**Table 5.**

*Opioids receptors end their effects.*

Opioids decrease the medullary sensitivity to CO2, which may cause respiratory depression and also, suppress the medullary cough centre, for this reason some studies advocate for its use as an antitussive. Opioids can activate the chemoreceptor trigger zone, causing nausea or vomiting, but this is relatively infrequent. This drug class decrease bowel motility and smooth muscle function, responsible for constipation, and rarely, urinary retention. To a varying degree, some opioids destabilise mast cells in a dose dependent fashion, causing histamine release, manifested with pruritus, urticaria and sometimes, orthostatic hypotension.

#### **4.2 Clinical effect**

Opioid agonist agents cause a range of mainly depressant and some stimulant actions of the CNS through specific receptors (**Table 6**). These drugs have little capacity to produce amnesia, do not alter seizure threshold and have no anticonvulsant activity [6].

Opioids given systemically produce analgesia through actions at two anatomically distinct regions: supraspinal and spinal sites. They efficiently reduce the intensity of pain and the associated fear. This is achieved by raising the pain threshold, modifying the reaction to pain, and inducing sleep. They are efficient for controlling dull pain rather than sharp intermittent pain. Opioids are less effective for the treatment of neuropathic pain.

Opioids actions are also towards reduction in the level of consciousness and eventually produce sleep, with the loss of responsiveness to verbal stimulation. In anaesthesia combinations, they produce a dose related decrease in the MAC for volatile anaesthetics, with a ceiling of 60–70% decrease in MAC [6]. Another important feature in the combination with the volatile agents is increase in cerebral vasoconstriction [6]. Opioids do not cause a loss of cerebral autoregulation or reactivity to CO2. During EEC recording, there is a ceiling effect, with a slowing EEG frequency and the production of high-voltage (delta) waves [6].

#### **4.3 Cardiovascular effects**

In normovolemic patients, opioids barely influence haemodynamic parameters, with minimal cardiac depression, no baroreceptors inhibitions and modest reduction in preload and afterload. Haemodynamic compromise may be detected in subjects whose cardiovascular integrity is dependable on a high level of sympathetic tone, because opioids decrease central sympathetic outflow when even small doses can cause hypotension and circulatory collapse [6]. Morphine has the greatest effect on the vascular system. Morphine has the greatest effect on histamine release and subsequent indirect effect on catecholamine release. This may lead to tachycardia with a reduction in systemic vascular resistance (SVR) and mean arterial pressure (MAP). This risk can be prevented by pre-treatment with an antihistaminic drug and volume loading [6].

Opioids induce a negative chronotropic effect through a central vagal stimulation. Pethidine, however, has a homology with atropine and can trigger tachycardia, and it is the only opioid to induce significant direct myocardial depression when used at high doses. Myocardial depression is observed also after extraordinary high doses of morphine and fentanyl, as during cardiovascular anaesthesia. Morphine has indirect positive inotropic effects at doses of 1–2 mg/kg, and blocks neurally and hormonally mediated venoconstriction to reduce preload, rendering it useful in the management of left ventricular failure [6].

**245**

*consumption.*

**Table 6.**

**4.4 Effects on other organ systems**

*Opioids effects on the CNS [6].*

Vision Edinger-

Opioids are the most efficient of all pain analgesics drugs for attenuating the stress response associated with pain, laryngoscopy and airway manipulation. The plasma concentration of stress hormones (cortisol, catecholamines, vasopressin, aldosterone and growth factor) increases during trauma, anaesthesia or surgery. This produce increased myocardial work, tissue catabolism and hyperglycaemia – effects associated with increased morbidity and mortality. Opioids reduce nociception inhibiting the pituitary-adrenal axis, decreasing central sympathetic outflow and influencing centrally mediated neuroendocrine response. Fentanyl

and its congeners are the most efficacious in this action (**Table 7**).

*Analgesics*

*DOI: http://dx.doi.org/10.5772/intechopen.94319*

**System Effect**

Multifocal myoclonus

Westphal nucleus

Peripheral effects

ICP No effect

Cerebrovascular SSEPs No effect

Musculoskeletal Gait Decrease physical performance

Ataxia

use of N2O

Neural Central Spectrum from abnormal eye movement, to contraction of

Apathy

pethidine

Thermoregulation Response Decrease thermoregulation response (as for volatile agents)

*SSEPs – somatosensory evoked potential, ICP – intracranial pressure, CMRO2 – cerebral metabolic rate of oxygen* 

brain barrier quickly Dysphoria in some individuals

Decrease spinal cord reflexes

Rigidity Muscular rigidity occurs 60–90 seconds post-injection and abolish after 10–20 minutes

Mediated via nucleus raphe magnus

extremities, to tonic-clonic movements

Decreased level of consciousness Decreased concentration and orientation

No capacity to induce EEG silence

Reversed by hypoxia and atropine

CBF No effect, but increased vasoconstriction with vasodilators No loss of autoregulation or CO2 reactivity CMRO2 reduced by up to 10–25%

venodilation, muscle relaxation

EEG Effects vary between different opioids: slowing of

Mainly thoracoabdominal and arms muscles, higher risk with advanced age, high speed of injection, increased dose,

Non-convulsive related, higher risk with pethidine

Euphoria: especially for opioids which cross the blood-

Subjective feelings of body warmth and heavy extremities

Miosis (via a decrease in inhibition to the nucleus) except

Promote hypothermia via decreased BMR (10–20%),

frequency, production of high voltage & waves

Opioids preserve circulatory stability to a greater extent than most other anaesthetic agents [6].


*Pain Management - Practices, Novel Therapies and Bioactives*

pruritus, urticaria and sometimes, orthostatic hypotension.

**4.2 Clinical effect**

sant activity [6].

for the treatment of neuropathic pain.

**4.3 Cardiovascular effects**

an antihistaminic drug and volume loading [6].

the management of left ventricular failure [6].

Opioids decrease the medullary sensitivity to CO2, which may cause respiratory depression and also, suppress the medullary cough centre, for this reason some studies advocate for its use as an antitussive. Opioids can activate the chemoreceptor trigger zone, causing nausea or vomiting, but this is relatively infrequent. This drug class decrease bowel motility and smooth muscle function, responsible for constipation, and rarely, urinary retention. To a varying degree, some opioids destabilise mast cells in a dose dependent fashion, causing histamine release, manifested with

Opioid agonist agents cause a range of mainly depressant and some stimulant actions of the CNS through specific receptors (**Table 6**). These drugs have little capacity to produce amnesia, do not alter seizure threshold and have no anticonvul-

Opioids given systemically produce analgesia through actions at two anatomically distinct regions: supraspinal and spinal sites. They efficiently reduce the intensity of pain and the associated fear. This is achieved by raising the pain

threshold, modifying the reaction to pain, and inducing sleep. They are efficient for controlling dull pain rather than sharp intermittent pain. Opioids are less effective

Opioids actions are also towards reduction in the level of consciousness and eventually produce sleep, with the loss of responsiveness to verbal stimulation. In anaesthesia combinations, they produce a dose related decrease in the MAC for volatile anaesthetics, with a ceiling of 60–70% decrease in MAC [6]. Another important feature in the combination with the volatile agents is increase in cerebral vasoconstriction [6]. Opioids do not cause a loss of cerebral autoregulation or reactivity to CO2. During EEC recording, there is a ceiling effect, with a slowing

In normovolemic patients, opioids barely influence haemodynamic parameters, with minimal cardiac depression, no baroreceptors inhibitions and modest reduction in preload and afterload. Haemodynamic compromise may be detected in subjects whose cardiovascular integrity is dependable on a high level of sympathetic tone, because opioids decrease central sympathetic outflow when even small doses can cause hypotension and circulatory collapse [6]. Morphine has the greatest effect on the vascular system. Morphine has the greatest effect on histamine release and subsequent indirect effect on catecholamine release. This may lead to tachycardia with a reduction in systemic vascular resistance (SVR) and mean arterial pressure (MAP). This risk can be prevented by pre-treatment with

Opioids induce a negative chronotropic effect through a central vagal stimulation. Pethidine, however, has a homology with atropine and can trigger tachycardia, and it is the only opioid to induce significant direct myocardial depression when used at high doses. Myocardial depression is observed also after extraordinary high doses of morphine and fentanyl, as during cardiovascular anaesthesia. Morphine has indirect positive inotropic effects at doses of 1–2 mg/kg, and blocks neurally and hormonally mediated venoconstriction to reduce preload, rendering it useful in

Opioids preserve circulatory stability to a greater extent than most other

EEG frequency and the production of high-voltage (delta) waves [6].

**244**

anaesthetic agents [6].

*consumption.*

#### **Table 6.**

*Opioids effects on the CNS [6].*
