Mixed Narcotic Agonists/Antagonists

These drugs all produce analgesia, but have a lower potential for abuse and do not produce as much respiratory depression.

A. Pentazocine

• Has a combination of opiate analgesic and antagonist activity.
• Orally, it has about the same analgesic potency as codeine.
• In contrast to morphine, cardiac workload tends to increase due to an increase in pulmonary arterial and cerebrovascular pressure. Blood pressure and heart rate both also tend to increase.
• Adverse reactions to Pentazocine

• Nausea, vomiting, dizziness.

• Psychotomimetic effects, such as dysphoria, nightmares and visual hallucinations.

• Constipation is less marked than with morphine.

B. Nalbuphine

• Has both analgesic and antagonist properties.
• Resembles pentazocine pharmacologically.
• Analgesic potency approximately the same as morphine.
• Appears to be less hypotensive than morphine.
• Respiratory depression similar to morphine, but appears to peak-out at higher doses and to reach a ceiling.
• Like morphine, nalbuphine reduces myocardial oxygen demand. May be of value following acute myocardial infarction due to both its analgesic properties and reduced myocardial oxygen demand.
• Most frequent side effect is sedation.

C. Butorphanol

• Has both opiate agonist and antagonist properties.Resembles pentazocine , pharmacologically., 3.5 to 7 times more potent than morphine., Produces respiratory depression, but this effect peaks out with higher doses. The respiratory depression that does occur lasts longer than that seen following morphine administration.
• Butorphanol, like pentazocine, increases pulmonary arterial pressure and possibly the workload on the heart.
• Adverse reactions include sedation, nausea and sweating.

D. Buprenorphine

• A derivative of eto`rphine. Has both agonist and antagonist activity. 20 to 30 times more potent than morphine.Duration of action only slightly longer than morphine, but respiratory depression and miosis persist well after analgesia has disappeared.
• Respiratory depression reaches a ceiling at relatively low doses.
• Approximately 96% of the circulating drug is bound to plasma proteins.
• Side effects are similar to other opiates:
  • sedation, nausea, vomiting,
  • dizziness, sweating and headache.

Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)

Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i.    Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)

Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia

Inhalational Anesthetics

The depth of general anesthesia is directly proportional to the partial pressure of the anesthetic agent in the brain. These agents enter the body through the lungs, dissolve in alveolar blood and are transported to the brain and other tissues.

A. Rate of induction and rate of recovery from anesthesia:

1. The more soluble the agent is in blood, the more drug it takes to saturate the blood and the more time it takes to raise the partial pressure and the depth of anesthesia.

2. The less soluble the agent is in blood, the less drug it takes to saturate the blood and the less time it takes to raise the partial pressure and depth of anesthesia.

B. MAC (minimum alveolar concentration)

The MAC is the concentration of the anesthetic agent that represents the ED₅₀ for these agents. It is the alveolar concentration in which 50% of the patients will respond to a surgical incision.

The lower the MAC the more potent the general anesthetic agent.

C. Inhalation Anesthetic Agents 

• Nitrous Oxide
• Ether
• Halothane
• Enflurane
• Isoflurane

Serotonin or 5-hydroxytryptamine (5-HT)

It is a neurotransmitter, widely distributed in the CNS, beginning in the midbrain and projecting into thalamus, hypothalamus, cerebral cortex, and spinal cord. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep-wake cycle.

Serotonin is thought to produce sleep by inhibiting CNS activity. 

In the blood, 5-HT is present in high concentration in platelets (regulator of platelets function) and also high concentration in intestine

Pharmacological effects:

Smooth muscles. 5-HT stimulates the G.I smooth muscle; it increases the peristaltic movement of intestine.
Serotonin contracts the smooth muscle of bronchi; 

Blood vessels. If serotonin is injected i.v, the blood pressure usually first rises, because of the contraction of large vessels and then falls because of arteriolar dilatation. Serotonin causes aggregation of platelets. 

Specific agonists

- Sumatriptan a selective 5-HT1D used in treatment of acute migraine.
- Buspirone a selective 5-HT1A used in anxiety.
- Ergotamine is a partial agonist used in migraine. It acts on 5-HT1A receptor.

Nonspecific 5-HT receptor agonist

o Dexfenfluramine used as appetite suppressant.

Specific antagonists

o Spiperone (acts on 1A receptor) and
o Methiothepin (acts on 1A, 1B, 1D receptors)

NSAIDs: Classification by Plasma Elimination Half Lives

Short Half Life (< 6 hours):

more rapid effect and clearance

• Aspirin (0.25-0.33 hrs),

• Diclofenac (1.1 ± 0.2 hrs)

• Ketoprofen (1.8± 0.4 hrs),

• Ibuprofen (2.1 ± 0.3 hrs)

• Indomethacin (4.6 ± 0.7 hrs)

Long Half Life (> 10 hours):

slower onset of effect and slower clearance

• Naproxen (14 ± 2 hrs)

• Sulindac (14 ± 8 hrs),

• Piroxicam (57 ± 22 hrs)

Dental implications of these drugs: 

1.    Adverse effects: gingival hyperplasia (phenytoin), osteomalacia (phenytoin, Phenobarbital), blood dyscrasias (all but rare)
2.    Drug interactions: additive CNS depression (anesthetics, anxiolytics, opioid analgesics), induction of hepatic microsomal enzymes (phenytoin, Phenobarbital, carbamazepine), plasma protein binding (phenytoin and valproic acid)
3.    Seizure susceptibility: stress can → seizures