Term
| What are the pharmakokinetics of the prototype opioid Morphine? |
|
Definition
Good absorption but high 1st pass effect leads to low bioavailability
Glucoronidation-> M3G-active metabolite with neuroexcitatory M6G (more potency at recceptor)
Renal excretion (half life 2 hours)
Acumulation of matabolites increases risk of adverse effects |
|
|
Term
| What are the molecular effects of opioid agonist binding to its receptor. |
|
Definition
Gi protein inhibit adenylyl cyclase
decrease opening of Ca2+ channels
increase potassium infulx causing hyperpolarization
Activate PKC, PLC signal transduction |
|
|
Term
| 1)What happens when an agonist binds to mu receptor? 2)Which endogenous agonist has the most affinity for this receptor |
|
Definition
| 1) supraspinal and spinal analgesia respiratory inhibition, slowed GI transit (constipation) modulation of hormone and neuro transmitter. 2) Endorphins |
|
|
Term
What happens when agonist binds to delta receptor?
Which endogenous agonist has the most affinity? |
|
Definition
1) spinal and supraspinal analgesia
modulation of hormone and neurotransmitter release
2) Enkephalins |
|
|
Term
What happens when agonist binds to kappa receptor?
Which agonist has the most affinity? |
|
Definition
1) supraspinal and spinal analgesia
PSYCHOMIMETIC EFFECTS (dysphoria)
slowed GI transit
2) Dynorphins |
|
|
Term
| How does tolerance develop to analgesics? |
|
Definition
| Tolerance develops to the euphoric, sedative and respiratory depressant effects not miosis constipation or convulsant effects. There is cross tolerance with other opioids. |
|
|
Term
| What are the signs and symptoms of opioid withdrawal? |
|
Definition
| rhinorrhea, lacrimation, yawning, chills, piloerection, hyperventilation, hyperthermia mydriasis muscular aches, vomiting, diarrhea, hostility |
|
|
Term
| What are the CNS effects of morphine? |
|
Definition
| analgesia, euphoria, cough suppression, miosis, truncal, rigidity, nausea |
|
|
Term
| What are the neuroendocrine effects of morphine like opioids? |
|
Definition
| stimulates release of arginine vasopressin prolactin, and somatotropin, inhibit the release of LH. |
|
|
Term
| What are the peripheral adverse effects of morphine like opioids |
|
Definition
bradycardia, hypotension in susceptible patients, constipation, biliary, and urinary colic, urinary retention, temp alterations, seizures at high doses
PRURITIS AND URTICARIA |
|
|
Term
| What are the therapeutic uses of morphine? |
|
Definition
severe pain (acute or chronic)
adjunct to analgesia
Dyspnea
Diarrhea |
|
|
Term
| What are some drug interactions of opioids? |
|
Definition
sedative-hypnotics increase CNS resp depression
Antipsychs TCAs increase sedation. resp depression, cardiovascular effects
MAOis high incidence of hyperpyrexia,coma, hypertension
Relative contraindication in all opioids |
|
|
Term
What is an absolute contraindication of opioids?
2) Are asthma, impaired pulmonary function, and head injuries contraindications to opioids? |
|
Definition
1) Meperidine
2) Yes, it can cause: a) bronchoconstriction in asthma pts
b)increase risk of acute pulmonary failure in impaired lung function
c) increase intracranial pressure in head injuries
|
|
|
Term
Which opioid is a prodrug and needs to be metabolized by CYP2D6 to start working.
What are its uses? |
|
Definition
1)Codeine
2) uses are cough suppressant
mild to moderate pain with NSAID and APAP. |
|
|
Term
| Which drug has a metabolite that has 2-3x's more CNS effects as the drug itself but has half the analgesic effect |
|
Definition
Meperidine
the metabolite is normeperidine and has half life of 15-20 hrs while merperidine's half life is 3 hrs
Strong MOR and KOR agonist and antimuscarinic effects
DOES NOT CAUSE MIOSIS |
|
|
Term
| What would you use for obstetrical labor that does not delay birth process and does not antagonize oxytocin but MAY PRODUCE RESP DEPRESSION IN NEWBORN |
|
Definition
Meperidine
Also used for moderate to severe pain not more than 2 days
adjunct to anesthesia or premed for a procedure |
|
|
Term
| Which drug may block shivering by anesthesia or infusion reactions by amphoterecin B or trastuzumab through alpha2 receptors? |
|
Definition
|
|
Term
Which one of thse drugs will cause an adverse reaction of tachycardia, hypotension neurotoxicity
contraindicated with MAOis and CYP inducers like Phenobarbital and Phenytoin |
|
Definition
|
|
Term
| Which opioid agonst has a rapid redistribution from CNS to other tissue due to its high lipid solubility. |
|
Definition
| Fentanyl-high potency for mu receptor |
|
|
Term
| What would you use to treat heroin use, chronic pain and opioid abstinence syndromes? |
|
Definition
Methadone
it is a long acting MOR agonist, biliary renal excretion increases in acidic pH |
|
|
Term
| Which opioid agonist lowers seizure threshild not as potent as the others |
|
Definition
|
|
Term
| Which opioid agonist are the antidiarrheals? |
|
Definition
Diphenoxylate
Lperamide
AVOID antidiarrheals in bowel obstruction |
|
|
Term
| Can you give pts who have been taking opioid agonists, opioid antagonists and partial agonists? |
|
Definition
|
|
Term
What is a ceiling effect?
What causes it? |
|
Definition
Ceiling effect is when you have analgesia and respiratory depression but no further effect beyond a certain dosage level.
Opioid agonist-antagonist and partial agonists causes it |
|
|
Term
| Which drug has psychomimetic effects at high doses? |
|
Definition
Butorphanol-since it is a kappa receptor agonist but a mu receptor antagonist
causes drowsiness, foalting feeling, nausea |
|
|
Term
| Which drug will need a large dose of naloxone to reverse resp depression due its slow dissociation but this can be prevented with prior administration of naloxine? HINT: it has high affinity for MOR (partial agonist) but its antagonist to KOR and DOR. |
|
Definition
|
|
Term
| What is the treatment of choice for opioid overdose with onset of 2min and duration of action of 30-120 min. Comes in subQ, IM, endotracheal |
|
Definition
|
|
Term
| What opioid antagonist is used for alcoholism, opioid dependance but has a narrow therapeutic window which can cause heaptocellular injury |
|
Definition
Naltrexone
Contraindication in acute hepatitis, liver failure, acute opioid withdrawal positive urine screen.
MUST GIVE ONCE THE PT IS COMPLETELY OFF OPIOID. |
|
|
Term
| What would you use for opioid induced constipation in pts with advanced illness who dont respond to laxative care? |
|
Definition
| Methylnaltrexone (peripherally acting opioid antagonist) |
|
|
Term
| What can happen with neuroexcitatory metabolites from glucoronidation in drugs like morphine and meperidine? |
|
Definition
| Can accumulate in patients with renal problems especially at high doses. |
|
|
Term
| Which drug cannot me used more than 48 hours or more than 600mg/day? Why? |
|
Definition
| Meperedine due to its toxic metabolite normeperidine which has neuroexcitatory and neurotoxic effects. |
|
|
Term
| Why should you be cautious when using naloxone to treat opioid induced respiratory depression? |
|
Definition
Due to its duration of action which is only 30-120min.
Pt may seem fine when drug is first given but can go into coma when action wears off. |
|
|
