Pharm Final- CNS1

1. Monoamines
2. Peptides
3. Amino Acids
4. Purines
5. Others (acetylcholine and histamine)

Dynorphins
Endorphins
Enkephalins
Neurotensin
Somatostatin
Substance P
Oxytoxin
Vasopressin

NE
Epi
Dopamine
Serotonin

Aspartate
glutamate
GABA
Glycine

Adenosine
Adenosine Monophosphate
Adenosine Triphosphate

It is not fully developed- can increase risk of toxicity of drugs

impedes drugs passage into the brain. Passage is ONLY limited to lipid-soluble agents that can pass by a specific transport system

If a drug is protein bound or highly ionized it will NOT be able to cross the bbb

-CNS drugs can take several weeks before therapeutic effect seen b/c of time it takes CNS to make adaptive changes for the drugs

-After drugs effects are seen & adaptive changes are made many of the SE subside (Phenobarbital: sedation, Morphine:N/V)

-Adaptive changes also affect tolerance & physical dependence & cause withdrawal Sx & continue until adaptive changes have had time to change back to pretx state.

1.Postoperative pain (SE: constipation & urinary retention)
2.Obstetric analgesia: Meperidine usually used due to less resp depression
3.Myocardial Infarction (MI): Morphine b/c dec resp depression& dec CV effects)
4.Head injury: Use sparingly b/c of dec resp dep
5.Cancer related pain
6.Chronic non-cancer pain

Enkephalins

Endorphins

Dynorphins

1) Mu- most opioids activate this one.

2) Kappa (some opioid activation)

3) Delta (NO Opioid activation)

-Endogenous opioids act on all 3 receptors!

1.Analgesia
2.Respiratory depression
3.Euphoria
4.Sedation
5.Cough suppression
6.Physical dependence
7.Decreased GI motility (constipation, urinary retention)

1.Analgesia
2.Sedation
3.Decreased GI motility (constipation)

1.Pure Opioid Agonist: activate Mu & Kappa (meperidine, morphine, codeine)
Has 2 categories:
1) Strong opioid agonist (Morphine)
2) Moderate to strong opioid agonist (Codeine)

2.Agonist-Antagonist Opioids: low to moderate mu & kappa rec activation (pentazocine, nalbuphine, butorphanol, buprenorphine)
if given with a pure opioid antagonist drug will block the effects of the agonist)

3) Pure Opioid Antagonist: act on mu & kappa without any analgesia or any of the other effects caused by opioid agonist. Use to reverse resp & CNS dep caused by opioid agonist (naloxone, nalmefene)

1. Morphine

2. Fentanyl/Duragesic

3. Alfentanil & Sufentanil

4. Remifentanil

5. Meperidine

6. Methadone

7. Heroin (C1)

8. Hydromorphone/Dilaudid

9. Oxymorphone/Numorphan

10. Levorphanol/Levo-Dromoran

Reliefs pain w/o affecting other senses such as touch, smell , hearing, sight & loss of consciousness)

More effective against constant, dull pain rather than sharp intermittent pain.

Respiratory depression:
-Is what usually causes death (esp. if alcohol or other narcotics (benzodiazepines, barbiturates etc…)
-may last 4-5 h
-**If resp rate < 12 breaths/min delay morphine*** (esp. if asthma, emphysema) can get as low as 2-4 breaths/min hypoxia sets in & pt goes into shock
-Resp dep can be reversed w/ opioid antagonist Naloxone (Narcan) or Nalmefene (Revex) with ventilator support
-Resp dep varies with route of administration:
7 min after IV
30 min after IM
90 min after SQ

-Constipation: produced by CNS & GI tract give stool softener (docusate), laxative (senna), or osmotic laxative (Na+ phosphate)

-Orthostatic hypotension: blunts barorec reflex

- Urinary retention

-tolerance develops to euphoria, sedation, analgesia & resp dep. Little tolerance to constipation & miosis
a. Cross Tolerance: dev b/n opioid agonist (morphine, heroin, oxycontin, codeine & oxycodeine) BUT cross tol does NOT dev b/n barbiturates, ethanol, benzo’s & general anesthetics
b. Pregnancy: does not cause birth defects

Physical dependence: occurs w/ continued use by adaptive cellular change. Morphine physical dep is intense but brief due to short half-life but w/ methadone physical dep is longer but less intense.

Dosing is individualized

Sharp stabbing pain need higher doses where as dull pain needs lower doses.

Elderly need lower doses b/c of dec liver fxn.**

Neonates need lower doses b/c bbb not fully dev

Morphine should be withheld if resp rate is below 12 beats/min

Should be dosed on a fixed schedule rather than PRN

Fentanyl (Duragesic): 100 x’s stronger than morphine, schedule II, Parenteral, transdermal, transmucosal

1) Mu- most opioids activate this one.

2) Kappa (some opioid activation)

3) Delta (NO Opioid activation)

-Endogenous opioids act on all 3 receptors!

1.Analgesia
2.Respiratory depression
3.Euphoria
4.Sedation
5.Cough suppression
6.Physical dependence
7.Decreased GI motility (constipation, urinary retention)

1.Analgesia
2.Sedation
3.Decreased GI motility (constipation)

1.Pure Opioid Agonist: activate Mu & Kappa (meperidine, morphine, codeine)
Has 2 categories:
1) Strong opioid agonist (Morphine)
2) Moderate to strong opioid agonist (Codeine)

2.Agonist-Antagonist Opioids: low to moderate mu & kappa rec activation (pentazocine, nalbuphine, butorphanol, buprenorphine)
if given with a pure opioid antagonist drug will block the effects of the agonist)

3) Pure Opioid Antagonist: act on mu & kappa without any analgesia or any of the other effects caused by opioid agonist. Use to reverse resp & CNS dep caused by opioid agonist (naloxone, nalmefene)

1. Morphine

2. Fentanyl/Duragesic

3. Alfentanil & Sufentanil

4. Remifentanil

5. Meperidine

6. Methadone

7. Heroin (C1)

8. Hydromorphone/Dilaudid

9. Oxymorphone/Numorphan

10. Levorphanol/Levo-Dromoran

Reliefs pain w/o affecting other senses such as touch, smell , hearing, sight & loss of consciousness)

More effective against constant, dull pain rather than sharp intermittent pain.

Respiratory depression:
-Is what usually causes death (esp. if alcohol or other narcotics (benzodiazepines, barbiturates etc…)
-may last 4-5 h
-**If resp rate < 12 breaths/min delay morphine*** (esp. if asthma, emphysema) can get as low as 2-4 breaths/min hypoxia sets in & pt goes into shock
-Resp dep can be reversed w/ opioid antagonist Naloxone (Narcan) or Nalmefene (Revex) with ventilator support
-Resp dep varies with route of administration:
7 min after IV
30 min after IM
90 min after SQ

-Constipation: produced by CNS & GI tract give stool softener (docusate), laxative (senna), or osmotic laxative (Na+ phosphate)

-Orthostatic hypotension: blunts barorec reflex

- Urinary retention

-tolerance develops to euphoria, sedation, analgesia & resp dep. Little tolerance to constipation & miosis
a. Cross Tolerance: dev b/n opioid agonist (morphine, heroin, oxycontin, codeine & oxycodeine) BUT cross tol does NOT dev b/n barbiturates, ethanol, benzo’s & general anesthetics
b. Pregnancy: does not cause birth defects

Physical dependence: occurs w/ continued use by adaptive cellular change. Morphine physical dep is intense but brief due to short half-life but w/ methadone physical dep is longer but less intense.

Dosing is individualized

Sharp stabbing pain need higher doses where as dull pain needs lower doses.

Elderly need lower doses b/c of dec liver fxn.**

Neonates need lower doses b/c bbb not fully dev

Morphine should be withheld if resp rate is below 12 beats/min

Should be dosed on a fixed schedule rather than PRN

Fentanyl (Duragesic): 100 x’s stronger than morphine, schedule II, Parenteral, transdermal, transmucosal

IV should be given slowly over 4-5 minutes

Morphine is Schedule II

OD- Give Naloxone

CNS depressants, Anticholinergics (constipation & urinary retention), hypotensive drugs, MAOI’s, Agonist-Antagonist

Respiration: Asthma, emphysema, obesity, smokers

Pregnancy: No birth defects but physical dep in fetus

Labor/delivery: can suppress uterine contractions & cause resp dep (can be reversed by naloxone) in neonate

Misc: Head injury, liver impairment, hypotension, urinary problems b/c or BPH

The only real difference b/n strong & moderate is the amt of analgesia & resp dep produced. Everything else is the same

Codeine
Hydrocodone
Oxycodone
Propoxyphene

+ strong pure opioid Agonist drugs

Pentazocine
Nalbuphine
Buprenorphine

All but Buprenorphine are antagonists at Mu Rec & Agonist at Kappa Rec

Analgesia
Sedation
Limited Resp Depression

Pentazocine is not used in MI due to inc CO in contrast to pure opioid agonist
-b/c no axn on Mu rec pentazocine produces little or no euphoria but DO mediated physical dep
-Psychotomimetic effects may result from stimulation of kappa rec so little or no potential for abuse (schedule IV)
-b/c pentazocine produces inc cardiac work morphine is preferred in pt with MI

-Allows pt to self administer meds on a PRN basis through an electronically controlled pump (IV, SQ & epidural)
-It is on a time controlled basis to prevent an overdose. Usually a certain dose/hour at 10 min intervals

Dose is delivered through a indwelling catheter.

Some deliver a bolus & some deliver a basal infusion

Morphine is the most common drug used in a PCA

Before starting the PCA a loading dose is given

Naltreone
Nalmefene
Naloxone

Primarily used for OD or to Reverse Resp depression after post operative & in opioid addiction

If it is given prior to a pt receiving opioids it will block the effect & if given after opioids it will reverse all of the effects.

-Relieves pain by methods unrelated to opioid receptors. They do NOT cause reps depression, dependence or abuse

-Tramadol
-Clonidine
-Ziconotide

Weak agonist of Mu receptors. Mostly by blocking uptake of NE & Serotonin= spinal inhibition of pain.
Naloxone will partially block tramadol's effect

Pain relief is delivered through continuous epidural infusion. Binds to pre and post synaptic alpha 2 rec in the spinal cord and blocks pain signals from periphery to the brain.

Centrally acting analgesic with intrathecal admin.

NOT a first line agent due to adverse run (hallucinations, confusion and muscle injury)