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ANS Pharmacology
GCOP ANS Pharmacology I
| Question | Answer |
|---|---|
| Which division of the ANS do muscarinic receptors belong to? | Parasympathetic |
| Which division of the ANS do nicotinic receptors belong to? | Parasympathetic |
| Which division of the ANS do alpha receptors belong to? | Sympathetic |
| Which division of the ANS do Beta receptors belong to? | Sympathetic |
| What type of receptors are usually post ganglionic receptors? | Nicotinic |
| What type of NTs stimulate most sympathetic receptors? | NE, E |
| Activation of what type of receptor stimulates sweat glands? | Muscarinic |
| What division of the ANS do sweat glands fall under? | Sympathetic |
| Where are Dopamine receptors found? | Pulmonary artery, renal proximal tubules |
| What are the main functions of the sympathetic nervous system? | Fight and Flight |
| What are the main functions of the Parasympathetic Nervous system? | Feed and Breed |
| Which NT does the sympathetic nervous system usually use? | NE |
| What NT does the parasympathetic NS use? | Ach |
| What is the CHT? | CHT = Na+ dependent choline transporter |
| What does the CHT do? | transports choline (with Na+) into the presynaptic nerve terminal |
| What drugs block CHT? | hemicholiniums |
| What is VAT? | vesicle associated transporter |
| What does VAT do? | Transports Ach into storage vesicles |
| What drug blocks VAT? | vesamicol |
| What is ChAT? | Choline acetyl transferase, enzyme that synthesizes Ach from acetyl-CoA and choline |
| What is VAMP? | vesicle associated membrane protein |
| What does VAMP do? | align vesicle with the release site and participate in triggering the release of transmitter |
| What is VAMP inhibited by? | botulinum toxin |
| What are SNAPs? | synaptosome-associated proteins |
| What do SNAPs do? | SNAPs align the release site, VAMPs align with SNAPs at release site |
| What are SNAPs inhibited by? | botulinum toxin |
| What is AchE? | Acetylcholinesterase |
| What does AchE do? | Breaks down Ach to choline and acetate |
| What are two types of presynaptic receptors? | heteroreceptors and Ach autoreceptors |
| What do heteroreceptors do? | When Ach binds it causes more Ach release (positive feedback) |
| What do Ach autoreceptors do? | When Ach binds it causes Ach release to stop (negative feedback) |
| What type of junction are CHTs, VATs, and ChATs associated with? | Cholinergic Junctions |
| What does the Sodium dependent carrier do? | transports tyrosine into the noradrenergic ending (along with Na+) |
| What does tyrosine hydroxylase do? | catalyzes Tyrosine --> Dopa |
| What is tyrosine hydroxylase inhibited by? | Metyrosine |
| What is the significance of tyrosine hydroxylase in the synthesis pathway of NE and E? | It is the rate limiting enzyme |
| What is VMAT? | vesicle monoamine transporter |
| What does VMAT do? | high affinity antiporter for catecholamines located in the wall of the storage vesicle |
| What drug inhibits VMAT? | reserpine |
| What does Dopamine-B-hydroxylase do? | converts Dopamine to NE once it has entered the vesicle via VMAT |
| What drugs inhibit VAMPs and SNAPs at the noradrenergic junction? | bretylium and guanethidine |
| What is the NET? | NE Transporter |
| What does the NET do? | carries NE and similar molecules from the synaptic cleft back into the cell cytoplasm (REUPTAKE) |
| What drugs inhibit NET? | cocaine, tricyclic antidepressants |
| What are the steps of catecholamine biosynthesis? | (a) Tyrosine + tyrosine hydroxylase → Dopa (inhibited by Metyrosine) (b) Dopa + Dopa decarboxylase → Dopamine (c) Dopamine + Dopamine-B-hydroxylase → Norepinephrine (d) Norepinephrine + Phenylethanolamine-N-methyltransferase → Epinephrine |
| What are the most common muscarinic receptors? | M1, M2, M3, M4, M5 |
| Which M receptors are stimulatory and use phospholipase C as a second messenger? | Odds - M1, M3, M5 |
| Which M receptors inhibit adenylate cyclase? | Evens - M2, M4 |
| What effect do M2 and M4 have? | open K+ channels, close Ca2+ channels → hyperpolarize |
| What effect does stimulation of M receptors have on the organs? | (1) Heart – beats slower and softer (2) Bronchioles – constricts smooth muscle (3) Stomach – increase in acid production (4) Intestine – increase in digestion (5) Pancreas – insulin release (6) Eye – close visual accommodation (7) Mouth – mouth wat |
| What is negative chronotropy? | decrease in heart rate |
| What is negative dromotropy? | decrease in conduction velocity |
| What is negative ionotropy? | Decrease in contraction strength |
| What are the effects of overstimulation of muscarinic receptors? | SLUDGE – salivation, lacrimation, urination, defecation, GI upset, Emesis |
| Where are muscarinic receptors generally found? | Organs and in brain |
| Sympathetic stimulation of what organ uses muscarinic receptors? | Sweat Glands |
| What are four choline analogs (choline esters)? | acetylcholine, methacholine, carbachol, bethanechol |
| Describe the half life of Ach. | Ach is extremely susceptible to AchE, which is why it has an extremely short t1/2 |
| What is bethanechol used to treat? | postpartum and postoperative nonobstructive urinary retention (helps you pee) |
| What effect does Carbachol have on the eyes? | It is a miotic agent (small pupils) |
| What is Carbachol used to treat? | Glaucoma |
| What are two muscarinic agonists that are natural alkaloids? | muscarine, pilocarpine |
| What is pilocarpine used to treat? | glaucoma |
| What type of drug is pilocarpine? | muscarinic agonist |
| What is the source of muscarine? | A poison found in mushrooms |
| What type of drug is Carbachol? | Muscarinic Agonist |
| What is an antedote for muscarinic toxicity? | atropine |
| What type of antagonists are Muscarinic blockers? | competitive antagonists |
| What type of effects will muscarinic antagonists have? | anti-parasympathetic effects (similar to sympathetic stimulation) |
| What are the two drug prototypes of Muscarinic antagonists? | Atropine and Scopolamine |
| What unpredictable effect does Atropine have at low doses? | paradoxical bradycardia |
| At therapeutic doses what effect does atropine have? | increased heart rate, atropine takes away muscarinic stimulation from the heart so that it will beat stronger and faster |
| What are the signs of muscarinic antagonist overdose? | RED, HOT, DRY and MAD |
| What are the two notable differences between atropine and scopolamine? | Atropine is a strong cardiac stimulant, scopolamine is only a weak cardiac stimulant Atropine has only minor CNS effects, Scopolamine has CNS effects because it crosses the BBB |
| What is scolopamine used to treat? | Nausea |
| Why are quaternary ammonium compounds useful? | The charged N group doesn't cross membranes well (goes where you put it) |
| What is notable about the structure of Ipratropium? How is it administered? | A quaternary ammonium group, inhalent |
| What is Ipratropium used to manage? | cholinergic-mediated bronchospasm associated with COPD |
| What is the most notable side effect of Ipratropium? | Dry Mouth |
| What is Tiotropium used to treat? | COPD, emphysema |
| What is the notable difference between tiotropium and ipratropium? | Tiotropium has a significantly longer t1/2 than ipratropium |
| Which drug has some M3 selectivity, ipratropium or tiotropium? | tiotropium |
| What are the clinical uses of muscarinic antagonists? | anti-diarrheal, Cardiovascular support, preoperative antisecretory agent, COPD, incontinence, nausea |
| How is glycopyrrolate used? | used as an anti-vagal drug with general anesthesia |
| What type of drug is Methscopolamine? | Muscarinic antagonist |
| What type of drug is Homatropine? | Muscarinic antagonist |
| What type of drug is Prothantheline? | Muscarinic anatgonist |
| What type of drug is glycopyrrolate? | Muscarinic antagonist |
| What is pirezepine used to treat? | acid-peptic disorders |
| Is pirenzepine selective? | Yes, M1, M4 |
| What is Darfenacin used to treat? | urinary and fecal incontinence |
| What receptor is Darfenacin selective for? | M3 |
| What is Oxybutynin used to treat? | incontinence |
| How does Oxybutynin work? | muscarinic antagonist, relaxes detrusor mm |
| What is Tolteridine used to treat? | incontinence |
| What type of drug is tolteridine? | muscarinic antagonist |
| What do the CNS tageted muscarinic antagonists do? | prevent extra-pyramidal effects caused by older antipsychotics, anti-parkinson's |
| What type of drugs are Benztropine, Trihexyphenidyl, Biperiden, and procylidine? | CNS targeted muscarinic antagonists |
| What four categories of drugs have significant anticholinergic side effects? | Antihistamines, Tricyclic Antidepressants, antipsychotics, benzodiazepines |
| What is the mechanism of action for indirect cholinergic agonists? | Cause stimulation of Ach receptors by blocking the degration of Ach by AchE (Ach will continue to work until it is removed from the synapse) |
| How many molecules of Ach does AchE remove per second? | 200,000-300,000 Ach per second, which is why blocking AchE has profound effects |
| There are two indirect cholinergic agonists that target muscarinic receptors. What are these two drugs used to treat? | Glaucoma - echothiphate, Diisopropylfluorophosphate (DFP) |
| Diisopropylfluorophosphate (DFP) was historically used to treat glaucoma. What is it also used for? | Insecticide |
| There are three indirect cholinergic agonists that target nicotinic receptors. What are these drugs used to treat? | Myasthenia Gravis |
| What is neostigmine used to treat? | Myasthenia Gravis |
| What type of drug is neostigmine? | Indirect cholinesterase agonist |
| What type of drug is pyridostigmine? | Indirect cholinesterase agonist |
| Why don't neostigmine, pyridostigmine, and ambenonium cross the BBB? | They have a quaternary ammonium group |
| What is the pathogenesis of Myasthenia Gravis? | It's an autoimmune disease. The immune system creates antibodies that attack and destroy the nicotinic receptors on the motor end plate of skeletal muscle resulting in weakness. |
| What is the mechanism of action of the drugs used to treat Myasthenia Gravis? | AchE inhibitors will increase the likelihood that enough N-AchR will be stimulated since more Ach will remain in the synapse |
| What is the extremely fast acting AchE inhibitor used in the Tensilon Test? | Edrophonium (Tensilon) |
| What are the possible outcomes of the Tensilon test? | Patient becomes stronger - positive diagnosis for MG or indication that AchE(-) dose is too low Patient is worse - Ach(-) dose too low, or its not MG |
| Why is the Tensilon test used to differentiate overdosing from underdosing in the treatment of MG? | The symptoms are the same for both |
| What are physostigmine, tacrine, denopezil, and galantamine used to treat? | Cognitive disorders of Alzheimer's disease (dementia) |
| What type of drugs are physostigmine, tacrine, denopezil, and galantamine? | Indirect Cholinergic Agonists |
| Besides therapeutic uses, what are the other applications for indirect cholinergic agonists? | Pesticides, Human poisons (ex Sarin) |
| What does inhibition of AchE cause to increase? | Skeletal muscle contractions (fasciculations) |
| What is a similiar enzyme to AchE that is found in the blood? | butyrylcholinesterase |
| What would occur in a AchE Inbibitor overdose? | loss of control and paralysis |
| What are the two parts to the AchE binding site? | Anionic (negative charges) and Esteratic Site (Histidine and Serine) |
| What is the first step in the binding of Ach to AchE? | Ach is drawn into binding pocket by electrostatic interaction between the negative charges in the anionic site and the positively charged N group on Ach |
| After binding the anionic site, what is the next step in the binding of Ach to AchE? | Ach binds to the Serine residue in the esteratic site |
| After Ach is bound to both site of AchE, what happens next? | The C--O--C bond is broken, leaving choline and serine-acetate. The serine-acetate bond is hydrolyzed in the presence of water, making acetic acid and regenerating the AchE enzyme. |
| What are the three main classes of cholinesterase inhibitors? | Quaternary Amines, Carbamates, Organophosphates |
| Which drug is an example of a quaternary amine AchE inhibitor? | Edrophonium |
| What is a characteristic of quaternary amine AchE inhibitors? | Very short acting (edrophonium) |
| What are two examples of a carbamate AchE inhibitor? | neostigmine, physostigmine |
| What is the duration of action of carbamate AchE inhibitors? | intermediate to long-acting |
| What is an example of an organophosphate AchE inhibitor? | diisopropylfluorophosphate |
| Why are quaternary ammonium AchE inhibitors short acting? | They don't stick to the AchE binding site well and will leave on their own |
| Why are carbamate AchE inhibitors longer acting? | They go through the same binding process as Ach but do not leave as quickly |
| Why are organophosphate AchE inhibitors considered permanent? | The hydrolysis of the phosphorylate esteratic site is so slow that it is considered irreversible |
| Why are organophosphate AchE inhibitors potentially toxic? | They irreversibly bind AchE enzymes and are very lipophilic. Their effects may last until new AchE is synthesized. |
| What drug is used to treat organophosphate poisoning? | 2-PAM (Pralidoxime) |
| What is a limitation of treatment using 2-PAM? | It must be given within a short time to prevent the aging process (before the leaving group leaves) |
| What is the aging process in organophosphate poisoning? | After the leaving group leaves, an isopropyl/phosphate group is permanently bound to the serine residue |
| What is the mechanism of action of pralidoxime (2-PAM)? | 2-PAM binds to the organophosphate and facilitates its removal from the AchE binding site. |
| What are the two treatment strategies for glaucoma? | increase in fluid drainage or decrease in fluid production |
| What is the mechanism of action in the treatment of glaucoma with muscarinic agonists? | Stimulation of M3 leads to the contraction of the ciliary and iris sphincter mm, promoting drainage |
| What are the types of Nicotinic receptor targets? | neuromuscular and ganglionic |
| What type of nictotinic anatagonists are mecamylamine, hexamethonium, and tertraethylammonium? | ganglionic blockers |
| What is one clinical use of ganglionic blockers? | tx of acute, dissecting aortic aneurysm (decrease BP) |
| Why do ganglionic blockers have limited clinical use? | they have limited specificity |
| What subunits make up neuromuscular nicotinic receptors? | α, β, δ, and ε subunits |
| What subunits make up ganglionic nicotinic receptors? | 2 - α, 3 - β |
| What is the prototypic nondepolarizing neuromuscular blocker (nicotinic antagonist)? | Tubocurarine |
| What is the action of a nondepolarizing neuromuscular blocker? | binds to receptor and prevents it from opening, cell membrane can't depolarize |
| What is the action of a depolarizing neuromuscular blocker? | binds receptor, opens it, and blocks channel from closing |
| What are the three different types of neuromuscular blocking drugs? | isoquinolone derivatives & steroid derivatives (nondepolarizing), depolarizing agents |
| Turbocurarine, atacurium, and doxacurium are what type of drugs? | isoquinoline neuromuscular blocking drugs (nicotinic antagonists) |
| Which neuromuscular blocking drug is used on poison arrows? | turbocurarine |
| What type of drugs are pancuronium, pipercuronium, vecuronium, and Rocuronium? | steroid based neuromuscular blockers (nicotinic antagonists) |
| To which neuromuscular blocker are all others' potencies compared? | turbocurarine - the protoype |
| What is the depolarizing neuromuscular blocker? | succinylcholine |
| What is the mechanism of action of succinylcholine? | initially causes depolarization and muscle twitches, then switches to nondepolarizing action |
| What is succinylcholine metabolized to? | succinate and choline |
| Does succinylcholine have a long or short t1/2? | very short t1/2 |
| What is meant by sympathomimetics? | mimic the effect of the sympathetic NS |
| What is meant by sympatholytics? | block the effects of the sympathetic NS |
| What does reserpine do? | blocks catecholamine entry into vesicles |
| What compound does catecholamine synthesis begin with? | Tyrosine |
| What is the correct order of products in catecholamine synthesis? | Tyrosine --> Dopa --> Dopamine --> NE --> Epi |
| Where in the presynaptic terminal is Dopamine converted to NE? | upon entry into vesicle |
| What are the three types of action sympathomimetic drugs can have? | direct acting, indirect acting, mixed acting |
| How does an indirect acting sympathomimetic drug work? | drug enhances release of NE from vesicles |
| How does a direct acting sympathomimetic drug work? | drug directly activates receptor |
| How does a mixed acting sympathomimetic drug work? | Drug acts both directly and indirectly |
| Structures of agonist drugs are often very similar to the NT. As a rule, how does the drug's affinity for Beta receptors change as the group on the terminal amine increases in size? | As the group on the terminal amine increases in size, the affinity for beta receptors also increases. |
| How is the action of NE, Epi and DA ended? | Action is terminated by reuptake by NET, uptake by glia, and metabolic breakdown by COMT and MAO |
| How do the potencies of MAO and COMT for NE, Epi, and DA compare to AchE's affinity for Ach? | COMT and MAO are not as potent |
| About how much of the NE reuptaken by NET is stored for reuse? | about 50% |
| What type of effect do amphetamines have on NET? | Amphetamines cause NET to reverse and pump NE out instead of in |
| What type of effect does cocaine have on NET? | cocaine block reuptake |
| What is the basic mechanism of action of MAO? | deamination |
| What is the basic mechanism of action of COMT? | methylation |
| MAO inhibitors interact with numerous other drugs. Why are they still used? | Some patients do not respond to other options |
| Where is MAO present outside the CNS? | MAO is present in the intestinal tract to neutralize neuroactive compounds |
| What are the two types of MAO? | MAO-A, MAO-B |
| COMT is widely distributed. Where is MAO located that COMT is not? | Inside neurons |
| Of the adrenergic receptors, which two work in opposite directions? | Beta-1 and alpha-2 |
| What type of G subunit do Beta receptors activate? | Gs - stimulatory |
| What type of G subunits do alpha-2 receptors activate? | Gi - inhibitory |
| What is the alpha-1 receptor's most notable effect? | vasoconstriction |
| What is the alpha-2 receptor's most notable effect? | decreases BP |
| What is the beta-1 receptor's most notable effect? | stimulates the heart to beat harder and faster |
| What is the beta-2 receptor's most notable effects? | dilation of blood vessels and bronchioles |
| What effect does stimulation of Beta-1 receptors have on the kidney? | increases renin release --> increases BP via cascade |
| What is the equation for mean arterial pressure? | MAP = 1/3(sys - dias) + dias |
| What is the alpha effect? | Stimulation of alpha receptors causes vasoconstriction, which leads to reflex bradycardia. If nicotinic receptors are blocked at ganglia and and alpha-1 agonist is given there will be no change in HR. This means that the bradycardia is reflexive. |
| What effect does Beta-2 receptor stimulation have on the arterioles? | Dilation caused by relaxation of smooth muscle cells |
| What effect does stimulation of Alpha-1 receptors have on the arterioles? | Constriction caused by the contraction of smooth muscle cells |
| Response of adrenergic receptors to NE and Epi is dose dependent. Which type receptor has an initial response to low doses? What is that response? | Beta-2 receptors will initially respond to low doses of NE/Epi. Stimulation of these receptors causes relaxation of the vascular smooth muscle and therefore dilation of blood vessels. |
| Response of adrenergic receptors to Epi is dose dependent. Which type receptor will respond (and persist) as the dose increases? What is that response? | At higher doses alpha-1 receptors will respond. Stimulation of these receptors leads to vascular smooth muscle contraction and vasoconstriction. |
| In experimental settings, administration of increasing amount of Epi leads to vasodilation followed by vasoconstriction. Why does this occur? | Epi has a higher affinity for Beta-2 Receptors, which is why they are activated at low doses. Alpha-1 receptors have greater intrinsic activity, which is why at higher doses the vasoconstrictive action of alpha-1 stimulation predominates. |
| What effect does NE have on alpha-1 receptors? | Stimulation of alpha-1 receptors by NE leads to vasoconstriction. This is first seen at lower doses and persists. |
| What effect does NE have on Beta-1 receptors? | Stimulation of Beta-1 receptors by NE leads to increase in heart rate, contractility and conduction. |
| Why are the cardiac effects of stimulation of beta-1 receptors seen mainly at higher doses? | At lower doses the baroreceptors will have been activated to suppress the heart. At high doses this reflex does not occur, which can be dangerous. |
| What are three clinical uses of epinephrine? | Tx of anaphylactic shock, cardiac emergencies, asthma emergencies |
| Which type of receptor will show the predominant effect when stimulated with Epi at low doses? | Beta receptors - 1&2 |
| Which type of receptor will show the predominant effect when stimulated with Epi at high doses? | Alpha-1 |
| What effect will stimulation of alpha-1 receptors by Epi have? | vasoconstriction |
| What effect will stimulation of Beta-1 receptors by Epi have? | ionotropic, chronotropic, dromotropic |
| What effect will stimulation of Beta-2 receptors by Epi have? | bronchodilation |
| Why would Epi be used for local anesthesia? | restricts blood flow to keep locals local (also reduces bleeding with incisions) |
| What effect will Dopamine have on adrenergic receptors? Which receptor(s)? | Dopamine works on Beta-1 receptors to have a stimulatory activity on the heart (stimulates NE release), also improves renal blood flow |
| What drug is the prototypic non-selective Beta agonist? | Isoproterenol |
| What is meant by non-selective Beta agonist? | Stimulates all Beta receptors |
| What effect does Isoproterenol have on each types of Beta receptors? | Beta-1 = cardiac stimulant, Beta-2 = bronchodilation and vasodilation |
| What is a disadvantage of non-selective Beta agonists? | They cause cardiac stimulation and vasodilation, which may not both be desirable |
| What type of drug is Dobutamine? | Beta-1 Agonist |
| What is Dobutamine's clinical use? | Increase Cardiac Output (ionotropic effect via Beta-1) |
| What type of drugs are albuterol, tertbutaline, salmeterol and formoterol? | Beta-2 Agonists |
| Which Beta-2 agonists are short acting? Which are long acting? | Short acting = albuterol, terbutaline; Long acting = salmeterol, formoterol |
| What is the main clinical use of Beta-2 agonists? | Tx of asthma and COPD |
| What is the clinical use of Ritodrine? | Tx of premature delivery, causes uterine relaxation |
| What does the term tocolytic mean? | tocolytic means to stop the process of labor and delivery |
| What are some adverse effects of Beta-2 Agonists? | Cardiac arrhythmia, hypokalemia, increase in blood glucose (concern for diabetes) |
| T/F - Having Beta-2 selectivity means that a drug will not stimulate Beta-1 receptors. | False - all Beta-2 agonists have some Beta-1 activity |
| What are the three main clinical uses of Alpha-1 agonists? | nasal decongestants, OTC diet aids, hypotension |
| What is a property of aloha-1 agonists that may make them inappropriate for long term use? | alpha-1 agonists use leads to tachyphylaxis (rapid tolerance development) |
| What is an example of a long acting alpha-1 agonist? Why is it long acting? | Oxymetazoline - its resistant to destruction by MAO and COMT |
| What is the route of administration of oxymetazoline and what is it used for? | topical nasal decongestant |
| What are two examples of alpha-1 agonist oral decongestant medications? | phenylephrine, pseudophedrine |
| Methoxamine and Mephentermine. Name the drug type and what their clinical use is. | Alpha-1 agonists, used to treat hypotension |
| Why is metaraminol used to treat paroxysmal supraventricular tachycardia? | Metaraminol is an alpha-1 agonist that causes vasocontriction. It is used to slow heart rate because of the alpha effect - reflex bradycardia. |
| What type of drug is metaraminol? | alpha-1 agonist |
| What type of drug is Midodrine? Why is it special? | Midodrine is actually a prodrug for desglymidodrine, an alpha-1 agonsit |
| What is Midodrine used to treat? | autonomic insufficiency and postural (orthostatic) hypertension |
| How can NE be administered? | only by injection |
| What is NE used to treat? | severe acute hypotension (shock) |
| How effective are alpha-1 agonists as weight reductions aids? | Not very |
| 2,4-dinitrophenol was a drug used for weight reduction that was effective. Why was it pulled from the market? | It causes cataracts and blindness |
| What are the alpha-2 receptor subtypes that are clinically relevant? What effects do they mediate? | Alpha-2A = involved in sedation and analgesia Alpha-2B = involved in hemodynamic effects |
| What are the three mechanims of action of alpha-2 agonism? | (1) Activation of inhibitory G proteins (2) Activation of G proteins that act on membrane bound channels (3) Activation of the nitric oxide, cGMP pathway |
| What does agonism of alpha-2 receptors cause? | inhibition of NE release, changes in BP and bradycardia, sedation, analgesia (overall - calms things down) |
| How are alpha-2 receptors involved in negative feedback? | Alpha-2 receptors are located on the presynaptic terminal. When stimulated by NE release they inhibit further NE release by activation of inhibitory G proteins, which decrease Ca++ influx and decrease synaptic vesicle fusion with the presynaptic membrane |
| How are alpha-2 receptors involved in pain sensation? | α2 activation can reduce nociceptive input into the spinal cord by direct inhibition of 1* afferent sensory neurons |
| What is type of drugs are Clonidine, Guanabenz, and guanfacine? What are they used to treat? | Alpha-2 Agonists, hypertension |
| T/F Many alpha-2 agonists have sympatholytic actions. | True. Although they are sympathomimetics, their stimulation of alpha-2 receptors on the presynaptic terminal decreases calcium influx and inhibits NE release resulting in a decrease of sympathetic activity. |
| What type of drug is a tizanidine? | alpha-2 agonist |
| What is tzanidine used to treat? | pain due to muscle spasm (it's a muscle relaxant) |
| What type of drugs are apraclonidine and brimonidine? | alpha-2 agonists |
| What are apraclonidine and brimonidine used to treat? What is their MOA? | They are used to treat glaucoma. They are used to decrease aqueous humor production and may increase outflow. |
| What other type of receptors (besides alpha-2) does Clonidine stimulate? | imidazoline receptors |
| What is the endogenous ligand for imidazoline receptors? | decarboxylated arginine |
| Where are imidazoline receptors located? What does their location say about their probable function? | Imidazoline receptors are located in the blood-pressure regulating areas of the ventral medulla (brain stem), which may explain the blood pressure effects of clonidine and other drugs |
| Why is methyldopa considered a false transmitter? | Methyldopa is converted to methyldopamine by dopa decarboxylase. Methyldopamine is then converted to alpha-methylNE by dopamine-Beta-hydroxylase. alpha-methylNE is stored in adrenergic nerve vesicles, replacing NE. However, this is not how it dec BP. |
| How does methyldopa lower BP? | its metabolite, alpha-methylNE, stimulates central inhibitory alpha-2 receptors |
| Which enzyme in the catecholamine synthesis pathway does methyldopa inhibit? | dopa-decarboxylase |
| What type of drug is phenoxybenzamine? | NON-competitive alpha-1 antagonist |
| Why is phenxoybenzamine a long-acting drug? | It forms an irreversible covalent bond with alpha-1 receptors (some selectivity) |
| What is phenoxybenzamine used to treat? | pheochromocytoma - abnormal excretion of NE and Epi by the adrenal medulla due to tumor |
| What type of drug is phentolamine? | non-selective competitive alpha receptor antagonist |
| Why is phentolamine used to treat? | pheochromocytoma |
| Why may a patient be more likely to experience reflex tachycardia when taking phentolamine versus phenoxybenzamine? | Phentolamine is a less selective alpha antagonist so it blocks alpha-2 receptors more than phenoxybenzamine |
| What are some expected outcomes with alpha antagonism? | decreased BP, reflexive increase in HR, stuffy nose, decrease in resistance to flow of urine, miosis (small pupils) |
| What type of drugs are prazosin, doxazosin, terazosin, and tamsulosin? | Alpha-1 selective competitive antagonists (these have even less propensity for reflex tacycardia than phentolamine or phenoxybenzamine.) |
| What are prazosin and doxazosin used to treat? | hypertension |
| What are terazosin and tamsulosin used to treat? | increase urine flow in those with BPH |
| Why would alpha-1 selective competitive antagonists used to treat Raynaud's disease? | Raynaud's disease is vasoconstriction of the extremities. Alpha-1 selective competitive antagonists cause vasodilation; this MOA would help treat raynaud's. |
| What is an extension effect of using alpha-1 antagonists to aid in emptying of the bladder in men with BPH? | Retrograde ejaculation. Alpha-1 antagonists help with emptying of the bladder by relaxing the muscles of the bladder. The sphincter that normally closes during ejaculation is less likely to do so when on these medications. |
| What type of drug is Yohimbe? | Alpha -2 antagonist |
| What is yohimbe used to treat? What is an issue associated with its use? | Yohimbe is used to treat sexual dysfunction disorders, it is erectogenic and stimulates the libido. The problem is that it will really increase BP, which is hazardous in the population most likely to use it. |
| Where did the term "essential" hypertension come from? | The Germans. They thought that high BP in some people was essential to their physiologic needs and otherwise did not cause any problems. We know now that this is not true. |
| What are some adverse effects of beta antagonists? | Bronchospasm (B2), decreased exercise tolerance, depression and slugishiness, decreased gluconeogenesis, lypolysis and glyconeogenesis, hypotension, syncope, rebound hypertension with abrupt withdrawal (MI) |
| Why can beta antagonists be dangerous in diabetics? | Beta antagonists decrease gluconeogenesis, lypolysis and glyconeogenesis, which may increase risk of hypoglycemic crisis. Beta antagonists shut down the signaling system that normally warns of hypoglycemia (tachycardia, anxiety, tremor) |
| What is the prototypic beta antagonist? Which receptor(s) does it effect? | Propanolol (B1 and B2) |
| Which beta blocker is also a alpha-1 antagonist? | lABetalol (only drug that blocks both) Due to asymmetrical shape with two optically active carbons and four diasteriomers, two of which are active and block B and alpha receptors |
| What does "cardioselective" mean? Which beta blocker is cardioselective? | selective for B-1, like metoprolol |
| What type of beta blocker is pindolol? | non selective, B1 and B2 |
| What are the main physiologic effects of beta blockers? | Slow heart, decrease force of contraction of heart, decrease gluconeogenesis and glycogenolysis, decrease renin release, decrease intraocular pressure |
| What does ISA stand for? | Intrinsic Sympathomimetic Activity, which means drugs that have ISA are partial agonists. These are helpful in treating patients who overrespond to other beta blockers. |
| Give and example of a B blocker with ISA. | Pindolol |
| What does MSA stand for? | Membrane stabilizing activity, drugs with MSA may improve some cardiac arrhythmias |
| name a beta blocker with MSA. | Acebutolol |
| From the chart given in the notes, name the four beta blockers that are cardioselective. | Metoprolol Esmolol Acebutolol Atenolol |
| From the chart given in the notes, name the five beta blockers that are non-selective. | Labetalol Nadolol Pindolol Propanolol Timolol |
| From the chart given in the notes, name the three beta blockers that have intrinsic sympathomimetic activity (ISA). | Acebutolol Labetalol Pindolol |
| What is significant about the half life of Esmolol? | It's extremely short - 10 minutes! |
| What is significant about the half life of propanolol? | Its 3.5-6 hours, but it is given BID, probably ok because it is highly lipid soluble |
| What drug can be used to treat muscarinc antagonist (ex antihistamines) overdose? | Physostigmine is the only revers AchE(-) lacking a charged quat amine moiety. As a tert amine, physostigmine crosses the BBB and binds to central AchE, increasing Ach and, reversing central anticholinergic delirium. Peripheral signs also are reversed. |
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