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Dopamine
- To much-Psychoses, Schizophrenia
- Chloropromazine-Thorazine
- Too Little- Parkinsons
- Levodopa
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GABA
- too little- Seizures anxiety
- Diaxepam-Valium
- Clonazepam-Klonopin
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Norepinephrine
- Too-little- Depression, ADHA, Harcolepsy
- TCS- Doxepin-Sinequan, Reuptake inhibition
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Seortonin-5HT
- Too little- Depression
- SSRIS- Fluoxetine-Prozac, Sertraline-Zoloft
- Too Much-Emesis
- Ondansetron-Zofran
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CNS= Central Vervouse System
- Brain Spinal chord
- Parallels Autonomic Nervouse System
- Not jsut Norepinenphrine & Acetylcholine
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PNS=Peripheral Nervouse sysstme
- Autonomic- involuntary (cardiac & smooth muscle)
- Sympathetic-Fight or flight
- Parasympathetic
- Somatic-Voluntary
- Pain & touch
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Monoamines(Catecholamines)
- Norepinephrine-sympathetic transmitter
- Dopamine
- 5-hydroxytryptamine (5-HT or Serotonin)
- Adrenergice: Referes to neurons that use catecholamine as neurotransmitters at teh synaps when a nerve mplus passes sympathetic fibers
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Acetylcholine-para
parasympathetic transmitter
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Gamma-amino butyric acid (GABA)
inhibitory
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Excitatory amino acids (EAA)
Glutamate
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Opioid activity
caused by actually by peptides
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Norepinephrine- Sympathetic transmitter
- 1. L-Tyrosine is converted to L-dopa which is then hydroxylated to Dopamine ( Presynaptic)
- 2. B-hydroxylase converts dopamine to norepinephrine (Presynaptic)
- 3)Norepi relase- Ca2+
- 4. Receptor binding
- 5-7
- 8. Catechol Omethyl transferase degrades catecholamines COMT (Post synaptic)
- 9. Reuptake into presynaptic neuron
- 10. Repackagin
- 11. Degraded by mitnochondrial MAO
- 12. Path for indirect sympathomimetics
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Dopamin
Dopaminergic Receptors
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Seortonin-5-HT
- Tryptophan is hydroxylated and decarbosylated to form 5-HT
- Stored in vesicles, released, taken up by pre-synaptic neurons, recycled or metaolized
- 5-HT is realsed by inhibitiory neurons
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Acetylcholine
- 1. Choline acetyltransferase catalyzes formation of acetylcholine from choline and acetyl CoA
- 2. Storage in vesicles
- 3. CA2+ stimulated release
- 4.Receptor binding
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Acetylcholine
MUSCARINIC-CNS
- 1. Choline acetyltransferase catalyzes formation of acetylcholine from choline and acetyl CoA
- 2. Storage in vesicles
- 3. Ca2+ sitmulated release
- 4. REceptor binding
- Nicotinic
- Muscarinic-CNS
- REuptake and hydrolysis by acetylcholine esterase
- 10. Breakdown products recycled
-
Acetylcholine
- Cholinergic antagonists used primary to treat parkinsons
- imbalnace produced by degradatio nof dopaminergic nerves
-
GABA - y-Amino butyric acid
- Inhibitory amino acid
- synthesized from glutamate
- Binds to GABA-A or Gaba-B receptors
- Clorid ion channel
- Stimulate influx of clorid
- Hyperpolarizes the neuron
- Benzodiazepine-Enhance GABA-A receptors ONLY
-
GABA enhancers (Benzodiazepines, Barbiturates) used:
- Anxiety
- Seizures
- Act as sedatives or muscle relaxants
-
HIstamine
- Role as CNS neurotransmitter is being extensivel explored
- Receptor subtyprs known: H1-4
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Rituzole-Rilutek
Target decrease in glutamate toxicty
-
Excitatory Amino Acis-EAA
- Glutamate and others
- Stimulation of EAA receptors increased cation conductance
- Important in learning, memory
-
Glutamate-induced toxicity
- Alzheimers
- Huntingtons
- Stroke
- Epilepsy
- Amyotrophic Lateral Schlerosis (ALS)
-
Opiates & Opiods
Opiate receptors located along the periaquiductal gray matter
Morphine and related compounds act on opiate receptors to relieve pain
In tiems of stress & pain endogenous peptides act on opiate receptors
-
Opiate receptor Agonists
- PEPTIDES
- Endorphins
- Enkephalins
- Dynaorphins
-
Schedule I
- High abuse risk, NO safe accepted medical use in the United STates
- Heroin, LSD, PCP, crack cocaine
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Schedule II
Drugs with a high abuse risk, but also have safe/accepted medical uses in the United States. Can Cause sever psychological or physical dependence
Morphine, cocaine, oxycodone(Percodan) methylphenidate (Ritalin) dextroamphetamien (Dexedrine), THC for N/V
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Schedule III-IV
Drugs categorized as prescription drugs. Potential abuse goes down with each level
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Paracellular squaous pathway
(extremly rare)
Water-soluble agents
-
Transcellular lipophillic pathway
Lipid-soluble agents
-
Transport proteins
- Glucose
- Levadopa
- amino acids
- nucleosides
-
Receptor-mediated trancytosis
-
Adsorptive transcytosis
Albumin, other plasma proteins
-
CNS active agents
stimulants and simililar agents
-
Caffeine: Nodoz tablet
Cafcit: injectible
Analeptic agent
A methylxathine
MOA: non-selectrive antagonist of adenosine receptors increased cAMP via phosphodiaseterase inhibition
REcuces the rate of bronchopulmonary dysplasi in infants with very low birth weight
Treatmetn excited or comatose alcoholic patients, postprandial hypotension
-
Analeptics
a drug used to stimulate the CNS that can induce convulsions in a dose-dependent manner
-
Doxapram HCL-Dopram
Analeptic
PNS STIMULANT
IND: Post-anesthesis drug induced respiratory depression apnea due to drugs othe rthan muscle relaxamant, stimulation of drug induced CNS depression, COPD associated with acute hypercapnia, apnea of prematurity
MOA: Stimulates Peripheral carotid chemorecpetors- increase tital voludm, and respiration rate,
-
Modafinil-Provigal
Racimic
Analeptics
- Ind: Narcolepsy
- MOA: Unknown, wakefulness-promoting effects similar to sympathomimetic agents,
- RACEMIC DRUG HAS different half lives- R-enantiomer has 3X the lifetime of the S-enantiomenr, 60% protein bound, deamidation & hepatic metabolism and glucornidation followed by predominately urinary excretion, p-glycoprotein substrate, coderate CYP induction, CYP2C19 inhibitor
-
Armodafinil-Nuvigil
R-enantiomenr
Analeptic
- IND: Narcolepsy
- MOA: UNKNOWN, Promots wakefulness-promoting effects
RACEMIC DRUG HAS different half lives- R-enantiomer has 3X the lifetime of the S-enantiomenr, 60% protein bound, deamidation & hepatic metabolism and glucornidation followed by predominately urinary excretion, p-glycoprotein substrate, coderate CYP induction, CYP2C19 inhibitor
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Amphetamines
A CNS Stimulant
-
Racemic Amphetamine Sulfate
Adderall
Adderall XR
Dextroamphetamine Sulfate-Dexedrine
1-phenyl-2 aminopropane-simplest
Various salts- Adderall
-
Methamphetamine HCL- Desoxyn
- Racemic
- Amphetamine
- Also has been used as an anorexiant
-
Lisdexamfetamine dimesylate- Vyvanse
Amphetamine
- A pro drug: Provides for once a day dosing with less abuse potential: Plasma protease will NOT hydrolyze the amide bond to release the drug
- Only GI protease is capable of this transformation
- LESS IV drug USE
-
Amphetamines-A CNS stimulatn
- MOA: enhance release and hinder dopamine reuptake
- indirect agonist
IND: ADHD, Narcolepsy
-
Amphetamines- A CNS stimulant
- No longer indicated for obestity, or antidepressant
- ADR: Addition tolerance, toxic psychosis, hypertention, angina hyperthyroidism
- CNS effects : increase arousal, wakefulness, increased confidence, ability to concentrate, exhilaration, anorexia, insomnia
- CV: contraindicated in abnormality
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