Opioids

Question 1

How do opioids inhibit the cough?

Answer 1

Opioids also suppress the cough reflex via the cough centers in the medulla

Question 2

Which opioid receptor is associated with depression of ventilation?

Answer 2

Mu

Question 3

Risk factors for opioid induced respiratory depression

Answer 3

Large opioid dose, advanced age, concomitant use of other central nervous system (CNS) depressants, and renal insufficiency (for morphine). Natural sleep also increases
the ventilatory depressant effect of opioids

Question 4

Opioids reduce heart rate and cause vasodilation by acting directly on the myocardium and blood vessels
T or F

Answer 4

F

The fentanyl congeners cause bradycardia by directly
increasing vagal nerve tone in the brainstem

Clinical doses of opioids do not
appreciably alter myocardial contractility

Opioids produce vasodilation by depressing vasomotor centers in the brainstem and, to a lesser extent, by a direct effect on vessels

Question 5

When opiods are administerd, they can caused muscle rigidity. The rigidity of which structure can make the bag ventilation a hard task?

Answer 5

vocal cord rigidity and closure

Question 6

Opioids causes muscle rigidity by acting directly in the muscle fibers

T or F

Answer 6

F

Although the mechanism of opioid-induced muscle rigidity is unknown, it is not a direct action on muscle because it can be eliminated by neuromuscular blocking drugs

Question 7

Opioids cause nausea and vomiting by acting in which structure?

Answer 7

They stimulate the chemoreceptor trigger zone in the area postrema on the floor of the fourth ventricle in the brain. This can lead to nausea and vomiting, which are exacerbated by movement.

Question 8

How do opioids causes pupillary constriction?

Answer 8

Pupillary constriction is induced by mu agonists. Opioids stimulate the Edinger–Westphal nucleus of the oculomotor nerve to produce miosis

Question 9

How do opiods affect de biliary system? How to terat this adverse effects?

Answer 9

Mu agonists can produce contraction of the gallbladder smooth muscle and spasm of the sphincter of Oddi, potentially
causing a falsely positive cholangiogram during gallbladder and bile duct surgery.

These effects are completely
reversible with naloxone and can be partially reversed by
glucagon treatment

Question 10

How do opioids affect the immune system?

Answer 10

Opioids depress cellular immunity. Morphine and the endogenous opioid beta-endorphin, for example, inhibit the transcription of interleukin-2
in activated T cells, among other immunologic effects.
Individual opioids (and perhaps classes of opioids) may differ in terms of the exact nature and extent of their immunomodulatory effects. Although opioid-induced
impairment of cellular immunity is not well understood, impaired wound healing, perioperative infections, and cancer recurrence are possible adverse outcomes

Question 11

Considerations in the administration of opioids in patients with compromised hepatic function

Answer 11

Even though the liver is the metabolic organ primarily
responsible for the biotransformation of most opioids, liver failure is usually not severe enough to have a major impact on opioid pharmacokinetics. Of course, the anhepatic. phase of orthotopic liver transplantation is a notable
exception to this general rule. Pharmacodynamic considerations can be important
for opioid therapy in patients with severe liver disease.
Patients with ongoing hepatic encephalopathy are especially vulnerable to the sedative effects of opioids.

Question 12

Considerations in the administration of opioids in patients with compromised renal function

Answer 12

Renal failure has implications of major clinical importance with respect to morphine and meperidine. For the fentanyl congeners, the clinical importance of kidney failure is much less marked. Remifentanil’s metabolism is not affected by kidney disease

Morphine is principally metabolized by conjugation
in the liver; the resulting water-soluble glucuronides (i.e.,
morphine 3-glucuronide and morphine 6-glucuronide M3G and M6G) are excreted via the kidney. The kidney also plays a role in the conjugation of morphine and may account for as much as half of its conversion to M3G and M6G. M3G is inactive, but M6G is an analgesic with a potency rivaling morphine. Very high levels of M6G and life-threatening respiratory depression can develop in patients with renal failure.

The clinical pharmacology of meperidine is also significantly altered by renal failure. Normeperidine, the main
metabolite, has analgesic and excitatory CNS effects that
range from anxiety and tremulousness to myoclonus and frank seizures

Question 13

How gender influences opioids effects?

Answer 13

Gender may have an important influence on opioid pharmacology. Morphine is more potent in women than in
men and has a slower onset of action in women. Some
of these differences may be related to cyclic gonadal
hormones and psychosocial factors

Question 14

how to calculate the dose of opioids in obese patients?

Answer 14

Opioid pharmacokinetic parameters, especially clearance, appear to be more closely related to lean
body mass (LBM) rather than to total body weight

Question 15

Unique features of codeíne

Answer 15

Codeine is actually a prodrug; morphine is the active compound. Codeine is metabolized (in part) by O-demethylation
into morphine, a metabolic process mediated by the liver
microsomal isoform CYP2D6.40 Patients who lack CYP2D6
because of deletions, frameshift, or splice mutations (i.e.,
approximately 10% of the Caucasian population) or whose
CYP2D6 is inhibited (e.g., patients taking quinidine) would
not be expected to benefit from codeine even though they
exhibit a normal response to morphine. Conversely,
patients with CYP2D6 gene duplications are expected to
exhibit excessive effect with codeine administration

Question 16

Unique features of tramadol

Answer 16

Tramadol is a centrally acting analgesic with moderate mu
receptor affinity and weak kappa and delta receptor affinity.
Tramadol inhibits serotonin reuptake and norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord.
Although providing analgesia both through opioid and serotonin receptor pathways, tramadol carries less risk of respiratory depression.
However, when combined with serotonin reuptake inhibitors
or other serotonergic medications, it does carry the risk of serotonin syndrome and of CNS excitability and seizures

Question 17

Unique features of nalbuphine

Answer 17

Is an opioid agonist-antagonist, nalbuphine has a potencyand duration of action similar to morphine. It can be used
as a sole agent for sedation with more limited ventilatory
depression and as an agent to reverse ventilatory depression
in opioid overdose while maintaining some analgesia, such as at the end of an anesthetic when a patient is exhibiting excessive opioid effect (usually in very small doses)

Question 18

What are the biased opioids?

Answer 18

Two distinct transduction pathways have been
described in connection with mu opioid receptor activation: the G protein–coupled signaling pathway is responsible for the analgesic, reward, and pleasure effects; the beta-arrestin pathway mediates the respiratory depression and gastrointestinal effects

Improved understanding of these signaling pathways has
led to the development of a novel class of opioids: the biased
agonists. The biased agonists are full agonists of the G protein–mediated pathway, but produce less recruitment of the
beta-arrestin pathway. Biased agonists, therefore, have the
full analgesic effects of conventional opioids with less risk of constipation and respiratory depression

The biased agonist oliceridine was approved by the U.S. Food and Drug Administration

Although biased agonists show promise in the treatment
of pain and the curbing of opioid epidemic deaths, they do
not eliminate all of the adverse effects of the previously
marketed opioids. Notably, they exert the same sedative
effects as classic opioids.