LEC 7 - Opioid Analgesics Flashcards by Raegan Chambers

Full agonists (8)

Morphine

Methadone

Oxymorphone

Hydromorphone

Fentanyl

Alfentanil

Sufentanil

Carfentanil

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Partial agonists (1)

butorphanol

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Agonist - Antagonist (2)

Buprenorphine

Nalbuphine

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Antagonists (2)

Nalozone

Naltrexone

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mu-agonist 5-HT NE reuptake inhibitor (1)

Tramadol

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Drugs that inhibit preception (5)

General anesthetics

Opioids

alpha2 agonists

Benzodiazepines

Phenothiazines

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Drugs that inhibit transmission (2)

Local anesthetics

Alpha2 agonists

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Drugs that inhibit peripheral sensitazation of nociceptors (transduction) (4)

Local anesthetics

Opioids

NSAID’s

Corticosteroids

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Drugs that modulate the spinal pathway (7)

Local anesthetics

Opioids

Alpha 2

Tricyclic antidepressants

NMDA antagonits

NSAIDs

Anticonvulsants

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What are the opioid receptors linked to?

Gi proteins

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What does Gi protein stimulus cause?

decrease cAMP

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What effects does opioids have on ion channels?

Close - Presynaptic Ca2+ channels (u + d + K)

Open - postsynaptic K+ channels (u)

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What effects does closing the Ca2+ channels have?

Decrease NT release

ACh

Glutamate

5-HT

Substance P

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What is the effect of opening post-synaptic K+ channels?

Hyperpolarization

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What are the major overall effects of opioids?

INhibition of pain transmitting ascending systems

Stimulating descending pain transmission inhibiting neurons

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What are the actions of opioids at the presynaptic terminal?

u/d/k receptors

decrease gCa2+

decrease NT release

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What effects does opioids have post-synaptically?

u receptors

Increase gK+ - IPSP

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Where in the body are mu receptors found?

Brain

Dorsal horn of spinal cord

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What are the effects of mu receptor activation?

Supraspinal + Spinal analgesia

Euphoria

Sedation

Miosis

Respiratory depression

Chemical dependence

Decrease GI motility (ACh effect)

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What NT are effected by mu receptors?

ACh

Dopamine

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Where in the body are kappa receptors found?

Cerebral cortex

Spinal cord

Brain regions

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What is the result of kappa receptor activation?

Spinal + Supraspinal analgesia

Mild sedation

Dysphoria

Miosis

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What NT is affected by kappa? What is the result?

Vasopressin

Stops release to induce diuresis

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Where are the delta receptors found?

Limbic system

Cerebral cortex

Spinal cord

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What occurs with delta receptor activation?

Spinal + Supraspinal analgesia Cardiovascular depression

What NT is affected by delta receptors?

Dopamine

What are the three endogenous opioids?

Endorphins Enkephalins Dynorphins

What levels of analgesia occur with opioid administration?

Brain Spinal cord (rarely peripherial)

What receptor has the largest analgesic effects?

What is the relationship between duration of action and 1/2 life with opioids? Why?

Duration of action normally shorted then 1/2 life Desensitization + Down regulation of receptors

What CNS occur with opioids at high and low concentrations?

Low - Depression High - Excitation

What respiratory effects are seen with opioids?

mu receptors = depressants will see panting due to change in thermoregulatory set point

What is the effect of the respiratory depression seen with opioids?

Increase in arterial CO2 tension Decreate in arterial O2 tension Decrease in pH

What are the cardiovascular effects of opiods?

For the most part spare the CV system Hypotension can occur

What can be seen in dogs with opioid administration that effects heart rate?

Vagal stimulation Bradycardia Induce barorecptor response

Why do you see vasodilation with opioid administration?

Histamine release

What are the GI effects of opioid administration?

IM - vomiting dogs IV decreases this effect Constipation + decrease gastric emptying

What are the pupilary effects of opioids?

Mioisis Mydriasis - Cats + Horses

Morphine - Vomit induction in Dogs

Stimulate chemoreceptor trigger zone

Morphine - Uses

Acute pain - dogs, cats, horses Sedative to reduce pacing + standing procedures - horse Antitussive - Dogs

Morphine - BA

\<20 % - dogs given PO Due to first pass effect

Morphine - Excretion

Renal

Morphine - Metabolism

Glucuronidation

Morphine - Adverse effects

Hyperexcitability Hypotension Cerebral hemorrhage/edema Abnormal body temp

What animals see hyperthermia with morphine?

Cats Horses Ruminants

Why is cerebral hemorrhage + edema a concern with morphine?

Respiration depressed Arterial CO2 increase INcrease cerebral blood flow - increased pressure

What animals see hypothermia with morphine?

Rabbits Dogs Primates

Tramadol - Mechanism

mu-receptor agonist inhibits reuptake of serotonin + NE

What contributes to tramadols analgesic effects?

Inhibition of serotonin + NE

Tramadol - use

Anlagesic + Antitussive

Tramadol - Admin

Tramadol - BA

65% cats/dogs

Tramadol - Metabolism

Liver

Tramadol - 1/2 life Dogs Cats Horses

Dogs = 0.8 to 1.7 hours Cats - 3 to 5 hours Horses = 1.5 to 4 hours

Methadone - Mechanism

mu-agonist May have NMDA receptor antagonist activity

Methadone - Admin

IV + IM + SC

Methadone - Use

Pre-med or Analgesic alternative in dogs/cats

Methadone - BA

80% SC very low with PO

Methadone - Protein binding

Albulmin - 60 yo 90%

Methadone - Metabolism

Liver - Cytochrome P450

Methadone - Adverse side effects

Less sedation + vomiting compared to morphine

Oxymorphone/Hydromorphone - Potency

ten times that of morphine

Oxymorphone/Hydromorphone - Uses

Analgesia Pre-meg Neruoleptanalgesia Anesthesia

Oxymorphone/Hydromorphone - Admin

IV + IM + SC + Rectal

Fentanyl - Mechanism

Potent mu-agonist

Fentanyl - Admin

IV + Patch

Fentanyl - Duration of Action

Patch - 72 hours

Fentanyl - Use

Anesthetic induction Potent analgesic

Fentanyl - Pain control

Intraoperative Postoperative Chornic pain

Fentanyl - Onset

More rapid then morphine due to increase lipid solubility

Fentanyl - Metabolism

CYP450

Fentanyl - Excretion

urine

Fentanyl - Adverse effects

Sensitive to noise Panting + defecation + flatulence Bradycardia Hypersalivation

How can bradycardia + hypersalivation due to fentanyl be treated?

Anticholinergic drug

Alfentanil - Potency

4x's less potent then fentanyl

Alfentanil - Mechanism

mu-receptor antagonist

Alfentanil - Admi

IV + IM + SC

Alfentanil - Metabolism

Liver - P450

Alfentanil - Use

Analgesic + Sedative Adjunctive anesthesia (cats)

Sufentanil - Potency

5 to 10x's more potent then fentanyl

Sufentanil - Admin

IV + IM + SC + Epidural

Sufentanil - Use

Adjunctive anesthesia Epidular analgesia Postoperative analgesia

Sufentanil - Metabolism

Liver - Small Intestine via O-demethylation

Sufentanil - Adverse effect

CNS + respiratory depression

Carfentanil - Potency

10,000 x's more then morphine

**Carfentanil - Admin**

Carfentanil - 1/2 life

2 to 24 hours needs a reversal due to this

Carfentanil - Adeverse effects

Disruption of body temp CNS + respiratory depression

Carfentanil - Reversal Agent

Naltrexone Longer duration of action

Butorphanol - Mechanism

Parital agonist for mu-receptor Full Agonist for kappa-receptor

Butorphanol - Use

Not a great alnalgesic Opioid reversal - reverses mu-receptor effects (sedation + respiratory depression) Antitussive - Dogs with chronic cough Analgesia in cats + cattle Colic Anti-emetic for chemotherapy Chemical resitrant in cattle

Butorphanol - Withdrawl

5 days meat withdrwal

Butorphanol - BA

Horses - 37% via IM in adults 67% in Foals

Butorphanol - 1/2 life

Horses 6 hours - adults 2 hours - foals

Butorphanol - Adverse effects in horses

Transient ataxia Sedation/Excitement Ileus Startle to loud Noises

Butorphanol - Dogs elimination

P-glycoprotein mediates elimination from CNS

Butorphanol - Adverse effects in Dogs

MDR1 mutation hets - 25% reduction in dose homos - 50% reduction in dose

What are the subtypes of the opioid agonist/antagonists?

1 - antagonize mu + activate kappa 2 -partial agonist for mu + antagonist for kappa

Buprenorphine - Potency

30x's the analgesic effect compared to morphine

Buprenorphine - Mechanism

Partial Agonist for mu Antagonist for kappa Very strong affinitiy for mu

Buprenorphine - Reversals

Resistant to Naloxone due to strong mu affinity

Buprenorphine - Admin

IV + IM + SC + Transmucosal + Topical

Buprenorphine - Use

Analgesic/Premed in Small Animals Analgesic in horses

Buprenorphine - Protein binding

96% binding

Buprenorphine - 1/2 life

5 to 6 hours Horses Cats Dogs

Buprenorphine - Metabolism

Liver via N-dealkylation Glucuronidation

Buprenorphine - Adverse effects

respiratory depression + sedation

Nalbuphine - Mechanism

Antagonist for mu-receptor Agonist for kappa-receptor

Nalbuphine - Potency

equal to morphine

Nalbuphine - Admin

IM topically

Nalbuphine - Use

Mild to moderate pain Pre-med Corceal ulcerations

Nalbuphine - Duration of action

Dogs = 45 minutes Cats = 2 to 3 hours

Nalbuphine - Protein binding

does not bind

Nalbuphine - Metabolism

Liver - Glucoronidation

Nalbuphine - Excretion

Urine

Nalbuphine - 1/2 life

Dogs = 1.2 hours

Naloxone - Mechanism

High affinity for mu-receptor Low affinity for kappa + delta Antagonist

Naloxone - Use

Post-op reverseal

Naloxone - Metabolism

Liver - CYP450

Naloxone - Excretion

Urine

Naltrexone - Mechanism

Long- acting antagonist mu/kappa/delta

Naltrexone - use

reversal

Naltrexone - Admin

IV + IM Oral

When is naltrexone given orally to dogs? How?

To treat behavioral problems in dogs Reduced endorphine binding