PAIN-RELIEVING DRUGS

They do not affect consciousness and do not inhibit other

types of sensitivity.

prostaglandins, adenosine triphosphate, protons) that stimulate pain receptors or nociceptors.

They are located on the endings of afferent fibers in the skin, muscles, visceral organs.
Impulses, caused by painful stimuli, spread along the C and A fibers and enter the posterior horn of the spinal cord. The first synaptic transmission from the afferent fibers to the interneurons takes place. Impulses spread along a number of pathways: to the higher CNS centers – reticular formation, thalamus, hypothalamus, basal ganglia, limbic system, cerebral cortex.

of the spinal cord, which is manifestered by the motor

reflex.
The third pathway is provided by the excitation of the lateral horn neurons, leading to the activation of the adrenergic (sympathetic) innervation.

several inhibitory mechanisms. These include local interneurones, which release opioid

peptides (enkephalins, endorphins, dynorphins), and descending enkephalinergic, noradrenergic and serotoninergic fibers. They originate in the brainstem and they are themselves activated by opioid peptides. Thus, opioid peptides released in both the brainstem and the spinal cord can reduce the activity of the dorsal horn relay neurons and can cause analgesia. The effects of opioid peptides are mediated by specific opioid receptors (, δ, κ).

partial agonists
Non – opioid analgetics
Non – opioid (non

– narcotic) analgetics: paracetamol
Drugs from different pharmacological groups with analgetic component of action
2. Drugs of mainly peripheral action (non-steroidal anti-inflammatory drugs)

causing a prolonged activation of opioid receptors (usually μ‐receptors).

Opioid analgesics produce marked inhibitory effect on the CNS. These include analgesia, drowsiness, antitussive action. Most of them change mood (euphoria) and cause drug dependence (psychological and physical). Some of them are derived from plants and some are synthesized.

than 10% morphine. Opium contains more than 20 alkaloids. According

to the chemical structure, some alkaloids are phenanthrene derivatives, other - isoquinoline derivatives.
Phenanthrene derivatives are morphine, codeine.
Isoquinoline derivatives is papaverin (antispasmodic drug).

agonists: buprenorphine, nalbuphine, butorphanole.
Antagonist of opioid receptors:
naloxone, naltrexone

pain stimuli in the central part of the afferent pathway.
Impairment

of subjective emotional perception of pain, pain assessment and reaction to it.

of antinociceptive system and disturbance of interneuronal transmission of pain

stimuli on different levels of the CNS.
Suppressive effect of morphine on the painful stimuli transmission in the spinal cord from the primary afferent fibers to the interneurones results from an increase of descending inhibitory effects and direct inhibitory action on the interneuronal transmission.

neurons of the posterior horns of the spinal cord and

on the level of presynaptic terminals.
M. stimulates presynaptic opioid receptors of the primary afferent terminals in the substantia gelatinosa and blocks Ca-channels. It decreases the release of mediators (glutamate, substance P), which participate in the nociceptive stimuli transmission.
Inhibition of the postsynaptic neurons is associated with their hyperpolarization (due to the activation of the postsynaptic K-channels).

impulse intensity in the ascending afferent pathways and decreases motor

and autonomic responses.
M. blocks the transmission of pain in the thalamus, reduces the summation of the pain impulses, and increases pain threshold.
The sedation action of M. changes pain perception and its emotional assessment also.

(renal, biliary, intestinal) – together with antispasmodic (atropine and papaverine);
For

sedation in anesthesia and in the postoperative period;
Neuroleptanalgesia, ataralgesia;
Chronic pain in incurable oncologic patients.

positive views of the surrounding environment, a feeling that future

is bright, irrespective of reality. Some individuals develop an opposite effect: feeling bad, negative emotions.
Sleep is usually superficial and easily interrupted by external stimuli.
Decrease of the body temperature (inhibition of the thermoregulation center, located in the hypothalamus).

center of the medulla oblongata and decreases its excitation in

response to carbon dioxide and reflex reactions. The respiratory rate slows down, but amplitude increases.
With a higher dose, respiratory rhythm decreases even more, the amplitude and minute volume decreases also. Irregular respiratory rhythm occurs; periodic respiration is possible.

has a marked antitussive activity. This effect is used for

relief of cough in the chest trauma and lung bleeding.
M. inhibits vomiting center, but stimulates the chemoreceptors of the trigger zone located at the bottom of the 4th ventricle that leads to the activation of the vomiting center. M. can cause nausea and vomiting.
M. stimulates the vagal center and causes bradycardia.
M. increases tone of smooth muscles, sphincters. It decreases the secretion of GI’glands and inhibits gastric motility and propulsive peristalsis of the intestine. It can cause constipations and urinary retention.

the exception of trimeperidin);
Different types of respiratory failure;
Severe head injury
Remember:

tolerance (including cross-tolerance) and drug dependence develops with all agonists of opioid receptors.

is 3-4 hours.
T. depresses the respiratory center to a

lesser degree than m.
It decreases the tone of the smooth muscles organs (ureters and bronchi), but also increases it (intestine, bile ducts). It is inferior to m. in its spasmogenic effect. It slightly intensifies contractility of the myometrium.

of pain relief is about 20-30 minutes after iv administration.

But duration of action after application of transdermal system is more than 72 hours.
F. causes a marked depression of the respiratory tract.
It increases the tone of the thoracic muscles. This worsens pulmonary ventilation.
Talamonal is the combination of F. and droperidole.

by 20-60 times in its analgesic activity and also has

a longer action. The effect develops slower than the effect of M.
It affects the gastrointestinal tract less than m.
Dependence potential is relatively low. The drug causes abstinence less than morphin.

but weak antagonist of -receptors.

artery pressure and cardiac work and is not recommended for

use in myocardial infarction.
Depresses respiration to a less degree than M.
Causes drug addiction more rarely.

weak antagonist of -receptors.
It is similar to M. in

its activity.
It rarely causes drug dependence.
It has almost no effect on hemodynamic.

and periodic respiration;
Skin is pale, cold and moist, and the

mucous membranes are cyanotic.
Marked miosis;
Bradycardia;
Increased knee-jerk.
Body temperature is falling.

laxatives (MgSO4) .
Special antagonists are used. They block all types

of opioid receptors, and eliminate all effects of N.A.
Antagonists are naloxone and naltrexone.

eliminated, and good mood, self-reliance appears.
Abrupt discontinuation of the

administration of the drug results in withdrawal syndrome (abstinence).
Fear, anxiety, depression, sleeplessness, aggressiveness appear. Most physiologic functions are disturbed. Sometimes collapse occurs; in severe cases abstinence can be the cause of lethal outcome.
Introduction of NA eliminates withdrawal syndrome.
Symptoms of chronic poisoning: decreasing of mental and physical abilities, weight loss, thirst, constipation, hair loss.

interacts with opioid receptors. It reduces the neuronal uptake of

serotonin and norepinephrine and so intensifies spinal inhibitory serotoninergic and adrenergic effects on the interneuronal transmission of the nociceptive impulses.
It minimally affects respiration and gastrointestinal functions.
Dependence potential is much lower than for opioid receptors agonists.