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110 Cards in this Set
- Front
- Back
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what are muscarinic agonists used for?
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glaucoma, Alzheimer's disease, urinary retention
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what 3 aa are found in muscarinic receptor?
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aspartate (forms ionic bond), threonine (forms H bond), and tyrosine (forms hydrophobic bond)
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Ing Rule of 5?
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NMT 5 atoms tra N and terminal H+ for best agonist activity
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Carbachol treats:
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glaucoma
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Bethanechol used for:
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urinary retention
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pilocarpine used for:
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glaucoma and sweart test
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how many active sites does ACHE have?
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12 active sites of 1
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what aa are in AcHE?
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serine, tryptophan, histidine (can act as acid or base)
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what are pyridostigmine and neostigmine used for?
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Myasthenia gravis
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what are echothiphate and isoflurophate used for?
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glaucoma
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what are malathion and parathion used for
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insecticides
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what is physostigmine used for?
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glaucoma and ods - anticholinergics (TCA, atropine)
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tacrine
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Cognex
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rivastigmine
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Elexon
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symptoms of irreversible AchE inhibitors:
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sweating, drooling, tearing, convulsions, bradycardia, hypotension, mucus in lungs, confusion, paralysis
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DOA of irreversible inhibitors of AchE?
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8 to 10 hours
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MOA of irreversible inhibitors of AchE
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serine residue on AchE enzyme forms a stable phosphorly ester with organophosphorous inhibitors
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what is aging?
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the phosphate bond that breaks is not the one connecting it to enzyme
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antidote to nerve gases?
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must use before aging has occurred
hydroxylamine: toxic to people b/c so strong and not specific pralidoxime chloride (2-PAM) |
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will 2-PAM cross BBB?
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NONONO
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does atropine cross BBB?
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Yes
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A Mark I kit contains 2 autoinjectors of what?
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2 mg atropine
600 mg 2-PAM |
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examples of insecticides that are irreversible Ache inhibitors:
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parathion
malathion dichlorfenthion schradan |
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examples of irreversible inhibitorsof AchE
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echothiophate
isoflurophate |
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muscarinic antagonists symptoms:
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Blind as a bat (myosis)
red as a beet dry as a bone hotter than hell mad as a hatter |
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ach antagonists aka....
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anticholinergics, antimuscarinics, cholinergic blockers, antispasmodics, or parasympatholytics
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what are ACh antagonists used for?
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smooth muscle spasms, overactive bladder, eye exams, gastric ulcers, cold and flu products, Parkinson's dx
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classic antimuscarinic:
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atropine from Belladonna (+/-) hyoscyamine
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(-) hyoscine antimuscarinicused for motion sickness?
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scopolamine (Trans-Derm scoop)
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muscarinic antagonist- type of aminoalcohol ester:
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Glycopyrrolate (Robinal)- reduce sweating
Trospium chloride (Sanctura)- overactive bladder |
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muscarinic antagonist-type of aminoalcohol
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trihexyphenidly (Artane)- tx parkinson symptoms
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muscarinic antagonist-type of amino ether
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benztropine (cogentin)- tx expyramidal symptoms of Parkinson's
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extrapyramidal symptoms of Parkinson's
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Although Parkinson's Disease is primarily a disease of the nigrostriatal pathway and not the extrapyramidal system, loss of dopaminergic neurons in the substantia nigra leads to dysregulation of the extrapyramidal system. Since this system regulates posture and skeletal muscle tone, a result is the characteristic bradykinesia of Parkinson's
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to open the nicotinic receptor how many Ach are needed?
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2 to turn on and open channel
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varenicline (Chantix) is what type of agonist?
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alpha 4 beta 2 nicotinic agonist
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what are nicotinic antagonists used for?
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bind to nicotinic receptor site, but have no efficacy. used as neuromuscular blockers- during surgery for muscle relaxation, tracheal intubation
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to be a nicotinic antagonist you have to block how many sites?
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1 Ach site only
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nicotinic receptor antagonist requires 2 positive charges (N+) separated by how many carbons and why?
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10-12 carbons for drug to bind to 1 Ach spot and 1 futher down
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what two types of nicotinic antagonists are there?
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depolarizing- succinylcholine
non-depolarizing- d-Tubocurarine, metocurine, vecuronium, pancuronium |
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salivary secretion is watery fluid in _____
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PANS
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salivary secretion is thick viscous fluid
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in SANS
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mydriasis occurs in ___
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SANS
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miosis occurs in ___
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PANS
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where does cholinergic autotransmission occur?
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in organs and tissue in the periphery, autonomic ganglia, CNS
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the majority of ____ _____ fibers are adrenergic
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majority of postganglionic sympathetic fibers are adrenergic
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choline is converted to Ach in the neuron by which enzyme?
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choline acetyltransferase
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how does choline get back into the neuron?
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Na+-dependent choline transporter (CHT)
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what are the 2 subtypes of nicotinic receptors?
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1. neural (N2 or Nn)- all autonomic ganglia, adrenal medulla, brain
2. muscular (N1 or Nm)- NMJ |
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what are the 3 types of muscarinic receptors?
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1. M1 neural- autonomic ganglia, CNS
2. M2 cardiac- heart 3. M3 glandular- smooth muscle, vasculature, endothelium, secretory glands |
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M2 receptor actions:
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in heart
- slows rate SA node depolarization (HR decreases) -decrease AV node conduction velocity (slows impulse from atria to ventricle) - decrease atria contractile force - slight decrease in ventricle contractility |
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M3 receptor actions in arterioles?
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dilation of erectile tissue and salivary glands
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M3 receptor action in arteries and veins?
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dilation via nitric oxide (endotheliam lining-indirect)
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M3 receptor action in bronchial smooth muscle
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constriction
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M3 receptor action in GI tract and bladder?
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-increased motility/contraction of smooth muscle
-relaxation/dilation of sphincters -increased gland, gastric acid secretion |
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M3 receptor activity in male sex organs?
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erection
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M3 receptor activity in eye
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contraction circular muscle (miosis)
contraction ciliary muscle (accommodation) |
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does the PANS directly innervate smooth muscles in vasculature?
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NOOOO
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Ne is converted to E in adrenal medulla via which enzyme??
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phenylethanolamine-N-methyltransferase (PMNT)
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dopamine is transported to vesicles via which transporter?
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vesicular monoamine transporter (VMAT)
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synthesis of NE from tyrosine
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tyrosine to L Dopa via tyrosine hydroxylase
L dopa to dopamine via L amino decarboxylase dopamine to NE which dopamine beta hydroxylase |
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what is the rate limiting step in synth of NE?
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tyrosine to dopa via tyrosine hydroxylase
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which two enzymes can degrade NE?
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MAO and catchol-o-methyl-transferase
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MAO-A degrades?
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5-HT, NE, DA
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MAO-B DEGRADES?
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DA>>>>5-HT, NE
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WHAT IS VMA (VANILLYLMANDELIC ACID)?
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major metabolic of catcholamines (NE, Epi, DA)excreted in urine
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alpha 1 adrenergic receptor causes contraction of what 5 things???
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contraction of:
pupil muscle (mydriasis) most vascular smooth muscle veins genitourinary smooth muscle bladder (trigone, sphincter) |
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alpha 1 receptor does what to males sex organs
to pilomotor smooth muscle intestinal smooth muscle |
ejaculation
erects hair decrease motility and tone |
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what does alpha 2 receptor do to presynaptic nerve terminals?
pancreas (beta cells)? platelets? some vascular smooth muscle? fat cells? |
inhibition of NT release
decreas insulin release aggregation contraction inhibition of lipolysis |
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action of beta 1 receptor?
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increase HR, renin release
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action of beta 2 receptor?
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glucogenolysis (liver and skeletal muscle)
relaxation (respir, uterine, eye, bladder) |
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action of beta 3 receptor
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lipolysis in adipose tissue
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action of D1 receptor?
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renal blood vessel dilation at smooth muscle
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action of D2 receptor?
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modulates NT release at nerve endings
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prototype for non depolarizing blocking agents:
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tubocurarine
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prototype of depolarizing agents:
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succinylcholine
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what percentage of Nm receptors do the non depolarizing agents need for action?
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70-80% occuptation at Nm receptors
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if you give too much non depolarizing agents what happens?
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neuromuscular blockage- constant relaxation state, neurotransmission is blockered, give AchE inhibitor, [ach], competition, eventually kicks non-depolarizing agent off recepter
when you give too much drug--it is promiscucous so it starts to also block V-G Na+ channels in muscle therefore it is constantly relaxed |
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what happens with high doses of non depolarizing agents in regard to motor end plate?
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inhibits of ion channels (sodium) in motor end plate, decreases ability of AchE inhibitors to reverse drug effect
to avoid this problem you must monitor the drug so you don't get the high state of relaxation b/c you cannot reverse it with AchE inhibitors |
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what are examples of inhibitory autoreceptors?
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alpha 2, M2, 5HT 1d, D2
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MOA of clonidine?
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Clonidine (Catapres) is a partial alpha agonist that causes a decrease in neurotransmission when it binds to alpha 2 receptor
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what is the MOA of Remeron?
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Remeron (mirtazapine) is a 5-HT 1d antagonist that binds to autoreceptor to increase NT levels
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How does Botox work?
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it blocks the transmission of nerve impulses to the targeted muscle by selectively preventing the release of ach at the NMJ therefore cholinergic transmission is disrupted at a specific site
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alpha- Methyltyrosine can do what???
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prevent NE synthesis
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cocaine and TCA are what types of inhibitors?
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Uptake 1 that can have s/t highs and l/t harmful effects on cv system
uptake 1 via neuronal membrane NE transporter (NET) uptake 2: nonneuronal |
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MAO
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the high level of tyramine kicks off NE from MAO and results in a hypertensive crisis (BP >180/120, occipital HA, stiff neck, N+V, sweating)
MAOIs impair the function of the enzyme monoamine oxidase, which is responsible for the breakdown of tyramine in your body. Elevated levels of tyramine can cause a dangerous increase in blood pressure and lead to stroke. So, it is important to avoid or limit foods that are high in tyramine while taking an MAOI. |
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uptake 1 is the primary way of terminating which 2 NTs?
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NE and DA
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what happens when there is an accumulation of NE?
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SANS
mydriasis, vasoconstriction, salivation, sweating, bronchodilation, increase in HR |
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what is the prototype of muscarinic agonists?
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Ach
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4 cv effects of muscarinic agonists?
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1. decrease in HR
2. decrease in rate conduction 3. decreaes force contraction in heart 4. blood vessel dilation indirect via NO |
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what are the effects of Metoclopramide>
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Reglan increses peristalsis, tone, motiliy via M3 receptor (muscarinic agonist)
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what are the effects of cevimeline?
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Evoxac is used for xerostomia and stimulates lacrimal, salivary, bronchial, and sweat gland secretions via M3 receptor (muscarinic agonist)
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what are the effects of Bethanechol?
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tx: urinary retention (muscarinic agonist)- contracts detrusor, relaxes trigone and sphincter, get voiding of urine
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MOA of pilocarpine?
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used for glaucoma (muscarinic agonist)- stimulate sphincter muscle contraction (miosis-M3), stimulate ciliary muscle muscle contraction (M3); good for ophthalmogical procedures
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MOA of Methacholine?
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challenge pts asthma and then use drug
contracts bronchial muscle (M3), stimulates bronchial gland secretion (M3) (muscarinic agonist) |
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MOA of pilocarpine?
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simulates contraction of meridional ciliary muscle, opens trabecular spaces, increase drainage of aqueous humor, decrease in intraocular P
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what does BChE metabolize?
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ester-type local anesthetics, NMJ blockers
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when Ach is hydrolzyed how many spots regions on the active site does it bind to?
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hydrolysis of Ach:
1. binding of Ach to 2 regions on active site of enzyme 2. splitting of ach which regenerates free ache |
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What does Neostigmine do?
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contracts detrusor, relaxes trigone + sphincter (M3), tx: urinary retention
medium-duration cholinesterase inhibitor |
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what is the reversible short-acting cholinesterase inhibitor?
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edrophonium
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physotigmine and the organophosphates have a greater effect at the ANS or NMJ???
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ANS> NMJ due to increased lipophilicity
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What is Demecarium?
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linked neostigmine
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what do low doses of Ach do(due to AchE inhibitors)?
intermediate doses? high doses? |
low doses: increase muscle tension
intermediate doses: muscle twitching and fibrillations high doses: paralysis (depolarization block) |
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neostigmine, pyridostigmine have a greater effect at the ANS or NMJ?
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NMJ>ANS
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when neostigmine (medium duration cholinesterase inhibitor) is hydrolzed by AChE what happens to AChE?
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it becomes carbamylated!!
labile covalent bond |
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what cholinesterase drug is used to diagnose myasthenia gravis?
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edrophonium (short-acting) inject MG pt areas around eyes, they will tighten up, very sensitive
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what cholinesterase drug/s is/are used to tx myasthenia gravis???
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neostigmine, pyridostigmine
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what are the effects on CNS with acute inhibition of AChE after the 1st neuronal excitation?
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confusion, ataxia, slurred speech, convulsions
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what are the effect on CNS with acute inhibition of AChE after the 2nd neuronal depression?
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loss of reflexes, respiratory failure, death
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what occurs in a cholinergic crisis?
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miosis, N,V,D, sweating, salivation, bradycardia, hypotension, penile erection, involuntary muscle twitching, severe weakness and paralysis, confusion, ataxia, slurred speeck, loss of reflexes, abnormal gait
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what is the antidote for a cholinergeric crisis?
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pralidoxime (PAM), atropine, and benzo
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