Opioids Organ Systems Effects (book)

Opioids and their Effects

Cardiovascular System

• Morphine does not cause direct myocardial depression or hypotension in supine and normovolemic patients
• However, it can cause orthostatic hypotension and syncope when patients change from a supine to a standing position
• Morphine decreases sympathetic nervous system tone to peripheral veins, resulting in venous pooling and subsequent decreases in venous return, cardiac output, and blood pressure
• It can also cause decreases in systemic blood pressure due to bradycardia or histamine release

Respiratory System

• Opioids produce dose-dependent depression of ventilation
• Depression of ventilation is characterized by decreased responsiveness of ventilation centers to carbon dioxide
• Opioids also interfere with pontine and medullary ventilatory centers, leading to prolonged pauses between breaths and periodic breathing
• High doses of opioids may result in apnea, but the patient remains conscious and able to initiate a breath if asked to do so

Neurological System

• Opioids depress cough by effects on the medullary cough centers, which are distinct from the effects of opioids on ventilation
• Dose-dependent depression of ciliary activity in the airways
• Opioids decrease cerebral blood flow and possibly intracranial pressure (ICP) in the absence of hypoventilation
• Morphine-induced sedation occurs in up to 60% of patients during morphine titration

Genitourinary System

• Morphine increases the tone and peristaltic activity of the ureter
• Opioids produce urinary urgency due to opioid-induced augmentation of detrusor muscle tone
• Antidiuresis occurs in animals, but not in humans, in the absence of painful surgical stimulation

Cutaneous Changes

• Morphine causes cutaneous blood vessels to dilate, resulting in flushing of the face, neck, and upper chest
• Histamine release accounts for urticaria and erythema commonly seen at the morphine injection site

Placental Transfer

• Opioids are readily transported across the placenta, which can result in depression of the neonate
• Maternal administration of morphine may produce greater neonatal depression than meperidine

Drug Interactions

• Ventilatory depressant effects of opioids may be exaggerated by amphetamines, phenothiazines, monoamine oxidase inhibitors, and tricyclic antidepressants
• Sympathomimetic drugs enhance analgesia produced by opioids### Opioid Effects
• Preoperative medication with an opioid can slow gastric emptying, increasing the risk of aspiration, and delay the absorption of orally administered drugs.
• Opioid-induced nausea and vomiting are caused by direct stimulation of the chemoreceptor trigger zone in the floor of the fourth ventricle.
• Morphine can cause nausea and vomiting by increasing gastrointestinal secretions and delaying passage of intestinal contents toward the colon.
• IV administration of morphine produces less nausea and vomiting than intramuscular (IM) administration, due to the opioid reaching the vomiting center as rapidly as it reaches the chemoreceptor trigger zone.
• Nausea and vomiting are relatively uncommon in recumbent patients given morphine, suggesting a vestibular component may contribute to opioid-induced nausea and vomiting.

Physical Dependence and Tolerance

• Tolerance develops to analgesic, euphoric, sedative, depression of ventilation, and emetic effects of opioids, but not to their effects on miosis and bowel motility.
• Physical dependence depends on the agonist effect of opioids and does not occur with opioid antagonists or opioid agonist-antagonists.
• Physical dependence on morphine typically requires about 25 days to develop, but may occur sooner in emotionally unstable persons.
• Discontinuation of the opioid agonist produces a typical withdrawal abstinence syndrome, including yawning, diaphoresis, lacrimation, and insomnia.

Withdrawal Symptoms

• Initial symptoms of withdrawal include yawning, diaphoresis, lacrimation, and coryza.
• Insomnia and restlessness are prominent, followed by abdominal cramps, nausea, vomiting, and diarrhea.
• Withdrawal symptoms reach their peak in 72 hours and then decline over the next 7 to 10 days.
• Tolerance to morphine is rapidly lost during withdrawal, and the syndrome can be terminated by a modest dose of opioid agonist.

Hormonal Changes

• Prolonged opioid therapy may influence the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, leading to endocrine and immune effects.
• Morphine may cause a progressive decrease in plasma cortisol concentrations.
• Opioids may modulate hormone release, including increased prolactin and decreased luteinizing hormone, follicle-stimulating hormone, testosterone, and estrogen concentrations.

Overdose

• The principal manifestation of opioid overdose is depression of ventilation, manifesting as a slow breathing frequency, which may progress to apnea.
• Pupils are symmetric and miotic unless severe arterial hypoxemia is present, which results in mydriasis.
• Treatment of opioid overdose involves mechanical ventilation with oxygen and administration of an opioid antagonist, such as naloxone.

Provocation of Coughing

• Preinduction administration of fentanyl, sufentanil, or alfentanil may be associated with significant reflex coughing.
• The exact cause of opioid-induced cough is unclear, but is thought to be due to an imbalance between sympathetic and vagal innervation of the airways and/or stimulation of juxtacapillary irritant receptors.