chapter 6: opioid analgesics and antagonists

what does endogenous mean?

produced from an organism, not coming from an outside source

what ate the types of opioid receptors?

1. Mu

2. Kappa

3. Delta

what do Mu receptors do?

1. inhibits pain

2. euphoria

3. respiratory depression

what do Kappa receptors do?

1. modulates pain

   1. agonists can produce sedation and aversive effects

what are sensory functions of opioids?

inhibition of painful stimuli

what are modulatory functions of opioids?

effects on GI tract, endocrine system, autonomic system, and motor function

what are emotional functions of opiods?

reward, addiction, euphoria, dysphoria

what are cognitive functions of opiods?

learning/memory, fear/distress

what acronym is used for pharmacokinetics?

ADME

1. absorption

2. distribution

3. metabolism

4. excretion

what are methods of opioid absorption?

1. orally

2. subcutaneous

3. intramuscular

4. oral/nasal

5. transdermal

what does subcutaneous mean?

underneath skin

what is the distribution of opioids?

higher concentrations in well perfused organs

what does perfused mean?

having fluid passing through

what are examples of well perfused organs?

brain, lungs, kidneys, liver

what is the metabolism for opioids?

mostly liver

where do oral opioids usually go through first pass metabolism?

hepatic CYP3A4/2D6

how are opioids excreted?

mostly urine, sometimes excreted in bile

what can opioids cause?

urinary retention

are opioids an analgesic?

yes

what is the standard opioid?

morphine

what is opioid sparing strategy?

combining a weaker opioid with a non-opioid analgesic can reduce opioid dose required

how do opioids cause euphoria?

Mu receptor agonist promotes dopamine release by inhibiting GABAergic interneurons

what do kappa receptor agonists/mu receptor antagonists do?

inhibit dopamine release and causes aversive effects

what can CNS depressants do when combined with opioids?

increase opioid sedation

how does opioid affect nausea?

mu agonists stimulates CTZ and vestibular system

what is the vestibular system?

network controlling balance, spatial orientation and head movement in inner ear and brain

what does spatial mean?

relating to space and physical dimension

what is CTZ?

chemoreceptor trigger zone

how can opioids affect respiratory depression?

mu agonists act directly on brainstem respiratory centers

what is the primary cause of death in opioid overdose?

respiratory depression

what increases the risk of respiratory depression when combined with opioids?

dose and concurrent CNS depressants

what do opioids do to coughs?

suppresses cough center in medulla

what can opioids do to the pupils?

mu and kappa agonists can cause pinpoint pupils

what are cardiovascular effects of opioids?

1. peripheral vasodilation

2. hypotension

3. reduced preload, contractile force, and heart rate

4. stimulates vagus nerve

what is peripheral vasodilation?

widening of blood vessels

what does preload mean?

stretching of cardiac muscle in ventricles before contracting

what is the vagus nerve?

nerve connecting brainstem to heart, lungs, and digestive tract

what is the vagus nerve important for?

PSNS, rest and digest

what are GI effects caused by mu and kappa agonists?

1. reduced GI secretions

2. decreased propulsive intestinal contractions

3. delayed digestion

4. increased water absorption

5. opioid induced constipated

what are neuroendocrine effects from opioids?

1. reduced libido in males

2. menstrual irregularities

3. pregnancy and neonatal concerns

what is tolerance?

decreased effectiveness of a drug after repeated use

what are opioid tolerance effects?

1. analgesia, sedation, euphoria

2. usually does not develop to pupil constriction or constipation

what are the 5 Cs or addiction/use disorder?

1. chronic use

2. compulsive use

3. impaired control

4. craving

5. continued use despite harm

what is detoxification?

1. substituting a longer-acting agonist for opioid being misused

2. gradually reducing dose

3. continue until patient is drug free

what are therapeutic uses of opioids?

1. acute pain (post-op)

2. chronic non-cancer/cancer pain

3. palliative care

4. cough suppression

5. diarrhea treatment

what is palliative care?

specialized medical care for serious illnesses

adding what may reduce amount of opioid needed?

NSAID or acetaminophen

what are examples of opioid agonists?

1. morphine

2. codeine

3. oxycodone

4. hydrocodone

5. hydromorphone (dilaudid)

6. meperidine (demerol)

7. fentanyl

8. oxymorphone

9. diphenoxylate/loperamide

what is the prototype opioid?

morphine

what opioid is most commonly used in dentistry?

codeine

what is codeine usually used as?

antitussive

what does antitussive mean?

cough suppressant

what is codeine’s analgesia power?

weak analgesic

what can codeine be combined with?

acetaminophen

what is oxycodone for?

moderate to severe pain

what can oxycodone be combined with?

aspirin or acetaminophen

oxycodone is how many times more potent than codeine?

10-12 times

what is oxymorphone?

more potent metabolite of oxycodone

what is diphenoxylate/loperamide?

opioid agonists used to treat diarrhea

how does diphenoxylate/loperamide treat diarrhea?

decreases GI propulsion/secretions and increases anal sphincter tone

what is the ceiling effect?

increased dose beyond a certain amount produces little addition effect

what is pentazocine?

weak mu antagonist and kappa agonist

what is pentazocine used for?

1. analgesia

2. sedation

3. respiratory depression

4. increased BP/HR

5. dysphoria

what is dysphoria?

state of uneasiness, emotional distress

what is butorphanol?

competitive mu antagonist and kappa agonist

what is butorphanol used for?

acute pain

who should avoid butorphanol?

patients with congestive heart failure and MI

what are symptoms of congestive heart failure (CHF)?

1. shortness of breath

2. fatigue

3. swelling in legs/ankle/belly

4. rapid/irregular heartbeat

5. persistent dry cough

what is buprenorphine?

partial mu agonist and kappa/delta antagonist

what is buprenorphine used for?

pain and opioid use disorder treatment

what are characteristics of buprenorphine?

1. long duration

2. high potency

3. ceiling effect for analgesia/respiratory depression

what do opioid antagonists do?

block opioid receptor effects

what are opioid antagonists used for?

OD treatment and opioid use disorder management

what are naloxone and naltrexone?

both nonselective opioid receptor antagonists

what is naloxone used for?

reverse opioid toxicity and OD

what is the duration of action for naloxone?

short

what is the duration of naltrexone?

long

what is naltrexone used for?

opioid and alcohol use disorders are an opioid free period

is naloxone or naltrexone more potent?

naltrexone

when is naloxone metabolized?

through first pass metabolism

how is naloxone administered?

parenterally

what is parenteral administration?

through fluid routes that bypass GI tract, like injections/infusion

what are effects of naltrexone?

reduces cravings and opioid related euphoria

what are adverse effects of naloxone?

can precipitate withdrawal in dependent patients

what are adverse effects of naltrexone?

1. nausea

2. vomiting

3. headache

4. insomnia

5. liver injury

what are therapeutic uses of opioid antagonists?

1. opioid induced toxicity

2. diagnosis of opioid dependence

3. treatment of opioid use disorder

4. treatment of opioid induced constipation

what is the distinction between naloxone and naltrexone?

1. naloxone: immediate OD reversal medication

2. naltrexone: longer acting, used in treatment of substance use disorders

what is tramadol?

synthetic codeine analog

what are characteristics of tramadol?

1. weak mu opioid receptor agonist

2. inhibits nor-epi and serotonin reuptake

3. used for mild-moderate pain

4. can cause seizures

what can tramadol not be combined with?

MAO inhibitors, SSRIs, and SNRIs because of interaction risks

what are adverse reactions of opioid use?

1. respiratory depression

2. sedation/drowsiness/dizziness/blurred vision

3. constipation

4. nausea/vomiting

5. urinary retention

6. (orthostatic) hypotension/syncope

7. miosis

8. tolerance/physical dependence

what is miosis?

pinpoint pupils

what is the classic toxicity triad of opioid overdose?

1. coma/CNS depression

2. respiratory depression

3. miosis

what is the emergency response required for suspected opioid overdose?

respiratory support, naloxone, EMS

what are contraindications of opioids?

1. reduced respiratory function (asthma and COPD)

2. chronic kidney disease/impaired renal function

3. liver disease

4. hypotension

5. head injury

6. pregnancy/nursing

7. physical dependence

8. concurrent use of CNS depressants

9. MAO inhibitors

what is a MAO inhibitor?

medications that inhibit monoamine oxidase

what does monamine oxidase (MAOs) do?

antidepressant, breaks down chemicals like serotonin, norepinephrine, and dopamine to increase their levels

what are selective serotonin reuptake inhibitor (SSRIs)?

anti-depressant/anxiety medications

how should patients take opioids?

1. with a full glass of water - may cause dry mouth

2. with food - to minimize GI irritation

what are patient instructions for opioids?

1. take with water/food

2. sedation is common - be careful driving

3. avoid important decisions

4. discuss concerns about addiction