pharmacology

1. LEC-3
Analgesics
OPIOIDS
NSAIDs

2. Pain:
Pain is a protective reflex for self-preservation
due to presence of tissue damage.
Analgesics: Medications that relieve pain
without causing loss of consciousness.
 Alleviation of pain depends on the specific type of
pain (nociceptive or neuropathic pain).
 For example, with mild to moderate arthritic pain
(nociceptive pain), non-opioid analgesics as non
steroidal anti-inflammatory drugs (NSAIDs) are often
effective.
 However, for severe acute pain or chronic malignant
or nonmalignant pain, opioids can be considered as
part of the treatment plan in select patients.

3. Opioids analgesics
 Opium: is the dried juice of the seed-head of opium
poppy.
 Opioids are natural, semisynthetic, or synthetic
compounds that produce morphine-like effects.
Classification
• Strong (e.g. Morphine)
• Moderate (e.g. Codeine)
• Weak (e.g. Propoxyphene)

4.  Mechanism of action: Opioids act by binding to specific
opioid receptors in the CNS to produce effects that mimic the
action of endogenous peptide neurotransmitters (as endorphins,
enkephalins, and dynorphins).
 The major effects of the opioids are mediated by three main
receptor families, commonly designated as μ (mu), κ (kappa),
and δ (delta).

5.  Systemic effects of opioid analgesics
1. Central nervous system: It cause Sedation, Respiratory
depression, Cough inhibition, Miosis, and powerful sense of
contentment and well-being (Euphoria) which may be caused
by disinhibition of the dopamine-containing neurons in the
brain.
2. Cardiovascular system: Peripheral vasodilatation leading to
hypotension, which benefit in acute myocardial infarction and
left ventricular failure by reducing pain, anxiety, and preload.
3. Gastrointestinal tract:
 Reduced peristalsis and delayed gastric emptying (cause
constipation),
 Directly stimulates the chemoreceptor trigger zone in the area
postrema that causes vomiting,
 Constrict the sphincter of Oddi and thereby increase pressure
within the biliary tree (biliary spasm).

6.  Clinical Uses
1. Analgesia (Codeine, morphine)
2. Cough Suppression (Codeine, Dextromethorphan)
3. Antidiarrheal (Diphenoxylate, Loperamide)
4. Acute Pulmonary edema (Morphine)
5. Anesthesia (Fentanyl)
 Opioids relieve pain by raising the pain threshold at the
spinal cord level and by altering the brain’s perception of
pain.
 Opioids relieves diarrhea by decreasing the motility and
increasing the tone of the intestinal smooth muscle. It also
increases the tone of the anal sphincter.

7.  Adverse effects
1. CNS: Sedation, euphoria, dysphasia, respiratory
depression, pruritis, nausea and vomiting (Many of these
effects diminish as tolerance develops).
2. GIT: Constipation and dry mouth ( lead to dental caries)
are more resistant to tolerance and remain problems.
3. Tolerance: Repeated use produces tolerance to the
respiratory depressant, analgesic, euphoric, emetic, and
sedative effects of opioids.
4. Physical dependence: Physical and psychological
dependence can occur with all opioids.
 Withdrawal produces a series of autonomic, motor, and
psychological responses that can be severe, although it is
rare that withdrawal effects cause death.

9. Non-Steroidal Anti-Inflammatory Drugs
(NSAIDs)

10.  NSAIDs and Prostaglandin (PG) synthesis inhibition
 NSAIDs are a group of chemically dissimilar agents that differ in their
antipyretic, analgesic, and anti-inflammatory activities.
 NSAIDs act through inhibition of the synthesis of prostaglandins.
They act primarily by inhibiting the cyclooxygenase enzymes that
leads to decreased prostaglandin synthesis with both beneficial and
unwanted effects.
 Functions of PGs vary depending on the tissue and the specific
enzymes at that particular site.
 For example, release of thromboxane A2 (TXA2) from platelets
triggers aggregation and local vasoconstriction.
 However, prostacyclin (PGI2), from endothelial cells, has opposite
effects, inhibiting platelet aggregation and producing vasodilation.
 Prostaglandins, prostacyclin (PGI2), and thromboxane A2(TXA2) are
produced from arachidonic acid by the enzyme cyclooxygenase.

11.  Inhibition of COX-2 is thought to cause the anti-
inflammatory and analgesic actions of NSAIDs, whereas
inhibition of COX-1 is responsible for preventing
cardiovascular events & other events.

12.  Classification of NSAIDs
A. Non-selective COX inhibitors (traditional NSAIDs)
1. Salicylates: Aspirin
2. Propionic acid derivatives: Ibuprofen, Naproxen,
3. Anthranilic acid derivative: Mefenamic acid
4. Aryl-acetic acid derivatives: Diclofenac.
5. Oxicam derivatives: Piroxicam.
6. Indole derivative: Indomethacin.
B. Preferential COX-2 inhibitors: Meloxicam.
C. Selective COX-2 inhibitors: Celecoxib.
D. Analgesic-antipyretic with poor anti-inflammatory action:
Paracetamol

13.  Action of NSAIDs:
1. Anti-inflammatory effect: due to the inhibition of the
enzymes that produce cyclooxygenase, or COX.
2. Analgesic effect: The analgesic effect of NSAIDs is thought to
be related to:
 The peripheral inhibition of prostaglandin production
 May also be due to the inhibition of pain stimuli at a
subcortical site.
3. Antipyretic effect: The antipyretic effect of NSAIDs is
believed to be related to:
 Inhibiting production of PGs in the hypothalamus,
 “Resetting” of the thermoregulatory system, leading to
vasodilatation and increased heat loss.

15.  Adverse effects:
 Because of the adverse effects profile, it is preferable to use NSAIDs
at the lowest effective dose for the shortest duration possible.
1. Gastrointestinal: ranging from dyspepsia to bleeding & peptic ulcer.
NSAIDs should be taken with food or fluids to diminish GI upset.
2. Renal effects: NSAIDs may result in retention of sodium and water
and may cause edema.
3. An increased risk for cardiovascular events, MI and stroke may be
associated with the use of any NSAIDs except aspirin.
4. CNS effects, such as headache, tinnitus & dizziness, may occur.
5. Allergy including urticaria, bronchoconstriction, and angioedema.
NSAIDs should be used with caution in patients with asthma.
6. Teratogenicity: NSAIDs should be used in pregnancy only if benefits
outweigh risks to the developing fetus. In the third trimester, NSAIDs
should generally be avoided due to the risk of premature closure of the
ductus arteriosus.

16.  Acetaminophen
 Acetaminophen inhibits prostaglandin synthesis in the CNS,
leading to antipyretic and analgesic effects.
 Acetaminophen has less effect on cyclooxygenase in peripheral
tissues (due to peripheral inactivation), which accounts for its
weak anti-inflammatory activity.
 Acetaminophen does not affect platelet function or increase
bleeding time. It is not considered an NSAID.
 Therapeutic uses
 Acetaminophen is used for the treatment of fever and the relief
of pain.
 It is useful in patients with gastric risks with NSAIDs and those
who do not require the anti-inflammatory effect of NSAIDs.
 Acetaminophen is the analgesic/antipyretic of choice for
children with viral infections or chickenpox (due to the risk of
Reye syndrome with aspirin).

17. END