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The dr started the lecture telling that the avg in our first exam is 70% which is very good and 92% passed the exam.

Local anesthetics
Drugs that reversibly block nerve conduction and produce transient loss of sensation in local areas of the body when applied locally to a nerve tissue in appropriate concentration. Chemically speaking, local anesthetics are of two types; the ester and the amide which composed of lipophilic group its aromatic usually connected by hypophilic amine by ester or amide. Depending on the ester or amide ??? which communicate the lipophilic group to hydrophilic amine.. You have to understand these chemical structures cause it has a relationship with the rate of metabolism of these drugs. Usually amide type are mainly metabolized in both the liver and the peripheral tissue specially the plasma by esterase enzyme. So we can expect that the rate of metabolism of the ester type is faster and greater than the rate of metabolizing of amide type. It means that the duration of action of ester is shorter than amide. Therefore hepatic diseases decrease the metabolism of local anesthetics. Example of ester : cocaine, Procaine, benzocaine, tetracaine. Example of amide : lidocaine, Prilocaine, mepivacaine, ropivacaine. - All the names of local anesthetics end with the suffix "Caine" Unluckily we have to understand and memories all of them because Theres no dental procedure which is painful could be performed without the use of local anesthetics. 2

 thats our destination because we are dentists and we have to know sth about these names They are a basic compound, their PKa is more than 7 8 to 9. The inflamed tissues have acid PH increase ionized fraction and decrease the effect of these local anesthetics, like when we go to the dentist with inflamed tooth, he might prescribed to us an antibiotics and analgesics and tell us to come back after one to two days later to perform the surgical procedure. The effect of local anesthetics is very low or vary in its minimum degree.. why? Because itll be highly ionized and it wont be absorbed to nerve tissue and will not produce its proper effect. Their action is to prevent both the generation and conduction of nerve impulse, inhibit the initiation or generation of nerve impulse and then they can inhibit the propagation of nerve impulse to adjacent area or to remote area. The main site of action is the cell membrane, nervous cell membrane. They bind to specific receptor in sodium channel. How the impulse is transmitted normally? Sodium channel will be opened and sodium ion will enter from the outside of cell membrane to the inside of cell membrane, making depolarization of the cell membrane, making an initiation of nerve impulse and the propagation or conduction or distribution of nerve impulse. The ion channel should be opened to block the initiation and generation of this nerve impulse, sodium channel should be blocked. in other word, the membrane will be stabilized so there will be no initiation or generation or conduction of nerve impulse. local anesthetics block the sodium channel so sodium ion will not enter or pass the cell membrane and will not enter to the inside.

Briefly : Mechanism of action of local anesthetics is simply by blocking the sodium ion channels which are located in the cell membrane and therefore preventing the generation and conduction of a nerve impulse. local anesthetics compete with calcium ion for ?sike? in cell membrane that control the passage of sodium across the membrane and by this way competing with calcium, they can block the transition through sodium channel, so increasing calcium ions will partially antagonize the action of local anesthetics. Its a matter of competition, local anesthetics compete with calcium ion to prevent sodium ion from entering the cell. Simply. If we increase the concentration of calcium, we will decrease the effect of local anesthetics. The net affect depend on concentration of competing drugs. For example; acetylcholine with atrophine, one compete with the other on cholinergic receptors so the net effect whether is due to acetylcholine or atrophine depend on concentration of each other, which is the higher has prominent effect. * Small non- Myelinated before long Myelinated? It means that the small nerve terminals are better affected by drugs local anesthetics than on larger nerves. Why? Because the small non-mylinated affected before the Myelinated. In Non- Myelinated the effect of local anesthetics will be direct. The cell membrane is exposed to the effect of the drug and its not covered by Myelinated sheath naked . While the Myelinated nerves, the majority of them is covered and Myelin sheath will act as a barrier for local anesthetics to come in contact with cell membrane or the nerve in certain small area called Myelin sheath gaps or nodes of Ranvier. Sensations are blocked in following sequence : Pain touch temperature pressure motor tone . 4

After injection of local anesthetics to a painful tooth for example, the first sensation which is lost is that the patient is relieved of his Pain then touch sensation that he cant feel his cheek with his finger, then temperature and pressure and later on you cant feel the sensation of pressing the area and lastly the movement of the area. Note : the movement of the mandible will not affected because the muscles are higher from site of injection of local anaesthetics. The recovery of local anesthetics : It will be in the reverse order like this Motor tone pressure temperature touch pain . Pharmacokinetics: The rate of absorption and duration of action depends on : 1- Site of injection 2. Dose and concentration 3. Local vascularity: the higher the blood supply the faster the onset of action and the shortest is the duration of action . 4. Presence of vasoconstriction: We know that one of therapeutic uses of adrenaline is to prolong the duration of local anesthetics. Dentists usually have two types of local anesthetics, the plain one and the mixed with vasoconstrictor either adrenaline or noradrenaline to increase the duration of local anesthetics action. For example if the duration of action of local anesthetics is half an hour as a plain, the mixed with vasoconstrictor duration action might extended up to 2 hours or more.

And the advantage of the mixed local anesthetics for the patient that instead of giving the plain local anesthetics with repeated injection we can replace it with single injection of mixed local anesthetics. As you know that not all patients can use adrenaline or noradrenaline. - Suppose a patient with hypertension comes to your clinic and he needs a surgical dental procedure which you should give him local anesthetics, what would you choose to give; plain or mixed? Either you give this patient plain local anesthetics with repeated injection every half an hour or every time he feels pain or we can use another type of vasoconstrictor but doesnt belong to sympathetic amine which can produce minimum effect on CVS. That vasoconstrictor that we can use in these cases is felypressin. Felypressin: vasoconstrictor preferred in patients with heart disease and hypertension. So we concluded that we should ask the patient about his history whether he has diseases like HTN and heart diseases or diabetic cause if we give him the wrong vasoconstrictor we might kill him. Sympathetic drugs should not be mixed with local anesthetics whether adrenaline or noradrenaline or felypressin to anesthetize lacrimal terminal organs like fingers or toes, ear lot and nose because they have limited blood supply and if we did so we might induce ischemic changes. Other terminal organs in male children in surgical procedure of circumcision, we should not use vasoconstrictor because the penis is also having limited blood supply, it will be regarded as the finger or the toes. any type of vasoconstrictor is contraindicated to be used in these sides of the body

Pharmacological actions of local anesthetics : 123Prevent initiation & generation and conduction of nerve impulse. On CVS, like the heart. They depress the conduction of the heart as we use it to treat the ventricular arrhythmias Xylocaine & lidocaine . On CNS brain:

CNS neurons are of two type; inhibitory and stimulatory, so the net affect of local anesthetics depend on the net effect on whether neurons are inhibitory or stimulatory. So after high doses, some of it will be absorbed to the blood and can produce CNS effect, small doses locally the CNS effect is very law or very mild, thats why we call them local anesthetics, they are producing their main effect locally but if they are given in very high doses, some of it will be absorbed to the circulation and can produce a remote effect on CNS or if we give these drugs IV. For example, treatment of ventricular arrhythmia which need not to use local anesthetics injection but IV injection. excitatory effect will be: restlessness, tremor and clonic convulsion this may be followed by 12depression and death due to respiratory depression. The stimulation maybe due to inhibition of inhibitory cortical synapses.

So inhibition of inhibition is stimulation. Higher doses depress both the inhibitory and the excitatory neurons which will lead to depression. At the beginning there will be stimulation. Why? Due to inhibition of inhibitory neurons. Later on , both types of neurons will be inhibited and the net result will be depression.

Toxicity of local anesthetics : Allergic reaction especially by ester type local anesthetics, while it's very rare in the amide type. Thats why the amide type usually preferable in dental practice because they have longer duration of action and less allergic reaction. The dangerous allergic reaction will be in form of asthma and anaphylaxis shock severe allergy and hypersensitivity that can be treated by using adrenaline . To relieve CNS toxicity, diazepam and Valium is used to decrease CNS STIMULATION. Diazepam is one of anxiolytic drugs or CNS depressor drug which well discuss later on. What are the therapeutic uses of local anesthetics ? 1) minor operation the most important one, like dental procedure. 2) ophthalmic surgery. 3) surface anesthesia of the skin & the mucus membrane. For example, gel could be applied on a painful dermatological conditions or burns, they could be rubbed by gel and the pain will be relieved immediately and completely. Mucus membrane, local anesthetics gel could be used in young children who have for example mouth ulcer or stomatitis or pharyngitis or inflammation of buccul mucus membrane that might lead to pain. 4) spinal anesthesia, which is injecting of local anesthetics into the CNS to anesthetize the lower part of the body. 5 ) anti arrhythmia especially Xylocaine & lidocaine or lignocaine that can be used in treatment if ventricular arrhythmia which might be life threatening arrhythmia. In general, there should be desire properties in chosen local anesthetics: 1- it should Not be irritant and should not damage the local tissues.

2- it should have high therapeutic index (TI), which means less incidence of toxic manifestations. 3. it Should be effective topically and by injection. 4. It should have rapid onset and enough duration of action to perform the surgical procedure. Method of administration of these local anesthetics : 1- Topical at surface anesthesia in form of gel whether on mucus membrane or skin. 2- Nerve block : to anaesthetize mandibular tooth which is supplied by mandibular nerve; its is the largest of the three branches of the trigeminal nerve. And it can be easily identified or located in the mandible behind the last molar and if you give single injection at this site youll anesthetize the hall mandibular teeth that are distal to this site .

3- Infiltration : if we want to anaesthetize a maxillary tooth which is supplied by nerves that cant be easily identified. Therefore, we give one injection near the affected tooth and the other at the back of the hard palate. 4- (IV) anesthesia biers block A Biers block is an injection of local anesthetic into a vein in your arm or leg. This numbs the nerves that supply that limb. The limb stays numb for 1-2 hours. During this time the operation can be performed on the arm or leg without causing you any pain.

The advantage of a Biers block is that you do not need a general anesthetic. You can stay awake for the operation. The anesthetist can give a sedative drug to make you feel relaxed and less anxious. 5. Spinal, injection of local anesthetics directly to the CNS 6. Epidural anesthesia; Epidural anesthesia is regional anesthesia that blocks pain in a particular region of the body. The goal of an epidural is to provide analgesia, or pain relief, rather than complete anesthesia. -This table will show you examples of LA, their routes of administration, their potencies and some properties: Esters: - Cocaine: rarely used and only topically , it was the first one discovered, it differs from the other local anesthetic in having high addictive property and it can produce vasoconstriction so it has a long duration of action. The dr just moved on to the next subject!! O.o

General anesthesia
Its a Reversible and controllable state of Analgesia. (relief of pain) amnesia. (memory disturbance or loss) loss of coconsciousness. (the patient will be unaware of himself) inhibition of sensory and autonomic reflexes. Variable degree of skeletal muscle relaxation by neuromuscular blocker.

The main deference between general and local anesthesia is the loss of coconsciousness. No general anesthesia without the loss of coconsciousness. But local anesthesia the coconsciousness is present . Preanasthetic medication: 10

The drugs which are given to the patient before the administration of general anesthesia. Why we need to give a drug before general anesthesia ? Produce sedation and decrease anxiety and apprehension by using diazepam , antihistamine, phenothiazine. To provide amnesia. To produce analgesia when there is pain such as opioids. Potentiate weak GA as nitric oxide (N2O). Facilitate induction without prolonging recovery. Reduce some undesirable side effects of general anesthesia such as H2 blockers as Cimetidine and anti-emetic as metoclopramide . To produce vagolytic effects the vagus is parasympathetic or anticholinergic effect as atropine and hyocine. Inhibiting vomiting and decrease the acid secretion of the stomach to reduce some undesirable effect by metoclopramide; its anti-emetic which can prevent vomiting. Classification of GA: Its either Inhalational or IV Intravenous depending on their route of administration. 1- Inhalational GA: It should be administered through endotracheal intubation passing a rubber endotracheal tube to the larynx to ensure that the patient inhaled all the gas or the volatile liquid and this procedure needs complete muscle relaxation and cannot be performed without the administration of neuromuscular blocker as succinylcholine. - Volatile liquids : 11

and its either and mainly the halogenated compounds or ethers . - Gases what's the difference between Volatile liquids and gases? Liquid evaporates into vapor and the gas is already in its gaseous state. The gas such as nitric oxide which commonly used nowadays , its gas under pressure, they come in cylinder. When the pressure is relieved it will be administrated in its gas state an inhaled by the patient . The process of GA is induction, maintenance, recovery: The time between the administration of GA until the patient start to lose his consciousness until complete loss of consciousness is called induction. Our aim in general anesthesia is to reach the state of complete loss of consciousness in which the sensation, motor activity, reflexes might be lost. The time of losing consciousness is called the period of effective anesthesia or maintenance of general anesthesia. Then after performing the surgical procedure the patient should be recovered, the consciousness should be back and retain to this patient. How ? by stopping the administration of general anesthesia. The time of stopping the administration of GA until the patient regain his whole consciousness is called the period of recovery. So good ideal anesthetic should have short induction period and short recovery period. Properties of an ideal GA: Should produce safe and pleasant anesthesia Good muscle relaxation Be potent, stable, non-irritant, and non-inflammable.

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General anesthesia started by ether and its highly inflammable and it has done enough fire accident during surgeries and it replaced by halogenated hydro compounds which is less inflammable or non inflammable Non-toxic and free of side effects . Produce rapid and smooth induction and rapid or fast recovery

Unfortunately, this ideal general anesthetic that has all this properties is still beyond our reach especially free side effects . Mechanism of action of inhalational GAs: - They depress CNS neuron activity by increasing their threshold and reducing the rise of the action potential by interfering with sodium influx. - They have similar mechanism of action of the local anesthetic, they prevent the entry of sodium into the CNS locally .. The GA administer the sodium influx systemically by inhalation or by IV administration. - They can increase transmission of inhibitory synapses as GABA transmitter. The main rout of administration of GA is inhalation, so they are taking to the systemic circulation by lungs. The first compartment to which GA reach is the alveolar air, then from AA to blood and then by the process of distribution it reaches the tissue; The target tissue for GA is the brain. So uptake and distribution depend on the depth of GA and its directly proportional with the tension of GA in the brain and the tension in the brain proportional to the tension in the blood and tension in the blood proportional to the tension in alveoli . -In other drugs we were talking about concentration but in GA we mention tension13

Tension : the partial pressure of the drugs . In a mixture of gases therell be a pressure this pressure is derived from the partial pressure of each component of these gases. Here the AA we dont have only GA ; we have GA and we have oxygen and nitrogen and carbon dioxide , all these form certain pressure . the partial pressure of GA is proportional to the depth of GA. In other words, The higher the partial pressure the higher the depth of GA and vice versa . So the rate of induction and recovery depend on the rate of change of tension in the brain and tension of the GA in AA nearly equivalent to the tension in the blood and nearly equivalent to the tension in the brain. The tension of the alveolar air is gradually increase when the patient start to inhale until it produce complete loss of consciousness and this maintenance period will continue as far as the valve of the container of gas or liquid is opened, then the recovery of GA when the anesthetist start to close the valve of the container of GA and the tension of GA in the brain, in the blood in the AA start to decline gradually by process of expiratory washing out till we reach minimum partial pressure and full recovery . The main organ of elimination of general anesthetic is the lung while in other drugs is the liver first and then the kidney. -and finally I reached the end of my damn lectureNada was with me in the lecture and during writing this lecture, raising me up and standing up with me to let this suicidal thing finish in peace, Thanks is meaningless here cause every part mn l tafree3 we made a story about it, love you. Dafdouf , the silence is our frienemy and theres no one in the world gets me lyk u This year I wish for nth but happiness to me and to you all specially do7a, walaa eman, 7aneen, haya, raja2,raneem, raya o lamees and my lady tuqa o samouraa o asraa ;), o my happiness fara7 o rawan o l sherera nouur :P o meen Kaman? Done by : Raghas .. 14