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Flashcards covering Autonomic Pharmacology, Asthma, Antiseizure Medications, and Parkinson's Disease from lecture notes.
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What are the two main divisions of the Peripheral Nervous System (PNS)?
Autonomic and Somatic divisions.
What is the primary characteristic of the Autonomic Nervous System (ANS)?
It is automatic and not under direct conscious control.
What does the Autonomic Nervous System (ANS) control?
Almost every organ of the body.
For what types of diseases are autonomic drugs frequently used?
Heart disease, cardiovascular disease (especially hypertension), respiratory disease (asthma), glaucoma, and GI disorders.
What are the main divisions of the Autonomic Nervous System?
Sympathetic (thoracolumbar), Parasympathetic (craniosacral), and Intrinsic divisions (Enteric and Intra-cardiac Nervous Systems).
How do sympathetic and parasympathetic nerves usually exert their effects?
They usually exert opposite effects.
What neurotransmitter do all nerves leaving the CNS use?
Acetylcholine (ACh).
From where do preganglionic nerves of the Sympathetic Nervous System emerge?
Thoracic and lumbar levels of the spinal cord.
What neurotransmitter do sympathetic preganglionic fibers use, and on what receptors does it act?
Acetylcholine (ACh), acting on ganglionic nicotinic receptors (nAChR).
What is the main postganglionic transmitter in the sympathetic nervous system?
Noradrenaline (norepinephrine), but ACh is used in sympathetic nerves to sweat glands.
What is the 'flight or fight' response associated with in the sympathetic nervous system?
A co-ordinated discharge of a diffuse, continuously active system.
From where do preganglionic nerves of the Parasympathetic Nervous System emerge?
Sacral and cranial levels of the spinal cord (e.g., Vagus = Xth cranial nerve).
What is the postganglionic transmitter in the parasympathetic nervous system, and on what receptors does it act in target tissues?
ACh, acting on muscarinic receptors (mAChR).
What is the general function of the parasympathetic system?
Directed system, vegetative function like digestion and secretion.
What are the two main plexuses of the Enteric Nervous System?
Myenteric Plexus (of Auerbach) and Submucous Plexus (of Meissner).
What type of input do sympathetic nerves provide to the Enteric Nervous System?
Inhibitory adrenergic input.
What type of input do parasympathetic nerves provide to the Enteric Nervous System?
Excitatory cholinergic input.
What enzyme synthesizes ACh in the cytoplasm?
CHOLINE ACETYL TRANSFERASE.
What neurotoxin blocks vesicle fusion and ACh release?
BOTULINUM TOXIN (BOTOX).
On what receptors does ACh act in autonomic ganglia or skeletal muscle?
Nicotinic receptors (nAChR).
On what receptors does ACh act at visceral targets?
Muscarinic receptors (mAChR).
What enzyme terminates the action of ACh?
ACETYLCHOLINESTERASE.
What substances block acetylcholinesterase?
Nerve gasses and insecticides.
What is the structural and coupling type of mAChR?
Heptahelical structure, G-protein coupled (metabotropic).
Give examples of mAChR subtypes and their locations/functions.
M1 in neurons, M2 in cardiac muscle, M3 in smooth muscle, endothelial cells, and glands.
How do M3 agonists affect endothelial cells and vascular smooth muscle?
They increase Ca2+ in endothelial cells, activating nitric oxide synthase, leading to NO release, activating soluble guanylyl cyclase, generating cyclic GMP, causing relaxation of vascular smooth muscle and dilation.
Where are muscarinic receptors located on blood vessels, and why is this significant?
On endothelial cells lining blood vessels, not directly on the smooth muscle itself, explaining endothelium-dependent relaxation.
What are the two main ways M2 muscarinic receptors act?
1) Inhibit adenylyl cyclase activity reducing cAMP. 2) Open K+ channels (GIRK Channels).
What type of channels are nAChRs?
Ligand-gated ion channels.
What ions are permeable through nAChRs, and what does this cause?
Na+/K+ permeable, causing depolarization (e.g., e.p.s.p. in autonomic ganglia).
What is the rate-limiting step in noradrenaline synthesis, and what enzyme performs it?
Conversion of Tyrosine to dihydroxyphenylalanine (DOPA) by TYROSINE HYDROXYLASE.
What enzyme converts Dopamine to noradrenaline (NA) inside vesicles?
DOPAMINE-β-HYDROXYLASE.
What drugs can release NA from vesicles?
AMPHETAMINE and tyramine.
What enzyme metabolizes noradrenaline in mitochondria of nerve terminals?
MONOAMINE OXIDASE (MAO).
What enzyme metabolizes circulating catecholamines taken up into the liver?
CATECHOL-o-METHYL TRANSFERASE (COMT).
What is the structural and coupling type of all adrenoceptors?
Heptahelical, metabotropic (G-protein coupled).
What are α1-adrenoceptors primarily responsible for when activated postsynaptically?
Vascular smooth muscle contraction and increased blood pressure.
Where are most α2-adrenoceptors located, and what is their primary function?
Mainly presynaptic on nerve terminals, acting as 'autoreceptors' to reduce their own (NA) release.
What is the main effect of β1-adrenoceptor activation (e.g., in the heart)?
Opening Ca2+ channels, increasing heart rate and force.
What is the main effect of β2-adrenoceptor activation (e.g., in bronchioles)?
Relaxation of vascular smooth muscle, e.g., dilating bronchioles.
What are the general cholinergic effects?
Relaxation of smooth muscle and secretion.
What are the general adrenergic effects?
Contraction and inhibition of secretion.
Do most visceral organs receive both parasympathetic and sympathetic innervation?
Yes, most do.
What are some exceptions to dual innervation in visceral organs?
Spleen, kidney, liver, fat cells, and most blood vessels (only sympathetic).
What determines the dominant influence on most target organs at rest?
Dominant influence of one or other branch of the autonomic system, either sympathetic tone or parasympathetic tone.
What effects does systemic administration of the muscarinic antagonist, ATROPINE, produce due to cholinergic tone?
Constipation, tachycardia, 'dry mouth', and urinary retention.
How does the baroreceptor reflex respond to a decrease in aortic blood pressure?
Decreased baroreceptor activity leads to increased efferent sympathetic outflow and decreased parasympathetic outflow, increasing heart rate and blood pressure.
What are some common choline esters used as cholinergic agonists?
Acetylcholine, Carbachol, Bethanechol, Methacholine.
What is the overall effect of muscarinic agonists on the cardiovascular system?
Slow heart rate, decreased force and rate of contraction, and endothelium-dependent dilation of blood vessels.
How do muscarinic agonists affect the respiratory system?
Cause contraction of bronchiole smooth muscle and increased secretion, which can exacerbate asthma.
What are the CNS effects of nicotine?
Mild stimulation at low doses, emesis at higher doses, and coma at highest levels.
How do anticholinesterases indirectly stimulate nicotinic and muscarinic receptors?
By preventing the hydrolysis of ACh.
What are the severe signs of nerve gas or insecticide poisoning?
Cardiac arrest, fluid in lungs, bronchioconstriction, and blockade of respiratory muscle contraction.
What eye condition is treated with cholinomimetics?
Glaucoma (high intra-ocular pressure).
How do anticholinesterases help in Myasthenia Gravis?
They increase the strength of contraction by preventing ACh hydrolysis at the neuromuscular junction, compensating for decreased nAChR expression.
What is the main therapeutic use of neuromuscular blockers?
Paralysis during surgery.
What is the prototypic muscarinic antagonist?
ATROPINE.
How are muscarinic antagonists used in Parkinson's Disease?
To control tremor by blocking muscarinic receptors and decreasing excessive cholinergic activity, balancing it with reduced dopaminergic activity.
Which muscarinic antagonist is useful in chronic obstructive pulmonary disease (COPD)?
IPRATROPIUM.
What do sympathomimetic drugs do?
Mimic the effect of the sympathetic nervous system.
How do indirectly acting sympathomimetics work, and give examples.
They displace stored catecholamines from vesicles (e.g., amphetamine, tyramine) or inhibit catecholamine re-uptake (e.g., cocaine and tricyclic antidepressants).
Despite both increasing intracellular Ca2+, why do M3 muscarinics relax vascular smooth muscle while α1 adrenergics contract it?
M3 muscarinic receptors are on endothelial cells and cause relaxation via NO release, whereas α1 adrenergics are on smooth muscle cells and cause direct contraction.
What do α1 receptor stimulation on blood vessels cause?
Vasoconstriction, increased arteriolar resistance, and increased blood pressure.
What are the effects of β1-adrenoceptor stimulation on the heart?
Increased Ca2+ influx, increased force and rate of contraction, increased conduction of A-V node, potentially leading to dysrhythmias.
What effect does a pure α agonist like phenylephrine have on BP and HR?
Increases peripheral resistance and decreases venous capacitance leading to increased BP, but decreased HR due to baroreceptor reflex.
What effect does a pure β agonist like isoproterenol have on cardiac output, peripheral resistance, BP, and HR?
Increases cardiac output (β1) and decreases peripheral resistance (β2), leading to a late fall in BP and an increase in HR.
What are common CNS effects of amphetamines?
Mild alerting, improved attention, elevation of mood, insomnia, euphoria, and anorexia.
What is the 'cheese effect,' and when does it become problematic?
Tyramine-induced catecholamine release; problematic in patients treated with MAO inhibitors, leading to severe hypertension and cardiac dysrhythmias.
What is cocaine's mechanism of action?
Inhibits NA and DA re-uptake, leading to elevated central catecholamines (especially dopamine), causing euphoria, alertness, and insomnia.
What is the molecular mechanism of action for amphetamines?
Substrate for catecholamine transporter (pumped in), releases dopamine/noradrenaline from vesicles, then pumped out by reversed transporter.
What are the main therapeutic uses of Isoproterenol (INA)?
Emergency treatment of cardiac arrest and heart block.
What are Dobutamine's receptor selectivity and primary effect?
Cardiac stimulant, β1 selective.
What are Salbutamol's receptor selectivity and primary effect?
Bronchodilator, β2 selective.
What are Phenylephrine's receptor selectivity and primary effect?
α-adrenoceptor agonist, vasoconstrictor.
How do α-adrenoceptor antagonists (α-blockers) affect peripheral vascular resistance and blood pressure?
They lower them by blocking sympathetic tone.
What are common adverse effects of α-blockers related to blood pressure and heart rate?
Postural (orthostatic) hypotension and reflex tachycardia.
What is Phentolamine used to treat?
Pheochromocytoma (adrenal medullary tumor).
What are therapeutic uses for Prazosin?
To treat urinary obstruction/prostatic hyperplasia (by relaxing prostate gland).
What is Propranolol, and what is its receptor selectivity?
Prototypical β-blocker, non-selective for β1/β2 receptors.
What are major therapeutic uses of β-blockers?
Hypertension, prophylaxis of angina pectoris, heart failure, cardiac dysrhythmias, hyperthyroidism, and anxiety.
What is Metoprolol's receptor selectivity?
β1 selective.
Why is Metoprolol preferred over non-selective β-blockers for some cardiovascular patients?
It's better for asthmatics, diabetics, and patients with peripheral vascular disease due to persistence of β2 adrenoceptor function.
What happens when α-adrenoceptors stimulate the pupillary dilator (iris radial muscle)?
MYDRIASIS (pupil size increases).
Describe how muscarinic stimulation affects the ciliary muscle.
Contraction, leading to accommodation (focus for near vision, MYOPIA) and increased outflow of aqueous humor, thus decreasing Intraocular Pressure (IOP).
What happens when β-adrenoceptor stimulation affects the ciliary epithelium?
Increased secretion of aqueous humor, thus β-blockers reduce IOP.
What is glaucoma characterized by?
Elevated Intraocular Pressure (IOP) that can cause optic nerve damage and blindness.
What is a typical combination treatment for open-angle glaucoma?
Topical β-blocker, plus cholinergic agonist or cholinesterase inhibitor, plus adrenaline or apraclonidine, plus carbonic anhydrase inhibitor.
What type of drug is Pilocarpine, and how does it reduce IOP?
Muscarinic agonist; causes ciliary muscle contraction and increased outflow of aqueous humor.
What are the untoward effects of Pilocarpine?
Miosis (reduced pupil size) and myopia (nearsightedness).
Why was Retigabine withdrawn from the market?
Due to pigment discoloration of the skin and eye.
What is Atropine used for in ocular pharmacology?
To dilate the pupil for ocular examination.
What is Horner's syndrome characterized by?
Interruption of the oculo-sympathetic nerve pathway, resulting in miosis (constricted pupil), ptosis (drooping eyelid), and anhidrosis.
How is cocaine used to test for Horner's syndrome?
Cocaine causes pupil dilation in normal people. In Horner's syndrome, the affected pupil does not dilate adequately due to sympathetic damage and lack of NA to reuptake.
What are the three main characteristics of asthma?
Inflammation of the airways, bronchial hyper-reactivity, and reversible airways obstruction.
What causes the immediate phase of an asthma attack, and what is the main physiological response?
Initial response to allergen provocation, mainly caused by spasm of the bronchial smooth muscle.
What characterizes the late phase of an asthma attack?
A progressive inflammatory reaction, often nocturnal, involving Th2 lymphocytes and activated eosinophils.
What is the primary mechanism of action of β2-adrenoceptor agonists in asthma?
Dilate the bronchi via direct action on smooth muscle cell β2-adrenoceptors, activating adenylate cyclase and increasing cAMP levels.
What are examples of short-acting β2-adrenoceptor agonists (SABAs)?
Salbutamol (albuterol) and Terbutaline.
What are common adverse effects of β2-adrenoceptor agonists?
Tachycardia, dysrhythmias, tremor, peripheral vasodilation, hypokalemia, and hyperglycemia.
What is the mechanism of action of Theophylline?
Inhibits phosphodiesterase (PDE) to prevent cAMP breakdown, increases cAMP levels, inhibits adenosine receptors, and inhibits the release of intracellular calcium.