Drugs Acting at Synaptic and Neuroeffector Junctional Sites Autonomic and Neuromuscular Pharmacology
Subcommittee:
Theobald, Jr., Robert J., Chair [email protected] Dretchen, L. Kenneth [email protected] Strandhoy, Jack W. [email protected] Westfall, Thomas C. [email protected]Drugs acting at synaptic and neuroeffector junctional sites autonomic and neuromuscular pharmacology Recommended Curriculum Equivalent: 1.0 hr Introduction and History
BOTULINUM TOXIN COCAINE entacapone metyrosine reserpine
Learning Objectives Physiology and pathophysiology Describe the anatomical projections of the sympathetic and parasympathetic
Describe the evidence for the development of the concept of neurotransmitters, co-
Describe homeostasis, fight-or-flight, and rest-and-repair with regard to the autonomic
Describe the central control of the autonomic nervous system. List and describe the responses of end organs to activation of each division of the
Describe the concept of dominant tone. Mechanisms of action Explain the mechanism and drugs that block uptake of choline into cholinergic
List drugs that Inhibit Catechol-o-methyl transferase peripherally List drugs that block storage vesicle transport systems Describe the mechanism by which drugs Inhibit reuptake of NE into adrenergic
Describe the mechanism by which drugs deplete NE by interfering with synthesis Notes Define words containing the suffixes, -ergic, -mimetic, - lytic, and –ceptive. Clinical Pharmacology Botulinum toxin only marginally effective for prophylaxis against chronic migraine headache. Not approved for treatment of episodic migraine headache. Relevance USMLE topic Principles of therapeutics
Central and peripheral nervous systemAAMC Medical School Objectives Topic C Project Report X Patient Safety-Table 1 Drugs acting at synaptic and neuroeffector junctional sites autonomic and neuromuscular pharmacology Recommended Curriculum Equivalent: 3.0 hr Drug Classes and Drugs to consider Learning Objectives Physiology and pathophysiology Describe synthesis, storage, release, and inactivation of cholinergic agonists. List the steps in the synthesis, storage, release and inactivation of acetylcholine, and
drugs that interface with those processes.
List the location of nicotinic and muscarinic receptors and their subtypes. Compare the two major cholinesterases: acetylcholinesterase (AChE) and
butyrylcholinesterase (BuChE) as to anatomical locations, sites of synthesis and function.
Mechanism of action Explain the mechanism of actions, including 2nd messenger systems of acetylcholine
Explain the differences in onset and duration of action and route of administration for
different groups of anticholinesterases.
Explain the chemical makeup of the active site of AChE (anionic and esteratic) as to
attraction, attachment and rates of breakdown of various substrates and inhibitors.
Distinguish the mechanism by which pralidoxime reactivates phosphorylated AChE. Actions on organ systems Describe the responses to activation of these receptors. Explain the reason why anticholinesterases classified as reversible or irreversible. Pharmacokinetics Describe the variations of pharmacokinetics of cholinergic drugs. Relate the onset of action of anticholinesterases, routes of administration, and the
duration of action of anticholinesterases with sites and type of attachment to the enzyme.
Explain why anticholinesterases are reversible or irreversible, and indicate which
anticholinesterases are in each category.
Explain the role of cholinesterase “aging” in the enzyme-inhibitor interaction.
Adverse effects, drug interactions and contraindications List the adverse effects of cholinergic drugs. List and describe the rationale for contraindications of cholinergic drugs. Describe the adverse effects, and their relevance, of the two classes of neuromuscular blocking drugs. Therapeutic uses List the therapeutic uses of cholinergic agonists. Describe the effects of accumulated acetylcholine at muscarinic and nicotinic
receptors in the periphery and the central nervous system.
List therapeutic uses for and adverse side effects of anticholinesterases. Explain why anticholinesterase agents can be used as insecticides (malathion,
parathion) and chemical warfare agents (sarin, VX series).
Explain why pralidoxime is not effective reactivating all phosphorylated AChE. Explain the concept of differential toxicity of malathion and parathion in different
Notes
Clinical Pharmacology
Pilocarpine may cause mental impairment when used topically, especially in the
Relevance USMLE topic Principles of therapeutics
Central and peripheral nervous system
Neuromuscular junction agonistsAntiglaucoma drugsMechanisms of toxicology
AAMC Medical School Objectives Project Report X Patient Safety-Table 1
Drug treatment of common conditionsDrugs acting at synaptic and neuroeffector junctional sites autonomic and neuromuscular pharmacology Recommended Curriculum Equivalent: 2.0 hr Drug Classes and Drugs to consider Learning Objectives Physiology and pathophysiology List the locations of and the differences between muscarinic and nicotinic receptors. Explain the rationale for historical uses in treatment of hypertension and autonomic Mechanism of action Describe nicotine’s agonist and antagonist properties. Actions on organ systems Contrast and compare the depolarizing and the competitive Neuromuscular Junction blocking drugs. Adverse effects, drug interactions and contraindications Explain why muscarinic antagonists cause xerostomia, blurred vision, photophobia,
tachycardia, anhidrosis, difficulty in micturition, hyperthermia, glaucoma and mental confusion in the elderly.
Explain why muscarinic antagonists are contraindicated in glaucoma, obstructive
disease of the gastrointestinal tract or urinary tract, intestinal atony.
List the adverse side effects of drug acting at autonomic ganglia. List the adverse side effects and drug interactions at the NMJ. Therapeutic uses Explain the rationale for the therapeutic use of muscarinic antagonists in diseases
such as bronchoconstriction, excessive salivation, and motion sickness. Explain the rationale for the therapeutic use to produce mydriasis and cycloplegia.
Explain why nicotine is not used clinically (except as a smoking deterrent), and its
historical, social and toxicological significance.
Explain the differential uses of competitive versus depolarizing Neuromuscular
Notes
Clinical Pharmacology All anticholinergic drugs relatively contraindicated in the elderly due to risk of Relevance USMLE topic Principles of therapeutics
for treatment of disorders of the nervous system – neuromuscular junction agonist and antagonists
AAMC Medical School Objectives Project Report X Patient Safety- Table 1
and diseases using frequently prescribed drugs for the treatment and prevention of disease
Drugs acting at synaptic and neuroeffector junctional sites autonomic and neuromuscular pharmacology Recommended Curriculum Equivalent: 3.5 hr Drug Classes and Drugs to consider Learning Objectives Physiology and pathophysiology List steps in the synthesis, storage, release and inactivation of norepinephrine and
Describe types and subtypes of adrenergic receptors, their locations, and physiologic
Describe receptor selectivity of norepinephrine and epinephrine. Describe the differences between direct and indirect acting adrenergic drugs.
Mechanism of action Describe the property of intrinsic activity as a characteristic of Direct Agonists binding
Describe the mechanism by which Indirect Agonists release neurotransmitters from
Describe the importance of Antagonists binding to receptors without intrinsic activity Actions on organ systems Explain why alpha-1 adrenergic antagonists are used to treat hypertension and benign
Explain why alpha-1 adrenergic agonists are important in the treatment of nasal
congestion, hypotension, paroxysmal atrial tachycardia, and are used to cause mydriasis and vasoconstriction (with local anesthetics).
Explain the mechanism for the use of alpha-2 adrenergic agonists in the treatment of
hypertension, and for topical treatment of glaucoma.
Adverse effects, drug interactions and contraindications List the adverse side effects of alpha1 and alpha2 agonists. Explain drug interactions with oxytocic drugs and monamine oxidase inhibitors. List the contraindications for alpha1 adrenergic agonists. List the adverse side effects of nonselective alpha and selective alpha adrenergic Therapeutic uses Explain why alpha-1 adrenergic agonists are important in the treatment of nasal
congestion, hypotension, paroxysmal atrial tachycardia, and are used to cause mydriasis and vasoconstriction (with local anesthetics).
Explain the mechanism for the use of alpha-2 adrenergic agonists in the treatment of
hypertension, and for the topical treatment of glaucoma.
Explain the limitations of the use of nonselective alpha-1, alpha-2 adrenergic
antagonists in the treatment of hypertension.
Notes Clinical Pharmacology A recent trend to use a combination of methylphenidate and modified release
clodidine to treat ADHD in older children. However, this should not be considered a first-line drug regimen. Caution in that clonidine should not be discontinued abruptly due to risk of rebound hypertension. Clonidine use is sometimes associated with adverse CNS activity including depression and psychosis. Adverse CNS events have also been observed in patients prescribed methyldopa.
Relevance USMLE topic Principles of therapeutics
for treatment of disorders of the nervous system
Autonomic drugsStimulants, amphetaminesAAMC Medical School Objectives Project Report X Patient Safety-Table 1
and diseases using frequently prescribed drugs for the treatment and prevention of disease
Drugs acting at synaptic and neuroeffector junctional sites autonomic and neuromuscular pharmacology Recommended Curriculum Equivalent: 1.5 hr Drug Classes and Drugs to consider Learning Objectives Mechanism of action Compare and contrast the pharmacology of the nonselective beta-adrenergic
agonists, epinephrine and isoproterenol.
Compare and contrast the pharmacology of the beta selective adrenergic agonists,
isoproterenol, albuterol, salmeterol, and dobutamine.
Compare and contrast the pharmacology of the beta-adrenergic antagonists,
Compare and contrast the pharmacology of the nonselective alpha and beta blocking
drug labetalol, with selective beta blocking drugs.
Adverse effects, drug interactions and contraindications List the adverse side effects of beta2 adrenergic agonists.
List the adverse side effects of beta adrenergic antagonists. Therapeutic uses Explain the mechanisms for the use of selective beta-adrenergic agonists in diseases
such as cardiac decompensation, asthma, premature labor, bronchospasm and emphysema.
Notes Clinical Pharmacology There is no beta adrenergic blocking drug that has not been associated with reactive bronchconstriction. Thus caution is advised in adult patients with a history of pediatric asthma. Use of these agonists as effective tocolytics in humans is not supported by good clinical evidence. Relevance USMLE topic Principles of therapeutics
Central and peripheral nervous system
for treatment of disorders of the nervous system
Autonomic drugs Stimulants, amphetaminesAAMC Medical School Objectives Project Report X Patient Safety-Table 1
and diseases using frequently prescribed drugs for the treatment and prevention of disease
ELS TOPÒNIMS DEL CADASTRE DE RÚSTICA DE 1964 Plàcid Pérez Pastor / Lluc Coll Bernat*Es coneix amb el nom de Cadastre un seguit de documents que tenen per objectiuel control de la riquesa agrícola per part de l’Estat, amb finalitats fiscals. Consisteix en unconjunt de plànols on es localitzen totes les propietats agrícoles d’un municipi, que escomplementen amb una relació indi