pharm: local anesthesia & opioid analgesics

how do local anesthetics work

• they suppress pain by blocking sodium channels and impulse conduction along axons

• only in neurons near the site of administration

• suppress pain without depressing the entire nervous system

why are local anesthetics used with vasoconstrictors like epinephrine?

• decreases local blood flow

• delays the systemic absorption of the anesthetic

• prolongs effects by trapping it in the blood vessels

• reduces risk of toxicity by trapping it locally

adverse effects of local anesthetics in CNS

• excitation followed by CNS depression

adverse effects of local anesthetics in cardiovascular system

• bradycardia

• heart block

• reduced contractile force

• cardiac arrest

• hypotension

the ability of an anesthetic to penetrate the axon membrane is determined by ?

• molecular size

• lipid solubility

• degree of ionization at tissue pH

lidocaine

• most widely used local anesthetic

• topical and injectable

• used for cardiac dysrhythmias

Cocaine

• ester type

• blocks reuptake of dopamine, norepinephrine, epinephrine, and serotonin

• pronounced effects on sympathetic NS and CNS

• topical for anesthesia of ear , throat and nose

Topical anesthesia guidelines

because of systemic toxicity:

• apply smallest amount needed

• avoid large areas

• avoid broken/ irritated skin

• avoid excercise, avoid wrapping the site/ applying warmth (heat increases absorption)

injectable anesthesia

• larger risk

• severe systemic reactions may occur

• resuscitation equipment should be immediately available

• IV line needs to be in place to permit rapid antidote if needed

infiltration

injecting anesthesia directly into immediate area of surgery or manipulation

nerve block

injecting anesthesia into or near nerves that supply the surgical field, but distant from the site itself

epidural

injecting a local anesthetic into the epidural space

analgesics

drugs that relieve pain without loss of consciousness

opioids

• most effective pain relievers

• general term defined as any drug, natural or synthetic that has actions similar to those of morphine

opiate

• the compounds present in opium

what are the 3 families of opioid peptides

• enkephalins

• endorphins

• dynorphins

• these are agonists of mu receptors

Mu receptor activation causes

• analgesia

• respiratory depression

• euphoria

• sedation

• physical dependance

Kappa receptor activation causes

• analgesia

• sedation

• psychomimetic effects seen with certain opioids

pure opioid agonist

• activate mu receipts and kappa receptors

• produce mu receptor effects including constipation

• morphine

agonist-antagonist opioids

• when given alone produce analgesia

• if given with pure opioid agonist, it can antagonize analgesia caused by pure agonist

• pentazocine and buprenorphine

pure opioid antagonist

• block both mu and kappa receptors

• does not produce analgesia or opioid effects

• reverses respiratory depression

• Naloxone (narcan) - competitive antagonist

• methylnaltrexone

methylnaltrexone

• pure opioid antagonist that treats opioid induced constipation, alcohol abuse

• prevents euphoria is abuser takes and opiod

where does morphine come from

seedpod of poppy plant

pharmacologic actions of morphine

• pain relief

• drowsiness

• mental clouding

• reduces anxiety

• sense of well being

adverse effects of morphine

• respiratory depression (tolerance may develop)

• constipation

• orthostatic hypotension

• urinary retetnion

• cough suppression (acts on receptor in medulla)

• emesis (stimulates chemoreceptors in the medulla)

• euphoria and dysphoria

• myosis

• neurotoxicity

adverse effects in prolonged use of morphine

• hormonal changes and suppressed immune function

pharmacokinetics of morphine

• not lipid soluble

• won’t cross BBB

• only a small portion of the dose reaches site of analgesic action

morphine withdrawal

• if someone reaches physical dependance

• unpleasant but not lethal like CNS depressant withdrawal

contraindications for morphine

• decreased respiratory reserve

• pregnancy/ labor

drugs that interact with morphine (5)

• CNS depressants

• anticholinergics

• hypotensive drugs

• agonist - antagonist opioids

• opioid antagonists

Classic triad of morphine toxicity

• pinpoint pupils

• coma

• respiratory depression

fentanyl

100x stronger than morphine

Risk evaluation and mitigation strategy (REMS)

developed by FDA to reduce opioid related injuries and death

strong opioid agonists include

• hydromorphone

• oxymorphone

• levorphanol

how are moderate opioid agonists different from morphine

• less analgesia

• less respiratory depression

• lower potential for abuse

codeine

• moderate to strong opioid agonist

• pain and cough suppression

• 10% converts to morphine in liver

• equivalent analgesic effect of oxycodone

hydrocodone

• moderate to strong opioid agonist

• most widely rx drug in US

• combined with acetaminophen = Vicodin

nonopioid centrally acting analgesic

• relieve pain by mechanisms largely unrelated to opioid receptors

• no respiratory depression, dependance or abuse

• Tramadol

clinical use of opioids

• asses pain

• determine doage

• determine dosing schedule

• avoid withdrawal, dependance, abuse or addiction