MED Chem Quiz 4

• To much-Psychoses, Schizophrenia
• Chloropromazine-Thorazine
• Too Little- Parkinsons
• Levodopa

• too little- Seizures anxiety
• Diaxepam-Valium
• Clonazepam-Klonopin

• Too-little- Depression, ADHA, Harcolepsy
• TCS- Doxepin-Sinequan, Reuptake inhibition

• Too little- Depression
• SSRIS- Fluoxetine-Prozac, Sertraline-Zoloft
• Too Much-Emesis
• Ondansetron-Zofran

• Brain Spinal chord
• Parallels Autonomic Nervouse System
• Not jsut Norepinenphrine & Acetylcholine

• Autonomic- involuntary (cardiac & smooth muscle)
• Sympathetic-Fight or flight
• Parasympathetic
• Somatic-Voluntary
• Pain & touch

• 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

parasympathetic transmitter

inhibitory

Glutamate

caused by actually by peptides

• 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

Dopaminergic Receptors

• 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

• 1. Choline acetyltransferase catalyzes formation of acetylcholine from choline and acetyl CoA
• 2. Storage in vesicles
• 3. CA2+ stimulated release
• 4.Receptor binding

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

• Cholinergic antagonists used primary to treat parkinsons
• imbalnace produced by degradatio nof dopaminergic nerves

• 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

• Anxiety
• Seizures
• Act as sedatives or muscle relaxants

• Role as CNS neurotransmitter is being extensivel explored
• Receptor subtyprs known: H1-4

Target decrease in glutamate toxicty

• Glutamate and others
• Stimulation of EAA receptors increased cation conductance
• Important in learning, memory

• Alzheimers
• Huntingtons
• Stroke
• Epilepsy
• Amyotrophic Lateral Schlerosis (ALS)

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

• PEPTIDES
• Endorphins
• Enkephalins
• Dynaorphins

• High abuse risk, NO safe accepted medical use in the United STates
• Heroin, LSD, PCP, crack cocaine

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

Drugs categorized as prescription drugs.  Potential abuse goes down with each level

Water-soluble agents

Lipid-soluble agents

• Glucose
• Levadopa
• amino acids
• nucleosides

• Insulin,
• transferrin

Albumin, other plasma proteins

stimulants and simililar agents

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

a drug used to stimulate the CNS that can induce convulsions in a dose-dependent manner

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,

• 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

• 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

A CNS Stimulant

1-phenyl-2 aminopropane-simplest

Various salts- Adderall

• Racemic
• Amphetamine
• Also has been used as an anorexiant

• 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

• MOA: enhance release and hinder dopamine reuptake
• indirect agonist

IND: ADHD, Narcolepsy

• 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