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61 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Name the two major division of the efferent portion of the nervous system?
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1) The somatic or voluntary nerves that control the skeletal muscles.
2)The autonomic nervous system, which operates largely below the level of consciousness, controls all other innervated structures in the periphery |
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Skeletal muscles are entirely
dependent on their innervation for activity and will atrophy if this connection is lost. |
The somatic or voluntary nerves
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Central control of autonomic nerve function arises in the hypothalamus,
limbic system and brain stem, with further integration occurring at peripheral ganglia that lie between the CNS and the neuroeffector junctions |
The autonomic nervous system,
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Name the major parts of the ANS?
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1 sympathetic
2 parasympathetic 3 Enteric system in the gut |
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primary signal for neurons leaving the CNS
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Ach
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what are the major pharmacological targets?
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1. Synthesis. Inhibit the
rate-limit step (uptake of choline into the nerve terminal). Hemicholinium 2. Storage. Inhibit the packaging of ACh into the secretory vesicle.Vesamicol 3. Prevent activation of the nerve terminal. Local anaesthetics 4. Interfere with influx of calcium into the nerve terminal. Hypermagnesia. Side-effect of aminoglycoside antibiotics,e.g. streptomycin NOT a target for “calcium channel blockers” 5. Modify exocytosis. Botulinum toxin inhibits Black widow spider venom activates 6. Action at the ACh receptors: *agonists *antagonists *presynaptic receptors *long-lasting agonists |
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How is Ach made?
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This process occurs in the cytoplasm of Ach nerve terminals. The enzyme responsible is Choline Acetyltransferase (ChAT).
ChAT is made in the cell body, sent down the axon to the terminal and causes the reaction. We get the Acetyl CoA part from glucose metabolism in mitochondria Choline, on other hand, is not made in-house. It’s pumped in from the extra-cellular space and this, my friends, is the rate limiting step |
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How is Ach release?
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Ach release is caused by an Action Potential
The AP comes down the axon. This causes an influx of Calcium ions. Calcium then causes the vesicles to fuse with the synaptic membrane and release their load into the synaptic cleft by exocytosis |
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How can Ach be blocked?
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by adding Magnesium which antagonize the effects of Calcium hence the release of Ach.
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what is Mepp's and what is its significance?
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Mepp's is miniature endplate potential.
Ach is released in small quantities without the signal of an AP it has been suggested that, this quantal release may serve as a trophic influence on the end plate |
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Name the major Cholinergic receptors
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Muscarinic
Nicotinic |
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Receptor inhibited by atropine?
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Muscarine
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subdivision of muscarinic receptors?
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M1- neuronal
M2 heart M3 Secretory gland Muscarinic receptors are also coupled to G proteins |
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what is the antagonist of Nicotine?
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Curare
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what is the effect of concentration of nicotine?
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Low conc.---causes stimulation followed by a recovery period
High conc.... causes stimulation followed by a depression due to sustained depolization of the receptors |
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stimulated by Ach and blocked by atropine
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Muscarinic receptors
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couple through Gq G proteins to increase cystosolic calcium levels
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MI
M3 M5 |
odd number mAchR
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couple through Gi G protein to increase potassium conductance
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M2
M4 |
generally inhibitory to celluar activity
even numbers mAchR |
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what kind of mAchR does the heart possess and what is the mechanism
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The heart possesses M2 receptors that decrease cellular activity when
stimulated. The primary mechanism for these effects is an increase in the plasma membrane permeability to K+ that results in hyperpolarization. |
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what is the effect of muscarinic action on the heart?
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Muscarinic action on the heart is directed to the SA node, atria and AV node
where M2 activation slows heart rate (negative chronotropic action), decreases the force of contraction (negative inotropic action) and suppresses AV conduction (negative dromotropy). |
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what is the effect of muscarinic on blood vessels and what is the receptor?
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the receptor is M3
it will promote vascualar dilation of the vessels |
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what is the effect of low dose Ach given IV?
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When a low dose of ACh is given I.V., it is metabolized quickly by the
plasma cholinesterases and the only pharmacologic actions observed are on the vascular system. The fall in blood pressure causes the baroreceptor reflex to increase sympathetic tone to the heart, and thus a reflex tachycardia. |
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what happens when a higher dose Ach is given I.V. ?
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When a higher dose of ACh is given I.V., it produces cardiac depression through direct action of ACh on the cardiac M2 receptors
Note: Still higher doses of I.V. ACh can produce complex results due to additional cardiac stimulation from activation of sympathetic ganglia nAChR and thus release of norepinephrine |
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what effect does atropine has on blood pressure?
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promotes some cutaneous vasodilation by reflex mechanism
Note: Atropine has very little effect on the blood pressure if given alone |
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Describe Atropine toxicity
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skin becomes very red, warm and dry: "atropine flush"
This effect is related to thermo-regulation since atropine blocks sweat formation. |
“red as a beet, dry as a bone, blind as a
bat, mad as a hatter”] |
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what is the therapeutic use of atropine?
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Atropine can be used therapeutically to treat sinus bradycardia
following myocardial infarction. |
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what is the effect of muscarinic agonist on the eye?
name one agonist |
Muscarinic agonist action is to produce miosis and it also favors drainage of fluid from the eyeball through the canal of Schlemm. This reduction in fluid can be useful to patients with
glaucoma. Pilocarpine |
“red as a beet, dry as a bone, blind as a
bat, mad as a hatter”] |
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what is the effect of muscarinc antagonist on the eye?
name one antagonist |
Muscarinic antagonists cause
pupillary dilation (mydriasis) that may be useful during eye examination. tropicamide |
“red as a beet, dry as a bone, blind as a
bat, mad as a hatter”] |
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what effect does atropine has on the G.I tract?
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“red as a beet, dry as a bone, blind as a
bat, mad as a hatter”] |
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what drug is given to restore GI motility
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Bethanechol
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what is the effect of muscarinic agonist on the urinary tract?
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stimulate urinary bladder's detrussor muscle to facilitate urination
Bethanechol is drug used for this purpose as well as G.I motility |
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effect of muscurainic agonist on respiration.
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Muscarinic agonists stimulate bronchiolar smooth muscle to contract.
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too much Ach action on nicotinic receptors will result in depolarization and block any further transmission to skeletal muscle
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depolarization blockade
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first partial nicotinic receptor agonist approved by FDA and what is its use
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Verenicle
may help smoking cessation |
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list the two kinds of skeletal muscle blocking drugs and give examples
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1) Competitive antagonists- d-tuboCURarine, atraCURium, doxaCURium and roCURronium
2) Depolarizing blockers ( agonist)- succinylcholine |
all the antagonist contains CUR in them
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what is the difference between tertiary amines and quaternary amines in terms of usage?
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tertiary amines are used orally for systemic effects
Quaternary amines are used for direct application |
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why is Ach therapeutic use limited?
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cuz it is rapidly broken down by pseudocholinesterase
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why are skeletal muscle relaxants not analgesic?
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they are quaternary amines and must be administered IV. It doesn't cross the blood brain barrier or placenta.
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why is curare not used much?
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tendency to release histamine in the patient and a block of the autonomic ganglia, both of which lead to hypotension.
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act in less than one minute
used in single dose after anesthia to relax larynx |
Succinylcholine
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Plasma pseudocholiesterase breaks it down
Polymorphism in population increase its half life Potassium dump is a side effect. may lead to cardiac arrest |
succinylcholine
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3 P's
Plasma pesudocholinesterase Polymorphism in population Potassium dump |
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differentiate between the two kinds of blockage caused by succinylcholine
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Phase I- blockage by gradual depolarization of the motor end plate
Phase II- if given over a long period of time via IV, the end plate eventually repolarizes but remains unable to transmit a signal |
Note:
There is a return of some muscle tone and administration of Neostigmine or Edrophonium can return normal function |
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Drug
skeletal muscle resistant blocks Ca release from SR used with pts with spasticity also treats malignant hyperthemia no effect on Ach release |
Dantrolene
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unique MOA
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2 categories of anti-cholinesterase agents
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reversible- bind noncovalently to AchE or are broken down by enzyme slowly therefore result in temp inhibition
Irrevesible- form covalent bonds. half life of hours to days. |
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examples of reversible Anti-Cholinesterease
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Physostigmine
Neostigmine Pyridostigmine Edrophonium Tacrine Rivastigmine Galantamine |
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Drug
tertiary amine affects both muscarinic and nicotinic receptors topical use to treat glaucoma like carbachol |
Physiostigme
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Drug
Quaternary amine synthetic blocks AchE augments GI, urinary function |
Neostigmine
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direct action against nAchR
good for myasthenia gravis reverses the effects of curare poisoning poor oral absorption |
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Drug
Quaternary amine synthetic better oral |
Pyrodostigmine
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similar to Neostigmine
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Drug
Blocks AchE affects Nicotinic receptor short action |
Edrophonium
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used for diagnosis of myathenia gravis
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Drug
Blocks AchE Competitive and reversible long lasting crosses BBB |
Tacrine
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first to treat alzeimer
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Drug
metabolized by CYP2D6 and CYP3A4 long lasting |
Donepezil
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limited effect with Alzeimer's cognition
fewer liver side effects |
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Drug
Inhibits PseudoChoeE Alzheimer's slowly |
Rivastigmine
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Drug
Reversible AchE competetive Alzheimer drug |
galantamine
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how do u diagnose myasthenia Gravis?
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A patient is
asked to exercise until muscular weakness is clearly present at which time edrophonium is administered I.V. If the patient is myasthenic, a marked increase in muscle force will be observed for about five minutes and then muscle force will begin to subside |
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what is the treatment of myasthenia gravis?
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Neostigmine
pyridostigmine |
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what is myasthenic weakness
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weakness experienced by MG during the course of anticholinesterase therapy. This weakness may be related to an exacerbation of
the disease, or inadequate blood levels of the anticholinesterase agent. |
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what is cholinergic crisis?
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In cholinergic crisis, the motor endplate is excessively stimulated by the
accumulating ACh and by the direct action of neostigmine on the motor endplate nicotinic receptors causing the resting membrane potential to be depolarized beyond the threshold. At this point, a depolarizing blockade results and muscle weakness occurs. Additional nerve stimulation or cholinergic agonist will intensify the muscle weakness. |
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what test is done to differentiate between Myasthenic weakness and cholinergic crisis
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administration of a small does of edrophonium
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list the names of irreversible AchE inhibitors
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Ecothiophate
Malathion/parathion |
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Drug
not active until metabolized by liver covalently binds AchE insecticide |
Malathion/parathion
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Drug
used topically on the eys to produce a sustained miosis(pupilary constriction) |
Echothiosphate
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