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Pharmacology-1
Autonomics
| Question | Answer |
|---|---|
| which specific nerves are involved in the parasympathetic system? | CN's 3, 7, 9, 10; and S2-4 |
| parasympathetic preganglionic fibers are _____? | long |
| postganglionic parasympathetic fibers are ____? | short |
| what is the preganglionic:postganglionic ratio is ____? | 1:1 |
| the adrenal medulla secretes catecholamines. what are the 2 and which is dominant? | epinephrine and norepinephrine; epinephrine is dominant (85%) |
| what are the targets for muscarinic receptors in both parasympathetic and sympathetic? | sympathetic muscarinic (sweat glands); muscuarinic parasympathetic (smooth muscle, cardiac muscle, gland cells) |
| tetrodotoxin? | puffer fish poision-- sodium channel blocking agent impairing axonal conduction |
| saxitoxin? | a shellfish poision; impairs the Na channel blocking agents impairing axonal conduction |
| batrachotoxin? | South American frog poision; causes increased permeability of Na channel to cause persistent depolarization changing axonal conduction |
| scorpion toxin? | cause persistent depolarization changing axonal conduction |
| where is the majority of Ach storage? | in the presynaptic nerve terminal (quanta) |
| when Ach is broken down, it is broken down into? | acetate and choline |
| what drugs will inhibit Ach synthesis by competing for choline uptake into the presynaptic terminal? | hemicholinium and triethylcholine |
| hemicholinium? | binds to choline, so choline can't be taken up into nerve terminal to make Ach |
| botulinum toxin? | blocks acetylcholine release from presynaptic nerve terminals; cholinergic antagonist |
| black widow spider venom? | promotes Ach release; cholinergic agonist |
| atropine? MOA | blocks Ach activity at postsynaptic muscarinic receptors; cholinergic antagonist |
| physostigmine? MOA | inhibits enzymatic metabolism of the AchE enzyme, so AChE is inhibited, prolonging effects of acetylcholine; cholinergic agonist |
| what are the 3 parts of the Ach structure? | cationic quaternary ammonium group, ester group, and an alkyl chain |
| AchE contains a complimentary region in its structure that binds to Ach. What is this structure? | an anionic group and an ester group |
| what are the catecholamines? | DEN: dopamine, epinephrine, and norepinephrine |
| what is the rate limiting step in catecholamine synthesis? | TYROSINE--> DOPA by tyrosine hydroxylase |
| describe the pathway of synthesis for catecholamines, excluding the enzymes involved. | tyrosine-->DOPA-->dopamine-->NE-->epinephrine |
| what happens in the NON-cytoplasmic reaction in catecholamine synthesis? | DOPAMINE is converted to NE inside the storage granule by dopamine beta hydroxylase |
| dopamine beta hydroxylase | a nonspecific enzyme that can converts DOPAMINE to NE inside the storage granule; since it's nonspecific it can also convert other catecholamines to "FALSE NT's" |
| where is NE converted to EPI? | adrenal medulla |
| what is the difference in storage between Ach and catecholamines? | Ach is stored in the presynaptic nerve terminal or other parts of the axon or cell body; catecholamines are stored in VESICLES |
| what actions are responsible for catecholamine destruction/termination? | reuptake, enzymatic degradation, or diffusion |
| what is UPTAKE 1 in the adrenergic system? | this is when a catecholamine is transported across the PRESYNAPTIC terminal inside the nerve and/or across the STORAGE VESICLE membrane back for storage |
| what is uptake 2 in the adrenergic system? | this is when catecholamines (DEN) are taken up, but in NON-NEURAL TISSUES |
| compare and contrast the enzymatic degradation of catecholamines and acetylcholine? | acetylcholine (enzymes play a much larger role, acetylcholinestare or butyrlcholinesterase); catecholamines (enzymes play a lesser role, MAO, COMT, metabolites) |
| where does monoamine oxidase work to break down catecholamines? | in the cytoplasm of the neuron |
| where does catechol-o-methyltransferase (COMT) work to break down catecholamines? | outside the neuron; so... those catecholamines that escaped reuptake 1 or those provided in the blood/tissue by the adrenal gland |
| what enzyme takes care of most of the catecholamine (mostly epinephrine) fromt the adrenal gland? | COMT |
| what is the difference in COMT and MAO? | MAO works inside the adrenegic nerves where COMT works outside. |
| what is the precurser to NE? | dopamine |
| where is the primary location of fuction of dopamine? | the brain: the basal ganglia |
| what does serotonin regulate (5-HT or 5-hydroxytriptamine) | regulates smooth muscle function in CVS and GI, and platelet fxn |
| what is the starting molecule for serotinin synthesis? | tryptophan |
| alpha methyldopa? | inhibits the synthesis of catecholamines; it competes with the synthetic enzymes dopa decarboxylase and tyrosine hydroxylase) producing fase neurotransmitters, inhibiting stoarge of active NT in vesicles |
| alpha methyltyrosine? | inhibits the synthesis of catecholamines; it competes with the synthetic enzymes dopa decarboxylase and tyrosine hydroxylase) producing fase neurotransmitters, inhibiting stoarge of active NT in vesicles |
| reserpine? | affects catecholamine (norepi, dopamine) in the GRANULE. |
| guanethidine? | inhibits STORAGE of dopamine and norepi; it doesn't allow them to be stored in the storage vesicle; also taken up by reuptake 1, causing transient increase in catecholamines, but the a long lasting decrease in adrenergic activity |
| which drugs are responsible for not allowing catecholamine storage in the vesicle (norepi and dopamine) | reserpine and guanethidine |
| There are drugs that can be taken up by UPTAKE 1 (adrenegic nerves), that cause a transient release of catecholamine followed by long lasting decrease in adrenergic activity? what 2 drugs do this? | guanethidine and bretylium |
| what drug can act at presynaptic adrenergic receptors to decrease NE release? | clonidine; adrenergic antagonist |
| which drugs block reuptake of catecholamines? | imipramine and cocaine, the block uptake 1, blocking reuptake of NE and DA |
| drug(s) affecting synthesis of catecholamines? | alpha methyldopa and alpha methyltyrosine |
| drug(s) affecting storage of catecholamines? | reserpine, guanethidine, and bretylium |
| drug(s) affecting release of catecholamines? (decreases release) | clonidine |
| imipramine? | blocks uptake 1, not allowing adrenergic nerves to reuptake NE and DA |
| cocaine? | blocks reuptake 1, not allowing NE or DA to be reuptaken (not a word) |
| where are muscarinic receptors found? | all all postganglionic parasympathetic cells and sweat glands and some blood vessels of the sympathetic system |
| There are ___ types of muscarine receptors. They each respond differently to stimulation. If an M1, M3, M5 type muscarinic receptor is stimulated by NT, what happens. | 5 types (M1 thru M5); it will cause G protein signal transduction to cause desired affect |
| There are ___ types of muscarine receptors. They each respond differently to stimulation. If an M2, M4 type muscarinic receptor is stimulated by NT, what happens. | 5 types (m1 thru m5); activation results in inhibition of adenyl cyclase, activation of K+ channels, and modulation of Ca+ channels |
| M1 muscarinic receptor-- what is the agonist, antagonist, and tissue associated? | agonist (Ach); antag (atropine, pirenzepine); tissue (autonomic ganglia, secretory glands, and CNS); M1 is gprotein linked |
| M2 muscarinic receptor-- what is the agonist, antagonist, and tissue associated? | agonist (Ach); antag (atropine), tissue (heart, smooth muscle) |
| M3 muscarinic receptor-- what is the agonist, antagonist, and tissue associated? | agonist (Ach), antag (atropine), tissue (smooth muscle, secretory glands, CNS) |
| M4 muscarinic receptor-- what is the agonist, antagonist, and tissue associated? | agonist (Ach), antag (atropine), tissue (smooth muscle, secretory glands, CNS) |
| M5 muscarinic receptor-- what is the agonist, antagonist, and tissue associated? | agonist (Ach), antag (atropine), tissue (CNS) |
| What type(s) of muscarinic receptors are found in the autonomic ganglia? | M1 |
| what types of muscarinic receptor(s) are found in the secretory glands? | M1, M3, M4 |
| what types of muscarinic receptor(s) are found in the CNS? | M1, M3, M4, M5 |
| which muscarinic receptor(s) is not found in the CNS? | M2 |
| what types of muscarinic receptor(s) are found in the smooth muscle? | M2, M3, M4 |
| what types of muscarinic receptor(s) are found in the heart? | M2 |
| where are nicotininic receptors found? | ganglia, neuromuscular junction, and adrenal medulla |
| what does nicotine do to nicotinic receptors in terms of stimuation? | stimulatory at low doses, inhibitory at high doses |
| is nicotine an agonist or antagonist? | both |
| The nicotinic receptor is a multisubunit recetor (2alpha, beta, gamma, delta). Where does Ach bind? | the alpha unit |
| Once Ach binds to the alpha unit of the nicotinic receptor, what happens? | the alpha unit then recognizes the beta, gamma, delta units, which then come together and form a channel allowing Na and Ca to pass, causing depolarization (this makes the nicotinic receptor a LIGAND-GATED ION CHANNEL, ach being the ligand) |
| There are ___ types of nicotinic receptors? Nn (aka N1 or N-G)...what is the agonist, antagonist, and tissue involved? | 2 (Nn or Nm); Nn's agonist (nicotine/Ach), antag (trimethaphan/nicotine), tissue (autonomic ganglia, adrenal medulla, CNS) |
| There are ___ types of nicotinic receptors? Nm (aka N2)...what is the agonist, antagonist, and tissue involved? | 2 types (Nn or Nm); agonist (nicotine/Ach), antag (tubocurarine, pancuronium, succinylcholine), tissue (NMJ) |
| Nm or N2 nicotinic receptors are only found where? | neuromuscular junction |
| If you wanted to inhibit skeletal muscle with a drug, what drugs could you use, and what receptor would you target? | Nm (aka N2) nicotinic cholinergic receptors, located at the NeuroMuscular juntion. You could use tubocurarine, pancuronium, and succinycholine. |
| You give a patient trimethaphan. What happens? | The Nn (or N1/NG) receptors are blocked in the autonomic ganglia, adrenal medulla, and CNS. |
| trimethaphan? | Nn (N1/NG) nicotininic cholinergic antagonist (functioning at autonomic ganglia, adrenal medulla, and CNS) |
| tubocurarine? | Nm (N2) nicotinic cholinergic receptor antagonist, functioning at NMJ |
| pancuronium? | Nm (N2) nicotinic cholinergic receptor antagonist, functioning at the NMJ |
| There are ___ adrenergic receptors? | 5: a1, a2, b1, b2, b3 |
| where are a1 receptors located, in general? | postsynaptic effector cells (heart, papillary dilator muscle, vascular smooth muscle) |
| where are a2 adrenergic receptors located in general? | primarily on presynaptic terminals, plateles, lipocytes, and some vascular smooth muscle) |
| where are b1 adrenergic receptors located, in general? | postsynaptic effector cells (heart, lipocytes, and juxtaglomerular cells) |
| where are b2 adrenergic receptors located, in general? | postsynaptic effector cells(respiratory, uterine, GI, and vascular smooth muscle, skeletal muscle, and liver), presynaptic noradrenergic nerve terminals, small percentage in heart |
| where are b3 adrenergic receptors located, in general? | adipose tissue, to mediate lipolysis |
| what is the metabolism of a1 adrenergic receptors? | stimulation leads to activation of membrane bound phospholipase C via G protein activation |
| what is the metabolism of alpha 2 adrenergic receptors | stimulation is ass with inhibition of adenylate cyclase and a fall in intracellular cAMP |
| B1 and B2 receptors are associated with what type of metabolism? | g protein |
| dopamine receptors are associated with what type of metabolism? | g protein |
| serotonin receptors are associated with what type of metabolism? | all are ass with G protein, except 5HT3 (which is ass with ligand-gated ion channel) |
| all of the serotonin receptors are associated g protein, except? | 5HT3 (ligand gated ion channel) |
| what are the physiologic effects of muscarinic agonists? | SLUDGE: increased salivation, lacrimation, urination, defication, GI upset, emesis |
| where do direct acting muscarinic agonists act? | at the cholinergic receptor |
| what are the 2 broad types of direct acting muscarinic receptor agonists? | alkaloid derivatives and choline esters |
| muscarine receptors can be directly stimulated by what 2 types of groups? | alkaloid derivatives and choline esters |
| muscarine? | a direct acting muscarinic agonist (alkaloid derivative type); from mushroom Amantia mscaria |
| pilocarpine? | direct acting muscarinic agonist (alkaloid derivative type); no major affects on heart, opthalmic solution (miosis, ctrx of ciliary muscle, fixed far vision, makes hard to focus, open angle glaucoma, can cause marked diaphoresis and salivation) |
| arecoline? | direct acting muscarinic agonist (alkaloid derivative type) |
| what are the drugs that act as DIRECT ACTING MUSCARINIG AGONISTS | Muscarine, pilocarpine, arecoline |
| You have a patient with open angle glaucoma. You treated her with ______. She is back in your clinic with new complaints. What are the most likely complaints? | pilocarpine, marked increase in diaphoresis and salivation |
| Direct acting muscarinic agonist that can also act at nicotinic receptors? | arecoline (can also be found in certain nuts of East India); and Ach, methacholine, and carbachol. NOT Bethanechol. |
| Muscarinic agonists include alkaloid derivatives and choline esters. what are the drugs in each? | ALK [muscarine, pilocarpine, arecoline); ESTERS (Ach, methacoline, carbachol, bethanechol (aka DuVoid)] |
| what is the main difference between the 2 types of direct acting muscarinic agonists? | alkaloid derivatives (MPA) are not susceptible to AchE. |
| bethanechol (DuVoid)? | direct acting muscarinic agonist (choline ester type); also acts on nicotinic, not susceptible to AchE, slect action on the GI and urinary bladder, used for postoperative urinary retention relief, postop abd distention, diab gastropar, GERD, post vagotmy |
| which direct acting muscarinic agonists are NOT susceptible to AchE? | the alkaloid derivatives (muscarine, pilocarpine, arecoline), and of the choline esters (Bethanechol--aka DuVoid, and carbachol) |
| which direct acting muscarinic agonists will also act at nicotinic receptors? | From the alkaloid derivatives group, arecoline. From the choline ester family, Ach, Methacholine, and carbachol. NOT bethanechol. |
| You have just performed surgery on a pt who is having some postoperative effects. Your patient cannot urinate and her abd is extremely extended. What should you give her? | bethanechol |
| You have a patient with diabetic gastroparesis. As a medical student, you are told to rx a direct acting musc agonist. What? | bethanechol |
| What does bethanechol do to nicotinic receptors? | NOTHING, it has NO nicotinic activity |
| what is the fxn of MOA and clinical application for methacholine? | it's a direct acting musc agonist (choline ester type) used for provocative challenge test for asthma; |
| methacholine was historically used to treat what? | tachycardia |
| which direct acting musc agonist (of the choline ester family) is the least susceptible to antagonism by atropine? | carbachol |
| You need to cause miosis in a pt. You need to select a direct acting muscarinic agonist of either type. Which could you choose? | you could choose any, but you would most likely choose pilocarpine or carbachol or even Ach. |
| When is bethanechol contraindicated? | during the presence of urinary tract obstruction |
| which choline ester (direct acting musc agonist) can be given IV or PO? | bethanechol |
| Of the direct acting muscarinic agonists, which are suceptible to AchE? | None of the alkaloid derivatives (muscarine, pilocarpine, arecoline); acetylcholine is the most suceptible, followed by methacholine. Carbachol and bethanechol are not affected by AchE. |
| Which direct acting musc agonist of the choline ester type has the most nicotinic activity? | carbachol |
| which direct acting musc agonist of the choline ester type has the most cardiac muscarinic affect? | methacoline>Ach>carbachol>bethanechol |
| which direct acting musc agonist of the choline ester type has the most muscarinic affect on the GI? | carbechol and bethanochol are the same>either methacholine or Ach |
| methacholine has the highest muscarinic affect on? | cardiac |
| which direct acting musc agonist of the choline ester type has the highest muscarinic affect on the bladder? | carbechol and bethanechol>either Ach or methacholine |
| which direct acting musc agonist of the choline ester type has the highest effect on the eye (topically)? | carbachol and bethanechol, followed by little effects from Ach or methanochol |
| Direct muscarinic agonists have pharmocological affects on which organs? | CVS, vascular tissue, GI, Urinary, Eye, Respiratory, Glands |
| What are the primary pharmacological affects of direct muscarinic agonists on the cardiovascular system? | vasodilation, decreased HR, decreased conduction rate, decrease in the force of contraction of the heart |
| negative chronotropic effect? | a decrease in heart rate, caused by the pharmacological affect of a direct muscarinic agonist |
| negative dromotropic effects? | a decrease in conduction rate of heart at SA and AV nodes as a pharmacological result from DIRECT ACTING MUSC AGONIST |
| negative inotropic effect? | a decrease in the force of contraction of the heart bc of a direct acting musc agonist. |
| What GI affects would you expect to see in a patient taking a direct acting musc agonist? | increase in tone, amplitude of ctrx, and peristaltic activity of the stomach and int, as well as enhanced act of GI tract. |
| What are some of the unwanted reactions of direct acting musc agonisits, because of GI involvement? | nausea, belching, vomiting, intestinal cramps, and defecation |
| What is the direct acting musc affect on the urinary system? | increased micturation; increased ureteral peristalsis, contraction of the detrusor muscle of the urinary bladder, increased maximal voluntary voiding pressure, and decrease in the capactiy of the bladder; the trigone and the external sphincter are relaxed |
| Direct installation of a direct act musc agonist into the eye will cause what? | miosis (secondary to ctrx of the smooth muscle of the iris), impaired accomodation to near vision ( ctrx ciliary muscle), spherical lens |
| when you increase parasympathetics, what happens to accomodation, vision, and shape of the lens? | near vision and miosis |
| direct acting muscarinic agonists are contraindicated in which patients? | asthmatics |
| what are the respiratory affects of direct acting musc agonists? | contraction of bronchial smooth muscle, tracheobronchial gland secretion is increased |
| what happens to glands during direct acting musc agonist stimulation? | all glands received parasymp supply are stimulated: lacrimal, tracheobronchial, salivary, digesting, exocrine |
| What is the MOA of indirect acting muscarinic agonists? | They work as AchE inhibitors. They block the hydrolysis of Ach causing accumulation at the cholinergic receptors. This causes both nicotinic and muscarinic affects. |
| Where are the primary targets for indirect acting muscarinic agonists? | eye, NMJ, heart, skM, GI tract, and urinary bladder. |
| Acetylcholinesterase can bind to Ach in 2 spots...? | esteric subsite and the anionic site |
| Indirect act musc agonists have varying lengths of activity. What determines this? | it depends on what type of bond the inhibitor forms with AChE [simple bond (H+), intermediate, covalent] |
| What are teh AchE reactivators? | Pralidoxime or Protopam (2Pam) |
| 2Pam (Protopam) is used with _____ for organophosphage poisoning. | atropine |
| protopam (2-PAM) and atropine are used together to trx what? | organophosphate poisioning |
| Where does 2-PAM (protopam) work best? | NMJ |
| Edrophonium? class, type of AchE inhibition, clinical use | indirect acting musc agonist, carbamate, reversible (short acting), dx of MG, supraventricular tachycardia termination |
| why is edrophonium short acting? | edrophonium is short acting because it forms a weak hydrogen bond with AchE making it reversible |
| Which indirect muscarinic agonist can help you dx myasthenia gravis? | edrophononium |
| what are the 2 subclasses of the indirect acting musc agonist drugs? | carbamate or organophosphate |
| what are the reversible indirect acting muscarinic agonists? | edrophonium, physostigmine, pyridostigmine, neostigmine, ambenonium, demacarium, tacrine, donepezil, rivastigmine, galantamine |
| what are the indirect acting musc agonists that are found within the organophosphate class? | echothiphate and isoflurophate |
| You are in the ER and your mother is having Supraventricular tachycardia. There is a box labeled "indirect acting muscarinic agonists." What would you want to grap out of the box to help your mom? | edrophonium, a reversible short-acting carbamate |
| Affects of indirect act musc agonist on eye? | miosis, ctrx of the ciliary muscle (near vision), decreased intraoccular pressure, possible decrease in aqueous humor production |
| Affects of indirect act musc agonist on GI tract? | enhanced gastric contractions, increase secretion of gastric acid; may see cramps, diarrhea, and defecation |
| Affects of indirect act musc agonist on NMJ? | small doses (short term) will see increase strength of contraction due to the increased residence time of acetylcholine in the synapse, allowing it to bind to multiple receptors; long term (large doses) may actually block NM transmission |
| Regarding the tx of MG, why is it important to use pyridostigmine. | Pyridostigmine is the drug of choice because it's a short acting, reversible indirect musc agonist. If you use short acting, this will increase the Ach available to help with muscle strength. In large doses (long acting drugs) you would have the opposit |
| Which, direct or indirect acting musc agonists, work better on vascular smooth muscle? | direct; there is less marked action in indirect acting because they can only exert activity where vagal innervation exists |
| physostigmine? class, acetylcholine inhibition? main clinical use? | indirect acting musc ago, reversible, carbamate, glaucoma |
| echothiophate? | indirect acting muscarinic agonist, organophosphate, irreversible, highly lipid soluble, rapidly absorbed, eliminated via plasma and tissue esterases and the cytochrome P450 system |
| how are organophosphates eliminated from the body? | plasma and tissue esterases and the cytochrome P450 system |
| of the reversible indirect acting muscarinic agonists, which is readily absorbed from the GI tract, subcutaneoud and membranous tissues? | physostigmine |
| how is physostigmine destroyed? | plasma esterases |
| neostigmine is poorly absorbed after ____ administration. | oral |
| Which dosage would be higher: oral vs parenteral doses of neostigmine? | oral |
| When do you use an indirect acting muscarinic agonist with caution? | asthma, hyperthyroidism, peptic ulcer disease, hx of bradycardia (or cardiac disease), history of hypotension |
| what are the contraindications for indirect acting musc agonists? | urinary tract obstruction, GI obstruction, ileus, closed angle glaucoma |
| therepeutic use of indirect musc agonists: GI? | paralytic ileus, bladder atony |
| therepeutic use of indirect musc agonists: eye? | glaucoma (physostigmine) |
| therepeutic use of indirect musc agonists: neuromuscular? | MG (neostigmine, pyridostigmine, ambenonoium) |
| therepeutic use of indirect musc agonists: alzheimers? | tacrine, rivastigmine, donepizil, galantamine |
| therepeutic use of indirect musc agonists: antimuscarinic intoxification? | physostigmine |
| what drugs can be used to treat MG? | indirect muscarinic agonists that are reversible: neostigmine, pyridostigmine, ambenonium. |
| what indirect musc agonists can be used to treat alzheimer's? | tacrine, rivastigmine, donepizil, galantamine |
| what are the therapeutic uses for indirect musc agonisits? | alzheimer's dimentia, glaucoma, myasthenia gravis, paralytic ileus, bladder atony, antimuscarinic intoxification |
| What is the prototype for muscarinic antagonists? | atropine |
| How do muscarinic antagonists work? | they block the action of Ach at the muscarinic receptor |
| muscarinic antagonists can be divided into what groupings | tertiary amines and quaternary amines |
| what are the major tertiary amines (muscarinic antagonists)? | atropine, scopalamine, homatropine (semi or synthetic) |
| what are the major quaternary amines (muscarinic antagonists)? | synthetic esters, propantheline, glycopyrolate, ipatropium, methscopolamine, homatropine methylbromide, methantheline |
| what are the semi or synthetic quaternary amines? | methscopolamine, homatropine methylbromide, methantheline |
| what is a major factor to consider in the use of quaternary amines? | they have reduced CNS action |
| what are the irreversible muscarinic antagonists? | there are none, they are all reversible |
| antimuscarinics are more likely to antagonize the effects of (exogenous or endogenous) muscarinics? | exogenous |
| Antimuscarinics have a varibale affect on receptors. It varies with tissue and dose. Explain this breakdown. | salivary, bronchial and sweat glands require a low dose; pupil and heart require moderate dose; GI and bladder require larger doses |
| Quaternary ammonium involved in the antimuscarinic drugs can also do what? | they possess a small degree of ganglionic and NMJ blocking activity |
| You suspect Myasthenia gravis in a patient. You use ______, a drug as a diagnostic assessment. It confirms your suspicion. What drugs can be used to treat? (the category, and the specific names) | edrophonium (dx), can use indirect acting muscarinic agonists to increase Ach: pyridostigmine, neostigmine, ambenonium |
| You are a psychiatrist treating inpatient patients. You have a majorly depressed patient who you are giving tricyclic antidepressants. He attempts to kill himself by taking the entire bottle. He is going into shock. How can you save hopefully save him? | He is suffering from central anticholinergic syndrome due to overdose with tricyclic antidepressants (which can also be produced by phenothiazine or also antihistamines). You can reverse this by giving PHYSOSTIGMINE (a carbamate, reversible indir musc ag |
| You are told by your attending that your patient is suffering from central anticholinergic syndrome. An overdose of what may cause this? | antihistamines, tricyclic antidepressants, phenothiazine |
| Explain the differences between the different alzheimer drugs (indirect acting musc agonists) | They are all reversible: Tacrine (qid), donepezil (qd), rivastigmine (bid), galantamine (recently FDA approved) |
| which alzheimer's medication (indirect acting musc agonist) requires being taken the most times per day, least? which was recently approved? | most= tacrine (qid); least= donepezil; recently approved=galantamine |
| which indirect muscarinic agonists can be used for glaucoma? what is the difference? | physostigmine, demacarium, echothiophate, isoflurophate (echo and iso are irreversible organophosphates, whereas the other are reversible carbamates) |
| Youre an anasthesiologist, and you need to relax a patient, so you provide neuromuscular blockade. What is a drug that can reverse this? | neostigmine (indirect acting muscarinic agonist) |
| A patient recently had abdominal surgery and is now suffering of bloating, vomiting, constipation. On PE, you hear no bowel sounds. You suspect paralytic ileus. What drug could you give to get the bowels moving? How should this be administered? | the indirect acting muscarinic agonist, neostigmine; neostig is not absorbed very well PO so either large dose PO or smaller dose IV |
| You have a patient suffering from bladder atony. What could you give? | indirect musc agonisit, neostigmine |
| You have a patient succcessfully responding to edrophonium. You confirm myasthenia gravis. Before administration of an indirect musc agonist like pyridostigmine, neostigmine or ambenonium, what should be investigated? | asthma, hyperthyroidism, peptic ulcer disease, hx of bradycardia, cardiac ds, hx of hypotension; CANNOT USE if pt has a urinary tract obstruction, GI obstruction, ileus, closed angle glaucoma |
| When do antimuscarinics work the best? | when they are antagonizing effects of EXOGENOUS COMPOUNDS, rather than Ach from PANS stimulation. |
| If you were to give a patient an antimuscarinic in low dose, where would you most likely see the antimuscarinic effects first? | low dose sensitivity tissues are salivary, bronchial and sweat glands. |
| You are giving a patient increasing doses of antimuscarinics. Hypothetically, hour 1 you give a low dose; hour 2 a moderate dose, and hour 3 a large dose. Explain what you would expect to see in each hour. | Hour 1: salivary, bronchial, and sweat glands decrease production; hour 2: mydriasis, increase in HR; hour 3: decreased GI motility and bladder fullness. |
| what are possible side effects of an antimuscarinic? | CNS affects, mydriasis, cycloplegia, dry sandy eyes, increased intraoccular pressure, tachycardia, brochodilation, inhib of upper/low resp secr, xerostomia, constipation, urinary ret (esp BPH), decr sweating |
| which tertiary amine (antimuscarinic) can be absorbed thru the skin? | scopalamine |
| You have a patient with incontinence. You treat him with Oxybutynin (a tertiary antimusc). What side effect should you warn him about? | xerostomia |
| What are the most common side effects of an antimuscarinic? | blurred vision, tachycardia, dry mouth, urinary hesistancy |
| Motion sickness prophylaxis? | scopalamine |
| How could treat parkinson's disease and/or extrapyramidal symptoms? | antimuscarinic (must be tertiary to penetrate CNS): nenztropine, trihexyphenidyl, procyclidine, biperden) |
| You have a patient suffering from misosis and fixed near vision. How could you fix this? | anti-muscarinic (cyclopentolate, homatropine, tropicamide) *Tertiary amines |
| You have a patient complaining of sympxs consistent with spastic colon and peptic ulcer disease. How could you treat? | antimuscarinic, tertiary amines: dicyclomine, glycopyrolate, methantheline, methscopolamine, propantheline, oxyphencyclimine). |
| Your patient is suffering from inability to breathe due to COPD. How could you treat? | antimuscarinic, tertiary amine: ipatropium |
| You have a patient with urinary incontinence and spastic bladder. How could you treat? | antimuscarinic, tertiary amine: flavoxate, oxybutynin, tolterodine |
| Contraindications for using antimuscarinics? | glaucoma (especially closed angle/narrow angle); hx of prostatic hyperplasia, and gastric ulcer. |
| You have a male patient complaining of urinary incontinence. You decide to treat with an antimuscarinic. Which would you choose? What else would you want to know? | oxybutynin, flavoxate, toltrodine; you would want to make sure he doesn't have a gastric ulcer, BPH, or glaucoma. |
| What is the chemistry of ganglionic blocking drugs, and the significance? | quaternary ammonium (or sulfonium) drugs, meaning they have poor oral and CNS penetration. |
| What is the MOA for ganglionic blockers? | competetive antagonism for Ach receptors or by clogging open ion channels. They are considered non-depolarizing competetive antagonists. |
| Which ganglionic blocker works by antagnozing the Ach receptor in the ganglia? | Trimethaphan |
| Which ganglionic blockers works by clogging the ion channel causing non-depolarizing competion for Ach? | hexamethonium |
| What is the clinical use for hexamethonium? | there is NO clinical use |
| what are the agonists that work at the autonomic ganglia? what is there clinical use? | nicotine, lobeline, epibatidine; there is NO clinical use |
| what are the names of the ganglionic blockers? clinical use? | hexamethonium (none), trimethaphan (hypertensive crisis) |
| what are the NMJ blockers? clinical use? | succinylcholine, tubocurarine, pancuronium, vecuronium |
| which NMJ blocker is an antagonist/ag? | succinylcholine |
| where is the sympathetic system dominant? | arterioles, veins, sweat glands |
| what are the effects of a ganglionic block? | tachycardia, mydriasis, cycloplegia, constipation, decreased gastric/pancr secr, urinary ret, xerostomia, anhidrosis, incr periph blood flow, hypotens, decr CO, decr ven return, peripheral blood pooling, dilation of veins, vasodil of arterioles |
| what is the therapeutic use of trimethaphan (Arfonad)? administered? | ganglionic N1/nn blocker; used in past for treatment of hypertension, used now rarely for hypertensive emergency dissecting aortic aneurysm; if given, must be given as a continuous IV infusion |
| What is the therapeutic use of mecamylamine (inversine)? administration? | ganglionic N1/nn blocker; used in past to treat hypertension; now used rarely for hypertensive crisis dissecting aortic aneuryism; must be given as continous IV infusion |
| What are the structures of the NMB's. | They all are bulky, contain 1 or more + charged quat ammonium group that can bind to cholinergic recep, poor oral abs, avoids CNS; succinycholine (2Ach, more flexible); Benzylisoquinoloine (tubo/mivacur) rigid; Aminosteroidal (pancur/vecur) rigid). |
| Why is the size and structure of NMB's important? | It determines the type and magnitude of side effects, as well as potency and ONSET of action of the drugs. |
| What are the 2 types of NMB's? | depolarizing, non-competitive & non-depolarizing competitive NMB's |
| what is the prototype drug for depolarizing, non-competitive NMB's | succinycholine |
| what is the prototype for non-depolarizing, competitive NMB's | tubocurarine, pancuronium. |
| Why is succinylcholine longer acting at the Ach receptor than Ach? | because succinylcholine is not degraded by Ach, but rather pseudocholinesterase (butyrlcholinesterase) which takes longer to degrade, so succinylcholine is around longer |
| How does succinylcholine work? | succinylcholine is a non-competitive depolarizing NMB that binds to Ach receptor but isn't broken down by AchE (instead pseudochol) which makes it longer lasting; this leads to persistent activity, causing muscle fasiculations |
| what is a phase 1 block (NMB)? | the initial phase is followed by block of NM transmission and flaccid paralysis |
| what is a phase 2 block (NMB)? | the receptor becomes desensitized to the blocker and no longer recognizes it, and returns the end plate potential to normal; this converts the block from depol to NON-DEPOLARIZING TYPE. |
| what is dual block (NMB)? what is an example of a drug that does this? | simultaneous exisence of phase 1 and phase 2 blockade; succinylcholine; when you get block of NM transmission and flaccid paralysis, minor fasiculations at first, followed by receptor desentization and normal EPP, conversion to non-dep type |
| what is the difference between depolarizing and non-depolarizing NMB's? | depolarizing are irreversible, and non-depolarizing are reversible bc of AchE |
| which NMB type is reversible? | competitive, non-depolarizing NMB's |
| The effects of non-depolarizing, competitive NMB's? | they can be reversed by an AchE inhibitor (which allows for more Ach, which can then compete more and displace); such as neostigmine |
| NMB's may also activate or antagonize other receptors...explain? | muscarinic stimulation, autonomic ganglia blockade, may cause release of histamine and norepinephrine |
| which drugs can affect mast cells directly, causing release of histamine, causing possible bronchospasm, hypotension, and excessive seretion? | NMB's |
| NMB's can affect other receptors. What happens when they affect autonomic ganglia? | at the ganglia or adrenal medulla, partial block may lead to hypotension and or tachycardia |
| NMB's can affect other receptors. What happens when they affect muscarinic receptors? | some NMB's have a vagolytic (decr parasymp) action, leading to tachycardia |
| which NMB can cause bradycardia, or hypertension and tachycardia? | succinylcholine (bc it has affect on vagal stimulation or sympathetic ganglia stimulation |
| succinylcholine? MOA, effect on autonomic ganglia, effect on cardiac muscarinic, histamine release, duration of action, metabolism, elimination? | depolarizing/noncompetitive; +aut gang, +card musc, slight histamine release, short DOA, metabolized and eliminated by pseudocholinesterase |
| which NMB is eliminated by Hoffman elimination? | atracurium, cisatracurium |
| which NMB is metabolized by pseudocholinesterase? | succinylcholine |
| which NMB is metabolized entirely by the liver? | rocuronium, vecuronium |
| which NMB's are metabolized by kidney? | doxacurium, metocurine, pancuronium, pipecuronium, tubocurarine |
| which NMB is metabolized/eliminated by plasma cholinesterases? | mivacurium |
| which NMB's are depolarizing non-competetive? | succinylcholine |
| What is the only NMB that stimulates the heart? | succinylcholine |
| which NMB's block cardiac muscarinic stimulation to heart? | pancuronium and rocuronium |
| what is the only NMB to stimulate autonomic ganglia? | succinylcholine |
| Which NMB is associated with STRONG histamine release? | tubocurarine |
| What is the hoffman elimation reaction? | spontaneous degradation occuring in the plasma |
| what approximates the volume of distribution in NMB's? | the extracellular fluid |
| why is the duration of paralysis while using a NMB brief? | the initial dose is redistributed in the ECF. When the doses are repeated, tissues become saturated and metabolism and excretion influence the DOA |
| In general, in NMB's, what determines them to be short acting vs long acting? | the way they are metabolized; if met by plasma cholinesterase (short acting), if met by other routes (longer acting). |
| You need to give an obese patient a NMB for anasthesia. What do you base the dosage on? | lean body mass |
| You need to anasthetize a neonate, an adult, and an elderly adult. Who gets the larger dose? | neonates require greater amounts of NMB related to receptor immaturity and because they have a larger volume of distribution |
| You need to anesthetize an elderly adult. What is the relevance of their dose? | elderly pts get smaller doses |
| You are a medical student observing the paralytic affect of succinylcholine on a pt. What do you observe? | First, the patient will undergo transient muscular fasiculation over the chest and abdomen. Paralysis effect progresses to neck, arms, and legs. Slight weakness of facial, lingual, and pharyngeal and laryngeal muscles. Respiratory weakness is not sig. |
| A patient has fasiculations over his chest and abdomen before become paralyzed after being given a drug? | succinylcholine; non-competitive depolarizing NMB |
| which NMB affects respiration? | non-depolarizing competitive |
| which NMB type works faster? | non-depolarizing competitive |
| what happens if a patient is given a non-depolarizing competitive NMB? | when given IV, onset is rapid; motor weakness starts in rapid moving muscles like eyes first, then limbs and neck. intercostals and diaphram next, respiration ceases. |
| A patient is recovering from being anaesthetized by a non-depolarizing competitive NMB, how would they recover? | first they would get respiration back, then trunk, limbs, and then smaller muscles like eyes. |
| what are the CNS effects of a NMB? | none; they don't penetrate the CNS |
| tubocurarine and mivacurium fall into which category (based on strx) of NMB's? | benzylisoquinoline derivatives |
| pancuronium and vecuronium fall into what category of NMB's based on structure? | aminosteroidal compounds |
| What happens to aminosteroids during their metabolism in the body? (pancuronium/vecuronium) | When they are metabolized, they retain activity |
| What happens to benzolisoquinoline derviatives after metabolism (tubocurarine, mivacurium) | metabolites of benzylisoquinoline derivatives do not retain activty after metabolism |
| You are doctor and your are being chased by a man. The only thing you have on you is an oral NMB, an IM injection of a NMB, and an IV injection. Which should you give. What is the order from quickest acting to least? | PO: poorly and irregularly absorbed from GI due to NCH4+; IM: adequately absorbed from IM injection; IV: rapid onset from IV injection |
| A man is saying that he was paralyzed a while ago and he thinks his wife (a doctor) used a NMB. It has been long enough that the drug has been metabolized. Where could you look to dx? | you could look for metabolites in urine, bile, plasma (assuming plasma cholinesterase hadn't completely metabolized) |
| A man is states he was shot with an arrow covered in tubocurine in the jungle. What would you expect to see? | hypotention secondary to histamine release and autonomic ganglia blocking (decreased CO and SVR) |
| Tubocurine causes hypotention. Is it primary or secondary, and why? | secondary hypotension is due to histamine release from mast cells |
| which NMB causes secondary hypotension, decreased CO, and decreased SVR. | tubocuramine |
| Why do you notice an increase in CO, HR, BP, and myocardial oxygen consumption with the administration of pancuronium? | bc pancuronium has vagolytic effects and blocks the reuptake of NE |
| which NMB blocks the reuptake of NE? | pancuronium |
| what happens if you give a patient pancuronium and then you give them a larger dose of it? | dose dependent increase in tachycardia and hypertension from vagolytic effects |
| which NMB causes dose-dependent increase in tachycardia and hypertension | pancuronium |
| what is vecuroniums effect on the heart? | none.. it has no vagolytic effects |
| You have a patient on a beta 1 antagonist. what happens if you give him vecuronium? | because vecuronium has no vagolytic affects it will futher lower HR or cause bradycardia |
| why does vecuronium have no affect on the heart? | it doesn't release histamine and it doesn't have any vagolytic affect |
| You need to give a patient a NMB for anaesthesiology, but you can't mess with their heart rate (up or down). Which could you use? | vecuronium, pipecuronium, dozacurium, rocuronium. |
| You have a patient that needs to be intubated. You need to use a NMB. The patient currently has a cardiac pacemaker for ventricular fibrillation. Which NMB? Which one would you avoid the most? | Could use those with no CV effects (vecuronium, pipecuronium, doxacurium, recouronium) AVOID SUCCINYLCHOLINE (brady or tachydysrhythmias |
| Explain how each of the following NMB's relates to the CVS: tubocurarine, pancuronium, atracarium, cisatra, vecuronium, pipecuronium, doxacurium, rocuronium, succinycholine? | tubo (hypoTN 2ndry to hist rel, decr CO, decr SVR); panc (ddtachy, HTN, blocks NE reup) atra (hypoTN--hist rel, tachy), cisatra (hypo, tachy if in lg doses), vec (no CV effects, brady if with other brady agents) pipe/doxy (none) rocur (minimal), succ (arr |
| 1. Succinylcholine 2. Atracurium 3. Cisatracurium 4. Tubocurarine. Put them in order of greatest histamine release to least | 4 > 2 > 1 > 3 tubo>atra>succ>cis |
| what is required to make cisatricurium release histamine? | large doses |
| You need to give a patient a NMB. The patient stops and tells you that the last time this was time his leg hurt for a long time afterword. What should you do? Is the patient just scared? | NMB can cause pain after recovery, which can prevented with a predose of non-depolarizing competitive NMB. |
| As a medical student, you see that your doctor gave a patient a predose of something, but the handwriting is scribbled, before giving a patient a NMB. What is it, and why did he do it? | non-depolarizing competive predose to prevent pain upon recovery |
| A patient comes to the ER after a car wreck where he suffered severe burns on his skin and has developed some resulting muscle atrophy, an intraabd infx from glass puncture. He needs intubated and needs a NMB. What must you NOT use? why? | succinylcholine, it may cause hypokalemia, bc succ cause's K+ efflux from cells into blood elevating serum K by 0,5 to 1.0 meq/L. |
| The use of succinylcholine is contraindicated in patients with _______ due to possible elevation of K+ by 0.5 to 1.0meq/L. | extensive burns, acute neurologic,severe intrabdominal infections, cardiac arrythmias, or skeletal muscle atrophy. |
| You're observing a surgery on a 92 year old woman for knee replacement. She has severe muscle atrophy due to not being able to use her knees. The anasthesiologist is going to use succinylcholine. You question her. Why? | in patients with muscle atrophy, succinylcholine is contraindicated bc it may cause hyperkalemia; and it may cause MMR making it hard to intubate |
| A doctor tells you he is safely going to use succinylcholine on a patient bc they have no risk factors. What could you conclude theoretically, medically about the patient? | they have no heart problems (no brady/tachydysrhythmias), no extensive burns, no intrabd infx, no skM atrophy, no eye injury, no glaucoma, no malignant hyperthermia |
| What do NMB's do to the eye? | increased intraoccular pressure, prolonged tonic ctrx of EOM with succ; avoid in eye injury and glaucoma |
| What eye problems keep you from using succinylcholine? | eye trauma or some types of glaucoma |
| what does succinylcholine do the IOP? | increases it about 8mm of Hg for about 10minutes |
| A patient is given succinylcholine for intubation. She complains that her eye is hurting. Her IOP was obviously affected. She asks you, "How long is this going to last?" What do you tell her? | about 10 mintues |
| You are doing a thorough hx on a patient before giving her succinylcholine for intubation. She says that one time her mom was given a drug for intubation she thinks that gave her a rxn. The dr's told her it was genetic. explain. | Malignant Hyperthermia: hypermetabolic state associated with depolarizing NMB's (hyperthermia, metabolic acidosis, tachy, accelerated muscle met, contractures) |
| In one room, you have 25,000 children and in another you have about 100,000 adults. If you were to follow statistics, how many children/adults would have malignant hyperthermia statistically? | 2 children (1 in 12,000), 3 adults (1 in 30,000) |
| malignant hyperthermia is more common in ____. | Children |
| A patient tells you that she has malignant hyperthermia. What is it? | genetic disorder, more common in children, hypermetabolic state associated with hyperthermia, metabolic acidosis, tachycardia, accelerated muscle metabolism, and contractures. |
| After intubation with a NMB, a patient gets really hot. Labs reveal metabolic acidosis, tachycardia, accelerated metabolism, and contractures. What's was the most likely drug given? | a depolarizing, non-competitive: succinylcholine |
| If you have to give a NMB for long periods and large doses, what should you be worried about? Large doses and long periods of tx are usually associated with what? | profound, long-lasting blockade and muscle atrophy. Associated with reduced rates of clearance. |
| What are the systemic effects of NMB's? start head to toe. | Incr ICP, incr IOP, MMR, a combo of vagolytic, ganglionic blockade, and histamine action producing different affects in heart and vasc, muscle fasiculation, incr gastric pressure |
| What do NMB's do to muscle? | can cause muscle fasiculations, pain on recovery, or muscle atrophy if used in large doses or for long periods due to reduced clearance, causes MMR |
| what do NMB's do to stomach? | increased intragastric pressure |
| A patient inhaled an anaesthetic because he was nervous before his surgery while the doctor wasn't looking. The doctor still needs to give a NMB. What should he do? | anesthetics can work synergistically with NMB's so he just needs to decrease the dose of the non-depolarizing competitive NMB's |
| what do aminoglycosides do, concerning a NMB? | they produce a NMB bc they inhibit release of Ach from the pregang terminal and also have an affect on the postjunctional mem. |
| A patient tells you she is taking an antibiotic, but you dont' know which one. Which antibiotics can cause a NMB? | aminoglycosides, tetracycline, polymyxin B, clindamycin |
| If a patient is taking tetracycline, polymyxin B, aminoglycosides, or clindamycin, and you have to give a NMB, what could be coadministered. | the NMB produced by the antibiotic can be antagonized by Ca+ and inconsistently by AchE inhibitors |
| You feel that it's been too long, that a patient should have recovered from a NMB. what could you do to speed up the process? | give the patient calcium salts, to increase release of Ach |
| What happens if you give a patient with a NMB calcium channel blockers? | it will enhance the block |
| AchE inhibitors can be given to antagonize a NMB. What type of NMB's do they work against? | non-depolarizing, competitive |
| What drug interactions will enhance a NMB? | inhaled anesthetics, aminoglycoside antibiotics, calcium channel blockers |
| How do you reverse a non-dep competive NMB? | AchE inhibitor, give antimuscarinic (atropine or glycopyrrolate) to antagonize Ach muscarinic effects. |
| Why should atropine or glycopyrrolate, specifically, be given with an AchE inhibitor to reverse an ND,c NMB? | you need the antimuscarinic because the AchE inhibitor will increase muscarinic effects. You choose atropine and glycopyrrolate specifically bc they don't act on nicotinic receptors . |
| which AchE inhibitors should be given during a NMB reversal along with an antimuscarinic (like atropine or glycopyrrolate) | neostigmine/pyridostigmine are the preferred agents |
| What will happen if, during a NMB reversal, you give too much AchE inhibitor (too much neostigmine or pyridostigmine)? | excess Ach will cause prolongation of channel opening which is similar to depolarizing agents |
| What are the therapeutic uses of NMB's? | adjuvant to general and local anaesthesia to obtain skeletal muscle relaxation, short-term tracheal intubation, difficult/long-term mechanical intubation, rapid control of status epilepticus |
| You have a patient present to the ER with status epilepticus who needs to be controlled. What can you use? | a NMB |
| what is the parent compound for catecholamines? | phenylethylamine (benzene ring +ethylamine side chain) |
| separation of the aromatic ring from the amino group by ____ carbons, produces the most sympathetic activity. | 2 |
| where are the OH groups located on the benzene ring for catecholamines? | OH groups at 3 and 4 |
| Catecholamines have an OH group on the benzene ring at position 3 and 4. removing 1 of the OH groups will dramatically reduce the potency of the catecholamine. which spot? | 3 |
| why is phenylephrine less potent that epinephrine? | it's missing the 3-OH, reducing potency |
| what doesthe lack of a 3-OH on the benzene ring do to its receptor activity | decreases alpha activity by 100-fold, with negligible beta activity |
| COMT is found in the gut and liver. If it encounters a catecholamine structure that it can't degrade, what have changed? | it's lacking a 3 or 4-OH on the benzene ring |
| what prolongs the bioavailability o catecholamine agents for oral administration and prolonged duration of effect, also reducing peripheral uptake? | lack of 3 and 4-OH on the benzene ring |
| what does lacking the 3 and 4-OH on the benzene ring do for bioavailability? | it improves bioavailability: improves oral absorption, prolonges duration of action, and reduces peripheral uptake because they are not degraded by COMT |
| what are noncatecholamine compounds in terms of structure? | loss of catechol groups, resulting in loss of direct sympathomimetic activity, relying directly on indirect MOA |
| noncatecholamines have lost the catechol OH groups, what does this do to the activity of the compound? | loss of direct sympathomimetic activity, resulting in reliance on indirect MOA |
| If a substitution with a non OH group is added to the parent catecholamine molecule, what happens? | it generally confers alpha receptor activity, with the exception of albuterol (a selective B2 receptor agonist) |
| why do ephedrine and amphetamie penetrate the CNS well? | because they lack both OH groups on the benzene ring, increasing bioavailability and decreasing degradation by comt |
| what are two catecholamines that lack the 3 and 4 OH group, allowing CNS penetration? | amphetamine, ephedrine |
| what will increase CNS distribution (for catecholamines)? | lack 3 and 4-OH group from benzene ring |
| how can you increase beta receptor activity? | by increasing the size of alkyl substituents on amino groups of cateecholamine structure |
| the addition of alkyl groups on the amino group of catecholamine structre does what? | increases beta receptor activity |
| If you add CH3 to NE, you get? | epinephrine, with enhanced beta activity |
| adding an alkyl group to the amine group of the parent structure (with 3 and 4OH groups) results in ______, adding 2 yields ____. | epinephrine, isoproterenol |
| which has more alpha activity: epinephrine or isoproterenol? why? | epinephrine, because isoproterenol has 2 alkyl additions to the amino group, which increases selectivity for beta and decreases alpha |
| phenylephrine has 1 alkyl group on its amino group, and epinephrine has 1 alkyl group. which has more alpha selectivity? which has more beta? | phenylephrine. **normally adding alkyl groups makes drugs more beta selective, but phenyephrine is an exception. the alkyl group additions make the drug more beta selective, but loss of the 3OH group on phenylephrine decreases beta receptor activity |
| what is required to select for beta 2 receptor activity? | requires large amino substituent on the amino group, but this increases beta in general. to specifically target beta2 must undego: 3,5 aromatic hydroxylation |
| 3,5 aromatic hydroxylation | increased beta2 receptor activity |
| describe in greatest order the alpha receptor activity of NE, epi, isoproterenol. | NE>epi bc epi has an alkyl group and epi>>>>>isoproterenol because iso has 2 and epi has 1. so NE is>>>>>>>>>>>alpha selective than isoproterenol |
| what is the alpha receptor activity of isoproterenol? | almost absent because of the alkylation of the amino group which makes it beta selective |
| direct acting adrenergic agonsits act as such because of addition of what? | beta OH group |
| dopamine is a direct acting adr agonist. how is it different in terms of structure? | it lacks a beta OH group, which is required for all other direct acting adr agonists |
| what does the beta OH group do for the alpha and beta recep activity? | enhances both |
| _______ is believed to be important in activating adrenoreceptors and may be important for hte storage of agent in neural vesicles. | Beta OH group, which is found in direct acting adr agonists |
| what does beta OH do to the lipid solubility of direct acting agonists. Explain the significance. Include dopamine. | the beta OH group lower the lipid solubility of the direct act adr agonists, which inevitable lowers the CNS action. dopamine, even though a dir act adr agonist, lack the beta OH group. |
| what adr receptors are in the eye? fxn? tx? | a1 (incr humor flow, mydriasis--radial), b2 (relaxes ciliary for accom to fv); glaucoma |
| what is a treatment that can be used to stimulate a1 receptors in the eye to increase aqueous humor flow to relieve pressure for glucoma? | atraclonidine |
| atraclonidine? | a1 agonist that incr aqueous humor flow, used in tx for glaucoma |
| Effects of indirect acting agents can be reduced in? | denervated tissues, pretreatment with reserpine, or cocaine |
| what is NE affect on resp tract? | little or none; the lungs are B2; NE is a1 |
| what is epinephrine's affect on lungs? | potent bronchodilator (epi is mixed a and b) |
| what is isoproterenols affect on lungs? | large bronchodilation (iso is B2) |
| what is isoproterenols effect on bv's? | little effect; vessels are pred a receptors, and iso is b2, so little effect |
| what catecholamines have large effect on vessel? | epi and norepi, those involving a |
| What makes a catecholamine have more effect? | limited beta agonist activity, because if you involve beta you get reflex mechanisms that adjust for homeostasis |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: cutenous/mucous membrane vascular resistance. | mediated by alpha 1, so norepi and epi; iso has no effect |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: smooth muscle. | involves both alpha and b2. norepi (incr vasc resistance to smM), epi (incr or decr), isoproter(decrease vasc resistance) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: renal vascular resistance? | regulated by alpha and d1. norepi (incr vr), epi (incr vasc resist), iso (decr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on total peripheral resistance? | norepi (increases), epi (incr), iso (decr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: contractility. | mediated by b1, a1; norepi (0 or small incr), epi (large incr), iso (large incr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: HR? | B1; norepi (decr, vagal reflex), epi (incr/decr), iso (large incr) |
| why does the application of norepinephrine slow the heart rate? | norepi is primarily alpha 1 mediated, so it will increase peripheral resistance incr BP, which stimulates vagal reflex, lowering HR |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: stroke volume? | norepi (0, incr, decr), epi (incr), iso (incr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: CO? | norepi (decr), epi (incr), iso (large incr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: mean bp? | norepi (increase most), epi (incr), iso (decr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: diastolic bp? | norepi (large incr), epi (incr, decr), iso (decr) |
| Considering Norepi, Epi, and Isoproterenol, explain which has more of an effect on: systolic bp? | norepi (large incr), epi (large incr), iso (0, decr) |
| At low doses of epi (0.01 to 0.1), what receptors are effected? | b1>b2>a |
| at higher doses of epi (>0.1), what receptors are affected? | alpha>b1, no b2 |
| at what dose will dopamine affect all types of receptors, a, b1 and b2? | at the larger dose (2.5-10mcg) |
| phenylephrine targets which receptors? | alpha |
| which noncatecholamine has the highest B2 potency? | metaproterenol |
| which noncatecholamines have alpha receptor fxn? | phenylephrine and methoxamine |
| what are the indirect acitng adr agonists? | amphetamine, dextroamphetamine, methylphenidate, cocaine |
| what are the mixed indirect acting adr agonsits? | ephedrine, dopamine, mataraminol |
| Historically isoproterenol has been used in severe ______. | bradycardia |
| What do you treat someone with ACLS (cardiac arrest due to vfib, electromechanical dissociation, or asystole) | epinephrine |
| what do you tx shock with? | continuous infusion of dopamine, epinephrine, norepinephrine, dobutamine |
| what do you treat CHF? | dobutamine, dopamine, or other investigation |
| what do you treat hypotension? | unusual indication to treat, usually complication of other |
| how do you treat anaphylacic reactions? | epinephrine or other beta agonist |
| You need to shrink someone's mucosa for an ENT procedure? | cocaine or epinephrine |
| A patient has priapism. How could you treat? | local injection of alpha agonist into penis may reverse |
| nasal decongestant? | alpha 1 agonists |
| asthma? | beta agonists |
| You need to stop preterm labor? | selective beta2 agonists |
| how can you tx htn with adrenergics? | central alpha 2 agonists (clonidine) |
| what are opthalmic uses for adrenergics? | for exam and management of glaucoma |
| Common treatments for adrenergic agonists? | ACLS, shock, CHF, anaphylaxis, local vascular effects, nasal decongestants, asthma, inhib of preterm labor, HTN, glaucoma, obesity, ADHD, narcolepsy |
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