LECTURE 6

Question 1

DRUG METABOLISM

Answer 1

1ST ORDER - EXPONENTIAL DECLINE, ORDERLY, DRUG CONCENTRATION IS HALVED AT EACH HALF LIFE
0 ORDER - LINEAR DECLINE (I.E. ALCOHOL - DISTRIBUTED/CLEARED FROM BODY IMMEDIATELY)

Question 2

OPIOIDS

Answer 2

EXTRACTED FROM POPPY PLANTS
OPIUM (GR. POPPY JUICE) AND ALCOHOL COMBINED TO TREAT MOST ANALGESIA IN 1800s
MORPHINE ISOLATED FROM OPIUM IN 1800s
DRUG ADDICTION AND CONTROLLING BECAME IMPOSSIBLE
OPIATE = EXUDATE OF POPPY
OPOID = NATURAL/SYNTHETIC DRUG THAT BINDS OPIOID RECEPTORS ENDOGENOUSLY
NATURAL IN 2 PLACES (CODEINE/MORPHINE)
ENDOGENOUS OPIATES (ENDORPHINS)
SYNTHETIC - PREPARED FROM MORPHINE (HEROINE) OR SYNTHESIZED (FENTANYL)
THEBAINE DERIVATIVES

Question 3

6 MAIN PHARMACOLOGICAL EFFECTS

Answer 3

1. ) SEDATION/ANXIOLYSIS - (DROWSINESS/LETHARGY, APATHY, COGNITIVE IMPAIRMENT, TRANQUILITY)
2. ) DEPRESSION OF RESPIRATION
3. ) COUGH DEPRESSION - SUPPRESSION OF COUGH CENTER IN BRAIN
4. ) PUPILLARY CONSTRICTION - MIOSIS (#1 INDICATOR OF AN OVERDOSE W/ OPIATES) VS. MEDRIASIS
5. ) NAUSEA/VOMITING - STIMULATES CHEMORECEPTOR TRIGGER ZONE IN MEDULLA
6. ) GI SYMPTOMS RELIEVE DIARRHEA AND YIELDS CONSTIPATION - SLOWS DOWN PERISTALSIS IN THE GI TRACT
7. ) OTHER - BRONCHOCONSTRICTION, ITCHING, DECREASED WBC/IMMUNE SYSTEM

Question 4

MECHANISM OF ACTION OF PAIN RELIEF

Answer 4

OPIOIDS REGULATE THE RELEASE OF NEUROTRANSMITTERS (SP, GLUT) BY ACTING PRESYNAPTICALLY (AND ENDOGENOUS ENDORPHINS)
INVOLVES CHANGES IN ION CONDUCTION
PAIN RELIEF VIA ANTI-HYPERALGESIA ON AFFERENT, HYPERPOLARIZATION, INHIBITION OF NT RELEASE
ANALGESIC AFFECT OCCURS AT PRE- AND POST-SYNAPTIC CELL

Question 5

3 MECHANISMS OF PAIN RELIEF

Answer 5

1.) MOR AT PERIPHERY - OPIATES CAN ALTER TRP CHANNEL SIGNALING OR CAUSE INHIBITION OF SIGNALING
CAUSES DAMPENING OF SIGNALING
2.) MOR AT PRE-SYNAPTIC TERMINAL OF DORSAL HORN LAMINA II - MORs ACTIVATED => INHIBITION OF INFLUX OF CA2+ => DECREASED FIRING POTENTIAL
CA2+ IN CELL CAUSES PRE-SYNAPTIC VESICLE TO BIND TO MEMBRANE AND RELEASE NEUROTRANSMITTERS
DECREASES RELEASE OF NT = DECREASED FIRING OF POST-SYNAPTIC CELL
NT- GLUTAMATE AND SUBSTANCE P
3.) MOR AT POST-SYNAPTIC TERMINAL OF DORSAL HORN LAMINA II - STIMULATION OF MOR CAUSES EFFLUX OF K+ => HYPERPOLARIZATION OF CELL AND DECREASED FIRING

Question 6

LAMINA II

Answer 6

INTEGRATION OF ASCENDING AND DESCENDING INFO

SUBSTANTIA GELATINOSA = LAMINA II (ALL NOCICEPTIVE INPUT SYNAPSES HERE)

Question 7

μ, MU, MOR RECEPTORS

Answer 7

ENDOGENOUS PEPTIDES - ENDORPHINS > ENKEPHALINS > DYNORPHINS BIND TO MOR
MAJOR ACTION - **INHIBITION OF RESPIRATION, ANALGESIA, SEDATION, SLOWED GI TRANSIT, LH SURGE, REPRODUCTION
ADVERSE EFFECTS - **SEDATION, MIOSIS, BRADYCARDIA, PRURITIS, NAUSEA/VOMITING, DEPRESSION VENTILATION, **PROMOTES ITCH
NOTES - **INCREASE ABUSE POTENTIAL
ANTAGONISTS - NALOXONE, NALTREXONE

Question 8

K, KAPPA, KOR

Answer 8

ENDOGENOUS PEPTIDES - DYNORPHINS&raquo_space; ENDORPHINS AND ENKEPHALINS
MAJOR ACTION - ANALGESIA, **SUPPRESSES ITCH, SLOWED GI TRANSIT
ADVERSE EFFECTS - **SEDATION, **DYSPHORIA, SUPPRESSES ADH, PSYCHOMIMETIC EFFECTS, **BLOCKS ANTI-DIEURETIC HORMONE => POLYURIA
NOTES - **DECREASED ABUSE POTENTIAL, A LOT OF STRESS/DEPRESSION RESEARCH
ANTAGONISTS - NALOXONE, NALTREXONE

SALVANORIN A - NATURAL HALLUCINOGEN - KOR

Question 9

δ, DELTA, DOR

Answer 9

ENDOGENOUS PEPTIDES - ENKEPHALINS > ENDORPHINS AND DYNORPHINS
MAJOR ACTION - ANALGESIA, MODULATES NT RELEASE AND HORMONES
ADVERSE EFFECTS - **SUPPRESSION OF RESPIRATION BUT CAUSES CONVULSIONS
NOTES - YIELDS PHYSICAL DEPENDENCE, REGULATES MOR, ANTI-DEPRESSANT
ANTAGONISTS - NALOXONE, NALTREXONE

**COULD AUGMENT MOR
MORPHINE CAN BIN

Question 10

2 WAYS OF CATEGORIZING OPIATES

Answer 10

1. ) FUNCTIONAL EFFECTS OF OPIATES - FULL VS. PARTIAL AGONIST, AGONIST VS. ANTAGONIST VS. FULL ANTAGONIST
2. ) STRENGTH OF OPIATES - WEAK VS. STRONG
   * IMPORTANT TO MATCH DRUG TREATMENT W/ PAIN EXPERIENCED

Question 11

WHO PAIN SCALE

Answer 11

STRONG - MORPHINE, FENTANYL, OXYCODONE
WEAK - CODEINE, TRAMADOL

FULL AGONIST - MORPHINE, FENTANYL, CODEINE, TRAMADOL
AGONIST-ANTAGONIST - NALBUPHINE, NALORPHINE (BINDS TO MOR AND BLOCKS ANOTHER OR - HAS LOW EFFICACY AT MOR- IF GIVEN W/ FULL AGONIST WILL BLOCK RECEPTORS AND DECREASE EFFICACY)

FULL ANTAGONIST - NALOXONE, NALTREXONE

Question 12

GENERAL LATENCY TO ONSET

Answer 12

ORAL - 15-30 MIN
INTRANASAL - 2-3MIN
IV - 15-30S
INHALATION - 6-12S

Question 13

MORPHINE

Answer 13

DURATION OF ACTION - 3 < X < 5 HRS
WHEN DIGESTED YIELDS 2 METABOLITES METABOLITES (ACTIVE)
1.) M6G - ACTIVE ANALGESIC WHEN IN COMBINATION W/ MORPHINE
2. M3G - INACTIVE ANALGESIC (CNS STIMULATOR)
ORAL = 30 MIN VS. IV = 5-10 MIN
17-33% BIOAVAILABILITY AFTER 1ST PASS METABOLISM