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941 Cards in this Set
- Front
- Back
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cholinomimetic drugs that are choline esters
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1. acetylcholine 2. methacholine 3. carbachol 4. bethanechol
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cholinomimetic drugs that are naturally occurring
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1. nitotine 2. muscarine 3. pilocarpine
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2 ways that cholinomimetic drugs enhance cholinergic function
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1. activate Ach directly through nicotinic and muscarinic receptors and 2. block AchE
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function of anticholinesterase agents
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indirectly increase cholinergic function
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list reversible anticholinesterase agents
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1. physostigmine 2. neostigmine 3. edrophonium 4. pyridostigmine 5. donepezil and tacrine
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list anticholinesterase irreversible agents
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1. parathion and malathion 2. sarin and soman
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what is the cholinesterase reactivator?
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pralidoxime (2-PAM)
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what are the 5 basic steps in neurotransmission
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1. synthesis 2. storage 3. release from presynaptic terminal 4. reception and post-syn response 5. termination of signal
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examples of muscarinic blocking drugs
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1. atropine 2. scopolamine 3. tropicamide 4. ipratropium 5. benzytropine 6. oxybutynin
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what are 6 example of places where cholinergic synapses are found?
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1. all parasyn neuroeffector junctions 2. all autonomic ganglia 3. skeletal NMJ 4. sympathetic innervation of adrenal medulla 5. sweat glands 6. brain and SC sites
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non-innevated ACh receptors are generally of what type?
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muscarinic
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how do cholinergic drugs decrease colinergic function?
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they usually occupy the receptor so the ACh molecules cannot act on them
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where does synthesis of ACh occur?
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cytoplasm of cholinergic nerves
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enzyme that catalyzes ACh synthesis
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choline acetylase
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rate-limiting step of ACh synthesis
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active pumping of choline into the nerve by a transport mechanism
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what blocks the transport of choline into the nerve that causes an eventual inhibition of choline function?
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hemocholinium (HC-3)
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what causes attachment of ACh granules to fuse with nerve terminal membranes during action potential
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influx of Ca
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what can inhibit exocytosis of ACh into synaptic space?
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anything that lowers extracellular Ca i.e. bot toxin and latrotoxin
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what prevents release of ACh from nerve terminal
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botulinum toxin
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what causes excessive fusing of ACh granules w/ nerve mem causing excessive release and depletion of ACh
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latrotoxin - spider venom
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where are acetylcholinesterases found?
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region of all cholinergic synapses
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where are pseudocholinesterases found?
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plasma and liver
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function of pseudocholinesterases
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less selective for ACh, acts on many ester linkages, helps degrade ACh that escapes from transmission sites and inactivates ACh injected IV
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M2 receptors are found
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in heart
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M3 receptors are found
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peripheral autonomic organs
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M1 receptors are found
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in GI tract and autonomic ganglia
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which muscarinic receptors are located in CNS
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M1-M5
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what does stimulation of muscarinic receptors in the heart do?
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slows heart by increasing K permeability causing prolonged phase 4 depolarizaiton
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T/F: muscarinic receps in heart directly stimulate ventricular contraction
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F: they have little effect on force of vent contraction
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what effect does systemic admin of ACh and muscarinic stimulants have on vascular sm
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profound vasodilation and decrease BP
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how does ACh cause blood vessel smooth muscle relaxation?
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ACh acts on non-innerv muscarinic receptors on endothelial cells that releases EDRF (NO)
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what do muscarinic agonists produce in the eye
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pupillary constriction (miosis) and spasm of accommodation (cyclotonia)
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what do muscarinic agonists do in the GI tract
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increase tone and motility
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what do muscarinic agonists do in bronchiolar smooth muscle
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modest constriction
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how must ACh be administered to have an effect
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injected
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what will be activated if ACh is given in low doses
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only muscarinic receptors, much higher amts are needed to stimulate nicotinic
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what drug is partially resistant to AChase, is a potent muscarinic stimulant, but has lost almost all nicotinic action of parent molecule
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methacholine
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why is methacholine not used as much in humans
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has too many generalized muscarinic effects
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what drug is very refractory to inactivation by AChase, has a potent nicotinic stimulating effects w/ little muscarinic actions, and releases ACh from cholinergic nerve endings
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carbachol
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what drug is used topically on eye to produce miosis and tx glaucoma
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carbachol
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which drug is only choline ester that has established clinical use
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bethanechol
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which drug is refractory to AChase inactivation and has mostly muscarinic stimuating effects, tx post-op urinary retention and atony of GI tract
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bethanechol
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how is bethanechol used clinically
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tx esophageal reflux due to stimulatory action on lower esophageal sphincter
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what are responses to injected nicotine
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activation of all autonomic ganglia and stim of skeletal muscle endplate nic receptors
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antidote for muscarine poisoning
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atropine
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which drug selectively activates muscarinic receptors, not highly charged so can cross BBB, and used to tx glaucoma
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pilocarpine
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food, drug and cosmetic act addresses what?
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drug safety
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what established the FDA?
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food, drug and cosmetic act
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what does the FDA oversee?
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manufacture, labeling and advertisement of drugs
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what did durham-humphrey amendment do?
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divided drugs into prescription only and OTC
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what did the kefauver-harris amendment do?
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required that EFFECTIVENESS be shown for all existing and new drugs
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what is the Investigational New Drug Application for?
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goes from manufacturer to FDA to test a new drug
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what are the 3 phases of drug testing?
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1- testing in healthy volunteers 2- tx of patients w/ indicated condition 3-private practitioners use drug in less controlled studies
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T/F: the New Drug Application can be made by the manufacturer during only phase 1 of clinical testing
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F: can be made during any phase
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what percentage of drugs that enter human testing reach the market?
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12%
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how long does drug testing process last?
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7-10yrs
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what is the patent life for a drug?
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17 yrs
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which drug class for pregnancy describes when risk cannot be ruled out
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C
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which drug class for pregnancy describes when no evidence of risk in humans
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B
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which drug class for pregnancy describes when there is positive evidence of risk
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D
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which drug class for pregnancy describes when it is contraindicated in pregnancy
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X
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which drug class for pregnancy describes when controlled studies in both humans and animals failed to show fetal harm
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A
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what is the only drug labeled as class A for pregnancy
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cromalin (for asthma)
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which act governs all aspects of controlled substance distribution in US?
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comprehensive drug abuse act
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what must all controlled substance Rx's contain?
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1. date of issue 2. name and address of pt 3. name, address and DEA# of prescriber, 4. manual signature of prescriber on C-II
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which drug schedule has no accepted medical use and high abuse potential
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C-I
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which drug schedule has low abuse potential with low psychological or physical dependence potential?
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C-IV
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which drug schedule has high abuse potential w/ an accepted medical use with severe psychological and/or physical dependence
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C-II
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which drug schedule do benzodiazepines, phenobarbital, propoxyphene, and chloral hydrate fall into?
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C-IV
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what drug schedule do codeine cough syrups, and lomotil fall into?
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C-V
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how much of a C-II drug can a practitioner CALL in an emergency?
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72h
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what is the main contributor to life threatening conditions i.e. stroke, heart failure, coronary artery disease and renal failure
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hypertensive disease
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what is described as mild hypertension
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if diastolic is 90-105
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what is described as moderate hypertension?
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diastolic is 105-120
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what is described as severe hypertension
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diastolic is above 120
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if diastolic BP is sustained above what level that requires immediate medical attention
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130
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what % of HT patients have HBP secondary to some known, underlying organic prob?
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10%
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pts w/ HT of unknown etiology are referred to as having what type of HT?
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"essential"
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the ultimate aim of anti-HT therapy is to produce a sustained lowering of BP by reducing what?
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total peripheral resistance (TPR)
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renin is secreted by?
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juxtaglomerular cells
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aldosterone is secreted by?
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adrenal cortex
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what happens when aldosterone is secreted?
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kidney conserves/reabsorbs Na and H20 to increase fluid volume-> increases BP
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what are 3 general examples of vasodilators used in HT?
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older oral vasodilators, ca blockers, parenteral vasodilators
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what are 2 general examples of angiotensin antagonists?
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ACE inhibitors and receptor blockers
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what are the 3 types of angina/
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1. atherosclerotic 2. vasospastic 3. unstable
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accumulation of metabolites in striated heart muscle produced in heart when there is inadequate tissue oxygen supply causes what
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angina
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what is the most frequent cause of angina?
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atherosclerotic plaques in large coronary arteries
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what condition does the buildup of atherosclerotic plaques in large coronary arteries refer to?
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classic/atherosclerotic angina
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what causes prinzmetal's or variant angina?
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transient spasms of coronary arteries
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acute coronary event occurring at rest caused by episodes of increased arterial vasoconstriction in assoc w/ bloot clots occurring in vicinity of arterial occlusion is called
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unstable angina
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what are the 2 major categories of drugs used in angina pectoris?
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vasodilators and cardiac depressants
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vasodilators in angina can be broken down into waht 2 groups?
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nitrates and calcium blockers
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cardiac depressants in angina can be broken down into what 2 groups?
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ca blockers and beta blockers
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examples of nitrates
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nitroglycerin and isosorbide dinitrate
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examples of ca channel blockers
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nifedipine, verapamil, diltiazem
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examples of beta-adrenergic antagonists
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propranolol
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what drug is taken sublingually, releases NO systemically and dilates all vessels
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nitroglycerine
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what drug can be taken orally and works the same as nitroglycerine
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isosorbide ninitrate
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which of the Ca channel blockers is NOT a cardiac depressant?
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nifedipine
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which of the Ca channel blockers is VERY cardiosuppressant
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verapamil
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which Ca channel blocker has some cardiac depressant and some vasospastic qualities
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diltiazem
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T/F: nitrates work against regular and vasospastic angina
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T
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T/F: all Ca channel blockers are vasorelaxants
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T
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In CHF, which side of the heart is affected when blood and fluid backs up into lungs producing SOB, being tired and having a cough
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left
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in CHF, which side of heart is affected when fluid builds up in veins causing peripheral (pedal) edema
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right
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which cardiac glycoside increases the contractility of the heart
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digoxin
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how does digoxin work?
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1. inhibits Na/K-ATPase pump 2. causes elevated [Na] intracellular 3. heart shifts to Na/Ca pump causing increased [Ca] intracellular 4. increased cardiac contraction
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examples of diuretics for CHF
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chlorotiazide and furosemide
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example of beta-adrenoceptor agonists for CHF
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dobutamine
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examples of angiotensin antagonists
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ACE inhibitor - lisinopril and angiotensin receptor agonist - losartan
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examples of beta-adrenoceptor antagonists
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metoprolol and carvedilol
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which CHF drugs are used to treat both CHF and HBP
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chlorothiazide, lisinopril, and losartan
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what are the 2 types of arrhthmias
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1. atrial tachycardia 2. ventricular arrhthmias
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what types of drugs are used to treat atrial tachycardia
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beta-adrenergic antagonists
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examples of beta-adrenergic antagonists
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propranolol and esmolol
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what type of drugs used to tx ventricular arrhthmias
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local anesthetics (lidocaine)
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which drug blocks beta adrenergic receptors for the long run: propranolol or esmolol?
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propranolol
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why is esmolol short acting?
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b/c broken down by enzymes in RBC's
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what is the cause of about 1 in 6 strokes
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atrial fibrillation
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what limits cardiac output and exercise with atrial flutter/fibrillation?
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rapid ventricular response rate and increase in HR w/ exercise
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what is the principal goal of antiarrhythmic drug therapy in atrial flutter/fibrillation
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reduction in ventricular rate and improvement in exercise tolerance
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how do you reduce ventricular rate and improve exercise tolerance?
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1. conversion of atrial flutter to atrial fibrillation 2. slowing conduciton and prolongation of refractoriness w/in AV node 3. conversion of atrial fibrillation to sinue rhythm
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T/F: atrial flutter is more common than atrial fib
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F
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how can you convert atrial fib to sinus rhythm safely
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w/ DC cardioversion or IV ibutilide
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T/F: the maintenance of sinus rhythm is possible in pts w/ organic heart disease
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F
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what is most appropriate long-term means of slowing ventricular HR and supressing increase in AV nodal conduction accompanying exercise
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depression of AV nodal function
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exogenous chemical agent used to modify physiology
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drug
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use of a chemical agent for therapeutic purposes
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pharmacology
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adverse affect of a drug
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toxicology
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therapeutic goal
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mimic a normal physiology or inhibit an abnormal physiology
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4 descriptors of drug action
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symptomatic, psysiological, cellular, molecular
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what body does to drug is called
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pharmacokinetics
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effect of drug on body (drug action)
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pharmacodynamics
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what are the order of drug receptor bonds in order from strongest to weakest
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covalent - ionic - hydrophobic
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distribution of hydrophilic drugs through large aqueous compartments - driven by the concentration gradient of permeating drug
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aqueous diffusion
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distribution of hydrophobic drugs across membranes
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lipid diffusion
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what is the most important limiting factor in drug distribution
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lipid diffusion
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proteins in the membrane that help transport compounds that are too insoluble in lipids or too large to go through membranes
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special carriers
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only what types of drugs can pass through membranes?
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uncharged
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whether a drug is charged or uncharged is determined by:
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1. whether drug is a weak acid or a weak base 2. pH of compartment
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the percentage of drug protonated can be quantified by what?
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henderson-hasselbach equation
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which type of receptor mediates the actions of endogenous chemical agents
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regulatory proteins (opiod receptors - morphine)
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what are the 4 types of receptors
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1. regulatory proteins 2. enzymes 3. transport proteins 4. structural proteins
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example of enzyme receptor
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dihydropolate reductase - methotrexate
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example of transport proteins receptors
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Na/K ATPase - digitalis glycosides
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example of structural protein receptor
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tubulin - colchicine
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concentration of drug needed to achieve 50% of max effect
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EC50
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max drug response
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Emax
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max num of binding sites/receptors
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Bmax
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concentration of drug required for 50% of binding sites to be occupied
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Kd
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which type of antagonist reversibly binds to a receptor
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competitive antagonist
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which type of antagonist binds to receptor and changes maximal effect
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irreversible antagoist
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with a competitive antagonist, what do you need to do to produce same physiologic response
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increase concentration of agonist
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what happens if you increase concentration of agonist w/ an irreversible antagonist
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doesn't change physiological response
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agonists that do not produce max effect produced by other agonists
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partial agonists
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what happens to Emax and EC w/ irreversible antagonists
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Emax decreases and Ec doesn't change
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what happens if you give increasing concentrations of partial agonist?
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attenuate response of full agonist
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which drug is more potent: the one that produces a greater response or the one that has a lower EC50?
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lower EC50 (less of this drug is required to produce the 50% max response of a larger dose of the other drug
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which drug has a greater efficacy: the drug that produces a greater response or the one with a lower EC50
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produces a greater response
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concentration at which 50% of the patients achieve he desired response
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median effective dose (ED50)
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concentration that is toxic to 50% of the patients
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median toxic dose - TD50
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concentration that is lethal to 50% of pts
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median lethal dose - LD50
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relationship b/w the amount of drug required to produce the desired effect to amt that produces an undesired effect
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therapeutic index/therapeutic window (ratio of ED50 to TD50)
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individual, unusual response to a drug
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idiosyncratic
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diminished/increased drug effect than what is seen in most indivduals
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hyperreactive/hyperresponsive
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allergic or immunologic responses to drugs
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hypersensitive
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decreased responsiveness to a drug w/ repeated administration
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tolerance
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rapid dimishment of responsiveness to a drug
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tachyphylaxis
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which route of administration has highest bioavailability (F%)
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IV
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fraction of unchanged drug reaching systemic circulation following administration
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bioavailability
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amt of drug metabolized by liver
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first-pass effect
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apparent volume into which a drug homogeneously distributes in the body
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volume of distribution (Vd)
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T/F: rate of clearance increases w/ drug concentration
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T
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the rate of elimination in first order elimination is dependent on what
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drug concentration
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most drugs follow what order of elimination
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first order elimination
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T/F: zero order elimination is dependent on drug concentration
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F
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examples of zero order
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ethanol, phenytoin, aspirin
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how do Vd and Cl affect half life
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increase Vd=increase half life
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immediate effects of drugs are related to what
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plasma concentrations
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delayed effects of drugs are due to what
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turnover of physiologic substrate or slow distribution of drug (ex warfarin)
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since drug binding is irreversible in cumulative effects, what is required for effect?
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dosing over time
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conversion of compounds from lipophilic substances to polar
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biotransformation
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biotransformation has what 2 actions
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1. terminates biological activity of a drug 2. facilitates elimination of drug from body
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over 90% of drugs have what 2 organs as their sites of biotransformation?
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liver and kidneys
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phase I metabolism
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introduce/unmask a functional group
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phase II metabolism
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conjugation of a polar group
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what types of reactions take place in Phase I cytochrome P450-dependent rxns
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oxidations - hydroxylations, oxidative dealkylation, oxidation, deamination
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what types of reactions are part of cytochrome P450-independent rxns
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dehydrogenation, reductions, hydrolysis
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which cytochrome P450-dependent drugs undergo hydroxlations
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propanolol, ibuprofen
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which cytochrome P450-dependent drugs undergo oxidative dealkylation
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morphine, caffeine
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which cytochrome P450-dependent drugs undergo oxidation
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thioridazine
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which cytochrome P450-dependent drugs undergo deamination
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amphetamine, diazepam
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which cytochrome P450-independent drugs undergo dehydrogenation
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ethanol
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which cytochrome P450-independent drugs undergo reductions
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chloramphenicol
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which cytochrome P450-independent drugs undergo hydrolysis
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aspirin
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which phase II metabolism drugs undergo glucoronidation
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morphine, acetominophen
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which phase II metabolism drugs undergo acetylation
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mescaline
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which phase II metabolism drugs undergo glutathione conjugation
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ethacrynic acid
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which phase II metabolism drugs undergo glycine conjugation
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nicotinic acid
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which phase II metabolism drugs undergo sulfate conjugation
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acetaminophen
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which phase II metabolism drugs undergo methylation
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epinephrine
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which phase II metabolism drugs undergo water conjugation
|
leukotriene A4
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endogenous compounds that may affect drug biotransformation
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glutathione, glucuronic acid, sulfate
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parasym pregang neurons project where?
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to gang at or near target (usually long)
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parasym postgang neurons project where?
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from gang to targets (usually short)
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CN3 projects to what parasym ganglion
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ciliary
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CN7 projects to what parasym ganglions
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pterygopalatine and submandibular
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CN9 projects to what parasym ganglion
|
otic
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sympathetic system originates where
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thoracolumbar spinal cord
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where do sympathetic pregang project to? long or short?
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project to sympathetic chain or preaortic ganglia - short projection
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where do sympathetic postgang project to? long or short?
|
from ganglia to targets - long projections
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what are the cholinergic nicotinic receptors
|
ganglionic (Nn) and skeletal muscle (Nm)
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what is the agonist/antagonist for ganglionic receptors
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agonist-nicotine, antag-hexamethonium
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what is the agonist/antag for Nm receptors
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ag-nicotine, antag-curare
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what is the ag/antag for muscarinic receptors
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ag-muscarie, antag-atropine
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what is the ag/antag for alpha adrenergic receptors?
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ag-ephedrine, antag-phenoxybenzamine
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what is the ag/antag for beta adrenergic receptors
|
ag-ephedrine, antag-propanolol
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when the parasym pregang synapses, what NT is released
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Ach
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when the parasym postgang synapses, what NT is released
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Ach
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when the sym pregang synapses, what NT is released
|
Ach
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when the sym postgang synapses, what NT is released
|
NE
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what does the activation of the adrenal medulla cause?
|
release of Epi or NE, general sympathetic activation
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where do parasyms come from to activate everything from belt down
|
sacral spinal nerves
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outflow from CNS in sym vs parasym
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sym-thoracolumbar (T1-L2)
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location of ganglia in sym vs para
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sym-close to CNS
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where are B receptors located
|
B1-heart, B2-bv's, lungs, bronchi, B3-adipose
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what happens to HR, force of ventricular contraction, and conduction velocity when innerv by sym vs para
|
sym- all 3 are increased, para-HR and conduction velocity are decreased and no effect on force of vent contraction
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what happens to iris when innervated by sym vs para
|
sym-pupils dilate, para-constrict
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|
|
what happens to bronchi when innerv. by sym vs para
|
sym-dilated (B2), para-constricted
|
|
|
does sym or para stimulate GI tract
|
para
|
|
|
what happens to salivary glands when innerv by sym vs para
|
sym-stimulated (viscous), para-stimulated (watery)
|
|
|
what does receptor "m" mean
|
cholinergic inhibitory, stimulated by ACh: vasodilation
|
|
|
what receptors are found in skeletal muscle, innerv or non-innerv?
|
a-innerv, B2-non-innerv, m-both
|
|
|
what receptors are found in gut, liver, spleen- innerv or non-innerv?
|
a-innerv, B2-non-innerv, m-non-innerv
|
|
|
what receptors are found in skin-innerv or non?
|
a-innerv, B2 - a few innerv, m-a few innerv
|
|
|
what receptors are found in coronaries - innerv or non?
|
a-innerv, B2-non, m-non
|
|
|
where do parasyms project to in the eye?
|
ciliary muscle and sphincter muscle or iris
|
|
|
where do syms project to in the eye?
|
dilator muscle of iris
|
|
|
sympathetic innervation of bv's are usually mediated by which receptor
|
b2
|
|
|
which wins out? vascular resistance or CO?
|
vascular resistance
|
|
|
T/F: all somatic nerves release ACh
|
T
|
|
|
what happens to BP if ACh is given in small doses
|
decrease in BP
|
|
|
what happens to BP if ACh is given in a small dose after atropine is given
|
no effect on BP b/c atropine blocked musc receptors
|
|
|
what happens to BP if ACh is given in a large dose after atropine is given
|
big increase in BP b/c ACh is now hitting nicotinic receptors
|
|
|
when nicotine is given repeatedly or in large doses, why does it block nicotinic receptors?
|
sustained depolarization
|
|
|
agents that indirectly enhance cholinergic function
|
anticholinesterases
|
|
|
anticholinesterases only have an effect on which type of receptors
|
only at innervated ACh receptors
|
|
|
main clinical use for AChase inhibitors
|
tx myasthenina gravis and glaucoma
|
|
|
what is used to tx atropine poisoning
|
physostigmine
|
|
|
what drugs are antidotes to curare
|
AChase inhibitors
|
|
|
main clinical use for physostigmine
|
topical for glaucoma
|
|
|
what actions does physostigmine have in eye
|
miosis and contraction of ciliary muscle
|
|
|
how is it imp that physostigmine is not highly charged
|
can enter CNS
|
|
|
what drug is the best choice for atropine poisoning
|
physostigmine
|
|
|
neostigmine directly stimulates nicotinic sites where?
|
on skeletal muscle endplates
|
|
|
the dual action of neostigmine makes it a drug of choice for what
|
myasthenia gravis
|
|
|
pyridostigmine is used to tx what
|
myasthenia gravis
|
|
|
which AChase inhibitors are CNS acting and used to tx cognitive dysfunction in Alzeimer's dx
|
donepezil and tacrine
|
|
|
which cholinomimetic can stimulate salivary flow
|
pilocarpine
|
|
|
which drug is used to distinguish myasthenia gravis from AChE blockade (cholinergic crisis)
|
edrophonium
|
|
|
Can be used as topical treatments for glaucoma,but most are insecticides and military nerve agents
|
irreversible AChases
|
|
|
what insecticide is converted in the liver to the active form
|
parathion
|
|
|
sarin and soman
|
Gaseous nerve agents used in chemical warfare. NOT reversible by cholinesterase reactivators
|
|
|
Used to treat muscarinic intoxication and intoxication with some irreversible organophosphate anti-cholinesterases
|
pralidoxime (2-PAM)
|
|
|
paralysis of the NMJ's due to excessive ACHASE inhibition
|
cholinergic crisis
|
|
|
paralysis of the NMJ's due to insufficient ACHASE inhibition
|
myasthenic crisis
|
|
|
what would muscarinic receptor blockers do to parasym innervated organ
|
lack of motility and secretions
|
|
|
what is the diff b/w atropine and scopolamine
|
atropine produces CNS excitation, scopolamine causes CNS depression
|
|
|
low doses of atropine cause what
|
slight paradoxical bradycardia due to CNS stim
|
|
|
higher doses of atropine cause what
|
they block peripheral muscarinic receptors at heart to produce tachycardia
|
|
|
atropine effect on heart
|
low doses- bradycardia, higher doses-tachycardia
|
|
|
atropine effect on skin
|
inhibition of sweating, hot dry skin
|
|
|
atropine effect on eye
|
mild to marked mydriasis, mild to marked cycloplegia
|
|
|
atropine effect on viscera
|
dry mouth, decreased saliv, reduced GI and urinary tone
|
|
|
atropine effect on CNS
|
confusion, restlessness, excitement --- hallucinations, delirium, coma
|
|
|
characteristics of atropine poisoning
|
hot dry skin, dilated pupils, maniacal behavior
|
|
|
what is a less potent and much shorter acting muscarinic antag
|
tropicamide
|
|
|
use for tropicamide
|
opthalmological exams
|
|
|
ipratropium is mainly used in what type of pts
|
COPD (asthma secondarily)
|
|
|
how does ipratropium work in COPD pts
|
bronchodilation w/o affecting bronchial secretions
|
|
|
musc blocker that crosses BBB and tx parkinson's
|
benztropine
|
|
|
musc blocker that tx bladder spasms postop that decreases bladder tone and improves continence
|
oxybutynin
|
|
|
will innervated or non-innerv receptors be affected by ganglionic transmission
|
innerv
|
|
|
ganglionic stim will excite which organs
|
all autonomic organs
|
|
|
which neurons/cells does nicotine stimulate
|
postgang neurons and adrenal chromaffin cells
|
|
|
prototype ganglionic blocking drug
|
hexamethonium
|
|
|
nicotine blocks autonomic ganglia when given in high doses due to what
|
sustained depolarization of postgang cells
|
|
|
T/F: hexamethonium blocks NMJ's
|
F - does not
|
|
|
predominant tone and effect of ganglionic blockade at arterioles
|
sypathetic - vasodilation
|
|
|
predominant tone and effect of ganglionic blockade at veins
|
sym - dilation
|
|
|
predominant tone and effect of ganglionic blockade at heart
|
parasym - tachycardia
|
|
|
predominant tone and effect of ganglionic blockade at iris
|
parasym - mydriasis
|
|
|
predominant tone and effect of ganglionic blockade at ciliary muscle
|
parasym - cycloplegia
|
|
|
predominant tone and effect of ganglionic blockade at GI tract
|
parasym - reduced tone and motility
|
|
|
predominant tone and effect of ganglionic blockade at urinary bladder
|
parasym - urinary retention
|
|
|
predominant tone and effect of ganglionic blockade at salivary glands
|
parasym - xerostomia
|
|
|
predominant tone and effect of ganglionic blockade at sweat glands
|
sym - anhidrosis
|
|
|
drugs can cause neuromuscular blockade by one of what 2 ways
|
1. compete w/ ACh for nicotinic receptors 2. sustained depolarization
|
|
|
prototype NMJ blocking drug
|
curare
|
|
|
how do local anes and tetrodotoxin inhibit nerve action potential
|
interfere w/ Na transport
|
|
|
what inhibits ACh release by blocking reuptake of choline into nerve ending
|
hemicholinium
|
|
|
what inhibits ACh release by blocking ACh release mech
|
botulinum toxin
|
|
|
what enhances ACh release
|
spider venom (latrotoxin) and catecholamines
|
|
|
what inhibits binding of ACh to receptor
|
NMJ blockers and snake alpha-bungarotoxins
|
|
|
T/F: competitive NMJ blocking drugs enter BBB
|
F: highly charged
|
|
|
T/F: competitive NMJ blocking drugs produce reduction in pain sensation
|
FALSE
|
|
|
gold standard of competitive NMJ blockers
|
tubocurarine
|
|
|
main side effect for tubocurarine - eliminated by?
|
hypotension - liver
|
|
|
how is doxacurium different from tubocurarine?
|
doesn't block autonomic ganglia or release histamine
|
|
|
organ of excretion for doxacurium
|
kidney
|
|
|
NMJ blocker w/ steroid nucleus
|
pancuronium
|
|
|
how is pancuronium same as doxacurium
|
no autonomic blockade no histamine release
|
|
|
more potent, shorter acting analog of pancuronium
|
vecuronium
|
|
|
only drug used clinically as depolarizing NMJ blocker
|
succinylcholine
|
|
|
how is succinylcholine inactivated
|
rapidly metabolized by plasma and liver pesudocholinesterases
|
|
|
drug of choice to relax laryngeal muscles before intubation
|
succinylcholine
|
|
|
what syndrome can appear due to succinylcholien
|
malignant hyperthermia
|
|
|
benzodiazeepine that enhances GABAergic inhibition in CNS
|
diazepam
|
|
|
side effect for diazepam
|
sedation at effective dose
|
|
|
function of diazepam
|
reduces all muscle spasms
|
|
|
drug that causes decrease in release of Glu and decrease in skeletal muscle tone while experiencing less sedation than diazepam
|
baclofen
|
|
|
drug used for relief of spasticity caused by MS and spinal cord injury
|
baclofen
|
|
|
drug that is CNS alpha2 stim, reduces skeletal muscle spasticity, causes less hypotension, but causes sedation and dry mouth
|
tizanidine
|
|
|
related to tricyclic antidepressants, tx muscular spasms assoc w/ musculoskeletal conditions
|
cyclobenzaprine
|
|
|
spasmolytic w/ side effects that are atropine-like and not effective in tx for spasms from spinal cord injury or cerebral palsy
|
cyclobenzaprine
|
|
|
Acts directly on skeletal muscle abd disrupts excitation-contraction coupling by blocking release of Ca needed for contraction
|
dantrolene
|
|
|
drug of choice for treating malignant hyperthermia
|
dantrolene
|
|
|
main adverse effects of dantrolene
|
generalized msucle weakness and sedation
|
|
|
muscle relaxant to tx generalized spastic disorders (cerebral palsy), effective longterm blockade of trans to muscle
|
botulinum toxin
|
|
|
drugs to tx paralytic ileus
|
physostigmine and bethanechol
|
|
|
drug to tx atony of bladder
|
bethanechol
|
|
|
drug to tx glaucoma
|
physostigmine, pilocarpine
|
|
|
drug to tx myasthenia gravis
|
neostigmine
|
|
|
drug to reverse NMJ blockade
|
neostigmine + atropine
|
|
|
preanesthetic medication
|
scopolamine
|
|
|
drug used in opthalmological exam
|
tropicamide
|
|
|
drug to tx motion sickness
|
scopolamine
|
|
|
4 sympathomimetics: catecholamines
|
1. Epi 2. NE 3. isoproterenol 4. dopa
|
|
|
6 non-catecholamine sympathomimetics - alpha agonists
|
1. tyramine 2. amphetamine 3. methamphetamine 4. methylphenidate 5. ephedrine 6. phenylephrine
|
|
|
5 non-catecholamine sympathomimetics - beta adrenoceptor agonists
|
1. terbutaline 2. albuterol 3. salmeterol 4. ritodrine 5. dobutamine
|
|
|
sympathomimetics: inhibitors of reuptake
|
1. cocaine 2. tricyclic antidepressants
|
|
|
CNS acting sympatho-inhibitory agents
|
1. clonidine 2. a-methyl DOPA
|
|
|
alpha-adrenoceptor blockers
|
1. phentolamine 2. phenoxybenzamine 3. prazosin 4. doxazosin 5. terazosin
|
|
|
beta-adrenoceptor blockers
|
1. propanolol 2. metoprolol 3. atenolol 4. pindolol 5. timolol 6. esmolol
|
|
|
alpha and beta-adrenoceptor antagonist
|
1. labetalol 2. carvedilol
|
|
|
most imp regulation of NE and Epi synthesis
|
end product inhibition
|
|
|
those neurons that synthesize, store, and release catecholamines
|
adrenergic neurons
|
|
|
what do adrenergic nerves regulate the function of
|
heart and blood vessels, visceral smooth muscle and glandular tissue
|
|
|
catecholamine molecule
|
amine with benzene ring with OH sub on 3 and 4
|
|
|
catecholamine released from post ganglionic sympathetic nerve fibers in peripheral nervous system
|
NE
|
|
|
what is released from chromaffin cells of the adrenal medulla
|
epi
|
|
|
is epi released from peripher nerves
|
no
|
|
|
NT released from neurons in CNS
|
epi and dopamine
|
|
|
aa that cat are derived from
|
tyrosine
|
|
|
tyrosine is converted to what
|
DOPA
|
|
|
DOPA is converted to..
|
dopamine
|
|
|
dopamine is converted to ? where?
|
NE in the storage vesicle
|
|
|
in the granule, NE is associated with ? and ?
|
ATP and a protein called chromoganin
|
|
|
what stimulates NE systhesis
|
increased neuronal activity by increasing tyrosine hydroxlase
|
|
|
which receptors can NE activate when released
|
a1, a2, or b1 on postsyn cell
|
|
|
rate limiting step in syn of NE in nerve terminals and epi in adrenal gland
|
Tyrosine hydroxylase (conversion of tyrosine to dopa)
|
|
|
what happens when action potential invades nerve terminal
|
influx of calcium
|
|
|
what enzymatically inactivates NE that enters postsyn cell
|
COMT (uptake II)
|
|
|
T or F Synaptic NE can also stimulate presynaptic alpha 2 receptors that act as a neg feedback to inhi further release of NT
|
TRUE
|
|
|
which enzymes in liver can inactivate NE that diffuses into systemic circ
|
MAO and COMT
|
|
|
what is the most important mech for the term of NE action, and what is it called?
|
re uptake back into the nerve terminal 60-90% - uptake I
|
|
|
if NE is not sequestered by the storage vesicle in the presyn term, what and where will it be inactivated?
|
MAO
|
|
|
MAO is assoc w/ what organelle
|
mitochondria
|
|
|
COMT is in high concen where
|
cytosol of liver cells
|
|
|
MAO is in high concentration in what organ
|
liver
|
|
|
what metabolite is sometimes screened for in patients suspected of harboring a tumor of the adrenal gland called pheochromocytoma
|
VMA
|
|
|
alpha 1 receptors are located where
|
post junctionally at most symp neuroeffector synapses except the heart and JG cells of the kidney
|
|
|
activation of alpha 1 receptors is excitatory or inhibitory
|
excitatory ( increased bp, pupil dilation via contraction of the radial muscle of iris, piloerection, viscous salivation, contraction of GI an durinary bladder
|
|
|
what systems are inhibited with alpha 1 receptors
|
Gi and urinary smooth muscle
|
|
|
what is the function of alpha 2 receptors
|
same as a1 + prejunc mem to provide a neg feedback mechanism to prevent excessive release of NE
|
|
|
where are the 2 places that beta 1 receptors are found
|
heart and JG apparatus of the kidney
|
|
|
what are the only receptors potently stimulated by NE
|
beta 1 receptors
|
|
|
what are beta receptors responsible for?
|
increasing heart rate, conduction, ad contractile force as well as the neural release of renin from the JG cells
|
|
|
what are the only innervated beta adrenoreceptors
|
beta 1
|
|
|
do beta 2 adrencoreceptors prefer epi or NE
|
epi
|
|
|
what is the result of beta 1 receptor stimulation
|
increased cardiac output
|
|
|
what will beta 2 receptors activation cause?
|
vascular vasodilation and reduction of bp, relaxation of smooth muscle of bronchial tree, inhibition of GI and urinary tract smooth muscle, and relaxation of gravid uterus
|
|
|
do b2 act directly on innerv or noninnerv
|
non-innerv
|
|
|
why are catechols not effective by oral route
|
b/c substrates for MAO and COMT
|
|
|
sympathomimetic drugs
|
mimic sympathetic function
|
|
|
2 ways sympathomimetics mimic sym function
|
directly by stim the adrenergic rec or indirectly allowing more NE to be present in the synaptic cleft
|
|
|
isoproterenol is a synthetic catecholamine iwth preference for which receptors?
|
all b adrenoreceptors
|
|
|
epinephrine works on what receptors
|
all alpha and beta
|
|
|
alpha adrenoreceptor activation is...
|
vasoconstriction
|
|
|
beta adrenoreceptor activation is...
|
vasodilation
|
|
|
are there more alpha or beta receptors
|
alpha (but less sensitive to epi)
|
|
|
which receptors are more sensitive to epi
|
beta (even though fewer in number)
|
|
|
which receptor is fewer in number, more sensitive to epi and has longer lasting effects
|
beta receptors
|
|
|
which receptor is greater in number, less sensitive to epi and has shorter duration of effects
|
alpha
|
|
|
what would the effect of a small bolus of epi be?
|
vasodilation due to beta2 response
|
|
|
what would the effect of a large bolus of epi be?
|
vasoconstriction and a pressor response -- alpha response
|
|
|
reversal of pressor response to depressor response after a-adrenoceptor blockade is called
|
epi reversal
|
|
|
when epinephrime stimulates beta 1 receptors, what is the effect on the heart?
|
increase heart rate and contractility
|
|
|
epi effect on b2 receptors
|
relax bronchial smooth muscle in the treatment of asthma and for treating bronchospasm during anaplylactic shock
|
|
|
epi acts via beta adrenoreceptors mechanisms to increase adenylate cyclase activity to form cAMP that has what metabolic effects?
|
1) increase plasma glucose by breakdown of liver glycogen 2) inhibits synthesis of glycogen 3) stimulates gluconeogensis 4) breaks down fats to fatty acids
|
|
|
NE acts on which receptors?
|
all alpha, and beta 1
|
|
|
a bolus injection of NE will have what outcome?
|
increase blood pressure due to both vasoconstriction and increased cardiac output
|
|
|
which has a longer 1/2 life: epi or NE?
|
epi
|
|
|
drug that potently acts on all b receptors to relieve bronchoconstrictive states
|
isoproterenol (ISO)
|
|
|
untoward side effects from isoproterenol
|
cardiac
|
|
|
A CNS defect in dopaminergic mechanisms results in what disease
|
parkinsons
|
|
|
dopamine has what effect on the kidney
|
vasodilation
|
|
|
at higher doses, what is the effect of dopamine
|
stimulate alpha and beta receptors to increase bp, and cardiac output
|
|
|
what drug, found in certain foods like beer, cheese, and wine, can cause a hypertensive crisis in pts taking MAO inhibitor to treat depression?
|
tyramine
|
|
|
tyramine causes massive release of what from sym nerve endings
|
NE
|
|
|
why is injestion of tyramine not harmful?
|
readily inactivated by MAO in gut and liver
|
|
|
what must happen for tyramine effect to manifest
|
nerve endings must contain NE
|
|
|
amphetamine and meth are what kinds of drugs
|
indirect sympathomimetics
|
|
|
why are amphetamines so toxic and lethal?
|
bc the ED50 increases but the LD50 remains the same
|
|
|
chronic toxicity to amphetamines can mimic what?
|
paranoid schizophrenia
|
|
|
what is the major finding at autopsy of amphetamine overdose>
|
cerebral hemorrhage that may be secondary to intense vasoconstriction of blood vessels
|
|
|
what are the 2 valid reasons for amphetamine use
|
1) hyperkinetic children to increase attention span 2) narcolepsy
|
|
|
methylphenidate is a mild CNS stimulant that causes what?
|
gerenalized CNS excitation that may cause convulsions
|
|
|
primary use of methylphenidate (Ritalin)
|
ADHD
|
|
|
medical uses for ephedrine
|
bronichial asthma (b effect) ear and nasal congestion OTC, opthalmology for short lasting mydriasis without cycloplegia
|
|
|
medical uses for phenylephrine
|
opthal for mydriasis, nasal spray
|
|
|
terbutaline is a modification of what drug
|
metaproterenol
|
|
|
which is longer acting: metaproterenol or terbutaline
|
terbutaline
|
|
|
which drug, terbutaline or metaproterenol, has a higher incidence of cardiac side effect?
|
terbulatine
|
|
|
drug used to prevent premature child birth
|
terbutaline
|
|
|
drug for astham, similar to terbutaline
|
albuterol
|
|
|
long acting beta 2 agonist that is used to treat bronchial asthma
|
salmeterol
|
|
|
beta 2 agonist that is approved for use to relax smooth muscle of the uterus and to delay premature child labor
|
ritodrine
|
|
|
what is the preferred method of delivery for ritrodrine
|
orally, even though only 30% effective
|
|
|
synthetic catecholamine analog of dopamine that is a highly selective beta 1 adrenoreceptor
|
dobutamine
|
|
|
does dobutamine stimulate dopamine receptors?
|
no
|
|
|
what is the effect of dobutamine on the heart?
|
increased cardiac output without the vasoconstriction associated with NE that would result in increased cardiac work
|
|
|
what drug is used for short term treatment of cardiac insufficiency
|
dobutamine
|
|
|
what is the effect of sympatho-inhibitory agents on the peripheral nervous system
|
vasoconstriction by alpha 2's, short lived
|
|
|
what is the effect of sympatho - inhibitory agents on the CNS?
|
hypotensive action that lasts for hours
|
|
|
those neurons that synthesize, store, and release catecholamines
|
adrenergic neurons
|
|
|
what do adrenergic nerves regulate the function of
|
heart and blood vessels, visceral smooth muscle and glandular tissue
|
|
|
catecholamine molecule
|
amine with benzene ring with OH sub on 3 and 4
|
|
|
catecholamine released from post ganglionic sympathetic nerve fibers in peripheral nervous system
|
NE
|
|
|
what is released from chromaffin cells of the adrenal medulla
|
epi
|
|
|
is epi released from peripher nerves
|
no
|
|
|
NT released from neurons in CNS
|
epi and dopamine
|
|
|
aa that cat are derived from
|
tyrosine
|
|
|
tyrosine is converted to what
|
DOPA
|
|
|
DOPA is converted to..
|
dopamine
|
|
|
dopamine is converted to ? where?
|
NE in the storage vesicle
|
|
|
in the granule, NE is associated with ? and ?
|
ATP and a protein called chromoganin
|
|
|
what stimulates NE systhesis
|
increased neuronal activity by increasing tyrosine hydroxlase
|
|
|
what is the rate limiting step in epi synthesis
|
Tyrosine hydroxylase
|
|
|
what happens when action potential invades nerve terminal
|
influx of calcium
|
|
|
how else can NE be released
|
sympathomimetic amines such as tyramine and amphetamine
|
|
|
T or F Synaptic NE can also stimulate presynaptic alpha 2 receptors that act as a neg feedback to inhi further release of NT
|
TRUE
|
|
|
What does COMT do
|
catechol - o - methyltransferase enzymatically inactivates NE that enters the post synaptic cell
|
|
|
what is this referred to as?
|
uptake II
|
|
|
what is NT degraded by if it diffuses into the systemic circulation
|
MAO and COMT in liver
|
|
|
what is the most important mech for the term of NE action
|
re uptake back into the nerve terminal 60-90%
|
|
|
if NE is not sequestered by the storage vesicle in the presyn term, what and where will it be inactivated?
|
MAO in the mitochondria
|
|
|
MAO is in high concentration in what organ
|
liver
|
|
|
what metabolite is sometimes screened for in patients suspected of harboring a tumor of the adrenal gland called pheochromocytoma
|
VMA
|
|
|
alpha 1 receptors are located where
|
post junctionally at most symp neuroeffector synapses except the heart and JF cell so fthe kidney
|
|
|
activation of alpha 1 receptors is excitatory or inhibitory
|
excitatory ( increased bp, pupil dilation via contraction of the radial muscle of iris, piloerection, viscous salivation, contraction of GI an durinary bladder
|
|
|
what systems are inhibited with alpha 1 receptors
|
Gi and urinary smooth muscle
|
|
|
what is the function of alpha 2 receptors
|
provide a neg feedback mechanism to prevent excessive release of NE
|
|
|
where are the 2 places that beta 1 receptors are found
|
heart and JG apparatus of the kidney
|
|
|
what are the only receptors potently stimulated by NE
|
beta 1 receptors
|
|
|
what are beta receptors responsible for?
|
increasing heart rate, conduction, ad contractile force as well as the neural release of renin from the JG cells
|
|
|
what are the only innervated beta adrenoreceptors
|
beta 1
|
|
|
do beta 1 adrencoreceptors prefer epi or NE
|
epi
|
|
|
what is the result of beta 1 receptor stimulation
|
increased cardiac output
|
|
|
what will beta 2 receptors activation cause?
|
vascular vasodilation and reduction of bp, relaxation of smooth muscle of bronchial tree, inhibition of GI and urinary tract smooth muscle, and relaxation of gravid uterus
|
|
|
sympathomimetic drugs
|
mimic sympathetic function
|
|
|
2 ways they can do this
|
directly by stim the adrenergic rec or indirectly allowing more NE to be present in the synaptic cleft
|
|
|
isoproterenol is a synthetic catecholamine iwth preference for which receptors?
|
all b adrenoreceptors
|
|
|
epinephrine works on what receptors
|
all alpha and beta
|
|
|
is epi effective when given orally
|
no
|
|
|
alpha adrenoreceptor activation is...
|
vasoconstriction
|
|
|
beta adrenoreceptor activation is...
|
vasodilation
|
|
|
are there more alpha or beta receptors
|
alpha (but less sensitive to epi)
|
|
|
which receptors are more sensitive to epi
|
beta (even though fewer in number)
|
|
|
which receptor is fewer in number, more sensitive to epi and has longer lasting effects
|
beta receptors
|
|
|
which receptor is greater in number, less sensitive to epi and has shorter duration of effects
|
alpha
|
|
|
what would the effect of a small bolus of epi be?
|
vasodilation due to beta response
|
|
|
what would the effect of a large bolus of epi be?
|
vasoconstriction and a pressor response -- alpha response
|
|
|
when epinephrime stimulates beta 1 receptors, what is the effect on the heart?
|
increase heart rate and contractility
|
|
|
epi works on beta 2 receptors to do what?
|
relax bronchial smooth muscle in the treatment of asthma and for treating bronchospasm during anaplylactic shock
|
|
|
epi acts via beta adrenoreceptors mechanisms to increase adenylate cyclase activity to form cAMP that has what metabolic effects?
|
1) increase plasma glucose by breakdown of liver glycogen 2) inhibits synthesis of glycogen 3) stimulates gluconeogensis 4) breaks down fats to fatty acids
|
|
|
NE acts on which receptors?
|
all alpha, and beta 1
|
|
|
a bolus injection of NE will have what outcome?
|
increase blood pressure due to both vasoconstriction and increased cardiac output
|
|
|
which has a longer 1/2 life: epi or NE?
|
epi
|
|
|
isoproterenol has what effect
|
potently acts on all B receptors to relieve bronchoconstrictive states
|
|
|
A CNS defect in dopaminergic mechanisms results in what disease
|
parkinsons
|
|
|
dopamine has what effect on the kidney
|
vasodilation
|
|
|
at higher doses, what is the effect of dopamine
|
stimulate alpha and beta receptors to increase bp, and cardiac output
|
|
|
what drug, found in certain foods like beer, cheese, and wine, can cause a hypertensive crisis in pts taking MAO inhibitor to treat depression?
|
tyramine
|
|
|
amphetamine and meth are what kinds of drugs
|
indirect sympathomimetics
|
|
|
why are amphetamines so toxic and lethal?
|
bc the ED50 increases but the LD50 remains the same
|
|
|
chronic toxicity to amphetamines can mimic what?
|
paranoid schizophrenia
|
|
|
what is the major finding at autopsy of amphetamine overdose>
|
cerebral hemorrhage that may be secondary to intense vasoconstriction of blood vessels
|
|
|
what are the 2 valid reasons for amphetamine use
|
1) hyperkinetic children to increase attention span 2) narcolepsy
|
|
|
methylphenidate is a mild CNS stimulant that causes what?
|
gerenalized CNS excitation that may cause convulsions
|
|
|
primary use of methylphenidate (Ritalin)
|
ADHD
|
|
|
ephedrine
|
agonist on all alpha and beta receptors in the body
|
|
|
medical uses for ephedrine
|
bronichial asthma (b effect) ear and nasal congestion OTC, opthalmology for short lasting mydriasis without cycloplegia
|
|
|
phenylephrine has what primary effect
|
alpha adrenergic effects
|
|
|
medical uses for phenylephrine
|
opthal for mydriasis, nasal spray
|
|
|
terbutaline is a modification of what drug
|
metaproterenol
|
|
|
which is longer acting
|
terbutaline
|
|
|
what drug is used to prevent premature child birth
|
terbutaline
|
|
|
which drug, terbutaline or metaproterenol, has a higher incidence of cardiac side effect?
|
terbulatine
|
|
|
drug for astham, similar to terbutaline
|
albuterol
|
|
|
long acting beta 2 agonist that is used to treat bronchial asthma
|
salmeterol
|
|
|
beta 2 agonist that is approved for use to relax smooth muscle of the uterus and to delay premature child labor
|
ritodrine
|
|
|
what is the preferred method of delivery for ritrodrine
|
orally, even though only 30% effective
|
|
|
synthetic catecholamine analog of dopamine that is a highly selective beta 1 adrenoreceptor
|
dobutamine
|
|
|
does dobutamine stimulate dopamine receptors?
|
no
|
|
|
what is the effect of dobutamine on the heart?
|
increased cardiac output without the vasoconstriction associated with NE that would result in increased cardiac work
|
|
|
what drug is used for short term treatment of cardiac insufficiency
|
dobutamine
|
|
|
what is the effect of sympatho-inhibitory agents on the peripheral nervous system
|
vasoconstriction by alpha 2's, short lived
|
|
|
what is the effect of sympatho - inhibitory agents on the CNS?
|
hypotensive action that lasts for hours
|
|
|
|
|
|
|
potent alpha 2 stimulant that readily penetrates into the CNS where it acts to decreases sympathetic tone to blood vessels and the heart
|
also may enhance vagal outflow
|
|
|
drug that has been used in treating the excessive symp activity exp during withdrawal from opoid and ethanol addiction
|
clonidine
|
|
|
what is a problem exp with withdrawal from clonidine itself?
|
dramatic rebound hypertension following cessation of clonidine therapy
|
|
|
what type of drug is alpha methyl dopa
|
antihypertensive - alpha 2
|
|
|
why does a methylnorepinephrine have a longer half life than NE?
|
not metabolized by MAO
|
|
|
problems exp with alpha blockade
|
postural hypotension, reflex tachycardia
|
|
|
what will alpha blockade produce?
|
reduction in bp
|
|
|
what are teh 4 most common side effects seen with alpha blockade?
|
hypotension, reflex tachycardia, failure to ejaculate, nasal congestion
|
|
|
what are the 5 alpha antagonists?
|
phentolamine, phenyoxybenzamine, prazosin, terazosin, doxazosin
|
|
|
what is phentolamine used for?
|
screening test for pheochromocytoma
|
|
|
what does phentolamine cause many false positive reactions
|
bc it releases histamine
|
|
|
which drug has a higher preference for alpha 1 receptors? phentolamine or phenxoybezamine
|
phenoxybenzamine
|
|
|
why does phenoxybenzamine have a longer duration?
|
because it binds comp at first, then after 30-60 min binds irreversibly by non competitive inhibition
|
|
|
why is prazosin useful in treating some hypertensive patients?
|
does not produce the large tachycardia seen with other alpha antagonists
|
|
|
what drugs are commonly used to treat the symptoms of benign prostatic hypertrophy?
|
terzosin and doxazosin
|
|
|
what is unique about terazosin and doxazosin?
|
longer half life permitting once per day dosing
|
|
|
beta 1 blockage will produce what outcomes
|
reduction in heart rate, myocardial contractility, conduction velocity and renin release
|
|
|
beta 2 blockade will produce what effect
|
prevention of relaxation of bronchial smooth muscle
|
|
|
beta blockers are used to treat what 5 conditions?
|
hypertension, angina, certain cardiac arrythmias, and CHF
|
|
|
what drugs are used to decrease the risk of myocardial reinfarction in patients at risk
|
beta blockers
|
|
|
what are 2 other uses of beta blockers?
|
glaucoma and prevention of migraines
|
|
|
when should beta blockers be used with caution? what 3 conditions?
|
bronchial astham, COPD, diabetes mellitus
|
|
|
what should beta blockers be used with caution in pts with diabetes?
|
they wont experience the usual expected tachycardia warning them of a hypoglycemic state
|
|
|
which beta blockers are non selective?
|
nadolol, timolol, propanolol, pindolol (never trick pink panthers)
|
|
|
which beta blockers are cardioselective?
|
betaxolol, esmolol, atenolol, metaprolol (BEAM)
|
|
|
which beta blocker is almost as potent of a LA as lidocaine?
|
propanolol
|
|
|
what is the effect of metoprolol?
|
selective for B1, so reduces plasma renin, but not as much effect on bronchial smooth muscle
|
|
|
what are the side effects of metoprolol?
|
fatigue, insomnia, headache, dizziness
|
|
|
what about atenolol is different from metoprolol?
|
much longer half life and less side effects
|
|
|
should atenolol be administered to pts with severe renal disease?
|
NO
|
|
|
what drug has Intrinsic sympathomimetic activity?
|
pindolol
|
|
|
which beta blocker is best tolerated during exercise?
|
pindolol, bc it is intrinsic sympathetic activity
|
|
|
what is the clinical use of timolol?
|
topical to relieve intraocular pressure
|
|
|
which drug is the treatment of choice for open angle glaucoma?
|
timolol
|
|
|
what beta blocker is suitable for patients where compliance is a particular problem?
|
nadolol- bc of long duration
|
|
|
why does esmolol have a very short half life?
|
rapid hydrolysis by cytosolic red blood cell esterases
|
|
|
what is the clinical use of esmolol?
|
acute emergency control of ventricular heart rate in pts with atrial fibrillation
|
|
|
why is esmolol used in acute emergency control of ventricular heart rate?
|
bc of its short half life of 10-15 min
|
|
|
which drug has both alpha and beta blocking properties?
|
labetalol
|
|
|
which blocking effect predominates?
|
alpha blocking effect predominates
|
|
|
which drug acts as a "free radical scavenger" in addition to being used for CHF?
|
carvedilol
|
|
|
cholinomimetic drugs that are choline esters
|
1. acetylcholine 2. methacholine 3. carbachol 4. bethanechol
|
|
|
cholinomimetic drugs that are naturally occurring
|
1. nitotine 2. muscarine 3. pilocarpine
|
|
|
2 ways that cholinomimetic drugs enhance cholinergic function
|
1. activate Ach directly through nicotinic and muscarinic receptors and 2. block AchE
|
|
|
function of anticholinesterase agents
|
indirectly increase cholinergic function
|
|
|
list reversible anticholinesterase agents
|
1. physostigmine 2. neostigmine 3. edrophonium 4. pyridostigmine 5. donepezil and tacrine
|
|
|
list anticholinesterase irreversible agents
|
1. parathion and malathion 2. sarin and soman
|
|
|
what is the cholinesterase reactivator?
|
pralidoxime (2-PAM)
|
|
|
what are the 5 basic steps in neurotransmission
|
1. synthesis 2. storage 3. release from presynaptic terminal 4. reception and post-syn response 5. termination of signal
|
|
|
examples of muscarinic blocking drugs
|
1. atropine 2. scopolamine 3. tropicamide 4. ipratropium 5. benzytropine 6. oxybutynin
|
|
|
what are 6 example of places where cholinergic synapses are found?
|
1. all parasyn neuroeffector junctions 2. all autonomic ganglia 3. skeletal NMJ 4. sympathetic innervation of adrenal medulla 5. sweat glands 6. brain and SC sites
|
|
|
non-innevated ACh receptors are generally of what type?
|
muscarinic
|
|
|
how do cholinergic drugs decrease colinergic function?
|
they usually occupy the receptor so the ACh molecules cannot act on them
|
|
|
where does synthesis of ACh occur?
|
cytoplasm of cholinergic nerves
|
|
|
enzyme that catalyzes ACh synthesis
|
choline acetylase
|
|
|
rate-limiting step of ACh synthesis
|
active pumping of choline into the nerve by a transport mechanism
|
|
|
what blocks the transport of choline into the nerve that causes an eventual inhibition of choline function?
|
hemocholinium (HC-3)
|
|
|
what causes attachment of ACh granules to fuse with nerve terminal membranes during action potential
|
influx of Ca
|
|
|
what can inhibit exocytosis of ACh into synaptic space?
|
anything that lowers extracellular Ca i.e. bot toxin and latrotoxin
|
|
|
what prevents release of ACh from nerve terminal
|
botulinum toxin
|
|
|
what causes excessive fusing of ACh granules w/ nerve mem causing excessive release and depletion of ACh
|
latrotoxin - spider venom
|
|
|
where are pseudocholinesterases found?
|
plasma and liver
|
|
|
M2 receptors are found
|
in heart
|
|
|
M3 receptors are found
|
peripheral autonomic organs
|
|
|
M1 receptors are found
|
in GI tract and autonomic ganglia
|
|
|
which muscarinic receptors are located in CNS
|
M1-M5
|
|
|
what does stimulation of muscarinic receptors in the heart do?
|
slows heart by increasing K permeability causing prolonged phase 4 depolarizaiton
|
|
|
T/F: muscarinic receps in heart directly stimulate ventricular contraction
|
F: they have little effect on force of vent contraction
|
|
|
what effect does systemic admin of ACh and muscarinic stimulants have on vascular sm
|
profound vasodilation and decrease BP
|
|
|
how does ACh cause blood vessel smooth muscle relaxation?
|
ACh acts on non-innerv muscarinic receptors on endothelial cells that releases EDRF (NO)
|
|
|
what do muscarinic agonists produce in the eye
|
pupillary constriction (miosis) and spasm of accommodation (cyclotonia)
|
|
|
what do muscarinic agonists do in the GI tract
|
increase tone and motility
|
|
|
what do muscarinic agonists do in bronchiolar smooth muscle
|
modest constriction
|
|
|
how must ACh be administered to have an effect
|
injected
|
|
|
what will be activated if ACh is given in low doses
|
only muscarinic receptors, much higher amts are needed to stimulate nicotinic
|
|
|
what drug is partially resistant to AChase, is a potent muscarinic stimulant, but has lost almost all nicotinic action of parent molecule
|
methacholine
|
|
|
why is methacholine not used as much in humans
|
has too many generalized muscarinic effects
|
|
|
what drug is very refractory to inactivation by AChase, has a potent nicotinic stimulating effects w/ little muscarinic actions, and releases ACh from cholinergic nerve endings
|
carbachol
|
|
|
what drug is used topically on eye to produce miosis and tx glaucoma
|
carbachol
|
|
|
which drug is only choline ester that has established clinical use
|
bethanechol
|
|
|
which drug is refractory to AChase inactivation and has mostly muscarinic stimuating effects, tx post-op urinary retention and atony of GI tract
|
bethanechol
|
|
|
how is bethanechol used clinically
|
tx esophageal reflux due to stimulatory action on lower esophageal sphincter
|
|
|
what are responses to injected nicotine
|
activation of all autonomic ganglia and stim of skeletal muscle endplate nic receptors
|
|
|
antidote for muscarine poisoning
|
atropine
|
|
|
which drug selectively activates muscarinic receptors, not highly charged so can cross BBB, and used to tx glaucoma
|
pilocarpine
|
|
|
T/F: all somatic nerves release ACh
|
T
|
|
|
what happens to BP if ACh is given in small doses
|
decrease in BP
|
|
|
what happens to BP if ACh is given in a small dose after atropine is given
|
no effect on BP b/c atropine blocked musc receptors
|
|
|
what happens to BP if ACh is given in a large dose after atropine is given
|
big increase in BP b/c ACh is now hitting nicotinic receptors
|
|
|
when nicotine is given repeatedly or in large doses, why does it block nicotinic receptors?
|
sustained depolarization
|
|
|
agents that indirectly enhance cholinergic function
|
anticholinesterases
|
|
|
anticholinesterases only have an effect on which type of receptors
|
only at innervated ACh receptors
|
|
|
main clinical use for AChase inhibitors
|
tx myasthenina gravis and glaucoma
|
|
|
what is used to tx atropine poisoning
|
physostigmine
|
|
|
what drugs are antidotes to curare
|
AChase inhibitors
|
|
|
main clinical use for physostigmine
|
topical for glaucoma
|
|
|
what actions does physostigmine have in eye
|
miosis and contraction of ciliary muscle
|
|
|
how is it imp that physostigmine is not highly charged
|
can enter CNS
|
|
|
what drug is the best choice for atropine poisoning
|
physostigmine
|
|
|
neostigmine directly stimulates nicotinic sites where?
|
on skeletal muscle endplates
|
|
|
the dual action of neostigmine makes it a drug of choice for what
|
myasthenia gravis
|
|
|
pyridostigmine is used to tx what
|
myasthenia gravis
|
|
|
which AChase inhibitors are CNS acting and used to tx cognitive dysfunction in Alzeimer's dx
|
donepezil and tacrine
|
|
|
which cholinomimetic can stimulate salivary flow
|
pilocarpine
|
|
|
which drug is used to distinguish myasthenia gravis from AChE blockade (cholinergic crisis)
|
edrophonium
|
|
|
Can be used as topical treatments for glaucoma,but most are insecticides and military nerve agents
|
irreversible AChases
|
|
|
what insecticide is converted in the liver to the active form
|
parathion
|
|
|
sarin and soman
|
Gaseous nerve agents used in chemical warfare. NOT reversible by cholinesterase reactivators
|
|
|
Used to treat muscarinic intoxication and intoxication with some irreversible organophosphate anti-cholinesterases
|
pralidoxime (2-PAM)
|
|
|
paralysis of the NMJ's due to excessive ACHASE inhibition
|
cholinergic crisis
|
|
|
paralysis of the NMJ's due to insufficient ACHASE inhibition
|
myasthenic crisis
|
|
|
what would muscarinic receptor blockers do to parasym innervated organ
|
lack of motility and secretions
|
|
|
what is the diff b/w atropine and scopolamine
|
atropine produces CNS excitation, scopolamine causes CNS depression
|
|
|
low doses of atropine cause what
|
slight paradoxical bradycardia due to CNS stim
|
|
|
higher doses of atropine cause what
|
they block peripheral muscarinic receptors at heart to produce tachycardia
|
|
|
atropine effect on heart
|
low doses- bradycardia, higher doses-tachycardia
|
|
|
atropine effect on skin
|
inhibition of sweating, hot dry skin
|
|
|
atropine effect on eye
|
mild to marked mydriasis, mild to marked cycloplegia
|
|
|
atropine effect on viscera
|
dry mouth, decreased saliv, reduced GI and urinary tone
|
|
|
atropine effect on CNS
|
confusion, restlessness, excitement --- hallucinations, delirium, coma
|
|
|
characteristics of atropine poisoning
|
hot dry skin, dilated pupils, maniacal behavior
|
|
|
what is a less potent and much shorter acting muscarinic antag
|
tropicamide
|
|
|
use for tropicamide
|
opthalmological exams
|
|
|
ipratropium is mainly used in what type of pts
|
COPD (asthma secondarily)
|
|
|
how does ipratropium work in COPD pts
|
bronchodilation w/o affecting bronchial secretions
|
|
|
musc blocker that crosses BBB and tx parkinson's
|
benztropine
|
|
|
musc blocker that tx bladder spasms postop that decreases bladder tone and improves continence
|
oxybutynin
|
|
|
will innervated or non-innerv receptors be affected by ganglionic transmission
|
innerv
|
|
|
ganglionic stim will excite which organs
|
all autonomic organs
|
|
|
which neurons/cells does nicotine stimulate
|
postgang neurons and adrenal chromaffin cells
|
|
|
prototype ganglionic blocking drug
|
hexamethonium
|
|
|
nicotine blocks autonomic ganglia when given in high doses due to what
|
sustained depolarization of postgang cells
|
|
|
T/F: hexamethonium blocks NMJ's
|
F - does not
|
|
|
predominant tone and effect of ganglionic blockade at arterioles
|
sypathetic - vasodilation
|
|
|
predominant tone and effect of ganglionic blockade at veins
|
sym - dilation
|
|
|
predominant tone and effect of ganglionic blockade at heart
|
parasym - tachycardia
|
|
|
predominant tone and effect of ganglionic blockade at iris
|
parasym - mydriasis
|
|
|
predominant tone and effect of ganglionic blockade at ciliary muscle
|
parasym - cycloplegia
|
|
|
predominant tone and effect of ganglionic blockade at GI tract
|
parasym - reduced tone and motility
|
|
|
predominant tone and effect of ganglionic blockade at urinary bladder
|
parasym - urinary retention
|
|
|
predominant tone and effect of ganglionic blockade at salivary glands
|
parasym - xerostomia
|
|
|
predominant tone and effect of ganglionic blockade at sweat glands
|
sym - anhidrosis
|
|
|
drugs can cause neuromuscular blockade by one of what 2 ways
|
1. compete w/ ACh for nicotinic receptors 2. sustained depolarization
|
|
|
how do local anes and tetrodotoxin inhibit nerve action potential
|
interfere w/ Na transport
|
|
|
what inhibits ACh release by blocking reuptake of choline into nerve ending
|
hemicholinium
|
|
|
what inhibits ACh release by blocking ACh release mech
|
botulinum toxin
|
|
|
what enhances ACh release
|
spider venom (latrotoxin) and catecholamines
|
|
|
what inhibits binding of ACh to receptor
|
NMJ blockers and snake alpha-bungarotoxins
|
|
|
T/F: competitive NMJ blocking drugs enter BBB
|
F: highly charged
|
|
|
T/F: competitive NMJ blocking drugs produce reduction in pain sensation
|
FALSE
|
|
|
gold standard of competitive NMJ blockers
|
tubocurarine
|
|
|
main side effect for tubocurarine - eliminated by?
|
hypotension - liver
|
|
|
how is doxacurium different from tubocurarine?
|
doesn't block autonomic ganglia or release histamine
|
|
|
organ of excretion for doxacurium
|
kidney
|
|
|
NMJ blocker w/ steroid nucleus
|
pancuronium
|
|
|
how is pancuronium same as doxacurium
|
no autonomic blockade no histamine release
|
|
|
more potent, shorter acting analog of pancuronium
|
vecuronium
|
|
|
only drug used clinically as depolarizing NMJ blocker
|
succinylcholine
|
|
|
how is succinylcholine inactivated
|
rapidly metabolized by plasma and liver pesudocholinesterases
|
|
|
drug of choice to relax laryngeal muscles before intubation
|
succinylcholine
|
|
|
what syndrome can appear due to succinylcholien
|
malignant hyperthermia
|
|
|
benzodiazeepine that enhances GABAergic inhibition in CNS
|
diazepam
|
|
|
side effect for diazepam
|
sedation at effective dose
|
|
|
function of diazepam
|
reduces all muscle spasms
|
|
|
drug that causes decrease in release of Glu and decrease in skeletal muscle tone while experiencing less sedation than diazepam
|
baclofen
|
|
|
drug used for relief of spasticity caused by MS and spinal cord injury
|
baclofen
|
|
|
drug that is CNS alpha2 stim, reduces skeletal muscle spasticity, causes less hypotension, but causes sedation and dry mouth
|
tizanidine
|
|
|
related to tricyclic antidepressants, tx muscular spasms assoc w/ musculoskeletal conditions
|
cyclobenzaprine
|
|
|
spasmolytic w/ side effects that are atropine-like and not effective in tx for spasms from spinal cord injury or cerebral palsy
|
cyclobenzaprine
|
|
|
Acts directly on skeletal muscle abd disrupts excitation-contraction coupling by blocking release of Ca needed for contraction
|
dantrolene
|
|
|
drug of choice for treating malignant hyperthermia
|
dantrolene
|
|
|
main adverse effects of dantrolene
|
generalized msucle weakness and sedation
|
|
|
muscle relaxant to tx generalized spastic disorders (cerebral palsy), effective longterm blockade of trans to muscle
|
botulinum toxin
|
|
|
drugs to tx paralytic ileus
|
physostigmine and bethanechol
|
|
|
cholinomimetic drugs that are choline esters
|
1. acetylcholine 2. methacholine 3. carbachol 4. bethanechol
|
|
|
cholinomimetic drugs that are naturally occurring
|
1. nitotine 2. muscarine 3. pilocarpine
|
|
|
2 ways that cholinomimetic drugs enhance cholinergic function
|
1. activate Ach directly through nicotinic and muscarinic receptors and 2. block AchE
|
|
|
function of anticholinesterase agents
|
indirectly increase cholinergic function
|
|
|
list reversible anticholinesterase agents
|
1. physostigmine 2. neostigmine 3. edrophonium 4. pyridostigmine 5. donepezil and tacrine
|
|
|
list anticholinesterase irreversible agents
|
1. parathion and malathion 2. sarin and soman
|
|
|
what is the cholinesterase reactivator?
|
pralidoxime (2-PAM)
|
|
|
what are the 5 basic steps in neurotransmission
|
1. synthesis 2. storage 3. release from presynaptic terminal 4. reception and post-syn response 5. termination of signal
|
|
|
examples of muscarinic blocking drugs
|
1. atropine 2. scopolamine 3. tropicamide 4. ipratropium 5. benzytropine 6. oxybutynin
|
|
|
what are 6 example of places where cholinergic synapses are found?
|
1. all parasyn neuroeffector junctions 2. all autonomic ganglia 3. skeletal NMJ 4. sympathetic innervation of adrenal medulla 5. sweat glands 6. brain and SC sites
|
|
|
non-innevated ACh receptors are generally of what type?
|
muscarinic
|
|
|
how do cholinergic drugs decrease colinergic function?
|
they usually occupy the receptor so the ACh molecules cannot act on them
|
|
|
where does synthesis of ACh occur?
|
cytoplasm of cholinergic nerves
|
|
|
enzyme that catalyzes ACh synthesis
|
choline acetylase
|
|
|
rate-limiting step of ACh synthesis
|
active pumping of choline into the nerve by a transport mechanism
|
|
|
what blocks the transport of choline into the nerve that causes an eventual inhibition of choline function?
|
hemocholinium (HC-3)
|
|
|
what causes attachment of ACh granules to fuse with nerve terminal membranes during action potential
|
influx of Ca
|
|
|
what can inhibit exocytosis of ACh into synaptic space?
|
anything that lowers extracellular Ca i.e. bot toxin and latrotoxin
|
|
|
what prevents release of ACh from nerve terminal
|
botulinum toxin
|
|
|
what causes excessive fusing of ACh granules w/ nerve mem causing excessive release and depletion of ACh
|
latrotoxin - spider venom
|
|
|
where are pseudocholinesterases found?
|
plasma and liver
|
|
|
M2 receptors are found
|
in heart
|
|
|
M3 receptors are found
|
peripheral autonomic organs
|
|
|
M1 receptors are found
|
in GI tract and autonomic ganglia
|
|
|
which muscarinic receptors are located in CNS
|
M1-M5
|
|
|
what does stimulation of muscarinic receptors in the heart do?
|
slows heart by increasing K permeability causing prolonged phase 4 depolarizaiton
|
|
|
T/F: muscarinic receps in heart directly stimulate ventricular contraction
|
F: they have little effect on force of vent contraction
|
|
|
what effect does systemic admin of ACh and muscarinic stimulants have on vascular sm
|
profound vasodilation and decrease BP
|
|
|
how does ACh cause blood vessel smooth muscle relaxation?
|
ACh acts on non-innerv muscarinic receptors on endothelial cells that releases EDRF (NO)
|
|
|
what do muscarinic agonists produce in the eye
|
pupillary constriction (miosis) and spasm of accommodation (cyclotonia)
|
|
|
what do muscarinic agonists do in the GI tract
|
increase tone and motility
|
|
|
what do muscarinic agonists do in bronchiolar smooth muscle
|
modest constriction
|
|
|
how must ACh be administered to have an effect
|
injected
|
|
|
what will be activated if ACh is given in low doses
|
only muscarinic receptors, much higher amts are needed to stimulate nicotinic
|
|
|
what drug is partially resistant to AChase, is a potent muscarinic stimulant, but has lost almost all nicotinic action of parent molecule
|
methacholine
|
|
|
why is methacholine not used as much in humans
|
has too many generalized muscarinic effects
|
|
|
what drug is very refractory to inactivation by AChase, has a potent nicotinic stimulating effects w/ little muscarinic actions, and releases ACh from cholinergic nerve endings
|
carbachol
|
|
|
what drug is used topically on eye to produce miosis and tx glaucoma
|
carbachol
|
|
|
which drug is only choline ester that has established clinical use
|
bethanechol
|
|
|
which drug is refractory to AChase inactivation and has mostly muscarinic stimuating effects, tx post-op urinary retention and atony of GI tract
|
bethanechol
|
|
|
how is bethanechol used clinically
|
tx esophageal reflux due to stimulatory action on lower esophageal sphincter
|
|
|
what are responses to injected nicotine
|
activation of all autonomic ganglia and stim of skeletal muscle endplate nic receptors
|
|
|
antidote for muscarine poisoning
|
atropine
|
|
|
which drug selectively activates muscarinic receptors, not highly charged so can cross BBB, and used to tx glaucoma
|
pilocarpine
|
|
|
T/F: all somatic nerves release ACh
|
T
|
|
|
what happens to BP if ACh is given in small doses
|
decrease in BP
|
|
|
what happens to BP if ACh is given in a small dose after atropine is given
|
no effect on BP b/c atropine blocked musc receptors
|
|
|
what happens to BP if ACh is given in a large dose after atropine is given
|
big increase in BP b/c ACh is now hitting nicotinic receptors
|
|
|
when nicotine is given repeatedly or in large doses, why does it block nicotinic receptors?
|
sustained depolarization
|
|
|
agents that indirectly enhance cholinergic function
|
anticholinesterases
|
|
|
anticholinesterases only have an effect on which type of receptors
|
only at innervated ACh receptors
|
|
|
main clinical use for AChase inhibitors
|
tx myasthenina gravis and glaucoma
|
|
|
what is used to tx atropine poisoning
|
physostigmine
|
|
|
what drugs are antidotes to curare
|
AChase inhibitors
|
|
|
main clinical use for physostigmine
|
topical for glaucoma
|
|
|
what actions does physostigmine have in eye
|
miosis and contraction of ciliary muscle
|
|
|
how is it imp that physostigmine is not highly charged
|
can enter CNS
|
|
|
what drug is the best choice for atropine poisoning
|
physostigmine
|
|
|
neostigmine directly stimulates nicotinic sites where?
|
on skeletal muscle endplates
|
|
|
the dual action of neostigmine makes it a drug of choice for what
|
myasthenia gravis
|
|
|
pyridostigmine is used to tx what
|
myasthenia gravis
|
|
|
which AChase inhibitors are CNS acting and used to tx cognitive dysfunction in Alzeimer's dx
|
donepezil and tacrine
|
|
|
which cholinomimetic can stimulate salivary flow
|
pilocarpine
|
|
|
which drug is used to distinguish myasthenia gravis from AChE blockade (cholinergic crisis)
|
edrophonium
|
|
|
Can be used as topical treatments for glaucoma,but most are insecticides and military nerve agents
|
irreversible AChases
|
|
|
what insecticide is converted in the liver to the active form
|
parathion
|
|
|
sarin and soman
|
Gaseous nerve agents used in chemical warfare. NOT reversible by cholinesterase reactivators
|
|
|
Used to treat muscarinic intoxication and intoxication with some irreversible organophosphate anti-cholinesterases
|
pralidoxime (2-PAM)
|
|
|
paralysis of the NMJ's due to excessive ACHASE inhibition
|
cholinergic crisis
|
|
|
paralysis of the NMJ's due to insufficient ACHASE inhibition
|
myasthenic crisis
|
|
|
what would muscarinic receptor blockers do to parasym innervated organ
|
lack of motility and secretions
|
|
|
what is the diff b/w atropine and scopolamine
|
atropine produces CNS excitation, scopolamine causes CNS depression
|
|
|
low doses of atropine cause what
|
slight paradoxical bradycardia due to CNS stim
|
|
|
higher doses of atropine cause what
|
they block peripheral muscarinic receptors at heart to produce tachycardia
|
|
|
atropine effect on heart
|
low doses- bradycardia, higher doses-tachycardia
|
|
|
atropine effect on skin
|
inhibition of sweating, hot dry skin
|
|
|
atropine effect on eye
|
mild to marked mydriasis, mild to marked cycloplegia
|
|
|
atropine effect on viscera
|
dry mouth, decreased saliv, reduced GI and urinary tone
|
|
|
atropine effect on CNS
|
confusion, restlessness, excitement --- hallucinations, delirium, coma
|
|
|
characteristics of atropine poisoning
|
hot dry skin, dilated pupils, maniacal behavior
|
|
|
what is a less potent and much shorter acting muscarinic antag
|
tropicamide
|
|
|
use for tropicamide
|
opthalmological exams
|
|
|
ipratropium is mainly used in what type of pts
|
COPD (asthma secondarily)
|
|
|
how does ipratropium work in COPD pts
|
bronchodilation w/o affecting bronchial secretions
|
|
|
musc blocker that crosses BBB and tx parkinson's
|
benztropine
|
|
|
musc blocker that tx bladder spasms postop that decreases bladder tone and improves continence
|
oxybutynin
|
|
|
will innervated or non-innerv receptors be affected by ganglionic transmission
|
innerv
|
|
|
ganglionic stim will excite which organs
|
all autonomic organs
|
|
|
which neurons/cells does nicotine stimulate
|
postgang neurons and adrenal chromaffin cells
|
|
|
prototype ganglionic blocking drug
|
hexamethonium
|
|
|
nicotine blocks autonomic ganglia when given in high doses due to what
|
sustained depolarization of postgang cells
|
|
|
T/F: hexamethonium blocks NMJ's
|
F - does not
|
|
|
predominant tone and effect of ganglionic blockade at arterioles
|
sypathetic - vasodilation
|
|
|
predominant tone and effect of ganglionic blockade at veins
|
sym - dilation
|
|
|
predominant tone and effect of ganglionic blockade at heart
|
parasym - tachycardia
|
|
|
predominant tone and effect of ganglionic blockade at iris
|
parasym - mydriasis
|
|
|
predominant tone and effect of ganglionic blockade at ciliary muscle
|
parasym - cycloplegia
|
|
|
predominant tone and effect of ganglionic blockade at GI tract
|
parasym - reduced tone and motility
|
|
|
predominant tone and effect of ganglionic blockade at urinary bladder
|
parasym - urinary retention
|
|
|
predominant tone and effect of ganglionic blockade at salivary glands
|
parasym - xerostomia
|
|
|
predominant tone and effect of ganglionic blockade at sweat glands
|
sym - anhidrosis
|
|
|
drugs can cause neuromuscular blockade by one of what 2 ways
|
1. compete w/ ACh for nicotinic receptors 2. sustained depolarization
|
|
|
how do local anes and tetrodotoxin inhibit nerve action potential
|
interfere w/ Na transport
|
|
|
what inhibits ACh release by blocking reuptake of choline into nerve ending
|
hemicholinium
|
|
|
what inhibits ACh release by blocking ACh release mech
|
botulinum toxin
|
|
|
what enhances ACh release
|
spider venom (latrotoxin) and catecholamines
|
|
|
what inhibits binding of ACh to receptor
|
NMJ blockers and snake alpha-bungarotoxins
|
|
|
T/F: competitive NMJ blocking drugs enter BBB
|
F: highly charged
|
|
|
cholinomimetic drugs that are choline esters
|
1. acetylcholine 2. methacholine 3. carbachol 4. bethanechol
|
|
|
cholinomimetic drugs that are naturally occurring
|
1. nitotine 2. muscarine 3. pilocarpine
|
|
|
2 ways that cholinomimetic drugs enhance cholinergic function
|
1. activate Ach directly through nicotinic and muscarinic receptors and 2. block AchE
|
|
|
function of anticholinesterase agents
|
indirectly increase cholinergic function
|
|
|
list reversible anticholinesterase agents
|
1. physostigmine 2. neostigmine 3. edrophonium 4. pyridostigmine 5. donepezil and tacrine
|
|
|
list anticholinesterase irreversible agents
|
1. parathion and malathion 2. sarin and soman
|
|
|
what is the cholinesterase reactivator?
|
pralidoxime (2-PAM)
|
|
|
what are the 5 basic steps in neurotransmission
|
1. synthesis 2. storage 3. release from presynaptic terminal 4. reception and post-syn response 5. termination of signal
|
|
|
examples of muscarinic blocking drugs
|
1. atropine 2. scopolamine 3. tropicamide 4. ipratropium 5. benzytropine 6. oxybutynin
|
|
|
what are 6 example of places where cholinergic synapses are found?
|
1. all parasyn neuroeffector junctions 2. all autonomic ganglia 3. skeletal NMJ 4. sympathetic innervation of adrenal medulla 5. sweat glands 6. brain and SC sites
|
|
|
non-innevated ACh receptors are generally of what type?
|
muscarinic
|
|
|
how do cholinergic drugs decrease colinergic function?
|
they usually occupy the receptor so the ACh molecules cannot act on them
|
|
|
enzyme that catalyzes ACh synthesis
|
choline acetylase
|
|
|
rate-limiting step of ACh synthesis
|
active pumping of choline into the nerve by a transport mechanism
|
|
|
what blocks the transport of choline into the nerve that causes an eventual inhibition of choline function?
|
hemocholinium (HC-3)
|
|
|
what causes attachment of ACh granules to fuse with nerve terminal membranes during action potential
|
influx of Ca
|
|
|
what can inhibit exocytosis of ACh into synaptic space?
|
anything that lowers extracellular Ca i.e. bot toxin and latrotoxin
|
|
|
what prevents release of ACh from nerve terminal
|
botulinum toxin
|
|
|
what causes excessive fusing of ACh granules w/ nerve mem causing excessive release and depletion of ACh
|
latrotoxin - spider venom
|
|
|
where are pseudocholinesterases found?
|
plasma and liver
|
|
|
M2 receptors are found
|
in heart
|
|
|
M3 receptors are found
|
peripheral autonomic organs
|
|
|
M1 receptors are found
|
in GI tract and autonomic ganglia
|
|
|
which muscarinic receptors are located in CNS
|
M1-M5
|
|
|
what does stimulation of muscarinic receptors in the heart do?
|
slows heart by increasing K permeability causing prolonged phase 4 depolarizaiton
|
|
|
T/F: muscarinic receps in heart directly stimulate ventricular contraction
|
F: they have little effect on force of vent contraction
|
|
|
what effect does systemic admin of ACh and muscarinic stimulants have on vascular sm
|
profound vasodilation and decrease BP
|
|
|
how does ACh cause blood vessel smooth muscle relaxation?
|
ACh acts on non-innerv muscarinic receptors on endothelial cells that releases EDRF (NO)
|
|
|
what do muscarinic agonists produce in the eye
|
pupillary constriction (miosis) and spasm of accommodation (cyclotonia)
|
|
|
what do muscarinic agonists do in the GI tract
|
increase tone and motility
|
|
|
what do muscarinic agonists do in bronchiolar smooth muscle
|
modest constriction
|
|
|
how must ACh be administered to have an effect
|
injected
|
|
|
what will be activated if ACh is given in low doses
|
only muscarinic receptors, much higher amts are needed to stimulate nicotinic
|
|
|
what drug is partially resistant to AChase, is a potent muscarinic stimulant, but has lost almost all nicotinic action of parent molecule
|
methacholine
|
|
|
why is methacholine not used as much in humans
|
has too many generalized muscarinic effects
|
|
|
what drug is very refractory to inactivation by AChase, has a potent nicotinic stimulating effects w/ little muscarinic actions, and releases ACh from cholinergic nerve endings
|
carbachol
|
|
|
what drug is used topically on eye to produce miosis and tx glaucoma
|
carbachol
|
|
|
which drug is only choline ester that has established clinical use
|
bethanechol
|
|
|
which drug is refractory to AChase inactivation and has mostly muscarinic stimuating effects, tx post-op urinary retention and atony of GI tract
|
bethanechol
|
|
|
how is bethanechol used clinically
|
tx esophageal reflux due to stimulatory action on lower esophageal sphincter
|
|
|
what are responses to injected nicotine
|
activation of all autonomic ganglia and stim of skeletal muscle endplate nic receptors
|
|
|
antidote for muscarine poisoning
|
atropine
|
|
|
which drug selectively activates muscarinic receptors, not highly charged so can cross BBB, and used to tx glaucoma
|
pilocarpine
|
|
|
T/F: all somatic nerves release ACh
|
T
|
|
|
what happens to BP if ACh is given in small doses
|
decrease in BP
|
|
|
what happens to BP if ACh is given in a small dose after atropine is given
|
no effect on BP b/c atropine blocked musc receptors
|
|
|
what happens to BP if ACh is given in a large dose after atropine is given
|
big increase in BP b/c ACh is now hitting nicotinic receptors
|
|
|
when nicotine is given repeatedly or in large doses, why does it block nicotinic receptors?
|
sustained depolarization
|
|
|
agents that indirectly enhance cholinergic function
|
anticholinesterases
|
|
|
anticholinesterases only have an effect on which type of receptors
|
only at innervated ACh receptors
|
|
|
main clinical use for AChase inhibitors
|
tx myasthenina gravis and glaucoma
|
|
|
what is used to tx atropine poisoning
|
physostigmine
|
|
|
what drugs are antidotes to curare
|
AChase inhibitors
|
|
|
main clinical use for physostigmine
|
topical for glaucoma
|
|
|
what actions does physostigmine have in eye
|
miosis and contraction of ciliary muscle
|
|
|
how is it imp that physostigmine is not highly charged
|
can enter CNS
|
|
|
what drug is the best choice for atropine poisoning
|
physostigmine
|
|
|
neostigmine directly stimulates nicotinic sites where?
|
on skeletal muscle endplates
|
|
|
the dual action of neostigmine makes it a drug of choice for what
|
myasthenia gravis
|
|
|
pyridostigmine is used to tx what
|
myasthenia gravis
|
|
|
which AChase inhibitors are CNS acting and used to tx cognitive dysfunction in Alzeimer's dx
|
donepezil and tacrine
|
|
|
which cholinomimetic can stimulate salivary flow
|
pilocarpine
|
|
|
which drug is used to distinguish myasthenia gravis from AChE blockade (cholinergic crisis)
|
edrophonium
|
|
|
Can be used as topical treatments for glaucoma,but most are insecticides and military nerve agents
|
irreversible AChases
|
|
|
what insecticide is converted in the liver to the active form
|
parathion
|
|
|
sarin and soman
|
Gaseous nerve agents used in chemical warfare. NOT reversible by cholinesterase reactivators
|
|
|
Used to treat muscarinic intoxication and intoxication with some irreversible organophosphate anti-cholinesterases
|
pralidoxime (2-PAM)
|
|
|
paralysis of the NMJ's due to excessive ACHASE inhibition
|
cholinergic crisis
|
|
|
paralysis of the NMJ's due to insufficient ACHASE inhibition
|
myasthenic crisis
|
|
|
what would muscarinic receptor blockers do to parasym innervated organ
|
lack of motility and secretions
|
|
|
what is the diff b/w atropine and scopolamine
|
atropine produces CNS excitation, scopolamine causes CNS depression
|
|
|
low doses of atropine cause what
|
slight paradoxical bradycardia due to CNS stim
|
|
|
higher doses of atropine cause what
|
they block peripheral muscarinic receptors at heart to produce tachycardia
|
|
|
atropine effect on heart
|
low doses- bradycardia, higher doses-tachycardia
|
|
|
atropine effect on skin
|
inhibition of sweating, hot dry skin
|
|
|
atropine effect on eye
|
mild to marked mydriasis, mild to marked cycloplegia
|
|
|
atropine effect on viscera
|
dry mouth, decreased saliv, reduced GI and urinary tone
|
|
|
atropine effect on CNS
|
confusion, restlessness, excitement --- hallucinations, delirium, coma
|
|
|
characteristics of atropine poisoning
|
hot dry skin, dilated pupils, maniacal behavior
|
|
|
what is a less potent and much shorter acting muscarinic antag
|
tropicamide
|
|
|
use for tropicamide
|
opthalmological exams
|
|
|
ipratropium is mainly used in what type of pts
|
COPD (asthma secondarily)
|
|
|
how does ipratropium work in COPD pts
|
bronchodilation w/o affecting bronchial secretions
|
|
|
musc blocker that crosses BBB and tx parkinson's
|
benztropine
|
|
|
musc blocker that tx bladder spasms postop that decreases bladder tone and improves continence
|
oxybutynin
|
|
|
will innervated or non-innerv receptors be affected by ganglionic transmission
|
innerv
|
|
|
ganglionic stim will excite which organs
|
all autonomic organs
|
|
|
which neurons/cells does nicotine stimulate
|
postgang neurons and adrenal chromaffin cells
|
|
|
prototype ganglionic blocking drug
|
hexamethonium
|
|
|
nicotine blocks autonomic ganglia when given in high doses due to what
|
sustained depolarization of postgang cells
|
|
|
T/F: hexamethonium blocks NMJ's
|
F - does not
|
|
|
predominant tone and effect of ganglionic blockade at arterioles
|
sypathetic - vasodilation
|
|
|
predominant tone and effect of ganglionic blockade at veins
|
sym - dilation
|
|
|
predominant tone and effect of ganglionic blockade at heart
|
parasym - tachycardia
|
|
|
predominant tone and effect of ganglionic blockade at iris
|
parasym - mydriasis
|
|
|
predominant tone and effect of ganglionic blockade at ciliary muscle
|
parasym - cycloplegia
|
|
|
predominant tone and effect of ganglionic blockade at GI tract
|
parasym - reduced tone and motility
|
|
|
predominant tone and effect of ganglionic blockade at urinary bladder
|
parasym - urinary retention
|
|
|
predominant tone and effect of ganglionic blockade at salivary glands
|
parasym - xerostomia
|
|
|
predominant tone and effect of ganglionic blockade at sweat glands
|
sym - anhidrosis
|
|
|
drugs can cause neuromuscular blockade by one of what 2 ways
|
1. compete w/ ACh for nicotinic receptors 2. sustained depolarization
|
|
|
how do local anes and tetrodotoxin inhibit nerve action potential
|
interfere w/ Na transport
|
|
|
what inhibits ACh release by blocking reuptake of choline into nerve ending
|
hemicholinium
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what inhibits ACh release by blocking ACh release mech
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botulinum toxin
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what enhances ACh release
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spider venom (latrotoxin) and catecholamines
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what inhibits binding of ACh to receptor
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NMJ blockers and snake alpha-bungarotoxins
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T/F: competitive NMJ blocking drugs enter BBB
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F: highly charged
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T/F: competitive NMJ blocking drugs produce reduction in pain sensation
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FALSE
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gold standard of competitive NMJ blockers
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tubocurarine
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main side effect for tubocurarine - eliminated by?
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hypotension - liver
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how is doxacurium different from tubocurarine?
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doesn't block autonomic ganglia or release histamine
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organ of excretion for doxacurium
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kidney
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NMJ blocker w/ steroid nucleus
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pancuronium
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how is pancuronium same as doxacurium
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no autonomic blockade no histamine release
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|
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more potent, shorter acting analog of pancuronium
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vecuronium
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only drug used clinically as depolarizing NMJ blocker
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succinylcholine
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|
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how is succinylcholine inactivated
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rapidly metabolized by plasma and liver pesudocholinesterases
|
|
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drug of choice to relax laryngeal muscles before intubation
|
succinylcholine
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|
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what syndrome can appear due to succinylcholien
|
malignant hyperthermia
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|
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benzodiazeepine that enhances GABAergic inhibition in CNS
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diazepam
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|
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side effect for diazepam
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sedation at effective dose
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|
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function of diazepam
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reduces all muscle spasms
|
|
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drug that causes decrease in release of Glu and decrease in skeletal muscle tone while experiencing less sedation than diazepam
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baclofen
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|
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drug used for relief of spasticity caused by MS and spinal cord injury
|
baclofen
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drug that is CNS alpha2 stim, reduces skeletal muscle spasticity, causes less hypotension, but causes sedation and dry mouth
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tizanidine
|
|
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related to tricyclic antidepressants, tx muscular spasms assoc w/ musculoskeletal conditions
|
cyclobenzaprine
|
|
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spasmolytic w/ side effects that are atropine-like and not effective in tx for spasms from spinal cord injury or cerebral palsy
|
cyclobenzaprine
|
|
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Acts directly on skeletal muscle abd disrupts excitation-contraction coupling by blocking release of Ca needed for contraction
|
dantrolene
|
|
|
drug of choice for treating malignant hyperthermia
|
dantrolene
|
|
|
main adverse effects of dantrolene
|
generalized msucle weakness and sedation
|
|
|
muscle relaxant to tx generalized spastic disorders (cerebral palsy), effective longterm blockade of trans to muscle
|
botulinum toxin
|
|
|
drugs to tx paralytic ileus
|
physostigmine and bethanechol
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|
|
drug to tx atony of bladder
|
bethanechol
|
|
|
drug to tx glaucoma
|
physostigmine, pilocarpine
|
|
|
drug to tx myasthenia gravis
|
neostigmine
|
|
|
drug to reverse NMJ blockade
|
neostigmine + atropine
|
|
|
preanesthetic medication
|
scopolamine
|
|
|
drug used in opthalmological exam
|
tropicamide
|
|
|
drug to tx motion sickness
|
scopolamine
|
