Neurophysiology

Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function

Nerve Fibers:

Myelinated = faster conducting

Unmyelinated = slower conducting

- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].

- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.

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.

Antiarrhythmic Drugs

Cardiac Arrhythmias 
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity) 
– Conduction (conductivity) 
– Both

MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm

ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse

Types of Arrhythmias

• Sinus arrhythmias 
– Usually significant only 
– if they are severe or  prolonged 

• Atrial arrhythmias 
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart 

• Nodal arrhythmias 
– May involve tachycardia and increased workload of the heart or bradycardia from heart block 

• Ventricular arrhythmias 
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation 

Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR) 
• To maintain NSR after conversion from AF or flutter 
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation 
• When dangerous arrhythmias occur and may be fatal if not quickly terminated 
– For example: ventricular tachycardia may cause cardiac arrest 

Mechanism of Action 
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers) 
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells 
 

Neurolept Anesthesia
An antipsychotic agent such as droperidol plus an opiate analgesic agent such as fentanyl or sufentanil. This latter agent is approximately eight to ten times more potent than fentanyl.

Etomidate  -Intravenous Anesthetics

- A nonbarbiturate anesthetic used primarily to induce surgical anesthesia.
- It does not produce analgesia.
- Etomidate has minimal effect on the cardiovascular system and respiration during induction of anesthesia.
- Like the barbiturates, etomidate decreases cerebral blood flow, cerebral metabolic rate and intracranial pressure.
- No changes in hepatic, renal or hematologic function have been reported.
- Myoclonic muscle movements are relatively common.
- Postoperative nausea and vomiting are more common with etomidate than with barbiturates.

Neuron Basic Structure (How brain cells communicate)

• Synapse:A junction between the terminal button of an axon and the membrane of another neuron
• Terminal button(orbouton):The bud at the end of a branch of an axon; forms synapses with another neuron; sends information to that neuron.
• Neurotransmitter:A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron.

Different types of Synapses
1-Axo-denrdritic 
2-Axo-axonal 
3-Axo-somatic

Chemical transmission in the CNS 

The CNS controls the main functions of the body through the action endogenous chemical substances known as “neurotransmitters”.
These neurotransmitters are stored in and secreted by neurons to “transmit”information to the postsynaptic sites producing either excitatoryor inhibitory responses.
Most centrally acting drugs exert their actions at the synaptic junctions by either affecting neurotransmitter synthesis, release, uptake, or by exerting direct agonistor antagonistaction on postsynaptic sites.