B-depolarizing agentsB-depolarizing agents Depolarizing agentsDepolarizing agents: Agonists at the nAChR : Agonists at the nAChR

(i.e., they act by stimulating the nAChR)(i.e., they act by stimulating the nAChR) Mechanism of action:Mechanism of action:Drugs like Drugs like succinylcholinesuccinylcholine attach to nicotinic attach to nicotinic

receptors & act receptors & act like Ach to depolarize the like Ach to depolarize the junction,junction, it cause it cause opening of sodium opening of sodium channel channel associated with nicotinic receptor which result associated with nicotinic receptor which result in in fasciculation leading to paralysis. fasciculation leading to paralysis.

Action of depolarizing Action of depolarizing agentsagents

Fasciculation'sFasciculation's followed by followed by paralysisparalysis Weak Weak histamine releasing histamine releasing action.action.

Theraputic usesTheraputic uses

1- Endotracheal intubation during induction of 1- Endotracheal intubation during induction of anesthesia (Muscle relaxant).anesthesia (Muscle relaxant).2- Rx of 2- Rx of electroconvulsive shock.electroconvulsive shock.3- Suitable for 3- Suitable for short or long periods of relaxation. short or long periods of relaxation.

pharmacokineticpharmacokinetic IV injection (continuous infusion)IV injection (continuous infusion) Short duration Short duration of action since this drug rapidly of action since this drug rapidly

Brocken downBrocken down by choline esterase enzyme. by choline esterase enzyme. Rapid recovery (fast hydrolysis).Rapid recovery (fast hydrolysis). Adverse effects:Adverse effects: HyperthermiaHyperthermia apneaapnea

Therapeutics uses of Therapeutics uses of cholinergic in dentistrycholinergic in dentistry

1-cholinomimetic drugs: 1-cholinomimetic drugs: stimulate stimulate salivationsalivation in patient with in patient with xerostomiaxerostomia

(dose:5-10 mg/3 times daily ,30 min (dose:5-10 mg/3 times daily ,30 min before meal)before meal)

2-2-anticholinergicanticholinergic drugs decrease the drugs decrease the flow of saliva during dental proceduresflow of saliva during dental procedures

Adrenergic drugsAdrenergic drugsSympathetic drugsSympathetic drugs

ANS - Adrenergic Drugs

adrenergic systemadrenergic system ACTIONS :ACTIONS : CNS: CNS: wakefulness, quick reaction to stimuli, wakefulness, quick reaction to stimuli,

quickened reflexesquickened reflexes PNS: PNS: - relaxation of the smooth muscles of the bronchi;- relaxation of the smooth muscles of the bronchi;- constriction of blood vessels;- constriction of blood vessels;- decrease in gastric motility.- decrease in gastric motility. HeartHeart: increase in the heart rate : increase in the heart rate Metabolism: Metabolism: increased use of glucose (sugar) andincreased use of glucose (sugar) and liberation of liberation of fatty acids from adipose tissuefatty acids from adipose tissue

Sympathetic Activation• on Stress ‘Fight’ or ‘Flight’

•Heart– HR, contractility, conduction velocity

• Vessels (arterioles):• Skin, cutaneous, visceral : constrict– Skeletal muscle, coronary: dilate

Sympathetic Activation

• Vessels (Vein): constrict•Eye– Radial muscle, iris: contract– Ciliary muscle: relax for farvision

•Lung– Tracheal and bronchial musc

le: relax

Adrenergic drugs have a wide variety Adrenergic drugs have a wide variety of uses for the treatment of: of uses for the treatment of: 1-1-HypovolemicHypovolemic shock. shock. 2-Moderate to severe of 2-Moderate to severe of hypotension.hypotension.3- Control of superficial 3- Control of superficial bleedingbleeding during during surgical and dental procedures of the surgical and dental procedures of the mouth, nose, throat, and skin.mouth, nose, throat, and skin.4- Bronchial 4- Bronchial asthma.asthma.

5- 5- Allergic reactions Allergic reactions (anaphylactic shock).(anaphylactic shock).6- Temporary treatment of 6- Temporary treatment of heart blockheart block; ; Ventricular arrhythmias (under certain Ventricular arrhythmias (under certain conditions),conditions),Cardiac arrestCardiac arrest7- 7- Nasal congestion Nasal congestion (applied topically);(applied topically);8- In conjunction 8- In conjunction with local anesthetics with local anesthetics to to prolong anesthetic action in medicine and prolong anesthetic action in medicine and dentistry.dentistry.

AdrenergicAdrenergic The Adrenergic Neuron Adrenergic neurons release

norepinephrine as the primary neurotransmitter.

These neurons are found in the sympathetic nervous system, where they serve as links between ganglia and the effector organs.

Neurotransmission Neurotransmission of adrenergic neuronof adrenergic neuron

The process involves five steps:The process involves five steps:1- synthesis,1- synthesis,2- storage, 2- storage, 3- release, 3- release, 4- and receptor binding of norepinephrine,4- and receptor binding of norepinephrine,5- followed by removal of the 5- followed by removal of the

neurotransmitter from the synaptic gap.neurotransmitter from the synaptic gap.

1- 1- Synthesis of norepinephrineSynthesis of norepinephrine: : TyrosineTyrosine is hydroxylated to is hydroxylated to dihydroxyphenylalanine dihydroxyphenylalanine (DOPA) (DOPA) by by tyrosine tyrosine hydroxylasehydroxylase..•DOPADOPA is then is then decarboxylated decarboxylated by the enzyme by the enzyme dopadopa decarboxylase to form decarboxylase to form dopaminedopamine in the in the cytoplasm of the presynaptic neuron.cytoplasm of the presynaptic neuron.

2- Storage of norepinephrine in vesicles:2- Storage of norepinephrine in vesicles:• Dopamine Dopamine is then is then transportedtransported into synaptic into synaptic vesicles by an vesicles by an amine transporter system .amine transporter system .•Dopamine is Dopamine is hydroxylated to form hydroxylated to form norepinephrine by the enzyme, norepinephrine by the enzyme, dopamine dopamine ββ--hydroxylase. hydroxylase. •[Note: [Note: Synaptic vesicles contain dopamine or Synaptic vesicles contain dopamine or norepinephrine norepinephrine plus adenosine triphosphate plus adenosine triphosphate (ATP).(ATP).

• In the adrenal medulla, In the adrenal medulla, norepinephrinenorepinephrine is is methylated to epinephrine,methylated to epinephrine, both of both of which are stored in chromaffin cells. which are stored in chromaffin cells.

• On stimulation, the On stimulation, the adrenal medulla adrenal medulla releases about releases about 80 % epinephrine and 80 % epinephrine and 20% norepinephrine20% norepinephrine directly into the directly into the circulation.circulation.

•3-Release of norepinephrine3-Release of norepinephrine: : •An action potential arrivingAn action potential arriving at the nerve at the nerve junction triggers an junction triggers an influx of calcium ions influx of calcium ions from from the the extracellularextracellular fluid fluid into the into the cytoplasm cytoplasm of the neuron.of the neuron.• The The increase in calcium increase in calcium causes causes vesiclesvesicles inside the neuron inside the neuron to fuse with the cell to fuse with the cell membrane membrane and expel and expel (exocytose) their (exocytose) their contents into the synapse. contents into the synapse.

• 4-Binding to a receptor: 4-Binding to a receptor: • Norepinephrine released from the Norepinephrine released from the

synaptic vesicles diffuses across the synaptic vesicles diffuses across the synaptic space and binds to synaptic space and binds to either either postsynaptic receptors postsynaptic receptors on the on the effector effector organ organ or to or to presynaptic receptors presynaptic receptors on the on the nerve ending.. nerve ending..

5- Removal of norepinephrine: 5- Removal of norepinephrine: Norepinephrine mayNorepinephrine may• 1) 1) diffuse out of the synaptic diffuse out of the synaptic space and space and enter the general circulation, enter the general circulation, •2) be 2) be metabolizedmetabolized to to O-methylatedO-methylated derivatives by derivatives by postsynaptic cell postsynaptic cell membrane- membrane- associated catechol O-methyltransferase associated catechol O-methyltransferase (COMT) (COMT) in in the synaptic space, the synaptic space,

• or 3) be or 3) be recaptured by an uptake system recaptured by an uptake system that that pumps the pumps the norepinephrine back into the norepinephrine back into the neuron. neuron.

• The uptake by the neuronal membrane The uptake by the neuronal membrane involves a involves a sodium/potassium-activated sodium/potassium-activated ATPase ATPase that can be inhibited by that can be inhibited by tricyclic tricyclic antidepressants, such as imipramine, or by antidepressants, such as imipramine, or by cocainecocaine

• Uptake of norepinephrine into the presynaptic Uptake of norepinephrine into the presynaptic neuron is the primary mechanism for neuron is the primary mechanism for termination of norepinephrine's effects.termination of norepinephrine's effects.

• Potential fates of recaptured Potential fates of recaptured norepinephrinenorepinephrine: Once norepinephrine : Once norepinephrine reenters the cytoplasm reenters the cytoplasm of the adrenergic of the adrenergic neuron, it may be taken up into neuron, it may be taken up into adrenergic adrenergic vesicles vesicles and be and be sequestered for release by sequestered for release by another action potentialanother action potential, or it may , or it may persist in a persist in a protected poolprotected pool. .

• Alternatively, norepinephrine can be Alternatively, norepinephrine can be oxidized oxidized by monoamine oxidase (MAO) by monoamine oxidase (MAO) present in present in neuronal mitochondria. neuronal mitochondria.

• The inactive products of norepinephrine The inactive products of norepinephrine metabolism are excreted in the urinemetabolism are excreted in the urine