Pharmacology for Dentistry Students 2023-2024 PDF

0 Introduction  Autonomic nervous system (ANS):  The autonomic nervous system (ANS) is the major involuntary, automatic portion of the nervous system. It is also known as the visceral, vegetative, or involuntary nervous system.  The ANS controls the activity of internal organs, earning its "autom...

0 Introduction  Autonomic nervous system (ANS):  The autonomic nervous system (ANS) is the major involuntary, automatic portion of the nervous system. It is also known as the visceral, vegetative, or involuntary nervous system.  The ANS controls the activity of internal organs, earning its "automatic" designation because it regulates organ function without our conscious input.  This system is distributed widely throughout the body, innervating the heart, blood vessels, glands, other visceral organs, and smooth muscle in various tissues, thereby regulating autonomic functions.  It is responsible for maintaining the body's internal environment (homeostasis) and manages the everyday requirements of vital bodily functions that occur without conscious control. The Anatomy of ANS:  The nervous system (NS) is divided into:  Central Nervous System (CNS), which includes the brain and spinal cord.  Peripheral Nervous System (PNS), comprising all nervous tissue outside the CNS.  The Peripheral Nervous System is further subdivided into:  Somatic Nervous System, which controls voluntary "motor" functions that innervate skeletal muscles.  Autonomic Nervous System, which controls involuntary "automatic" functions.  The Autonomic Nervous System is subdivided into:  Sympathetic Nervous System, responsible for the "fight or flight" response.  Parasympathetic Nervous System, responsible for the "rest and digest" response. Pathway of Neural Signals:  Signals that reach the brain are transmitted through the sensory pathway.  Processing occurs in the brain when the signal reaches it.  The signal is then transmitted from the CNS to the effector organs through the motor pathway.  The Autonomic nervous system is the efferent (motor) part that carries the transmission from the CNS to the effector organ.  The Enteric autonomic nervous system: is part of the autonomic nervous system located in the gastrointestinal tract (GIT) that controls GI motility, activity, and secretion. 1  The autonomic nervous system (ANS) is composed of efferent neurons that innervate the smooth muscle of the viscera, cardiac muscle, vasculature, and exocrine glands, thereby controlling digestion, cardiac output, blood flow, and glandular secretions.  The sympathetic nervous system increases the force of contraction, leading to an increase in cardiac output.  Stimulation of the sinoatrial (SA) node by:  By parasympathetic nervous system it will decrease heart rate.  while sympathetic it's increased heart rate.  The blood vessels, which are controlled by the sympathetic nervous system Mostly the all secretion will be increased by stimulation of the parasympathetic nervous system, regulate blood flow:  If there is vasoconstriction, blood flow will decrease.  If there is vasodilation, blood flow will increase. Physiological changes that could occur when you are attacked by a bear include the following:  Remember: fight or flight, so the sympathetic nervous system will be activated.  Increase heart rate.  Increase blood pressure & Increase sweating.  Increase blood flow to skeletal muscle (vasodilation). As a response to the sympathetic: (fight and flight)  Blood flow will increase to organs that are in intense (high) need, like skeletal muscles.  Most other organs will experience vasoconstriction, reducing blood flow to these organs:  Blood will be shifted (transported) from other organs such as skin and the digestive system to skeletal muscles.  GI motility will be inhibited.  Blood pressure, heart rate, and respiration (bronchodilation) will increase.  The adrenal medulla will be stimulated and will secrete norepinephrine (noradrenaline) and epinephrine (adrenaline). (80-85% Epinephrine)  Bladder function will shut down: decrease in urination (urinary retention), the sphincter will close, and the detrusor muscle will relax.  Metabolism increases glucose levels because there is an increased need for glucose, achieved by liver glycogenolysis and increased glucose production through gluconeogenesis.  Pupils dilate, a condition known as mydriasis, due to an increase in pupil size. 2 Organ responses to ANS stimulations:  Most organs have dual innervation of Sympathetic & Parasympathetic, with their actions opposing each other. The Eye:  Sympathetic response:  Mydriasis ⇒ increase in the pupil size, by contraction of Radial Muscles.  The radial muscle: It is innervated by the sympathetic system, Its contraction causes Mydriasis (dilation of pupil size).  Receptor: alpha.  Parasympathetic response:  Miosis: the pupil size will be decreased, by contraction of circular Muscles.  The iris sphincter (circular) muscle: It is innervated by the parasympathetic system, and Its contraction causes Miosis (constriction of pupil size).  Receptor: M3 receptor. NOTE:  The ciliary muscle: it is innervated mainly (Only) by the parasympathetic system, their contraction lead to accommodation to near vision.  Ciliary muscle is responsible for:  Accommodation for viewing objects at varying distances, by changes the shape of the lens within the eye.  Regulates the flow of aqueous humour, it's important in the intraocular pressure.  Contraction of the ciliary muscle (cyclospasm) lead to accommodation to near vision.  Relaxation of the ciliary muscle lead to accommodation to far vision. The Lungs:  Sympathetic response ⇒ Bronchodilation. Beta 2 receptor  Receptor: Beta 2 receptor. M3 receptor receptor  Parasympathetic response ⇒ Bronchoconstriction.  Receptor: M3 receptor. The Heart:  Sympathetic response ⇒ Increase in:  Heart rate SA (sinoatrial) node, force of contraction, cardiac output. 3  Conduction velocity at AV (atrioventricular) node, & Ventricular contractility.  By stimulation of B1 receptor. Parasympathetic: M2 receptor  Parasympathetic response ⇒ Decrease in:  Heart rate & conduction velocity at AV node.  At high dose of muscarinic agonists can lead to heart block.  Receptor: M2 receptor. Sympathetic: B1 receptor Urinary bladder:  Sympathetic response: Beta 2 receptor  Decrease in the Urination (urinary retention).  Relaxation of bladder muscle (detrusor muscle) (B2 receptor) and contraction (closure) of sphincter (Alpha 1 receptor)  Parasympathetic response: Alpha 1 receptor  Contraction of bladder muscle (detrusor muscle) and relaxation of sphincter (urination). GIT:  Sympathetic response:  Relaxes smooth muscles, decrease peristalsis (constipation), tone and secretions.  Receptor: β2.  When the drug is an agonist on a sympathetic (NS), the same effects occur.  Parasympathetic response:  Contraction of smooth muscle, Increases peristalsis (diarrhea) and increase tone (cause colic pain).  Increase in acid secretion from parietal cell of the stomach.  Receptor: M3 receptor. The Kidney:  Only Sympathetic innervations:  Increase renin, and this will lead to activation renin angiotensin aldosterone system. (RAAS)  Increased angiotensin II, lead to vasoconstriction.  Increased aldosterone released, lead to (sodium, water) retention and potassium excretion.  Increase the total peripheral resistance ⇒ lead to increased blood volume ⇒ so lead to hypertension.  So when hypotension (decreased the renal blood flow), the renin release will be activation.  Receptor ⇒ Beta 1: increases Renin Secretion, Alpha 1: Decreases Renin. 4 Adrenal medulla:  Only Sympathetic innervations:  Secretion of norepinephrine (noradrenaline) and Epinephrine (adrenaline). Blood vessels:  Only Sympathetic innervations:  In skin, mucous membrane and splanchnic area: constriction (vasoconstriction).  In skeletal muscles: dilation (vasodilation). Female Genitalia:  Only Sympathetic innervations:  Uterus: uterine relaxation.  We use beta (β2) agonist (Sympathetic agonist) in the case of premature labor to relax the uterus. Male Genitalia:  Sympathetic response ⇒ ejaculation.  Parasympathetic response ⇒ erection. Liver:  Sympathetic Response:  Increases glucose by glycogenolysis and gluconeogenesis (B2 receptor). Skin:  Only Sympathetic innervations:  Sweat gland.  Pilomotor muscles: When the muscle contracts, will erect the hair (causes goosebumps). lacrimal gland:  The lacrimal gland is innervated by the parasympathetic system.  Activation of muscarinic receptors at lacrimal glands increase lacrimation. NOTE:  Organs that have opposite effect of the two systems: Eye, Heart, Smooth muscles of the gut, Bladder, bronchi.  Organs that have only sympathetic innervations:  Adrenal medulla, kidney, blood vessels, Liver (Glycogenolysis), Skin (Sweat gland, Pilomotor muscles). 5 (ANS) transmission  The ANS carries signals from the CNS to the effector organs.  Within the ANS, two neurons are required to reach a target organ: a preganglionic neuron and a postganglionic neuron.  The ANS has a two-neuron system with ganglia between them:  Preganglionic neuron: Arises from the CNS and synapses at the ganglia.  Postganglionic neuron: Arises from the ganglia and synapses at the effector organs.  The neurotransmitters involved in transmission are acetylcholine (ACh) and norepinephrine (NE). Adrenergic (sympathetic) neurons:  Nerve endings that release norepinephrine (NE).  Norepinephrine binds to adrenergic receptors (Alpha 1,2; Beta 1,2).  Catecholamines (NE, epinephrine, dopamine) and related drugs bind to the adrenergic receptor. Cholinergic neurons:  Nerve ending that releases Ach.  Acetylcholine binds to cholinergic receptors (Muscarinic, Nicotinic).  Acetylcholine, related drugs binds to the cholinergic receptors. Types of receptors 1.Cholinergic receptors:  Acetylcholine related drugs, (activated by Ach).  Muscarinic receptor.  Nicotinic receptor. 2.Adrenergic receptors:  Norepinephrine, catecholamine (NE, EP, Dopamine) related drugs, (activated by Ep, NE, dopamine.  Alpha ⇒ (α1, α2)/ Beta ⇒ (β1, β2). According to the picture: All Preganglionic neuron: (sympathetic & parasympathetic)  Cholinergic Preganglionic neuron:  Will release acetylcholine (Ach).  (Ach) Interact with the nicotinic receptors, at the ganglia. 6 Postganglionic neuron:  Sympathetic:  Will release Norepinephrine (NE).  (NE) Interact with the adrenergic receptors (alpha & beta), at the Target tissue.  Parasympathetic:  Will release Acetylcholine (Ach).  (Ach) Interact with the Muscarinic receptors, at the Target tissue. Exceptions of these rules:  Sympathetic Postganglionic fibres of Sweat glands:  Will release Acetylcholine (Ach).  (Ach) Interact with the Muscarinic receptors, at the eccrine sweat gland.  Postganglionic neuron that innervate renal blood vessels will release dopamine,  This dopamine when it's activated with dopaminergic receptors in the renal blood vessels will lead to vasodilation.  The adrenal medulla has not Postganglionic neuron:  The nicotinic receptor found in the adrenal medulla  And activation in the Chromaffin cells will lead to release (epinephrine 80%, Norepinephrine). Somatic NS (Voluntary motor):  There are no ganglia in this system.  Neurons (fibers) that arise from the CNS and innervate the skeletal muscles.  Neuromuscular junctions: Will release Acetylcholine (Ach).  (Ach) Interact with the nicotinic receptors, at the skeletal muscles. 7 Summary Questions from slides  Which one of the following is characteristic of parasympathetic stimulation? A. Decrease in intestinal motility. B. Inhibition of bronchial secretion. C. Contraction of circular muscle in the iris of the eye (miosis) D. Contraction of sphincter of urinary bladder. E. Increase in heart rate.  Which of the following is characteristic of the sympathetic nervous system? A. Its actions are mediated by muscarinic and nicotinic receptors. B. Its effects are only mediated by norepinephrine. C. It predominates during physical activity. D. Its stimulation causes relaxation of sphincter of urinary bladder. Answer: C Answer: C  Patient presents with salivation, lacrimation, urination, and defecation as side effects of a medication. Which one of the following receptors mediates the actions of this drug? A. Nicotinic receptors. B. α Receptors. C. Muscarinic receptors. Answer: C D. β Receptors. 8  Nicotinic receptor sites do NOT include which one of the following sites? A. Bronchial smooth muscle. B. Adrenal medullary cells. C. Parasympathetic ganglia. D. Skeletal muscle end plates. E. Sympathetic ganglia. Answer: A  Which one of the following is the primary neurotransmitter normally released in the sinoatrial node of the heart in response to a blood pressure increase? A. Acetylcholine. B. Dopamine. C. Epinephrine. D. Glutamate. Answer: E E. Norepinephrine. Best wishes 9