Katzung Chapter 30: Antidepressant Agents, Chapter 31: Opioid Agonists and Antagonists and Chapter 32: Drugs of Abuse

Mu opioid receptor

Stimulation produces , euphoria, respiratory depression and physical dependence, analgesia

Kappa/opioid/Delta opioid receptor

Stimulation produces analgesia

Tolerance

With frequently repeated administration of therapeutic doses of opioids there is a gradual loss in effectiveness

Physical Dependence

Occurrence of a withdrawal or abstinence syndrome when the drug is stopped or an antagonist is administered

Hyperalgesia

Persistent administration of opioid analgesics has been observed to increase the sensation of pain

Morphine

Strong naturall occuring opioid agonist from the poppy plant (Papaver somniferum),

binds w/ high affinity to the mu opioid receptor

Buprenorphine

High binding affinity but low intrinsic activity at the mu opioid receptor,

antagonist at the delta and kappa receptors,

combined with nalaxone for the treatement of opiate addiction

Neuraxial

Injection of an anesthetic drug into the fatty tissue that surround the nerve roots (epidural) or into the cerebrospinal fluid (spinal)

Fentanyl

available as a sustained release,

transdermal patch (3 days),

indicated for the management of persistent unremitting pain,

Strong opioid agonist,

Fentanyl

b/c of respiratory depression…

FDA recommends a fentanyl patch (25 mcg/h) be reserved for pt w/ established oral morphine requirement of at least 60 mg/d for 1 week or more

Butorphanol

Kappa receptor agonist, may be a mu receptor partial agonist or antagonist, available as intranasal preparation

Nalaxone

Opioid antagonist, used to treat opioid overdose, has a short half-life so it needs to be administered frequently

Heroin Hydromorphone Levorphanol

Strong opioid agonist

Methadone

Strong opioid agonist,

longer half-life,

used for detoxification

Codeine Oxycodone Hydrocodone

Mild to moderate opioid, partial agonist that is usually combined with aspirin or acetaminophen

Loperamide

Mild opioid agonist, used for diarrhea

Tramadol

Centrally acting analgesic,

blocks serotonin reuptake

weak mu receptor agonist

Dextromethorphan

Oioid agonist with antitussive actions but little or no CNS effects, not for use in children under 6 years old

Naltrexone

Opioid natagonist with a longer duration of action used in alcohol and nicotine abstinence programs

Ziconotide

Blocks N type,

Vg Ca channel

prevents release of NT,

apprved for chronic pain (intrathecally)

Methylnaltrexone

Opioid antagonist, used to treat opioid-induced constipation

Alvimopan

Opioid antagonist,

used to treat postoperative ileus

Tricyclic antidepressant

Block the reuptake of norepinephrine and/or 5-HT into the presynaptic membrane

Amitriptyline

Tricyclic antidepressant

Imipramine

Tricyclic antidepressant

Selective Serotonin Reuptake Inhibitors

Greater ability to block the reuptake of serotonin (5-HT) compared to norepinephrine reuptake

Fluoxetine

Antidepressant, Selective Serotonin Reuptake Inhibitors

Eating disorders esp. bulimia nervosa

potent inhibitors of p450 2D6 “E” (breaks drug in liver)

Premenstrual dysphoric disorder (PMDD)

Paroxetine

Antidepressant, Selective Serotonin Reuptake Inhibitors

Discontinuation syndrome

potent inhibitors of p450 2D6 “E”

Sertraline

Antidepressant, Selective Serotonin Reuptake Inhibitors

Premenstrual dysphoric disorder (PMDD)

Discontinuation syndrome

Citalopram

Antidepressant, Selective Serotonin Reuptake Inhibitors

Escitalopram

Antidepressant, Selective Serotonin Reuptake Inhibitors

Fluvoxamine

Antidepressant, Selective Serotonin Reuptake Inhibitors

Venlafaxine Desvenlafaxine

Antidepressant, blocks reuptake of both norepinephrine and serotonin (ven)

Levomilnacipran Milnacipran

Antidepressant, blocks reuptake of both norepinephrine and serotonin (an)

Duloxetine

Antidepressant, blocks reuptake of both norepinephrine and serotonin

Bupropion

Antidepressant

modest-to-moderate inhibitor of norepinephrine and dopamine reuptake,

more significant effect is presynaptic release of catecholamines

and used in smoking cessation,

Trazodone

Antidepressant, 5HT2 receptor antagonist

Mirtazapine

Antidepressant, mechanism is unknown

Lithium

Used to treat manic/depressive disorder (bipolar), inhibition the inositol triphosphate (IP3) second messenger system

Addiction

Compulsive drug-seeking behavior and cravings and for a drug for personal satisfaction

Anandamide 2 arachidonyl glycerol

Endogenous cannabinoids,

bi—> presynaptic CB1 receptors —> inhibit release of glutamate & GABA

Dronabinol

Prescription Delta 9-tetrahydrocannabinol

f-Hydroxybutyric acid

Bind to GABA-b receptors (metabotropic) activating potassium channels and causing hyperpolarization

Nicotine

Influx of sodium ions after stimulation of acetylcholine ion channels

Cocaine

Blocks reuptake transporters (dopamine, NE and 5HT) in the CNS

Methylenedioxymethamphetamine

Release of biogenic amines by reversing the actions of transporters similar to amphetamines but w/ a preference for the serotonin transporter (SERT)

Lysergic diethylamide

5HT2a receptor agonist in the prefrontal cortex enhancing glutamate transmission

Mescaline

From peyote, 5HT2a receptor agonist in the prefrontal cortex enhancing glutamate transmission

Psilocybin & psilocin

From mushrooms, 5HT2a receptor agonist in the prefrontal cortex enhancing glutamate transmission

Phencyclidine Ketamine

Use dependent inhibition of glutamate receptors,

Nitrous oxide

Nitrates that is used as an inhalant, dilates blood vessels

Amyl nitrate

Nitrates that is used as an inhalant, dilates blood vessels

Benzene Toluene

Aromatic hydrocarbon used as an inhalant