CNS Stimulants 2
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- What are the indirectly acting sympathiomimetic amine drugs?
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Amphetamine
methamphetamine
methylphenidate - Alternative drug to amphetamines to treat narcolepsy?
- Modafinil (provigil)
- Amphetamines are considered what schedule drug?
- II: high abuse potential and high propensity to cause psychological dependence
- What is the amphetamine structure like?
- A catecholamine x more lipid soluble--rapidly penetrates the BBB
- What does NH4Cl- have to do with amphetamines?
- It acidifies the urine and increases its rate of elimination. Used in detox.
- What is the mechanism of action for amphetamines?
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1. Pentrates the neuron terminal by diffusion and riding the amine transporters
2. It displaces amines in the vesicles (NE, DA, 5-HT); b/c it is a weak-base and disrupts pH.
3. The displaced amines leave the terminal via reverse uptake by the transporters.
OVERALL: Massive release of NE and DA (>5-HT) into the synaptic cleft - What is the ph of amphetamines?
- pKa: 9.9= weak base b/c an amine
- What are the respective effects of massive release of DA and NE?
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DA= "high" and addictive properties (reward pathway)
NE=sleep-supressing effect - What are the SE of amphetamines in the periphery?
- a and B Adrenergic Receptors (NE): increase atrial pressure and tachycardia
- What are the CNS SE of amphetamines?
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*inc. alertness
*delayed sleep
*anorexia
*dec. fatigue
*euphoria
*inc. motor and speech activity - What is the rebound phenomemon with amphetamines?
- After the Major CNS effects: period of depression, hypersomnia, depression
- What are the effects of amphetamines at high doses?
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*psychotic state-sim. to paranoid schizo.
*can trigger convulsions
*severe HTN and stroke - How do you treat amphetamine OD/toxicity?
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*nitroprusside or a-blocker if BP severely elevated
*Sedative drugs - What are the therapeutic uses of Amphetamines?
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*hypersomnia=narcolepsy
*obesity - What are the drugs used to treat narcolepsy?
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Amphetamines= D-amphetamine or methylphenidate (i.e. ritalin)
Modafinil=not amphet. tx's narc - What drugs are used to treat cataplexy component of narcolepsy?
- clomipramine(TCA) or fluoxetine (SSRI) (anti-depressants)
- What are the drugs used to treat obesity?
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Orlistat (pancreatic lipase inhibitor)
Sibutramine (meridia)-inhibit NE and serotonin re-uptake - What is Sibutramine?
- It is a selective NE and serotonin re-uptake inhibitor that does not affect DA. Used as an anorectic drug for severe obesity.
- What is methylphenidate?
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Piperidine derivative of amphetamine.
(Ritalin)
tx-ADHD - What are alternative tx for ADHD?
- TCA-deipramine, clonidine, atomoxetine(related to clonidine)
- What is the mechanism of action of cocaine?
- Blocks uptake of DA, NE and 5-HT. Increase synaptic levels of the amines.
- What is crack?
- is cocaine base. Very lipid soluble and smokable
- What are the clinical uses of cocaine?
- A local anesthetic-nasal and oral made in a form that will not enter the CNS
- What is the action of DA receptor antagonists in a cocaine patient?
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I.e: Neuroleptics
*alleviate the cocaine-induced psychosis, and the convulsions but do not change Peripheral toxic sx - What drug is used to stop cocaine convulsions?
- Diazepam IV (benzo)
- What are methylxanthines?
- Alkaloids found in tea, coffee, cocoa and other plants.
- What are the 3 main effects of theophylline and caffeine in the CNS?
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1. increased alertness
2. respiratory stimulation
3. convulsive potential at high dose - What is the mechanism of action for methylxanthines?
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1. Low dose: (teas) competitive inhibition of CNS adenosine A1 and A2 receptors.
2. High does: (theophylline-asthma) inhibit PDE and inc. cAMP. - What is the function of adenosine in the brain?
- Depresses neuronal function by activating A1R coupled to K-channels. Post and Pre-syn. Presyn= inhibition of NT release
- Where are the A2 receptors located?
- A2R-high conc. in the striatum-role in motor function.
- What are the medical uses of methyxanthines?
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1. Primary apnea of prematurity (caffeine or theophylline)- b/c of weak hypoxia chemoreflexes that can't overcome adenosine in brainstem.
2. Asthma tx- high doses the bronchodilatory effect - How would you describe the nicotine compound?
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*lipid-soluble drug well absorbed by the skin and mucosa.
*Activates nicotinic R - What is the mechanism of Nicotine at low doses?
- Activate N-R in autonomic ganglia, lungs/airways and CNS--largely a presynaptic receptor--inc. release of DA by depolarization of the terminals
- What are the effects of Nicotine at high doses?
- N acts on all nicotinic receptors and produces a depolarizing blockade and receptor desenesitization at autonomic ganglia and NMJ. EFFECT: peripheral CVS collapse, muscle weakness, resp. failure->death
- what are the SE of Nicotine at low doses?
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*Nausea-stim lung,airway affer. and area posterma
*inc. respiration (carotid chemo)
*tremor, inc. alertness, fac. memory and attention, muscle relax (?via renshaw cell activation of SC)
*activ auto ganglia (both) and adrenal medulla--GI and CVS - What is the half-life of nicotine?
- 2hrs, heavy smokers titrate blood in narrow lmits
- Clinical uses of nicotine?
- Treatment of addiction by replacement therapy.
- What are the major groups of Stimulants?
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1. Indirect acting sympathiomemetic amines: amphetamines, methyphenidate, cocaine
2. Methylxanthines
3. Nicotine