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158 Cards in this Set
- Front
- Back
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*Opioids/Analgesics
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Generic - codeine, hydrocodon, oxycodon
Trade - Percodan, Vicodin & Percocet, Oxycontin |
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SSRI/Anti-depressants
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Generic - fluoxetine
Trade - Prozac |
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*Major Tranquilizers
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ANTIDOPAMINERGIC
Generic - haloperidol Trade - Haldol |
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Minor Tranquilizers (Sedatives/Anti-anxiety, hypnotics)
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GABAERGIC
Generic - diazepam Trade - Valium |
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Psychedelics/Hallucinogens
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SEROTONERGIC
Chemical - LSD |
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*Stimulants/Psycho-stimulants
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DOPAMINERGIC
Generic - amphetamine Trade - Adderall |
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Time Course
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Onset and duration of action
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MED
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Minimum Effective Dose
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ED-50
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Dose that gives 50% of maximum effect
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LD-50
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Dose that kills half of population
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TI/Therapeutic Index
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LD-50/ED-50
How many Rx doses needed to risk death A higher TI is safer |
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Half Life
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Time it takes to eliminate half the drug from the blood
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Leftward Curve
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More potent
Lower ED-50 |
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Rightward Curve
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Less Potent
Higher ED-50 |
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Agonist
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Produce NT effect AT RECEPTOR
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Antagonist
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Block effect of Neurotransmitter by occupying receptor
Rightward shift in Agonist effect |
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Partial Agonist
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Have limited maximum effect when alone
Rightward shift when used as a pre-treatment in full agonists |
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Cajal
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Each neuron is a unit
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Loewi
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Discovered first neurotransmitter (Acetylcholine) using two frogs hearts
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GABA
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Inhibitory (IPSP)
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Glutamate
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Excitatory (EPSP)
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Dopamine (2) DA
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1. SN > dorsal striatum (MOTOR)
2. VTA > nucleus accumbens (MOTIVATION/DRUG ABUSE) |
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Serotonin 5-HT
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SSRI (ANTIDEPRESSANTS)
Raphe > everywhere (BEHAVIORAL INHIBITION) |
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Norepinephrine NE
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LC > everywhere (ATTENTION)
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Precursor
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Boost endogenous NT
EX. l-dopa |
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Releaser
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Cause leaks from nerve terminal
EX. d-amphetamine, Deprenyl |
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Direct Agonist
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Binds to receptor site & mimics effects of NT
EX. morphine |
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Reuptake Inhibitor
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Prevent reabsorption of NT into nerve terminal
EX. SSRI, cocaine |
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Enzyme Inhibitor
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Prevent degradation of NT by enzymes
EX. MAOI - Deprenyl |
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Opium
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From the poppy
Contains: 1. Morphine 2. Codeine |
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Laudanum
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Alcohol + Opium
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Heroin
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diacetylmorphine
Synthesized by inventor of Aspirin, marketed by Bayer as non-addictive alt. to codeine in cough meds PRECURSOR to morphine |
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Opioid Therapeutics
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Anti-cough
Anti-diarrheal Addiction treatment Analgesic Anesthetic |
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Opioid Side-effects
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RESPIRATORY DEPRESSION
Nausea Sedation Constipation Abuse Liability |
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fentanyl
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AGONIST
Trade - Sublimaze "China White" common analgesic for surgery |
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oxycodone
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AGONIST
Trade - Oxycontin Sustained release capsule |
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meperidine
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AGONIST
Trade - Demerol MPTP |
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loperamide
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AGONIST
Trade - Immodium AD HUGE first-pass effect = no high |
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methadone
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AGONIST
Trade - Dolophine Used in REPLACEMENT therapy for opioid addiction Addicts drink methadon once per day |
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naloxone
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ANTAGONIST
(also used for fertility enhancement) Trade - Narcan Used to save in overdose |
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buprenorphine
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PARTIAL AGONIST
Trade - Buprenex Less abuse liability, less effect LONG lasting |
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Suboxone
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buprenorphine + naloxone
Used in Heroin TX |
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Harrison Act 1914
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Regulated import, distribution, & production of opiates
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Pure Food & Drug Act 1906
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Labels were added and restrictions were placed on opioids as well as cocaine
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Vicodin
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AGONIST
(G) hydrocodon + acetominophen |
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Percodan
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AGONIST
(G) oxycodone + aspirin/acetominophen |
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Oxycontin
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AGONIST
(G) oxycodone, controlled release capsule |
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Demerol
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AGONIST
(G) meperidine |
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Sublimaze
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AGONIST
(G) fentanyl |
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Immodium AD
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MU RECEPTOR AGONIST
(G) loperimide |
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Dolophine
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AGONIST
(G) methadone, LAAM |
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Narcan
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ANTAGONIST
naloxone |
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Revia
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AGONIST
(G) naltrexone Used for addiction treatment Blocks heroin effect = withdrawl LITTLE compliance |
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Most commonly prescribed opoids
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1. Percodan/Percocet
2. Oxycontin 3. Vicodin Rx opioids=new opioid abuse=higher numbers of users |
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Potency
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fentanyl>heroin>morphine>acetominophen
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DM/dextromethorphan
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cough suppressant
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LAAM
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For addicts who can't go to methadone clinics everyday
LAAM is MUCH longer lasting |
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Mu Receptors
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Therapeutic Effect
Abuse Related Effects |
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Kappa Receptors
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Salvinorin A, "Salvia"
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Tolerance
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Need more drug for same effect
RIGHTWARD SHIFT |
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Dependence
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Adverse consequences in absence of drug
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Withdrawl
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Spontaneous emergence in absence of drug
PRECIPITATED BY AGONISTS |
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Etiology of Parkinson's Disease
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Age +
1. idiopathic 3. encephalitis 4. manganese in youth 5. MPTP |
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MPTP
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Byproduct of designer drug attempt to make Demerol
MPTP+MAO = MPP+ Can be blocked with MAOI |
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Construct Validity
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MPTP animal model has construct validity
(RE) construct disease |
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Locomotor Activity Test
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TESTS SENSITIZATION
hyperactivity |
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Prevalence of PD
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1/40 of U.S. population
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Akinesia
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Lack of movement in patient's with PD
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Ways to replace lost DA in striatum
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1. PRECURSOR to DA boost production of NT or;
2. Direct agonist replace DA 3. Enzyme inhibitors (MAOI/Deprenyl) |
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Sinemet
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l-dopa + carbidopa
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Choreiform
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Involuntary Motor Movements caused by l-dopa
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Nerve Terminal
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Pre-synaptic membrane
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Dendrite
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Post-synaptic membrane
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Cocaine HCl (salt)
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i.v.
i.n. p.o. (coca-cola, vin mariani) HALF LIFE OF 40 MINUTES |
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Cocaine Base; "freebasing"
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Cocaine HCl + solvent (ether) = Cocaine Base
crack (rocks) p.o. (coca leaves) |
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Freud & Cocaine
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Freud proposed cocaine as TX for "nervous exhaustion" and morphine addiction
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Fleischl
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Freud treated Fleischl with cocaine for morphine addiction, but he took REPEATED HIGH DOSES and developed psychosis
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Karl Kohler
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Used cocaine for eye surgery, still used today
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Vin Mariani
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wine + cocaine
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History of Coca Cola
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1. wine + cocaine
2. caffeine + cocaine + soda water 3. caffeine |
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Ephedrine
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Used for TX of asthma in place of adrenaline/epinephrine
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Amphetamine
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Shortage of Ephedrine = amphetamine prescribed for asthma
HALF LIFE OF 14 HOURS |
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Methamohetamine
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Same high as cocaine, but lasts much longer
Ephedrine (cold meds) + chem. synth. = amphetamine (meth) |
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History of Asthma TX
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1. Adrenaline (body)/Epinephrine (brain)
2. Ephedrine 3. Amphetamine |
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Narcolepsy
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Ritalin
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ADD/ADHD
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Adderall
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Sleep/work shift d/o
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Provigil
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methylemidate
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Ritalin
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amphetamine
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Adderall
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modfanil
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Provigil
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Opioids vs. Stimulants
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Opioids:
NOT DA dependent tolerance (RIGHTWARD SHIFT) therapeutic: pain/analgesic side effect: respiratory depression mu opioid receptor direct agonist tolerance Stimulants: DA dependent sensitization (LEFTWARD SHIFT) therapeutic: add, narco., sleep d/o side effect: abuse/addiction DA indirect agonist sensitization |
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Amphetamine vs. Cocaine
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Amphetamine:
1/2 life of 14 hours! MAOI (blocks enzymes) Releaser Reuptake inhibitor Does not rely on production of brain NT Cocaine: 1/2 life of 40 minutes reuptake inhibitor requires that brain produces DA in VTA |
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Where Opioids Act
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Central Grey: Post-synaptic Nucleus Accumbens, mu opioid receptors
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Where Stimulants Act
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Pre-synaptic Nerve terminals for dopamine in nucleus accumbens
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Where l-dopa Acts
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Dorsal striatum
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Self Administration
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Measures abuse liability
and reinforcing effects Nucleus Accumbens key to self administration of heroin and cocaine |
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Tail Withdrawal
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Measures analgesia
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Where Opioids Act
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Central Grey: Post-synaptic Nucleus Accumbens, mu opioid receptors
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Where Stimulants Act
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Pre-synaptic Nerve terminals for dopamine in nucleus accumbens
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Where l-dopa Acts
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Dorsal striatum
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Self Administration
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Measures abuse liability
and reinforcing effects Nucleus Accumbens key to self administration of heroin and cocaine |
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Tail Withdrawal
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Measures analgesia
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Where Opioids Act
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Central Grey: Post-synaptic Nucleus Accumbens, mu opioid receptors
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Where Stimulants Act
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Pre-synaptic Nerve terminals for dopamine in nucleus accumbens
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Where l-dopa Acts
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Dorsal striatum
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Self Administration
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Measures abuse liability
and reinforcing effects Nucleus Accumbens key to self administration of heroin and cocaine |
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Tail Withdrawal
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Measures analgesia
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Where Opioids Act
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Central Grey: Post-synaptic Nucleus Accumbens, mu opioid receptors
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Where Stimulants Act
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Pre-synaptic Nerve terminals for dopamine in nucleus accumbens
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Where l-dopa Acts
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Dorsal striatum
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Self Administration
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Measures abuse liability
and reinforcing effects Nucleus Accumbens key to self administration of heroin and cocaine |
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Tail Withdrawal
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Measures analgesia
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Schizophrenia Incidence
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1% of population
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Symptoms of Schizophrenia
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Thought disorder***
Hallucinations Delusions Blunted affect Withdrawal |
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Medication for Scz.
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Deniker & Laborit-Antihistamine (Thorazine)
Resperpine (from snakeroot) |
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Brodie and Schorr
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THEORY that antipsychotics block SEROTONIN receptors
INCORRECT |
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Carlsson/Dopamine hypothesis of scz.
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Mirror image of Pk. disease
antipsychotics actually block DOPAMINE receptors |
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Greengard, DA subtypes
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Greengard believed it was D1 receptor
but... antipsychotics are D2 RECEPTOR ANTAGONISTS |
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Typical Antipsychotics/ "older"
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chlorpromazine (Thorazine)
haloperidol (Haldol) Work on positive symptoms Prone to side effects: Parkinsonian (rigidity) Tardive Dyskinesia |
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Atypical Antipsychotics
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clozapine (Clozaril)
Along with DA D2 blockade, 5HT2A receptors, etc... 1. Eliminates both + and - sx 2. Low side effects 3. Usually effective in tx resistant patients |
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Common mechanism of action of antipsychotic drugs at synapse?
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DOPAMINE D2 RECEPTOR ANTAGONIST
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Side effects of antipsychotics
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1. Acute "EPS", Parkinsonian = rigidity
2. Chronic = tardive dyskinesia (invol. movement) PERMANENT |
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Depolarization blockade***
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The brain fights Haldol the first time by increasing DA, but after several days -week VTA gets tired of fighting
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Hypofrontality
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Less activity in frontal cortex
Maybe due to glutamate hypothesis |
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Animal Models in SCZ
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Lack of animal models because experiments test for side effects we DON'T want
Locomotor test: Catalepsy Pencil Test: Catalepsy **PPI: Pre-pulse inhibition of startle: measures sensory filtering The higher the D2 AGONIST = less startled Normals show high inhibition, scz's do not PPI HAS PREDICTIVE VALIDITY FOR THERAPEUTIC EFFECTS |
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DA pathways
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VTA ----- Nucleus Accumbens (motor)
SN ------- Dorsal Striatum (motivation) |
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Glutamate Hypothesis
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Too little glutamate, glutamate not getting released in ventral striatum...but we do not restore glutamate because it is toxic.
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Unipolar/Major depression symptoms
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-Dysphoria (loss of interest in usual activities)
-Recurrent thoughts of death/suicide -Blunted affect -Anorexia -Fatigue -Insomnia |
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Bipolar (Manic-depression) symptoms
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-One or more manic episodes
...Inflated self esteem Decreased need for sleep Talkativeness Excessive activity |
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1. MAOI
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MAOI's increase DA, 5HT or NE in synapse by inhibition of breakdown
Ipronazid (anti-tuberculosis) Side effects = high blood pressure, controlled by diet |
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2. Tricyclics
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Tricyclics block the reuptake of DA 5HT or *NE*
Imipramine |
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3. SSRI (Serotonin selective reuptake inhibitors)
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MOST WIDELY USED
Prozac (fluoxetine) Paxil (paroxetine) Zoloft (sertaline) Celexa (citalopram) Low side effects |
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4. Other antidepressants
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INHIBIT DA AND NE REUPTAKE
Wellbutrin, Zyban (buproprion) |
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Lithium
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Mood Stabilizer used for Bipolar
Cade = guinea pigs lethargic, actually nauseous MECHANISM OF ACTION IS UNKNOWN bad side effects: kidney and thyroid |
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ECT
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90% success rate
MECHANISM OF THERAPEUTIC EFFECT IS UNKNOWN |
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Discontinuation syndrome
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Withdrawal symptoms
-Manic episodes -Thoughts/acts of suicide -Psychoses |
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HPA (stress) axis
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Stress kills brain cells in hippocampus
Hypothalamus Pituitary Adrenal |
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Animal procedures for depression
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-Learned helplessness-NO PREDICTIVE VALIDITY
-Forced swim test-therapeutic-HIGH PREDICTIVE VALIDITY -MPTP-HIGH CONSTRUCT VALIDITY |
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GABA-ergic drugs/Minor tranquilizers
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Anti-anxiety
Anti-convulsant Sedative-hypnotic Anesthetics |
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Barbiturates
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Luminal (phenobarbital)
low TI dependence only good for sleep |
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Benzodiazepines
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Librium (chlordiazepoxide)
Valium (diazepam) Anti-anxiety WITHOUT drowsiness less dependence high TI=safe |
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Z drugs
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"sleeping pills"
Ambien (zolpidem) Lunesta (zopiclone) Sonata (zaleplon) |
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Anxiolytics
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Used to treat anxiety
Commonly benzodiazepines -Valium (diazepam) -Ativan (loazepam) -Klonipin (clonazepam) |
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Sedative-hypnotics
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Sleeping pills
Barbiturate: Phenobarbital z drugs: Ambien, Lunesta |
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Anti-convulsant/anti-epileptics
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ALL MINOR TRANQUILIZERS/GABA-ERGICS USEFUL AS ANTI-CONVULSANTS
Ativan (lorazepam) Depakote |
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Pharmacodynamics of minor tranqs/gaba-ergic drugs
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Increase GABA transmission, often as GABA-A receptors
Increase Cl- intake, resting IPSP |
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Punished responding Animal Model
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Also known as the "conflict test"
HIGH PREDICTIVE VALIDITY decreased responding due to INHIBITION OF BEHAVIOR, not to analgesic effect |
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LSD
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EXTREMELY POTENT
Pd: PARTIAL AGONIST AT 5HT2A Profound tolerance |
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Mescaline, Psilocybin (mushrooms), Psilocin
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less potent than LSD
AGONIST of 5HT2A |
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MDMA (Ecstasy)
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Less potent than psilocybin, cocaine, LSD, amphetamine
5HT & DA REUPTAKE INHIBITOR AND 5HT2A AGONIST neurotoxicity and hyperthermia |
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Ketamine
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ANTAGONIST AT GLUTAMATE (NMDA) RECEPTORS
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Methamphetamine vs. Ecstasy
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METHAMPHETAMINE
REUPTAKE INHIBITOR RELEASER ENZYME INHIBITOR Neurotoxic Potent Affects DA neurons in striatum ECSTASY (MDMA) REUPTAKE INHIBITOR OF DA & 5HT 5HT2A DIRECT AGONIST Neurotoxic Not potent Causes cell loss in the raphe Hyperthermia |
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Cannabinoids mechanism of action
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CB1 receptor AGONIST
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Tolerance of Cannabinoids
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PROFOUND
...and no major physical withdrawal |
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Mechanism of action of nicotine
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Acetylcholine AGONIST at nicotine receptors (alpha-4, beta-2, specifically)
NOT MUSCARINIC |
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Behavioral effects of nicotine
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Slightly improves cognitive function, memory
Mild analgesic effects Mild psychomotor stimulation Alterness Appetite suppression |
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Nicotine tolerance
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PROFOUND
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Caffeine mechanism of action
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Adenosine A2A receptor AGONIST
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