BIOL 200 - Lecture 06

BIOL 200 - Lecture 06 - Drugs of the Central Nerous System...

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Unformatted text preview: Drugs of the Central Nerous System Stimulation Increases: Convulsions or Seizures Sensory Acuity Motor Activity Tremors & Hallucinations Anxiety Euphoria Normal --Neutral Sedation (Drowsy) Hypnosis (Sleep) General Anesthesia Coma Death Death Depression Inhibits: Sensory Acuity Motor Activity Abuse, Tolerance & Dependence Abuse: difficult to determine Tolerance: the state where one must increase the dose of a drug in order to achieve/maintain the desired effect. Dependence Dependence: does not occur from limited therapeutic use / limited social use. But, dependence is an inevitable consequence of repeated, continuous or moderate use. (both psychological and physical) Psychological dependence What is it? A person is psychologically dependant on a drug if he/she must take the drug to have an acceptable feeling of well being. This is the attitude that contributes to it’s likelihood of abuse. Physical dependence What is it? The craving for a drug that results from the development of cellular tolerance. It is the presence of physical dependence that leads to withdrawal symptoms when the drug is discontinued. There can be no physical dependence with cellular tolerance. The neurochemistry of the brain and spinal cord change to off set the drug’s effect…this leads to dependence. Dose must be increased to maintain effect (person has no choice) The Triad Triad: Cellular Tolerance Physical dependence Withdrawal Symptoms CNS stimulants MOA: increase the excitability of the CNS increases levels of nor-epinephrine in the brain. Agents: Amphetamines Xanthines Cocaine / cocaine derivatives Therapeutic uses for CNS stimulants Amphetamines: narcolepsy, weight control (?), attention deficit - hyperactivity disorder Xanthines: pain from headache (vasoconstriction in brain), asthma, bronchitis, emphysema (bronchorelaxation), counter drowsiness Cocaine derivates: local anesthetics Side effects of CNS stimulants Amphetamines: CNS: to much stimulation…nervousness, anxiety, sleeplessness Cardiovascular: too much nor-epi..increase adrenergic response. Increase HR, BP, potential arrhythmias. Weight loss, malnutrition Kids: suppression of growth Possible bone marrow suppression CNS Depressants An agent which decreases the excitability of the tissue in the CNS. Produces sedation, hypnosis, general anesthesia, coma, death All drugs in this category can be used as sedatives, hypnotics or general anesthetics…it is dose dependant. The higher the dose the greater the depression. CNS depressant terms: Sedative: drugs administered at a dose level to cause mild drowsiness or sedation or to reduce restlessness & anxiety. Hypnotic: drugs which are administered at a dose level to induce sleep or allow an individual to stay asleep. (they can be awoken from this sleep) General Anesthetic: a drug given at a dose to depress the CNS to a degree that causes a loss of consciousness (unarousable), as well as analgesia. Sedative Hypnotic Agents The oldest, largest and most studied class of CNS drugs. These drugs produce varying degrees of CNS depression depending on the dose administered. They produce generalized depression of the cellular activity of many organ systems as well as the tissue within the CNS The synapse is the site of action. Drug classes: barbiturates, benzodiazepines, antihistamines Barbiturates & Benzodiazepines MOA: act at gabba receptor / chloride ion channel complex. Both barbiturates and benzos act on these complexes. They bind different allosteric sites. Gabba is an inhibitory neurotransmitter and will produce inhibitory postsynaptic potentials. Chloride flows through the channel and decreases resting membrane potential. The neuron, therefore, is less likely to be stimulated. Benzos: gabba dependent Barbiturates: gabba independent Therapeutic Uses: Sedative Hypnotics Relieves anxiety Sleep disorders Epilepsy (barbiturates) Side effects Drowsiness Impaired performance or decreased perception and judgment Hangover effect Hyperalgesia (barbiturates only) Overdose- respiratory depression (barbiturates, but can be true of any depressants in combination) Cautions Additive with other sedative-hypnotics Drug abuse and habituation Withdrawal state: the most severe possible Symptoms can last up to 6 weeks or longer General anesthetics Goals of general anesthesia 1. 2. 3. Analgesia (narcotics, Ketamine) Loss of consciousness (gases, nitrous oxide) Muscle relaxation (maybe curare) Inhalation Intravenous Types: Antiepileptic Agents MOA: 2 ways 1. Decreasing movement of ions into the nerve cells (block Na) and therefore, reduce repetitive firing of neurons. Phenytoin, oxycarbazine 2. Alters the activity of neurotransmitter (increasing GABA or decrease glutamate) Benzos (clonazepam), Barbiturates (phenobarbital), newer AED’s Goal of treatment Control the seizures without significant CNS impairment. Frequent adverse effects: Sedation - locomotor and CNS Kidney and liver damage Blood diseases Each agent has it’s own adverse effects Parkinson’s Disease Problem: loss of dopaminergic neurons resulting in an imbalance of dopamine and acetylcholine in the basal ganglia (substancia nigra) Treatment: 1. Increase dopamine 2. Decrease acetylcholine Antiparkinsonian Agents Leva-dopa - replaces dopamine Carbidopa Bromocriptine - stimulates postsynaptic dopamine receptors Selegiline - decreases MAO-B, which leads to a decrease in the degradation of dopamine Anticholinergic drugs: blocks Ach receptors and helps to restore a “false” balance Artane, Cognetin, Kemadrin Treating Pain Analgesics: agents that relieve pain without a loss of consciousness. 2 kinds: 1. 2. Narcotics (opiods) Non-narcotics (salicylate, acetaminophen, NSAIDs) Narcotics Nonnarcotics Acts on CNS For severe pain Associated with tolerance, abuse, physical dependence vs. Acts on periphery & CNS decreases release of prostaglandins For low to moderate pain headache, arthritis, peripheral pain Not generally abused and does not cause addiction. Therapeutic Effects: Salicylates vs. Aniline type (acetaminophen) Relief of pain headache, dysmenorrhea, arthritis Relief of pain same except not for arthritis Antipyretic decreases fever Antipyretic decreases fever Antiinflammatory Rheumatoid arthritis Rheumatic fever decreases scarring of heart valve No Antiinflammatory No Anticoagulant Anticoagulant effect For venous or coronary thrombosis. After myocardial infarction and to help prevent stroke Acute Side Effects and Toxicities: Salicylates vs. Aniline type (acetaminophen) G.I. irritation and decreased coagulation (bleeding) with continued use gastric mucosa usually heals in 3 days Caution: black stools. No CNS stimulation respiratory stimulation to point of respiratory alkalosis No Toxicities with Chronic Use: Salicylates vs. Aniline type (acetaminophen) No Hearing loss not as likely to take chronically because not for arthritis Hearing ringing in ears hearing loss (reversible) dizziness (inhibits enzyme in the cochlea) Possible slight decr. GFR negligible compared to phenacetin or even acetaminophen toxicity No significant liver damage Caution: if patient already has liver or kidney damage Kidney or liver damage Irreversible liver damage with one overdose of acetaminophen No blood disease No link to bladder cancer Blood diseases - anemia Poss. link to bladder cancer Note: After acetaminophen over dosage, prompt treatment (within 10 hours) with acetylcysteine (Mucomyst®) can prevent hepatic damage and death in many patients. Psychotrophic Agents Antidepressants Antianxiety agents Antipsychotic agents Drugs to treat Manic Depressive episodes Catecholamine Theory of Mood Norepinephrine imbalances implicated Low levels --> depression High levels --> anxiety Has been expanded to include Serotonin …still probably OVER SIMPLIFIED Yet 2/3 of patients are helped by increases in these neurotransmitters. Depression Can occur as a natural component of psychological processes and as a result of pathological processes. Can occur as a primary affective disorder, a reaction to drug(s), as well as with a wide variety of diseases. Twice as common in women Suicide is 30 times more likely in a depressed individual Total cost (5yrs ago) of depression in the US = 50 billion $/yr Characterized by: Depressive mood Loss of interest in activities Los of pleasure in previously satisfying activities Antidepressant agents MOA: increase nor-epi and often serotonin levels in the synapse (mostly re-uptake inhibitors) Drugs: Tricyclics Monoamine Oxidase Inhibitors Newer agents: Serotonin reuptake inhibitors Tetracyclics Antianxiety agents Prescribed more frequently than any other CNS class. Designed for short term use. Drugs: Sedative Hypnotics Beta Blockers Buspirone Psychosis Severe mental disorder characterized by: disordered thought processes Blunted or inappropriate emotional responses Bizarre behavior (hypo or hyperactivity, agitation, aggressiveness, hostility, combativeness, social withdrawal) Hallucinations delusions Schizophrenia: etiology unclear. Most likely results from abnormal neurotransmission in the brain Dopamine implicated (high levels) Drug therapy is aimed at block dopamine transmission (also some serotonin) Treatment goals Reduce the bizarreness of behavior Do not expect a “cure” THERAPEUTIC USES: Schizophrenia Manic phase of bipolar disorder Antiemetic & hiccups (?!!) MOA: blocks dopamine receptors in the chemoreceptor trigger zone Side effects Sedation: big problem Fatigue, indifference, apathy, drastic changes in personality Anticholinergic: dryness Antiadrenergic effects: orthostatic hypotension Extrapyramidal effects: repetitive, involuntary, purposeless movements of lips, face and torso Endocrine imbalances (depression of the hypothalamus) Zyprexa (olanzapine) In 2005 a mulit-site, double blind study (the CATIE project) compared several atypical antipsychotic agents to an older typical antipsychotic agent (Perphenazine). Zyprexa is the only drug that outperformed the older typical antipsychotic med. Results: Greater reduction of psychopathology Decreased hospitalizations Longer duration of successful treatment Unfortunately, associated with relatively severe metabolic side effects. Weight gain, increased blood glucose, cholesterol and triglycerides New Drug - LY2140023 Eli Lilly - in phase 2 Human Trials Mechanism: Targets glutamate receptors 9/07 - study published in Nature Medicine Subjects experienced significant improvement and suffered few side effects No weight gain No increase in prolactin levels No extrapyramidal symptoms Drugs to treat Manic Depressive Episodes Lithium is the only drug to specifically treat bipolar disorder. How does it work? Lithium is a monovalent cation that competes with calcium, magnesium, potassium and sodium in body tissues and at binding sites. It alters sodium transmission in nerve and muscle cells. It effects a shift toward intraneural catecholamine metabolism. The specific MOA in mania is unknown, but it does affect the synthesis, storage, release and reuptake of the central monoamine neurotransmitters (NE. 5-HT, DA, Ach and GABA). Its antimanic effects may be the result of increases in NE uptake and increases in serotonin receptor sensitivity. Cautions with lithium Abnormal sodium loss Lithium competes with sodium for reabsorption at the proximal tubule. If sodium levels are low, more lithium will be reabsorbed. Possible pathological renal damage Endocrine Abnormalities Hypothyroidism Diabetes insipidus Dangers in Pregnancy Cardiovascular malformations, kidney damage, euthyroid goiter, hypoglycemia ...
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This note was uploaded on 09/26/2009 for the course BIOL 200 taught by Professor Egan during the Summer '09 term at Golden West College.

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