CNS, Pains, and Opiods

Blood Brain Barrier

Protects the brain from harmful substances

• Only allows lipid-soluble drugs to get through

• Protein or highly ionized drugs cannot cross

Adaption of the CNS to Prolonged Drug Exposure

Certain drugs take several weeks for full therapeutic effects to take place. Overtime you may have decreased side effects to a drug but that doesn’t mean the therapeutic effects are decreasing. Your bodies systems learn how to process it.

Tolerance

Decreased response occurring during the course of prolonged drug exposure.

• May need to increase dosage to have full therapeutic effect

Physical Dependence

State in which abrupt withdrawal leads to withdrawn syndrome.

• Lasts 5-10 days with peak @ day 3

• Sx vary

Neuropathic Pain

Injury to the nerves in the body mostly from chronic illness.

Nociceptive Pain

Pain caused by injury to tissue. Including thermal, chemical, and mechanical pain.

Nociceptive Pain Process

1. Transduction: injury occurs at tissue site and sensitizing chemicals get released

   • Bradykinin

   • Prostaglandin

2. Transmission: The action potential goes from the site of injury to the spinal cord to the brainstem and thalamus then to the cortex for processing.

3. Perception

4. Modulation

   • Body trying to improve pain in patient with release of chemicals to inhibit nociceptive impulses

Classification of Drugs (3):

• Pure Opioid Agonists

• Agonists-Antagonists Opioids

• Pure Opioid Antagonists

1. Bind to receptor site and change the perception of pain, block pain impulses

2. Do the same thing but not as much some impulses may still be present.

3. Displace agonist from receptor site, does not do anything to pain but helps with overdose.

Most Common Receptor Site

Mu

Strong Opioid Agonist

Prototype: Morphine

Indication: Severe Pain (8-10 Scale)

MOA: binds to opioid receptor sites in the CNS and inhibits ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.

Morphine Black Box Warning

Addiction, Misuse, abuse; respiratory depression, risk of medication errors

Reduced Dosing with

concomitant renal impairment

Pregnancy Category

C

Pharmacokinetics

Administered: Oral, IV, IM, SQ, Epidural, Intrathecal

Not very lipid soluble - takes time to get to the brain

Primarily Binds to MU Receptors

Other Strong Opioids:

• Fentanyl

• Hydromorphone

• Meperidine

• Methadone

• Oxymorphone

Morphine ADR’s

Respiratory Depression

• Onset 7 Mins W/ IV

• NSG Considerations with certain age groups, those with CNS depression, and those with respiratory problems

Orthostatic Hypotension

• Your BP drops due to delayed response by baroreceptor reflex and by dilating peripheral arterioles and veins

Sedition

• Drowsiness and Mental Clouding

Neurotoxicity

• Risk factors include renal impairment, pre-existing cognitive impairment, and prolonged high dose opioid use

• Manage W/ high fluid intake and dose reduction

Constipation

• Slows GI tract propulsions

Urinary Retention and Hesitancy

• Tightens bladder and prevents urinating

Emesis

• Happens on initial dose

Cough Suppression

• Avoid giving to those w/ pneumonia

Biliary Colic

• Induces spasm of common bile duct can intensify pain

Elevation of Intracranial Pressure

• Do not give to those with head injuries

Morphine Toxicity

3 Signs

• Comma

• Respiratory Depression

• Pinpoint Pupils

Morphine Toxicity Treatment

• Airway Support

• Naloxone (Narcan)

Moderate Opioid Agonists

Prototype: Oxycodone (Roxicodone)

Indication: Moderate Pain 4-7

Mechanism of Action: binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception and response to pain

Opioid ADRs

similar, not as pronounced as morphines

Combination Drug + Other Moderate Opioids

Percocet: Oxycodone and Acetaminophen

• Works better because it increases affinity of oxycodone and also allows you to prescribe less oxycodone

Others:

• Condone

• Hydrocodone

Opioid Antagonist

Prototype: Naloxone (Narcan)

MOA: Pure opioid antagonist that competes and displaces opioids at opioid receptor sites

• Greatest affinity for mu receptors

Non-Opioid Centrally Acting Analgesics

Prototype: Tramadol

MOA: Combination of opioid and non-opioid mechanisms

• Weak opioid receptor bond

• Blocks re uptake of serotonin and norepinepherine

Drug Interactions

CNS Depressants

ADR

Suicidality