect of limiting rapid firing of the brain cells A good broad-spectrum AED has several mechanisms, including blocking the enzyme carbonic anhydrase, which affects the acidity of brain tissue. has effects on GABA (at least in very high doses), and a neurotransmitter called NPY
to block seizures, and maybe also on calcium channels. basal ganglia cells require a proper balance of two substances called dopamine and acetylcholine , both
involved in the transmission of nerve impulses. Most Parkinson’s medications fit into one of the following broad categories: another alternative to levodopa for early PD These drugs work by blocking (inhibiting) the effect of a chemical in the brain called monoamine oxidase-B (MAO-B). This chemical is involved in the breakdown of levodopa
and dopamine. If the action of MAO-B is inhibited then the effect of
any dopamine lasts longer relatively new drugs. help to stop the breakdown of levodopa by the body, so more of each dose of levodopa can get into the brain to work DEPRESSION Complex abnormalities in cholinergic, catecholaminergic (noradrenergic, dopaminergic) and serotonergic (5-HT) transmission Mechanisms AED include blockade of voltage-gated channels(Na+ or Ca+ ), Enhancement of inhibitory GABAergic impulses, or interference with excitatory glutamate transmisson Symptoms of Depression Intense feelings of sadness
Inability to experience pleasure in usual activities
Changes in sleep patterns and appetite
loss of energy
suicidal thoughts ANTIDEPRESSANTS Antidepressants down regulate receptors indirectly or directly by inhibiting reuptake of 5-HT (as with SSRIs) andnorepinephrine or dopamine or by blocking MAO. Most clinically useful antidepressant drugs potentiate, either directly or indirectly, the actions of the norepinephrine and/or serotonin in the brain. Antidepressants are generally categorized by how they affect the naturally occurring chemicals in the brain to change the mood. There are several different types of antidepressants. Selective serotonin reuptake inhibitors
(SSRIs) Group of chemically diverse antidepressant
drugs that specifically inhibit serotonin reuptake. blockage leads to increased concentrations of
neurotransmitter in the synaptic cleft and, ultimately
to greater polysynaptic neuronal activity Serotonin and norepinephrine reuptake inhibitors (SNRIs) Selectively inhibit the re-uptake of both serotonin and norepinephrine. Atypical Antidepressants Mixed group of agents that have actions at several sites. Bupropion - Acts as a weak dopamine and norepinephrine reuptake inhibitor.
Mirtazapine - Enhances serotonin and norepinephrine neurotransmisson via mechanisms related to its abilty to block Alpha 2 receptors.
Nefazodone and Trazodone - weak inhibitors of serotonin reuptake Tricyclic Antidepressants TCAs block norepinephrine and serotonin reuptake into the neuron. Potent inhibitors of the neuronal reuptake of norepinephrine and serotonin into presynaptic Nerve Terminals. TCAs also block serotonergic, Alpha-adrenergic, histaminic
and muscarinic receptors. Monoamine oxidase inhibitors A mitochondrial Enzyme. most MAO inhibitors form stable complexes with the enzyme, causing irreversible inactivation THANK YOU