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130 Cards in this Set
- Front
- Back
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50 mg/dL or .05% blood ethanol level is how many drinks?
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about 2
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will the neurological effects of alcohol be more when the BAC is rising or lowering?
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rising
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the letha levels of ethanol are lowered when the body is exposed to what?
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other CNS depressors
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describe the metabolism of ethanol.
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gastric alcohol dehydrogenase gets 10 to 20% of elimination and is more active in men than women. Hepatic metabolism is the main location for alcohol metabolism and it is first converted by alcohol dehydrogenase to acetaldehyde then to acetate by acetaldehyde dehydrogenase and finally to CO2. Note there are different allels of alcohol dehydrogenase. cytochrome p450 2E1 also clears alcohol and this can lead to toxicity of other drugs like acetaminophen (bc cyt p450 is induced and will make more of the toxic acetamenophen metabolite). Note acetaldheyde dehydrogenase is more active so not much acetaldehyde accumulates.
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what are the blood level ranges of alcohol associated with inccordination, slow reaction time, and blurred vision? Visual impairment, staggering, and slurred speech? Marked incoordination, stupor, hypoglycemia, convulsions? Coma and death?
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.1-.15, .15-.3, .3-.5, .5 and up
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describe the pharmacokinetics of alcohol.
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low levels of ethanol will saturate the metabolizing enzymes, elimination is 0 order (constant rate not dependent upon alcohol concentrations AKA michaelis menten)
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what is the direct mechanisms of action of ethanol?
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altered membrane fluidity, GABAa-Cl channel is activated (possibly due to ethanol binding site), NMDA (excitatory glutamate receptors) are suppressed, and other receptors and signalling kinases are activated
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cirrhosis of the liver via chronic alcohol is thought to be due to what?
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acetaldehyde (a metabolite of ethanol) forms new molecules in the cells and then the immune system attacks the liver
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what vitamin deficiencies are common in alcoholics?
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folate and thiamine
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what other molecules due to alcohol metabolism can cause damage to tissues?
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free radicals
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what are conditions always caused by alcohol?
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alcoholic psychoses, alcohol dependence syndrome, alcoholic polyneuropathy, alcoholic gastritis, alcoholic fatty liver, alcoholic cirrhosis of the liver, acute alcoholic hepatitis, excessive BAC
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what are indirect diseases attributable to alcohol?
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tuberculosis, cancer of the lip, mouth, esophagus, larynx, liver, and breast, diseases of stomach and GI tract, acute and chronic pancreatitis, cirrhosis of the liver without mention of alcohol
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what are two acute effects of alcohol on the brain and nervous system that are not well known?
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decrease in body temp and endocrine alterations to the stress response
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what are the chronic effects of alcohol on the brain and nervous system?
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brain shrinkage, wernicke-korsakoff, alteration in brain functions at the molecular level, and hemorrhagic stroke.
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what are the effects of alcohol on the GI system?
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increased acid leading to ulcers and impaired absorption of nutrients especially folic acid and B vitamins. Pancreatitis, alcoholic hepatitis, fatty liver, cirrhosis of the liver.
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what are the musculoskeletal effects of alcohol?
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acute muscle damage and weakness, decreased bone mass, increased risk of fractures.
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what are the effects of alcohol on blood and the immune system?
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anemia often due to decreased absorption of folic acid or thiamine. Risk of infection from pneumonia, TB, HIV, and hep C. Increased cancer risk possibly due to immune suppression. Trauma and burn injury patients with alcohol in their systems at the time of injury may have more infections, longer hospital stays, and poorer prognosis
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what are the cardiovascular effects of alcohol?
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low to moderate consumption can decrease risk of CV disease, but not recommened to start drinking. Cardiomyopathy and arrythmias occur in chronic alcoholics
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what are the four criteria to check for alcohol abuse?
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fails to live up to most important responsibilities, endangers themselves or others, gets into trouble with the law, experiences difficulties in relationships or jobs.
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what is the common questionaire to test for alcoholism?
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cut down? Annoyed at others when they tell you? Guilty from drinking? Eyepoener?
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what are the alcohol withdrawal symptoms?
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craving, tremor, irritability, nausea, sleep disturbance, tachycardia, hypertension, sweating, perceptual distortion, seizures (12 to 48 hours after last drink), delirium tremens
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what are the pharmacologic treatments of alcoholism?
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disulfiram (decreases metabolism of acetaldehyde thus vomitting), naloxone or naltrexone (opiate antagonists), acamprosate (GABA analog that works by some mechanism)
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how is THC metabolized and excreted?
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in the liver, not by p450 enzymes and these metabolites are excreted in feces unchanged
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what is a common endogenous cannaboid and how does it act as a neuromodulator?
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anandamide, can decrease signalling from a presynaptic cell.
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cannaboid receptors are tied to what signalling molecules?
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Gi thus neg impact on A cyclase. Positively coupled to MAP kinase
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what are some non CNS effects of marijuana?
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tachycardia, orthostatic hypotension, bronchodilation, and immunosuppression
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what are the two stages of CNS effects of marijuana?
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stimulant which is first and then relaxation later
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what are the withdrawal symptoms of marijuana?
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irritability, restlessness, sweating, nausea, anorexia, insomnia, hand tremor
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what is the cannaboid derivative that is used to treat nausea seen in chemo patients? What is the problem with it?
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dornabinol, it causes immune suppression
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how do cannaboids increase food intake in AIDS and cancer patients?
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reward center of mesolimbic DA pathways is increased, and after short term food restriction, it modulates hypothalamic orexin signaling.
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what is a cannaboid being tested for pain relief in cancer?
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sativex
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how can cannaboids be neuroprtoectants and anti-inflammatory agents?
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may be used following ischemic and inflammatory damage. Block glu induced excitotoxicity, regulate Ca influx into cells, act as NMDA antagonists, affect microglia and other immune responses, antioxidant properties.
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list some therapeutic uses of the cannaboids.
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glaucoma, movement disorders of the basal ganglia, anti epilepy, treat cholera via CB receptors in gut, and autoimmune diseases…
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what is the physiologic basis of LSD?
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complex serotonin mechanisms
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what is the physiologic basis of mescaline?
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serotonin and DA agonist
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what is the physiological basis of psilocybin?
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serotonin agonist
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characterize the effects of hallucinagens.
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sympathomimetic
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MDMA has properties of what two drugs?
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methamphetamine and mescaline
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the primary reason for death from ecstacy use is what?
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hyperthermia resulting in liver, kidney, and CV system failure
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how would you treat a "bad trip" of LSD? A flashback?
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benzos or barbituates. Neuroleptics
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describe the problem with MDMA metabolism?
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it can interfere with its own metabolism thus potentislly toxic doses may be reached
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what chemicals are released from ecstacy stimulation on the CNS?
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NE, sero, and DA
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among current MDMA users, former users, polydrug users, and no drug use, who has the worst memory?
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former MDMA users
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describe phencyclidine.
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more dissociative than hallucinogenic, very addictive, low doses are sympathomimetic while higher doses are hallucinogenic. NMDA receptor antagonist
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this drug is simillar to PCP but has a lower potency and is shorter acting.
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ketamine
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what are the opiods used to treat pain?
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morphine, fetanyl, codeine, meperidine, methadone
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what are the NSAIDs used to treat pain?
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aspirin, acetaminophen, ketorolac, celecoxib
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what are the antidepressants used to treat pain?
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amitriptyline, imipramine, doxepin
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what are the anticonvulsants used to treat pain?
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carbamazepine, phenytoin, gabapentin
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what is the vasoactive agent used to treat pain?
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ergotamine
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what are the local anesthetics?
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lidocaine, bupivacaine, benzocaine
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what are adjuvants to pain meds?
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propanolol, prednisone, amphetamine, antihistamines, midazolam
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what is allodynia?
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pain due to a stimulus that does not normally produce pain
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what is causalgia?
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sustained burning pain - allodynia and hyperpathia after traumatic nerve lesion
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what is neuropathic pain?
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sympathetically mediated pain from nerve damage
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describe neuroplasticity.
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involved in central sensitization, may be involved in phantom limb pain
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describe primary hyperalgesia.
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activation of cutaneous, visceral or somatic nociceptors that do not adapt to continued stimulation which can lead to a decrease in pain threshold as in the case of primary hyperalgesia.
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describe secondary hyperalgesia.
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silent nociceptors which are normally not activated until tissue is injured and then they persistently fire which may lead to central sensitization and thus secondary hyperalgesia.
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what are the two primary afferent fibers of pain and describe them.
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A delta which is thinly myelinated and transmits mechanical and mechanothermal receptors responsible for initial, sharp, well localized pain. C fibers are non myelinated and they transmit from all types of nociceptors.
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describe the pain pathway once it hits the spinal cord.
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synapse in dorsal horn on laminae I and II then to projection neurons, excitatory or inhibitory interneurons. Projection neurons cross the cord and go up the ST tract (or spinoreticular or spinomesencephalic), they then go to the thalamus and other areas of brain. RF receives pain and will be responsible for the aversive drive and motivation/affective dimensions of pain. hypothal and limbic system are for emotional response. cortex is for perception and the affective (response) compoinent
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what are the three ways to inhibit central pain?
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spinal (gate control theory- rub your leg after you hit it), supraspinal descending control from PAG, pharmacologic agents with central action (opiods, antidepressants, anticonvulsants)
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what are pharmacologic agents that act on peripheral pain?
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NSAIDs and local anisthetics (block sodium conductance)
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what is the WHO ladder for treating chronic pain?
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start with non opiod; add adjuvant as needed. Use low potency opiod for mild to moderate pain with or without an ajdjuvant or non opioid. Initiate full agonist high potency opiod with or without adjuvant and non opiod
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what types of pain are antidepressants useful in treating?
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pain resulting from nerve injury: primary fibrositis, neuropathy, central pain, phantom limb paion
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what is the alpha 2 adrenergic agonist used to treat pain and what are its specefic effects?
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clonidine; if given spinally it enhances opiod effects, effective in opiod dependent patients
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what medications are useful for acute relief of migraines and what is their mechanism?
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sumatriptan and zolmatriptan which are serotonin agonists
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what is the medication of choice for treatment of trigeminal neuralgia?
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anticonvulsants like carbamazepine, gabapentin, phenytoin
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what drug is a weak opiod agonist and also inhibits reuptake of NE and sero with fewer opioid side effects and low abuse liability?
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tramadol
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what are the full opioids?
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morphine, fetanyl, and methadone
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what are the preventive therapies for migraines? Abortive?
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propanolol, verapamil, cyproheptadine, amitriptyline, phenytoin, and NSAIDs. Sumatriptan and other triptans (contraindicated in patients with CV disease), ergotamine, NSAIDs, prednisone, and butorphanol
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how does botox work in terms of pain management and what is it used to treat?
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it blocks Ach release and produces flacid paralysis of skeletal muscles, injected into muscles around the eyes and forehead for migraine treatment if conventional therapies do not work.
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what can cause neuropathic pain?
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diabetic neuropathy, central stroke pain, AIDS
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what drugs are used to treat neuropathic pain?
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amitriptyline, doxepin, desipramine (all TCA's), mexilitine (local anesthetic), and gaba pentin
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what drugs do you use for pain with a sickle cell crisis?
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treat like cancer pain: NSAIDs, codeine, meperidine, morphine plus TCA's and anticonvulsants may be used as adjuvants
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what is the new peptide antagonist that may be useful in migraines?
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olcegepant
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what is the mechanism of action of ziconotide, its side effects, and types of pain relieved?
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blocks Ca channels, psychosis and many others, cancer and AIDs (chronic pain)
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describe the type of pain relieved by NSAIDs and opioids as well as their anti-inflammatory and antipyretic qualities.
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NSAIDs are used for muskuloskeletal pain while opioids are used for any severe or dull continuous pain. NSAIDs are antipyretic and anti-inflammatory while opioids are not.
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why do you give a much smaller dose of morphine in the spinal cord than in an IV solution or pill?
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little morphin crosses the BBB but if put directly in the CNS it does not need to pass the BBB.
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how is morphine metabolized and are the metabolites analgesic?
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glucuronidated in the liver, most of the metabolites are more potent analgesics than morphine itself. Note it also has an extensive first pass metabolism
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disease of what organs may affect morphine metabolism and why?
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liver (this is where it is metabolized) and renal disease (mode of excretion).
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what are the CNS effects of opioid agonists?
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analgesia, sedation (narcosis), euphoria, respiratory depression (due to reduced CO2 sensitivity in the medullary respiratory centers), miosis, nausea and emesis, antitussive, altered thermoregulation, and neuroendocrine effects.
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what are the peripheral actions of the morphine?
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GI tract (less secretions, less tone, less peristalsis, thus constipation), constricts the sphincter of oddi to increase biliary tract pressure and produce symptoms of epigastric distress or biliary colic, increases other smooth muscle tone like ureter and uterus (thus harder to pee and long labor), peripheral vasodilation (due to histamine release from mast cells) with possible orthostatic hypotension, chronic morphine treatment is immunosupressive, skin flushes due to vasodilation.
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what side effects of morphine do not occur in other opioids?
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vasodilation and gall bladder issues
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what are the opioids mechanisms of action?>
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prevent neurotransmission, thus prevent perception of pain
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what are the therepeutic uses of morphine?
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pain management, treatment of diarrhea, relief of dyspnea
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use morphine with great care in patients with what?
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decreased respiratory reserve, head injury (due to increased intracranial pressure from morphine), reduced blood volume (morphine has hypotensive effects), asthma, and biliary colic
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what is the treatment for opioid overdose?
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the narcotic antagonist naloxone
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what opioids are more potent analgesic than morphine?
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hydromorphine and diacetylmorphine (heroin)
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what derivative of codein is found in cough syrups and is more analgesic than codeine?
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hydrocodone
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what drug is a derivative of codein that has a long lasting pill form that is often abused?
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oxycodone
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what are the phenylpiperdine derivatives (not chemically related to the opioids)?
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meperidine (demerol), fentanyl, sufentanil, alfentanil, diphenoxylate, loperamide
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describe meperidine.
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less potent than morphine, metabolite can accumulate and lower CNS seizure threshold, less constipating effects than morphine, mildly stimulates the uterus (used safely for obstetrical analgesia), interacts with MAOI's, drug of abuse in medical profession
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describe fentanyl and its cousins…
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much more potent than morphine, highly lipophilic, crosses BBB fast. Used in anesthesia and pre-operative and post operative treatment.
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what are the diphenylheptane derivatives?
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methadone, propoxyphene, and LAAM
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describe methadone.
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effective oral analgesic similar to morphine, protracted withdrawal symptoms, used in suppressing withdrawal during opioid abstinence
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describe propoxyphene.
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less effective as an analgesic than methadone or codeine, for mild-mod pain, used with adjuvants
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describe LAAM
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used for heroin addicts
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describe the two morphinans.
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levorphanol is the L isomer that is a good analgesic with less nausea and vomiting while dextomorphan is the D isomer that is not an analgesic or addictive, it is used in cough syrups
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what are the opioids with mixed agonist/antagonist activity that are used to precipitate withdrawal symptoms and treat pain?
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pentazocine, nalbuphine, buprenorphine, nalorphine, butorphanol,
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this drug is used to treat heroin addiction now bc it has longer retraction of withdrawal symptoms than methadone.
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buprenorphine
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what are agonists of the mu receptor and what are its effects?
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morphine, fetanyl and derivatives, causes analgesia, resp depression, euphoria, reduced GI motility
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what are the agonits for the kappa opioid receptor and what are its effects?
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pentazocine, butorphanol, and buprenorphine. Selective activation may cause dysphoria
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delta opioid receptor does what?
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not well understood, produces analgesia
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what are enkephalins?
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endogenous opioid peptides that are 5 AA's long, activate mu and delta
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which endogenous opioid peptide is much more analgesic than morphine?
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beta endorphin
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which endogenous opioid peptide only activates kappa opioid receptors?
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dynorphin
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what are the endogenous mu receptor agonists?
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endomophin
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1/3 of methamphetamine is excreted in what?
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urine.
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what are the acute effects of meth?
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euphoria, wakefulness, high all day if ingested, and decreased appetite
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what are the physiological effects associated with chronic methamphetamine abuse?
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tremor, weakness, dry mouth, weight loss, cough, sinus infection, sweating, burned lips, sore nose, oily skin/complexion, headaches, diarrhea, annorexia
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what is formication?
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the sensation that drugs are crawling all over your body…
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compare and contrast cocaine and methamphetamine.
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meth is man made, can produce hours of a high, 50% of drug is removed in 12 hours, and has limited medical use. Cacaine is plant derived, smoking it produces a 20 to 30 minute high, 50% of the drug is removed from the body in one hour, can be used as a local anesthetic
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what is the mechanism of action of methamphetamine?
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blocks the re-uptake of biogenic amine NT's like DA, NE, and sero, simillar to cocaine. It also induces the release of biogenic amine NT's via monoamine transporter from presynaptic neurons in the synapse. It can also inhibit MAO at higher doses.
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when is methamphetamine lethal?
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when an abuser takes a very high dose after a period of extended abstinence (they are no longer tolerant) or when a new user takes the same high dose that an experienced and tolerant user takes.
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what are the lethel effects of methamphetamine?
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uncontrollable hyperthermia, seizures and convulsions, hypoxic stress, hypertensive crisis, and CV complications
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what are the cognitive impairments of someone who has a severe methamphetamine dependence?
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poorer performance in memory, attention, and concentration as well as persistent psychosis and paranoia
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what are the neuro chemical levels in someone who is postmortem after meth overdose?
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decreased DA, tyrosine hydroxylase, and dopamine transporters
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what study results suggest neurotoxicity involved in meth?
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PET scan shows reduction of dopamine transporters in the caudate and putamen even after 3 years of abstinence
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what areas in the brain have the greatest loss due to meth use?
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hippocampus and limbic system
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what is the mechanism that causes meth induced neurotoxicity?
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they increase amount of ROS thus increasing amount of apoptosis
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how does meth produce ROS?
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DA release and subsequent enzyme oxidation (DA to DOPAC and H2O2 via MAO, DA to superoxide radicals via O2), mito disruption, increased excitatory amino acids like glut
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how do cells die in an acute meth overdose? Chronic binge?
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DAT takes up meth, alters pH and enzyme activity, DA is released and oxidized thus it loses its function, pH alteration causes mito to open and let Ca in, thus cell death. Binges produce increased Ca by same mechanism and the increase glut release, DA release, and Ca efflux causing apoptosis
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what kind of neurons does meth destroy?
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mainly DA (can cause parkinson like symptoms if in striatum) but can also cause nonspecefic neuronal damage
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describe drug dependence.
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continues to use drug despite potential medical or social consequences (cannot stop, need it for normal functioning, physical and biologically based)
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describe drug addiction
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this is behavioral not physical, it is about getting and using the drug, quantitative not qualitative, NOTE one who is addicted is likely to be dependant, but not necessarily the other way around. Ex. May be dependent on opiates for pain relief only not to get high. Addicted ppl are more likely to relapse.
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what is dispositional tolerance?
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changes in pharmacokinetics like metabolism so that less of the drug is available at the sight of action
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describe pharmacodynamic tolerance.
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adaptive changes occur at the sites of action so that the response is reduced in the presence of the same concentration of the drug
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what are rebound effects?
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seen in withdrawal, get opposite effects of drugs. Eg. Hyperexcitability from benzo withdrawal
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the faster the drug is removed…
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the greater the chances of withdrawal
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what type of reinforcement is seen in a relapse during withdrawal?
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both positive and negative reinforcement, thus it is very powerful.
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