ANESTHETICS

An anesthetic is a drug that causes anesthesia—reversible loss of sensation. They contrast with analgesics (painkillers), which relieve pain without eliminating sensation. These drugs are generally administered to facilitate surgery. A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia, although others are used commonly by all disciplines. Anesthetics are categorized in to two classes: general anesthetics, which cause a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body while maintaining consciousness. Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects, however, adverse effects may also be increased

There are several steps involved in reaching surgical anesthesia:

1. Analgesia: Pain is abolished but consciousness is retained. This type of anesthesia is used in child birth in the form of Entonox which is 50% nitrous oxide and 50% oxygen and when inhaled it is enough for the pain to recede but there is no loss of consciousness. The sense of hearing is often enhanced in this
state.

2. Delirium: this is not a pleasant stage. The client is more or less unconsciousn and can suffer from fitting and violence. This stage should be crossed as quickly as possible. Sometimes death can occur in this stage due to vagal inhibition.

3. Surgical Anesthesia: is characterized by progressive muscular relaxation. It is imp during many surgical procedures that the muscle be in a relaxed state. This muscle relaxation leads to respiratory paralysis else the patient is on a respirator. Various reflexes of the body are indicators of which stage has been reached.
 
4. Medullary paralysis: this stage begins with respiratory failure and can lead to circulatory collapse.      This stage is avoided through careful monitoring.

General anasthetics :

Inhalation: 

Inhalational anaesthetic substances are either volatile liquids or gases, and are usually delivered using an anaesthesia machine. An anaesthesia machine allows composing a mixture of oxygen, anaesthetics and ambient air, delivering it to the patient and monitoring patient and machine parameters. Liquid anaesthetics are vapourized in the machine.

The three agents introduced were nitrous oxide still in use as a gaseous anesthetic. Ether – diethylether is still used occasionally. Chloroform – is not used today due to its toxicity but other halogenated compounds are being used such as haloethane. 

Many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. Desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide. Older, less popular, volatile anaesthetics, include halothane, enflurane, and methoxyflurane. Researchers are also actively exploring the use of xenon as an anaesthetic.

Injection:

Injection anaesthetics are used for induction and maintenance of a state of unconsciousness. Anaesthetists prefer to use intravenous injections, as they are faster, generally less painful and more reliable than intramuscular or subcutaneous injections. Among the most widely used drugs are:

• Propofol
• Etomidate
• Barbiturates such as methohexital and thiopentone/thiopental
• Benzodiazepine such as midazolam
• Ketamine is used in the UK as "field anaesthesia", for instance at a road traffic incident, and is more frequently used in the operative setting in the US.

The volatile anaesthetics are a class of general anaesthetic drugs composed of gasses and liquids which evaporate easily for administration by inhalation. All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with in water, and as gases they dissolve in oils better than in water).



Mechanism of action of general anesthetic:  

Lipid theory:

Their action is principally confined to the cns. They are all very lipophillic, and this is essential as the drug must cross the bbb. Cell membranes are both lipophillic and hydrophilic depending on the site of the membrane, the lipid layer is interspersed between the islands of proteins and it is thought that there are
sodium channels present within these islands. When the lipophilic anesthetic enters the lipid membrane, the whole membrane is squeezed and causes distortation this can cause a marginal blockage of the sodium channels. This then can prevent neural conduction. Different parts of the cns are more sensitive
to this action.

Ion channels:

General anaesthetics inhibit excitatory functions of some central nervous system (CNS) receptors, such as neuronal nACh, glutamate, or 5-HT3 receptors. Some general anaesthetics also excite inhibitory receptors, notably GABA_A receptors and TREK. GABA_A is a major target of the IV anaesthetics thiopental and propofol.General anaesthetics may decrease transmitter release presynaptically or decrease excitability of postsynaptic neuron

Pharmacokinetics of inhalation anaethetics:

Since these drugs are given in a gaseous form their pharmacokinetic differs. The amount of gas absorbed will depend on the pressure at which the gas is being inhaled more the pressure more the gas will be absorbed. The speed of absorption of the gas is determined by the solubility of the gas in the plasma. The
more soluble the gas the slower it will be absorbed and the less soluble the more  faster it will be absorbed. Ether is highly soluble but nitrous oxide is not. The reverse is true when the person returns to consciousness. The less soluble the drug the faster the person returns to consciousness as compared to a person from more soluble drug.

Local Anesthetics: 

Are drugs that block the transmission of nerve impulse between the pns and the cns. The main purpose is to prevent pain impulse from the nociceptors reaching higher centers. Mainly used in minor surgical procedures. When given all structures supplied by nerve roots originating below the site of injection are
rendered inactive.

The conduction of impulse between nerve fibers depends on the interchange between ions inside and outside of the cell. Under normal conditions the main intracellular ion is K and extracellular ion is Na. when a nt binds there is a complex series of biochemical rxn and this leads to the opening of the Na
channels and the Na enters the cytoplasm and K leaves the cytoplasm. This interchange continues right till the end of the neuron until a point where the nt is released to carry the message onwards. As the message travels down the end that received the message reverts back to its original state with Na outside and K
inside. Local anesthetics work by inhibiting the movement of Na thru channels in the plasma membrane. By doing this they inhibit the transmission of the nerve impulse. This action is dose dependent, more drug more inhibition. In unmyelinated nerves the whole of the Na channels are blocked whereas in
myelinated  fibers only the nodes of ranvier are blocked. All local anesthetics are ionisable  molecules and their action depends on the pH of the medium.



Classification

1. Naturally occurring local anaesthetic:- Ex- Cocaine (ester).
2. Esters: -
   a) P-aminobenzoic acid derivative (PABA)- Benzocaine, Procaine, Tetracaine, Butacaine, orthocaine, Benoxinate.
   b) Esters of benzoic acid- Meprylcaine, Cyclomethycaine,(propoxycaine), Hexylcaine, Piperocaine.
3. Amides or Anilides :- Lignocaine, Prilocaine, Mepivacaine, Bipivacaine, Pyrrocaine, Etidocaine, Diperodone.
4. Piperidine or Tropane derivatives :-Alpha- Eucaine, Benzamine, Euphthalmin.
5. Quinoline derivatives :- Dibucaine (Chincocaine)
6. Isoquinoline derivative:- Dimethisoquine.
7. Miscelleneous :- Phenacaine (Amidine), Pramoxine, Euginol, benzyl alcohol, Phenol, Dyclomine, Saligenin.

Local anesthetics can be divided into two groups:

Amides , have prolonged action and hence metabolism is slow. e.g.prilocaine, cinchocaine,bupivacaine.

Esters, have shorter action and hence metabolism is fast. E.g. cocaine, procaine, amethocaine,