pharma

2. ANALGESICS
The word analgesic derives from Greek an (without) and algos
(pain).
Drugs that selectively inhibit the perception (sensation) of
pain.
Analgesic any drug that relieves pain selectively without
blocking the conduction of nerve impulses, markedly altering
sensory perception, or affecting consciousness.
This selectivity is an important distinction between an
analgesic and an anesthetic.

3. CLASSIFICATION OF
ANALGESICS
Analgesic are divided into two main groups.

4. ANALGESICS
Opioid
analgesics
Natural opium
alkaloids
Semi-
synthetic
opiates
synthetic
opioids
Non opioid
analgesics

5. OPIOID ANALGESICS
Narcotics / morphine like analgesics are included in this
category. The opioid analgesics were once
called narcotic drugs because they act on the brain and can
induce sleep. The opioid analgesics can be used for either
short-term or long-term relief of severe pain.

6. SUBCLASSES OF OPIOID
Further divided into three subclasses which are;
 Natural opium alkaloids
• Morphine
• Codeine (most commonly use strong analgesic, less addictive than
morphine, similar to morphine except for the replacement of a OH
group with OCH3 group).
• Methadone
• Hydromorphone

7. CONTINUE…
 Semi-synthetic opiates
 Diacetylmorphine
 Oxymorphone
 Pholcodeine
 Synthetic opioids
 Pethidine
 Methadone
 Dextropropoxyphene

8. NON OPIOID ANALGESICS
NSAIDS (non-steroidal anti-inflammatory drugs) / non
narcotics/ aspirin like analgesics
 Non opioid analgesics which alleviate pain by reducing
local inflammatory responses. In contrast, the anti-
inflammatory compounds are used for short-term pain relief
and for modest pain, such as that of headache, muscle strain,
bruising, or arthritis.

9. PAIN
A protective mechanism to warn of damage or the presence of
disease.

10. CLASSIFICATION OF PAIN;
On basis of onset and duration there are two types of pain
PAIN
ACUTE
PAIN
CHRONIC
PAIN

11. ACUTE PAIN
Sudden in onset.
Usually subsides once treated.
CHRONIC PAIN
Persistent (continual) or recurring (happen or occur again).
Often difficult to treat.

13. MAJOR SOURECS OF PAIN
Source Area involved Characteristics treatment
Somatic Body framework Throbbing
Stabbing (sharp)
Narcotics
NSAIDs
visceral Kidneys
Intestines
Liver
Aching (usually
moderately
pain)
Throbbing
Narcotics
NSAIDs
neuropathic Nerves Burning
Tingling
Narcotics
NSAIDs
Antidepressants
Anticonvulsants

14. Non opioid analgesics ( anti-
inflammatory analgesics)
Most anti-inflammatory analgesics are derived from three
compounds discovered in the 19th century
 salicylic acid,
 pyrazolone,
 phenacetin (or acetophenetidin).
 Although chemically unrelated, the drugs in these families
have the ability to relieve mild to moderate pain through
actions that reduce inflammation at its source.

15. SALICYLIC ACID
 Salicylic acid has the formula C7H6O3.
 it is colorless crystalline organic acid.
 Salicylic acid as a medication is used most commonly to help remove the outer
layer of the skin. As such, it is used to treat warts (Warts are typically small,
rough, and hard growths that are similar in color to the rest of the skin) psoriasis
(Psoriasis is a long-lasting autoimmune disease characterized by patches of
abnormal skin. These skin patches are typically red, itchy, and
scaly), dandruff, acne, ringworm(Dermatophytosis, also known as ringworm, is a
fungal infection of the skin).

16. PYRAZOLONE
3-PYRAZOLONE 5-PYRAZOLONE
The drugs of these families have the ability to relieve mild to
moderate pain through actions that reduce inflammation at its
source.

17. PHENACETIN
Phenacetin (or acetophenetidin) is a pain-relieving and fever-reducing drug, which
was widely used between its introduction in 1887 and the 1983 ban imposed by
the U.S. Food and Drug Administration.
Mechanism of actions;
its analgesic effects are due to its actions on the sensory tracts of the spinal cord. In
addition, phenacetin has a depressant action on the heart, where it acts as a
negative inotrope. It is an antipyretic, acting on the brain to decrease the temperature
set point. It is also used to treat rheumatoid arthritis (Rheumatoid arthritis (RA) is a
long-term autoimmune disorder that primarily affects joints. It typically results in
warm, swollen, and painful joints). It is metabolized in the body
to paracetamol (acetaminophen), which is also a clinically relevant analgesic.
A hand affected by rheumatoid arthritis

18. SALICYLIC ACID
DERIVATIVES;
Acetylsalicylic acid, or aspirin, which is derived from
salicylic acid, is the most widely used mild analgesic.
It is considered the prototype for anti-inflammatory
analgesics.

19. PHENACETIN DERIVATIVES;
Acetaminophen (a derivative of phenacetin) and the aspirin-
like drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs),
which include compounds such as ibuprofen, naproxen, and
fenoprofen.

20. PYRAZOLONE DERIVATIVES
Pyrazolone derivatives, with some exceptions, are no
longer widely used in many countries, because of their
tendency to cause an acute infection known
as agranulocytosis (Agranulocytosis, also known as
agranulosis or granulopenia, is an acute condition
involving a severe and dangerous leukopenia (lowered
white blood cell count), most commonly of neutrophils
causing a neutropenia in the circulating blood. It is a
severe lack of one major class of infection-fighting white
blood cells).

21. MECHANISM OF ACTIONS
Inhibition of the synthesis of prostaglandins;
Aspirin and NSAIDs appear to share a similar molecular mechanism
of action—namely, inhibition of the synthesis
of prostaglandins (natural products of inflamed white blood cells) that
induce the responses in local tissue that include pain and
inflammation.
 In fact, aspirin and all aspirin-like analgesics, including indomethacin
and sulindac, which are derived from a heterocyclic organic
compound known as indole, inhibit prostaglandin synthesis and
release.

22. CONTINUE….
Division of agents;
All these agents can be further divided into nonselective
COX inhibitors and selective COX inhibitors.
COX, or cyclooxygenase;
COX, or cyclooxygenase, is an enzyme responsible for the
synthesis of prostaglandins and related compounds.

23. CONTINUE…
Forms of COX;
It has two forms. COX-1 and COX-2
COX-1, which is found in most normal tissues.
COX-2, which is induced in the presence of inflammation.
Because COX-2 is not normally expressed in the stomach.

24. CONTINUE…
Advantage of COX-2 inhibitors;
The use of COX-2 inhibitors (e.g., rofecoxib, celecoxib) seems to
result in less gastric ulceration than occurs with other anti-
inflammatory analgesics, particularly aspirin. However, COX-2
inhibitors do not reduce the ability of platelets to form clots, a benefit
associated with aspirin and other nonselective COX inhibitors.

25. COMPARISON
Preferences in COX selectivity and the possibility of additional
molecular actions of NSAIDs may explain differences in the therapeutic
effects between aspirin, acetaminophen, and NSAIDs. For example,
aspirin is effective in reducing fever, as well as relieving inflammation,
while acetaminophen and NSAIDs are more potent antipyretic (fever-
reducing) analgesics. Acetaminophen, on the other hand, possesses
inferior anti-inflammatory activity compared with aspirin and NSAIDs
and thus is relatively ineffective in treating inflammatory conditions
such as rheumatoid arthritis.

26. CONTINUE…
Despite this, acetaminophen is a popular mild analgesic and
antipyretic and is a suitable alternative to aspirin for patients who
develop severe symptoms of stomach irritation, because it is not as
harmful to the gastrointestinal tract.

27. COMMONLY USED
ACETOMINOPHIN
Paracetamol (N-acetyl-P-Amino phenol)
It is analgesic and antipyretic drug.
Orally induced drug has maximal effects of two to four hours.
Over doses causes damaging of liver and kidneys.

28. SIDE EFFECTS
As might be expected from their common mechanisms of
action, many of the anti-inflammatory analgesic drugs
share similar side effects.

29. HYPERSENSITIVITY
Hypersensitivity responses to aspirin-like drugs are thought to be
due to an accumulation of prostaglandins after the pathways that
break down prostaglandins are blocked. These responses can be fatal
when very strong anti-inflammatory compounds are given.

30. PEPTIC ULCERS, LIVER DAMAGE &
RENAL TOXICITY
Inhibition of prostaglandin synthesis may result in other serious side
effects, such as peptic ulcers and a reduced ability of platelets in the
blood to aggregate and form clots.
Liver damage occasionally occurs after administration of
acetaminophen.
Renal toxicity is sometimes seen with use of NSAIDs.

31. ASPIRIN SIDE EFFECTS
Aspirin itself, taken in overdose, can cause
Deafness
Ringing in the ears
Diarrhea
Nausea
Headache, which disappear when the dose is reduced or stopped.
Reye syndrome

32. REYE SYNDROME
Aspirin is also thought to be a causative agent of Reye syndrome, a rare
and serious degenerative disease of the brain and fatty tissue of the liver
that accompanies certain viral infections in children and young adults.
Some aspirin-like analgesics also have specific toxic effects

33. OPIOID ANALGESICS
The term opioid has been adopted as a general
classification of all those agents that share chemical
structures, sites, and mechanisms of action with the
endogenous opioid agonists (endogenous substances are
those produced inside the human body).

35. GROUP OF ENDOGENEOUS
SUBSTANCES
There are three groups of endogenous substances which
are;

36. CONTINUE…
 Enkephalins
 Stimulates delta receptors
 Endorphins
 Act on mu and delta receptors
 Reduces pain and has positive effect on brain
 Dynorphins
 Stimulates the kappa receptors
 All three have opioid like actions and are found in the body
 They are naturally occurring peptides that possess analgesic action and addiction
potential.
 These receptors can be blocked by naloxone, which is a morphine antagonist.

37. OPIOID SUBSTANCES
Opioid substances encompass all the natural
and synthetic chemical compounds closely related
to morphine, whether they act as agonists (cellular
activators) or antagonists (substances that block the
actions of agonists).

38. ADDICTIVE DRUGS
Although interest in these drugs had always been high
because of their value in pain relief and because of
problems of abuse and addiction, interest intensified in the
1970s and ’80s by discoveries about the naturally
occurring morphine like substances, the endogenous
opioid neuropeptides.

39. OPIUM
Opium is the powder from the dried juice of the poppy Papaver
somniferum.
When taken orally, opium produces sleep and induces a state of
peaceful well-being.
Its use dates back at least to Babylonian civilization.
In the early 19th century opium extract was found to contain more than
20 distinct complex organic bases, called alkaloids, of which
morphine, codeine, and papaverine are the most important. These pure
alkaloids replaced crude opium extracts in therapeutics.

40. MECHANISM OF ACTION
In the 1950s several new morphine like drugs were
developed. Despite the increase in the number of
compounds available for pain relief, however, little was
understood of their sites and mechanisms of action.

41. ENKEPHALINS;
The first real breakthrough came from the discovery, by
neuroscientists John W. Hughes and Hans W. Kosterlitz at
the University of Aberdeen in Scotland, of two potent
naturally occurring analgesic Penta peptides (peptides
containing five linked amino acids) in extracts of pig
brain. They called these compounds enkephalins, and
since then at least six more have been found.

42. ENDORPHINS;
Larger peptides, called endorphins, have been isolated,
and these contain sequences of amino acids that can be
split off as enkephalins.

43. TYPES OF RECEPTORS
There are at least three types of receptors on
brain neurons that are activated by the enkephalins.
Morphine and its congeners are thought to exert their
effects by activating one or more of these receptors.

44. USES OF OPIOID DRUGS
Pain reliever;
Opioid drugs are useful in the treatment of general postoperative pain,
severe pain, and other specific conditions.
The use of opioids to relieve the pain associated with kidney
stones or gallstones presumably depends on their ability to affect opioid
receptors in these tissues and to inhibit contractility.
Relief of respiratory distress;
Low doses of opioids are also used for relief of the respiratory distress
that accompanies acute cardiac insufficiency complicated by the
buildup of fluid in the lungs.

45. CONTINUE…
Relieve abdominal distress;
Opioids are also able to relieve the abdominal distress and fluid loss
of diarrhea.
Used in drug therapeutics;
Several commonly used natural or synthetic derivatives of morphine are
used in drug therapeutics.
Codeine;
Codeine, a naturally occurring opium alkaloid that can be made
synthetically, is a useful oral analgesic, especially when used in
combination with aspirin.

46. CONTINUE…
Meperidine
Meperidine was an early synthetic analog of morphine, marketed under
the trade name Demerol, that was originally thought to be able to provide
significant short-lasting analgesia and little or no addiction because of its
shortened duration of action; however, this belief proved false.
 Methadone;
Methadone, a synthetic opioid analgesic, has long-lasting analgesic
effects (six to eight hours) when taken orally and is used to moderate the
effect of withdrawal from heroin addiction.

47. OPIOID ANTAGONIST DRUGS;
Among the opioid antagonist drugs, naloxone and its longer-lasting
orally active version, naltrexone, are used primarily to reverse
morphine overdoses and to reverse the chemical stupor of a wider
variety of causes, including alcohol intoxication and anesthesia. In
opioid overdoses, these drugs provide recovery within minutes of
injection. They can, however, also precipitate severe withdrawal
reactions in a person addicted to opiates.

48. SIDE EFFECTS OF NARCOTIC
ANALGESICS
Chest pain
Trouble breathing (respiratory depression)
Abnormal heart beats
Cardiac arrest
Death

49. Narcotics applications in dentistry;
Narcotics analgesics are extremely effective in reducing
acute dental and postoperative pain
The narcotics analgesics have established a niche for the
treatment of pain in those situations where the NSAIDs
are less effective.
Hydrocodone, oxycodone. Codeine and occasionally
meperidine are the narcotics used to treat dental pain.

50. MORPHINE SIDE EFFECTS
 Vomiting
 Respiratory depression
 Decreasing of blood pressure
 Side effects of opioid analgesics
 Respiratory depression
 Euphoria
 Relaxation and sleep
 Tranquilization
 Decreased blood pressure
 Constipation
 Hypothermia
 Flushed and warmed skin

51. SIDE EFFECTS OF ANALGESIC
 Constipation.
 Drowsiness.
 Dizziness.
 Upset stomach.
 Ringing in your ears.
 Skin itching or rash.
 Dry mouth.
 Aggravation of asthma
 Heart burn