Opioid & Non-opioid Analgesics

Question 1

Pain and how does it occurs?

Answer 1

Psycho-physiological state due to intense stimuli.
Occurs after stimulation of nociceptive receptors & conduction of pain impulses to CNS (nociceptive system)

Question 2

Endogenous opiod peptides?
Where produced?
On what they act?

Answer 2

1) endomorphins, enkephalins
2) In CNS (anti-nociceptive system)
3) Act by activation of so-called opioid
receptors.

Question 3

What are analgesics?

Answer 3

Any drugs used to achieve relief from pain.

Question 4

What does analgesics include?

Answer 4

1) Opioid analgesics - Morphines
2) Non-opioid analgesics - Paracetamols
3) Analgesics to treat pain syndromes
Chronic neuropathic pain
-antidepressants *amitriptyline
*clomipramine
*duloxetine
-anticonvulsants *gabapentin
*pregabalin
*carbamazepine

Question 5

What are opiod analgesics?

Answer 5

*Natural or Synthetic.
*Opioid receptor agonists.
*Resembles the action of endogenous opioid peptides in the CNS.

Question 6

Function of opioid analgesics?

Answer 6

Regulate the transmission and modulation of pain.

Question 7

Opiod receptor types and locations.

Answer 7

mu, delta, kappa
Located in the brain and spinal cord.

Question 8

What is the main opioid receptor involved? What happens when stimulated?

Answer 8

mu,
Leads to respiratory depression, euphoria, physical drug dependence.

Question 9

Activity of peripheral opiod receptors?

Answer 9

Regulate intestinal movements.
Leads to increase of tone & decrease of motility,
Consequence - constipation develops

Question 10

What happens when presynaptic opioid receptors get stimulated? And how it happens.

Answer 10

Inhibits the release of pain mediators from presynaptic terminals of the afferent neurons. Eg: Glutamate, Substance P
(Change in the ionic transmembrane current)/(Inactivate Ca channels)

Question 11

What happens when postsynaptic opioid receptors get stimulated?

Answer 11

Activation of K+ channels.
Hyperpolarization of postsynaptic neurons.

Question 12

Opioid agonist classification.

Answer 12

Pure agonists, Mixed agonists, pure opioid receptor antagonists

Question 13

Examples for pure agonists. (Opiod receptor)

Answer 13

*Strong agonists - fentanyl, morphine, meperdine, methadone, trimeperidine

*Weak agonists - codeine, propoxyphene, tramadol

Question 14

Examples for mixed agonists? (Opioid receptor)

Answer 14

Antagonists - pentazocaine, buprenorphine

Partial agonists - tramadol, tapentadol

Question 15

Pure opiod receptor anatagonists examples?

Answer 15

Naloxone
Naltrexone
Alvimopan
Methynaltrexone

Question 16

Speciality of mixed agonists and antagonists? (Pentazocaine)

Answer 16

Stimulate different types of receptors.
Agonist to kappa receptors.
Antagonist to mu receptors.

Question 17

For what can mixed agonists-antagonists or partial agonists be used?

Answer 17

In combination with potent agonists express antagonistic properties on receptors.

Cause withdrawal symptoms in patients.
Decrease analgesia in patients with pain.

Question 18

What effect does pure opioid receptor antagonists contain?

Answer 18

Eliminate effects of opioid analgesics.

Question 19

Naltrexone used for?

Answer 19

Elimination of the feeling of recieving opioids in the patients with opioid dependence during the treatment.

Question 20

What POR antagonists used for prevention of constipation or spastic intestine obstruction after the surgery?

Answer 20

Alvimopan
Methylnaltrexone

Question 21

POR antagonists used in prevention of the respiratory depression caused by overdose of opioid analgesics?

Answer 21

Naloxone

Question 22

Facts of morphine?

Answer 22

*Prototype of opioid analgesics.
*A strong agonist to opioid receptors.
*effects are central and peripheral.

Question 23

The central effects of morphine and other strong agonists. The depressant
effects on the CNS.

Answer 23

Analgesia
Respiratory depression
Depression of cough center
Sleep

Question 24

How does strong opioid agonists bring about analgesic effect?

Answer 24

• analgesia is caused by changing the perception of the pain.

it changes in response to the pain (the pain is perceived as something extraneous)
and euphoria (a strong sense of satisfaction and well-being).
The euphoria and analgesia are interconnected, i.e. the more pronounced euphoria, the
stronger analgesia, and vice versa.

Mixed agonist-antagonist and partial
agonist drugs cause less euphoria and analgesia. Therefore, they are weaker as analgesics than the strong opioid receptor agonists like morphine.

Question 25

How does strong opioid agonists bring about respiratory depression?

Answer 25

Caused by decreasing the respiratory
center sensitivity to CO₂.

The breathing rate is decreased and drugs overdose can stop it (death). Reducing the breathing rate is caused by morphine, it is useful when dyspnea is combined with pulmonary edema (morphine decreases the patient’s fear of dyspnea).
The accumulation of CO2, leads
to a relaxation of cerebral vessels and increased intracranial pressure, which
is dangerous in case of skull injuries

Question 26

What opioid analgesics depress cough centers?

Answer 26

Codeine
Dextromethorphan (not an opioid analgesics but have a similar chemical structure)

Question 27

How can you explain about sleep effect due to strong agonists?

Answer 27

Elimination of pain. Patients calm down and fall sleep.

Question 28

The stimulants effects on the CNS by morphine and other strong agonists opioid)

Answer 28

*nausea and vomiting
(due to the stimulation of the vomiting
center through the chemoreceptor trigger zone).
It presents a problem when
the opioid analgesics are used in surgery.

• miosis (contraction of the pupil)
is caused by increasing the para-sympathetic influence of the oculomotor nerve nucleus.
Tolerance does not develop to this effect and it can (along with rare breathing and coma) serve
as diagnostic criteria for opioid overdose. However, trimeperidine (Promedolum) and meperidine, opioid analgesics with atropine-like properties,
do not narrow the pupil;

• convulsions
can occur after an overdose of meperidine, trimeperidine
(Promedolum) in patients with renal failure due to the accumulation of toxic
metabolites (normeperidine).

*the rigidity of trunk muscles
Reduces the volume of respiratory movements and can disrupt the patient’s breathing (especially in the elderly).

Question 29

The peripheral effects of strong agonists (opioid) or morphine.

Answer 29

*Constipation
*Reducing the uterus tone
*Spasm of smooth muscles in the biliary & urinary tract.
*Release of histamine by mast cells.

Question 30

Drug of choice in non infectious diarrhea?

Answer 30

Loperamide (imodium)
(Similar to meperidine in chemical structure)

Question 31

What drugs used to eliminate risk of constipation and spastic ileus after intestinal surgery?

Answer 31

Selective antagonists of the GI Tract.
Alvimopan
Methylnaltrexone

Question 32

Drug which can cause some stimulation of the uterus?

Answer 32

Meperdine
Trimeperdine

Question 33

How does opioid analgesics differ from each other?

Answer 33

(a) the duration of the action
(fentanyl is short,
morphine is intermediate,
methadone is long)

(b)the risk of the drug dependence
(it is maximal in the strong opioid receptor agonists).

Question 34

The use of opioids?

Answer 34

*Elimination of pain during childbirth &
pain during surgery.
*• elimination of intensive acute (myocardial infarction, trauma, burns,
colic) and
chronic (cancer)
pain of non-inflammatory origin
* cough

Question 35

Adverse effects of opioid analgesics.

Answer 35

an extension of their pharmacological effects:
respiratory depression,
drug addiction,
nausea,
vomiting,
constipation,
convulsions (a toxic dose of trimeperidine, meperidine, morphine and tramadol)
psychotomimetic reactions (hallucinations, nightmares, anxiety)

Question 36

What do you know about opioid drug dependence?

Answer 36

*Very heavy physical and psychological disease.
*Pronounced tolerance all effects of opioid analgesics except constipation & miosis.
*Demands a constant increase dose of the opioid.
*Abrupt cessation would cause severe withdrawal symptoms.
Eg: abstinence syndrome

Question 37

Facts about Abstinence syndrome?

Answer 37

Sign of physical drug dependence.

(*)Signs of psychological dependence
Nervousness
Sweating
Thirst
Drug reception

At the beginning are signs of severe physical dependence
(*)Disturbances to the ANS
accelerated heart rate
Shortness of breath
Mydriasis
Muscle & Abdominal pain
Vomiting
Diarrhoea
Fever
Sneezing
Lacrimation
“goose” skin

Question 38

How to treat drug addiction? (Opioid Analgesics)

Answer 38

For the treatment of drug addiction,

(Methadone)
is useful (a strong opioid agonist with similar properties to morphine).
Because long-acting methadone causes much milder withdrawal symptoms than morphine and other strong opioid receptor agonists, it is useful in a daily gradually decreasing dose for the
treatment of opioid dependence.

(Buprenorphine)
is used instead of methadone for the treatment of opioid dependence.

Both substances are administered in tablets with a gradual decrease in a daily dose to complete the withdrawal. A long-acting antagonist of opioid receptors naltrexone is used for prevention of the relapse in the treatment of drug addicts because the
blockade of opioid receptors prevents all effects of opioid analgesics including euphoria.

Question 39

How to treat acute poisoning by morphine and its analogues?

Answer 39

Treated by intravenous injection of the opioid receptor antagonist
“naloxone”.
It quickly (within 30 seconds) displaces opioids from the cells of the respiratory center and restores normal breathing. Its action is short (1-2 hours).
A repeated administration of naloxone is required in case of long-acting opioid poisoning.
In the latter case,
“nalmefene” (the analogous of naloxone)
is preferred with the duration of the action for about 8-10 hours.

Question 40

Features of Morphine (strong agonists of opioid receptors)

Answer 40

1) Administered parenterally. (Due first strong first-pass effect.
2) In liver, metabolised weakly with glucuronic acid in infants compared to adult.
3) shouldn’t be prescribed for pain relief during childbirth and in new born.

Question 41

Features of Meperidine? (Strong agonists of opioid receptors)

Answer 41

1) Acts weaker & shorter than morphine
2) Less depressant action on the
respiratory center.
3) Drug of choice - obstetrics & pediatrics
4) May cause tachycardia, dry mouth, mydriasis (due to antimuscarinic properties)
5) Spasm of smooth muscles smaller in comparison to morphine (due M-cholinoceptor blocking properties).
6)No significant influence on cough
& intestine motility.
7) Overdose - tremor & spasms
(Symptoms of neurotoxicity)

Question 42

Features of Methadone? (Strong agonists of opioid receptors)

Answer 42

1)Completely absorbed by GI tract.
2)Longer duration of action.
(Half time - 24 hours)
3)Not inferior analgesia when compared
Morphine.
4)Cause mild euphoria due to slow onset of effect.
5)a long-term effect & good absorption during oral administration,
are used to alleviate the opioid addicts from suffering caused by abstinence syndrome. For this purpose, methadone is given in a gradually decreasing daily dose.

Question 43

Features of Fentanyl? (Strong agonists of opioid receptors)

Answer 43

1)Acts stronger than morphine
2)but briefly
3)used in conjunction with neuroleptic droperidol (enhance the effect)
4)This combination used in surgical operations.
5)Analogues of Fentanyl
Fentanil
Sufentanil
Remifentanil

Question 44

Features of codeine? (Weak agonists of opioid receptors)

Answer 44

1)weak agonist of opioid receptors
2)drug addiction is less than morphine. 3)Like others weak agonists, codeine is often used in combination with non-opioid analgesics
aspirin or acetaminophen
for relief of mildpain.
4)well absorbed in the gastrointestinal tract.
5)It is effective for relief of cough in low doses which do not cause analgesia and euphoria.

Superseded by dextromethorphan (does not cause drug addiction at all)

Question 45

Partial agonists and mixed agonists-antagonists. The main features
of these drugs in comparison with strong agonists are:

Answer 45

1)Lower risk of development of drug dependence.

2)Relatively weak inhibitory influence on the respiratory center.

3)they can cause withdrawal syndrome in the patients that use morphine or other strong agonists of opioid receptors.

Question 46

Features of Pentazocaine?

Answer 46

1) Mixed agonist-antagonist of opioid receptors.

2) kappa receptor agonist.

3) μ receptor antagonist.

4)Unlike morphine, pentazocine
causes tachycardia and increases the blood pressure due to the sympathetic
nervous system stimulation.

5)It causes withdrawal syndrome due to the blockade of μ receptor in drug-addicted people. Development of the drug addiction to pentazocine is rare due to dysphoria (due to k receptor agonist properties).

Question 47

Features of Buprenorphine?

Answer 47

1) High-affinity partial u receptor agonist and high-affinity 8 and K receptor antagonist.

2)Long duration of action

3)Used to treat opioid addiction.

4)The risk of addiction is low.

5)It does not cause constipation,
does not effect on the cardiovascular system,
but often causes nausea.
Dysphoria (including fear, nightmares) occurs
more frequently in comparison with pentazocine.

It is used mostly for post-operative pain and severe pain (cancer) in the abdominal cavity.

Question 48

Features of Tramadol?

Answer 48

1)Weak agonist of μ receptors.
2) Effects of tramadol are
also associated with the increased serotoninergic processes in the central
nervous system (with the blockade of neuronal serotonin reuptake).

3) no effect on the respiratory center and cardiovascular system.

4)It has a strong sedative effect (therefore, it cannot be used by drivers).

5)Drug dependence develops if to use tramadol in high doses (400 mg daily
or more).

5) A specific side effect of tramadol is increasing the risk of convulsions due to the decrease of the convulsions threshold.

6)Withdrawal symptoms of tramadol are also accompanied by convulsions.

7)Tramadol is used like other similar partial agonists (in the patients withmoderate pain) and
for atypical pain (chronic neuropathic pain) caused by the destruction
of the nerve fibers,
for example,
in severe diabetes mellitus.

Question 49

What are Non-opioid Analgesics?
(Analgesic-Antipyretic Drugs)

Answer 49

1) Artificially isolated part of non-steroidal anti inflammatory drugs.that aren’t used as anti inflammatory drugs.

2)used only as analgesics & antipyretic drugs
(To reduce elevated body Temperature)

Question 50

What is the basis of isolation of this subgroup from NSAIDS?

Answer 50

Absence (Paracetamol)

Very weak anti-inflammatory effect (metamizole)

High risk of adverse reactions/Long term use
(Ketorolac)

Question 51

What drug is used as eyedrops after cataract removal operation?
And it’s category?

Answer 51

Ketorolac
(Non-opioid analgesics)

Question 52

Derivative types of analgesics-antipyretics?

Answer 52

• derivatives of aniline-
paracetamol (acetaminophen - USAN).

• derivatives of anthranilic acid - mefenamic acid,
meclofenamic acid.

• some derivatives of pyrazolone
-metamizole (analgin),
propiphenazone.

• some derivatives of acetic acid -ketorolac.

Question 53

The mechanism of action - (analgesics-antipyretics drug)

Answer 53

1)Coincides with the mechanism of the action of NSAIDs.

they are blockers of cyclooxygenase.

Cyclooxygenases are enzymes involved in the synthesis of prostanoids
(prostaglandins and their derivatives: prostacyclin, thromboxane).

Question 54

Side effects of analgesics-antipyretics drugs?

Answer 54

1)gastrointestinal disturbances up to ulceration.
2)Paracetamol has the minimal risk of
gastrointestinal side effects
the maximal risk is linked with the use of ketorolac (for this reason ketorolac use is not allowed longer than for 5 days).

Paracetamol is associated with risk of hepatotoxicity with chronic use,
especially in alcoholics.