M6: Analgesics (Pain Relivers)

Question 1

Classification of Analgesics

Answer 1

1. Narcotic Analgesis (Opioids)
2. Non-Narcotic Analgesics (Antipyretics)

Question 2

Types of NARCOTIC Analgesics (Opioids)

Answer 2

1. Endogenous (natural)
   DRUGS = Endorphins, Enkephalins, Dynorphins
2. Plant Alkaloids (natural)
   DRUGS = Morphine, Codeine, Thebaine
3. Semisynthetic
   DRUGS = Diamorphine (heroin), Oxycodone, Hydromorphone, Buprenorphine
4. Synthetic
   DRUGS = Pethidine, Methadone, Fentanyl, Tramadol, Pentazocine

Question 3

Pharmacology of Opioids
- Types
- Action
- Therapeutic Indications

Answer 3

Opioids bind to specific receptors in CNS & other tissues

OPIOD RECEPTORS
G-protein coupled receptors
Types:
1. delta (S): S1 and S2
- analgesia
- resp distress
- affective behaviour
- reinforcing action
- reduced GI motility

2. kappa (K): K1, K2 and K3
   - analgesia
   - resp distress
   - sedation
   - dysphoria and hallucinations
   - miosis
   - physical dependence
3. mu (u): u1, u2 and u3
   - analgesia
   - resp distress
   - sedation
   - euphoria
   - miosis
   - reduced GI motility
   - physical dependence

ACTION OF OPIODS:
1. Desirable:
- analgesia
- sedation
-antitussive

2. Sometimes Desirable
   - constipation
   - hypotension
3. Undesirable:
   - nausea/vomiting
   - resp distress
   - confusion, leads to coma
   - tolerance
   - addiction
   - physical dependence

THERAPEUTIC INDICATIONS OF OPIOIDS:
1. Pain (analgesic effect)
2. Anxiety
3. Cough (codeine)
4. Diarrhea (opium only)
5. Opioids dependence (methadone & buprenorphine)

Question 4

Opioids as Analgesics

Answer 4

1. Strongest known analgesics
2. Act mainly on mu & kappa receptors.
3. Variable dose with no upper limit
4. Type of pain: SEVERE
   Acute: e.g., post-operative
   Chronic:
   - Specially in terminal conditions as cancer (palliative care)
   - Dependence is not the main concern!
   - Most annoying adverse effect is: CONSTIPATION
5. Gradual stoppage of drug:
   To avoid withdrawal manifestations

Question 5

Opioids as Pain Killers

Answer 5

1. Mainly u and K Receptors
2. Local = decreased presynaptic release of chemical transmitters that are mobolized by pain impulse

Central = activation of descending inhibitory pathways to block pain input

Question 6

Tolerance, Addiction, and Dependence of OPIODS

Answer 6

1. Tolerance:

• After repeated use, body adapts to opioids decreased drug potency higher dose is needed to obtain same analgesic effect
• Cross tolerance:
  Tolerance to an opioid (as morphine) tolerance to other opioids (as meperidine)

2. Addiction:

• Psychological attachment to certain effects of opioids (as euphoria) compulsive repeated use

3. Physical dependence:

Development of opioid withdrawal syndrome after:
- Cessation of drug administration
- Administration of an opioid antagonist

Question 7

Opioid Withdrawal Syndrome

Answer 7

1. CNS stimulation
2. Tachypnea (increased respiratory rate)
3. Tachycardia & hypertension
4. Severe flulike illness – rhinorrhea, sneezing
5. Yawning, lacrimation, diaphoresis
6. Nausea, vomiting, & diarrhea
7. Abdominal cramping, leg cramping
8. Tremors & muscle twitching
9. Piloerection (gooseflesh)
10. Dilated pupils

Question 8

Opioid Antagonists

Answer 8

1. Antagonists:
   DRUG = Naloxone
2. Mixed agonists/antagonists:
   DRUG = Pentazocine

Question 9

Naloxone

Answer 9

1. Competitive opioid receptor antagonist
2. Has no analgesic effect
3. Causes withdrawal symptoms
4. Therapeutic use:
   - Treatment of opioid drug overdose (antidote)
   - Diagnosis & treatment of opioid dependence
   - Should always be available when opioid agonist drugs are used through IV route

Question 10

Pentazocine

Answer 10

1. Has agonist action (analgesia)
2. Also has weak antagonist action
3. If used with opioid agonists (as morphine) → can induce withdrawal symptoms

Question 11

Drug Therapy of Dependence

Answer 11

1. Methadone OR Buprenorphine (partial antagonist):
   - Same opioid effect → prevent withdrawal manifestations
   - Much less dependence
2. Naloxone:
   - Opioid antagonistic effect
   - Blocks drug-seeking behavior
   - Antagonist
3. Herion = full agonist
   - full activity zone

Question 12

Acute Opioid Toxicity

Answer 12

MANIFESTATIONS:

1. Mild/early:
   - Pinpoint pupils
   - Hypoventilation: slow, shallow respiration
   - Hypotension & bradycardia
   - Flaccid muscles
2. Severe/late:
   - Severe respiratory depression
   - Respiratory arrest
   - Severe cardiovascular depression
   - Seizures (with pethidine overdose)
   - Coma
3. CPR-3H:
   - Coma
   - Pin point pupil
   - Respiratory depression
   - Hypotension
   - Hypothermia
   - Hyporeflexia
4. Treatment:
   Naloxone (antidote):
   - Reverses toxic - manifestations
   - Shorter half-life
   - Repeat dose