Amabelle Mazel Z. AgrabioCindy Lou A. TunguiaNervous System*

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CNSBrain and Spinal CordActs as control for regulating physical and mental processesNeurons are the brains functional units*

The brain is a collection of about 10 billion interconnected neurons. Each neuron is a cell that uses biochemical reactions to receive, process and transmit information.NeurotransmittersChemical substances that carry messages from one neuron to another or from a neuron to other body tissues, such as cardiac or skeletal muscles.*

The synapse is a small gap separating neurons. Receptors Proteins embedded in the cell membranes of neurons. A neurotransmitter must bind to receptors to exert an effect on the next neuron in the chain.*

Drugs affecting Central Nervous System Drugs*

Depressants Stimulants

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Mild CNS depressant: decreased interest in surroundings, inability to focus.Moderate CNS depressant: drowsiness or sleep, decreased perception of heat or cold.Severe CNS depressant: unconsciousness or coma, loss of reflexes, respiratory failure and death.*

Mild stimulation: wakefulness, mental alertness, and decreased fatigue.Moderate stimulation: hyperactivity, excessive talking, nervousness, and insomnia.Excessive stimulation: confusion, seizures, and cardiac dysrrhythmias. *

Anticonvulsants: help prevent seizures by suppressing the spread of abnormal electric impulses from the seizure focus to other areas of the cerebral cortexAll anticonvulsants are CNS depressants and may cause ataxia, drowsiness, and hepatotoxicityExamples:Phenobarbital (short-acting barbiturate)Primidone (structurally similar to phenobarbital)Diazepam (used IV to treat status epilepticus)Clorazepate (adjunct anticonvulsant)Potassium bromide (adjunct anticonvulsant)*

Tranquilizers: used to calm ; reduce anxiety and aggressionSedatives: used to quiet excitation; decrease irritability and excitementAnti-anxiety drugs: lessen anxiousness, but do not make drowsyExamples in these groups:Phenothiazine derivatives (acepromazine, chlorpromazine)Benzodiazepines (diazepam)Alpha-2 agonists (xylazine, detomidine, medetomidine)*

Analgesics: drugs that relieve painAnalgesics are categorized as non-narcotic or narcoticNarcotic analgesics are used for moderate to severe painNarcotic refers to opioid (natural) or opioid-like (synthetic) products*

Opioids:Do not produce anesthesia; patients still respond to sound and sensationProduce analgesia and sedation, and relieve anxietySide effects: respiratory depression, excitement if given too rapidlyProduce their effects by the action of opioid receptorsMu = found in the brainKappa = found in the cerebral cortex and spinal cordSigma = found in the brain*

Examples of opioids:OpiumMorphine sulfateMeperidineHydromorphoneButorphanolHydrocodoneFentanylEtorphineBuprenorphinePentazocine*

Opioid antagonists:Block the binding of opioids to their receptorsUsed to treat respiratory and CNS depression of opioid useExamples include naloxone and naltrexone*

Neuroleptanalgesics:Combination of an opioid and a tranquilizer or sedativeCan cause a state of CNS depression and analgesia and may or may not produce unconsciousnessCombination products may be prepared by veterinarianExamples include acepromazine and morphine; xylazine and butorphanol*

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An effective sedative (anxiolytic) agent should reduce anxiety and exert a calming effect with little or no effect on motor or mental functions.

A hypnotic drug should produce drowsiness and encourage the onset and maintenance of a state of sleep that as far as possible resembles the natural sleep state.*

Hypnotic effects involve more pronounced depression of the central nervous system than sedation, and this can be achieved with most sedative drugs simply by increasing the dose.

Graded dose-dependent depression of central nervous system function is a characteristic of sedative-hypnotics.*

Benzodiazepines: not to lead general anesthesia, raraly death. Barbiturates: the older sedative-hypnotics, general depression of central nervous system. With such drugs, an increase in dose above that needed for hypnosis may lead to a state of general anesthesia. At still higher doses, it may depress respiratory and vasomotor centers in the medulla, leading to coma and death.Other classes of drugs: chloral hydrate, buspirone, et al. *

The first benzodiazepine, chlordiazepoxide, was synthesised by accident in 1961.*

About 20 are available for clinical use. They are basically similar in their pharmacological actions, though some degree of selectivity has been reported. *

1. Reduction of anxiety and aggression : affects the hippocampus and nucleus amygdalae

2. Sedation and induction of sleep: (1) the latency of sleep onset is decreased; (2) the duration of stage 2 NREM sleep is increased; (3) the duration of slow-wave sleep is decreased.

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Reasons for their extensive clinical use: (1) great margin of safety; (2) little effect on REM sleep; (3) little hepatic microsomal drug-metabolizing enzymes; (4) slight physiologic and psychologic dependence and withdrawal syndrome; (5) less adverse effects such as residual drowsiness and incoordination movement.

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3. Anticonvulsant and antiseizure They are highly effective against chemically induced convulsions caused by leptazol, bicuculline and similar drugs but less so against electrically induced convulsions.

The can enhance GABA-mediated synaptic systems and inhibit excitatory transmission.

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4. Muscle relaxation relax contracted muscle in joint disease or muscle spasm.

5. Other effects lead to temporary amnesia decrease the dosage of anesthetic; depress respiratory and cardiovascular function.

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Benzodiazepines act very selectively on GABAA-receptors, which mediate the fast inhibitory synaptic response produced by activity in GABA-ergic neurons.

The effect of benzodiazepines is to enhance the response to GABA, by facilitating the opening of GABA-activated chloride channels (an increase in the frequency of channel opening, but no change in the conductance or mean open time).*

Benzodiazepines bind specifically to a regulatory site on the receptor, distinct from the GABA binding site, and enhanced receptor affinity for GABA.

The GABAA-receptors is a ligand-gated ion channel consisting of a pentameric assembly of subunits.*

Well absorbed when given orally;They bind strongly to plasma protein, and their high lipid solubility cause many of them to accumulate gradually in body fat. Distribution volumes is big.Metabolic transformation in the microsomal drug-metabolizing enzyme systems of the liver, eventually excreted as glucuronide conjugates in the urine.*

They vary greatly in duration of action, and can be roughly divided into Short-acting compounds: triazolam, oxazepam(15-30min, t1/2 2-3 h)Medium-acting compounds: estazolam, nitrazepam (40min, t1/2 5-8 h)Long-acting compounds: diazepam, flurazepam(50h)

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Acute toxicity: Benzodiazepines in acute overdose are considerably less dangerous than other sedative-hypnotic drugs. Cause prolonged sleep,without serious depression of respiration or cardiovascular. The availability of an effective antagonist, flumazenil.*

Side-effects during therapeutic use: drowsiness, confusion, amnesia, impaired coordination. Main disadvantages are interaction with alcohol, long-lasting hangover and the development of dependence.Tolerance and dependence: induction of hepatic drug-metabolising enzymes; a change at the receptor level;*

ClassificationUltra-short-acting barbiturates: act within seconds, and their duration of action is 30min. Therapeutic use of Thiopental: anesthesiaShort-acting barbiturates: have a duration of action of about 2h. The principal use of Secobarbital : sleep-inducing hypnotics.*

Classification

(3)Intermediate-acting barbiturates: have and effect lasting 3-5h. The principal use of Amobarbital is as hypnotics.(4)Long-acting barbiturates: have a duration of action greater than 6h. Such as Barbital and Phenobarbital. Therapeutic uses: hypnotics and sedative, and antiepileptic agents at low doses.

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Barbiturates depress the CNS at all level in a dose-dependent fashion. Now it mainly used in anesthesia and treatment of epilepsy; use as sedative-hypnotic agents is no longer recommended. *

Reasons: (1) have a narrow therapeutic-to-toxic dosage range. (2) suppress REM sleep. (3) Tolerance develops relatively quickly. (4) have a high potential for physical dependence and abuse. (5) potent inducers of hepatic drug-metabolizing enzymes.*

(1) Barbiturates share with benzodiazepines the ability to enhance the action of GABA, but they bind a different site on the GABA-receptor/chloride channel, and their action seems to prolong the duration of the opening of GABA-activated chloride channels.

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(2) At high doses, barbiturates can inhibit the release of the Ca2+-dependent neurotransmitter. *

High lipid solubility allows rapid transport across the blood-brain barrier and results in a short onset.Removal from the brain occurs via redistribution to the other tissues results in short duration of action.Barbiturates and their metabolites the excretion via the renal route. Alkalinization of the urine expedites the excretion of barbiturates. Treatment of acute overdosage: Sodium bicarbonate.*

Sedative-hypnotic agentsBe used in the emergency treatment of convulsions as in status epilepticus.Anesthetic (or be given before anesthetic)Combination with antipyretic-analgesicTreatment of hyperbilirubinemia and kernicterus in the neonate.

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After effect: hangover---dizzy, drowsiness, amnesia, impaired judgment, disorientation.

Tolerance: decreased responsiveness to a drug following repeated exposure because of down-regulation of receptors and induction of hepatic drug-metabolising enzymes.

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Dependence: including psychologic and physiologic dependence. Withdrawal symptoms: excitation, insomnia, tremor, anxiety, hallucinations and sometimes convulsions.Depressant effect on respiration: can cross the placental barrier during pregnancy and secrete to breast milk. Others: Skin eruptions and porphyria

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Phenothiazines (Tranquilizers)IndicationsGood sedation for healthy animals undergoing elective proceduresAnti-emetic*

PhenothiazinesContraindications Convulsing/epileptic patients, seizure history or head traumaAcepromazine may reduce the seizure thresholdShock (hypovolemia) and hypothermia because of peripheral vasodilation that can lead to hypotensionDepressed patientsCaution with geriatrics and pediatrics; use a lower dose or consider alternative agents such as benzodiazepinesLiver or kidney diseaseAllergy testing because of antihistamine effect*

PhenothiazinesOther effectsAntiarrhythmic effectMay cause excitement rather than sedationPersonality changes that usually subside within 48 hours*

Benzodiazepines (Benzodiazepines)IndicationsConvulsing/epileptic patientsPatients with a history of seizureCSF taps or myelogram proceduresMinimal cardiovascular or respiratory depressionUseful in geriatric or pediatric Ideal for older, depressed or anxious patientsWorks effectively as an induction agent when used with ketamine *

Benzodiazepines (Benzodiazepines)ContraindicationsMay cause excitementDoes not sedate but has antianxiety and calming effectsMay make more difficult when inhibitions and anxieties are removed*

Benzodiazepines (Benzodiazepines)Valium is in a propylene glycol solution, is insoluble in waterMay precipitate with other drugsPropylene glycol is irritating and may sting at the injection siteDoes not work well when given via routes other than IV*

Benzodiazepines (Benzodiazepines)Other pointsMidazolam is water soluble and readily combines with opioids (oxymorphone, butorphanol)Effects are reversed with flumazenil if adverse effects are seen *

2-AgonistsAre derivatives of thiazineExamples: Xylazine (Rompun, Anased)RomifidineDetomidine (Dormosedan)Medetomidine (Domitor)*

2-AgonistsStimulates the 2-adrenoreceptors causing a decrease in norepinephrineIndicationPotential side effects limit use to sedation only, not for preanesthetic medication*

2-AgonistsHave some short-lived (16 to 20 minutes) analgesic effectsWill cause vomitingXylazine and Detomidine are used most frequently*

2-AgonistsContraindicationsConsiderable potential for side effects especially if administered IVProfound cardiovascular effects include bradycardia, profound hypotension, decreased contractility and stroke volume and second degree heart blockContraindicated when concerned about respiratory function, hepatic and renal function*

2-AgonistsContraindicationsAssociated with temporary behavior and personality changesReduces pancreatic secretions causing transient hyperglycemia (exacerbates dehydration)Opioids will exacerbate these side effects*

OpioidsCommonly used:MorphineOxymorphone (Numorphan)Butorphanol (Torbugesic, Torbutrol)HydromorphoneMeperidine (Demerol, Pethidine)Fentanyl *

OpioidsAct by reversible combination with one or more specific receptors in the brain and spinal columnAlso classified according to their analgesic activity and their addiction potentialPure agonists are more effective for severe painIn order of decreasing potency they are:FentanylOxymorphoneBuprenorphineButorphanolMeperidinepentazocine*

OpioidsCommonly used as an analgesic in premedication, as an induction agent or can be used for balanced anesthesia and post-operative pain controlProvides some sedation and may potentiate the action of the sedative that it is given withhas a synergistic effect*

OpioidsCommonly used as an analgesic in premedication, as an induction agent or can be used for balanced anesthesia and post-operative pain controlFentanyl, sufentanil and oxymorphone are often part of a balanced anesthetic regimenFentanyl is available as a transdermal patch in various sizes for long-term analgesia Used as neuroleptanalgesia in combination wit tranquilizerMorphine can be injected epidurally or sub-arachnoidally for regional analgesia*

OpioidsFentanyl patchesTakes 8 to 12 hours to reach effectiveness but will last for several daysVery few cardiovascular side effectsDoes not significantly contribute to vasodilation or hypotensionHeating pads can increase transdermal uptake*

OpioidsReversible by use of pure antagonists such as naloxone or nalmefeneCompete with opioids for the specific receptor sitesPossible to titrate the naloxone dose so as to remove the side effects yet maintain analgesia*

OpioidsOther effects in addition to analgesiaEither stimulate or depress the central nervous systemDepends on the dose, species and opioid agentExcitement occurs if given rapidly IV*

OpioidsOther effects in addition to analgesiaCardiopulmonary effects BradycardiaPossible hypotension with release of histamineEspecially if given IVMorphine and meperidineIncreased muscle contraction in low dosesInotropic effectmorphine*

OpioidsOther effects in addition to analgesiaRespiratory depression is dose dependentGastrointestinal effects depend on the agentMay initially include diarrhea, vomiting and flatulenceConstipation may occur as a result of prolonged GI stasisAddiction*

OpioidsContraindicationsPrevious history of opioid excitementMorphine has a higher incidence of producing vomiting so should be avoided in cases of GI obstruction and diaphragmatic herniaClassified as a narcotic in Canada and is a Schedule II controlled drug in the US *

DefinitionStimulants are a substance which tends to increase behavioral activity when administered*

Two disorders treated with CNS stimulants are narcolepsy and Attention Deficit Hyperactivity DisorderCNS stimulants act by facilitation initiation and transmission of nerve impulses that excite other cells.New drugs act selectively to inhibit reuptake or norepinephrine in the nervous system.*

Signs and symptoms:1- Elevate Mood2- Increase Motor Activity3- Increase Alertness4- Decrease need for SleepIn case of overdose lead to convulsion and death.

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- They can be divided based on their site of action: 1.Cerebral stimulants (amphetamines) 2.Medullary stimulants (picrotoxin) 3.Spinal stimulants (strychnine)

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Analeptics (CNS stimulants) Reversal of anaesthesia-induced respiratory depressionAnorexiants Thought to suppress the appetite control centre in the brainADHDStimulate the areas in the brain responsible for mental alertness and attentivenessNarcolepsyIncrease mental alertnessMigraine headachesCaffeine, co-administered with other drugs, used to treat headaches

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Wide range, dose relatedTend to speed up body systemsCommon adverse effects include:Palpitations, tachycardia, hypertension, angina, dysrhythmias, nervousness, restlessness, anxiety, insomnia, nausea, vomiting, diarrhea, increased urinary frequency*

MOAs : Block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. - Clinical use:1. Narcolepsy.2. Attention-deficit hyperactivity disorder

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Adverse effects:- Cardiovascular: Hypertension- Endocrine metabolic: Weight loss- Gastrointestinal: Abdominal pain , Loss of appetite, Xerostomia- Neurologic: Headache , Insomnia - Psychiatric: Feeling nervous *

After injecting, the mice with amphetamine you well notice: - Hair erection- Licking, gnawing.- Stereotype- Sniffing

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MOA: Non-competitive antagonist of GABA receptors.After injecting the mice with picrotoxin you wellnotice: - Clonic convulsion characterized by : 1. Asymmetric2. Intermittent3. Spontaneous 4. Coordinated*

MOA:Competitive antagonist of the glycin receptors. After injecting the mice with Strychinine you wellnotice: - Tonic convulsion characterized by : 1. Symmetric 2. Reflex in origin3. Continuous 4. Uncoordinated.

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MethylphenidateBrand Name: RitalinClassification Therapeutic: CNS stimulantAction: Produces CNS and respiratory stimulation with weak sympathomimetic activity. Therapeutic Effects: Increased attention span in ADHD. Increased motor activity, mental alertness, and diminished fatigue in narcoleptic patients. *

carbamazepine (Epitol, Tegretol)clonazepam (Klonopin)diazepam (Valium)divalproex (Depakote)ethosuximide (Zarontin)Fosphyenytoin (Cerebyx) gabapentin (Neurontin)Drug List*

lamotrigine (Lamictal)levetiracetam (Keppra)lorazepam (Ativan)oxcarbazepine (Trileptal)phenobarbital (Luminal Sodium)phenytoin (Dilantin)Drug List*

primidone (Mysoline)topiramate (Topamax)valproic acid (Depakene)zonisamide (Zonegran)Drug List*

amantadine (Symmetrel)benztropine (Cogentin)bromocriptine (Parlodel)entacapone (Comtan)levodopa (Dopar)levodopa-carbidopa (Sinemet)Drug List*

levodopa-carbidopa-entacapone (Stalevo)pergolide (Permax)pramipexole (Mirapex)ropinirole (ReQuip)selegiline (Eldepryl)tolcapone (Tasmar)Drug List*

azathioprine (Imuran)cyclophosphamide (Cytoxan)edrophonium (Enlon, Reversol)neostigmine (Prostigmin)pyridostigmine (Mestinon)Drug List*

atomoxetine (Strattera)clonidine (Catapres, Catapres-TTS)desipramine (Norpramin)dexmethylphenidate (Focalin), C-IIdextroamphetamine-amphetamine (Adderall), C-IIDrug List*

imipramine (Tofranil)methylphenidate (Concerta, Metadate, Ritalin, Ritalin-SR), C-IInortriptyline (Aventyl, Pamelor)pemoline (Cylert), C-IVDrug List*

riluzole (Rilutek)Drug List*

baclofen (Lioresal)glatiramer acetate (Copaxone)interferon beta-1a (Avonex, Rebif)interferon beta-1b (Betaseron)mitoxantrone (Novantrone)tizanidine (Zanaflex)Drug List*

donepezil (Aricept)galantamine (Reminyl)ginkgo memantine (Namenda)rivastigmine (Exelon)tacrine (Cognex)Drug List*

Drugs affecting Peripheral Nervous System Drugs*

Sympathetic: (Adrenergic)ActivatorsSympthomimeticsAgonistsBlockersSympatholyticAntagonistsReceptorsAlpha 1 & 2Beta 1 & 2DopamineParasympathetic (Cholinergic)ActivatorsParasympathomimeticsAgonistsBlockersAnticholinergicsAntimuscarinicsParasympatholyticsAntagonistsReceptorsMuscarinicNicotinic N & M

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Muscarinic agonists: no agentsMuscarinic antagonists (anticholinergics): 7 agents Ganglionic blockers: no agentsNeuromuscular blockers: no agentsCholinesterase inhibitors: neostigmine, physostigmine (difference and use)*

Neostigmine (Prostigmine) (anticholinesterase) prototypePrimarily used to treat Myasthenia Gravis

Pyridostimine (Mestinon) Myasthenia Gravis

Donepezil (Aricept) Works in the CNS to inhibit synthesis of AcetylcholinesteraseUsed to treat Alzheimers disease

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Direct acting Cholinergic drugs

Directly stimulates the nerve ending to secrete acetylcholine

Bethanechol (Urecholine)Used to treat urinary retention*

Limited uses:Urinary retentionIncrease GI peristalsisGlaucoma, eye surgeryAdverse effectsBradycardia, hypotensionExcess saliva, cramps, diarrheaUrinary (contra: bladder obstruction &surgery)Asthma exacerbation*

SourcesMuscarinic agonistsCholinesterase inhibitorsMushroomsSymptomsProfuse salivation, tearing, bronchospasm, diarrhea, bradycardia, hypotensionTreatment: atropine*

AnticholinergicsAgents to know foreverAtropine: strongest, general useOxybutinin (Ditropan): overactive bladderTolerodine (Detrol): overactive bladderScopolamine: sedation, motion sicknessIpratropium, Tiotropium: lungsDicyclomine (Bentyl): IBS, diarrhea*

Mechanism: blocks muscarinic receptors by competing with Acetylcholinehigh doses will block nicotinic as wellRoute: PO, topically (eye), injection

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Pharmacologic effects: heart rate secretions (GI, tear, salivary) smooth muscle (peristalsis, urination)Dilate eye (mydriasis) CNS excitabilityTherapeutic UsesPreanesthesia (make sure heart doesnt stop)Eye surgery: (dilate eye)Bradycardia: heart rateIntestinal hypertonicity, hypermotility (slows GI tract)Muscarinic Agonist Poisoning (antidote)*

Xerostomia (Dry Mouth)Blurred vision, photophobiaElevation of IOPUrinary retentionConstipationAnhidrosis (no sweat)TachycardiaAsthma: secretions too thick and crustyDementia*

Dry as a boneRed as a beatHot as a hareBlind as a batMad as a hatter**Must determine whether psychosis is real or anticholinergicTreatment:Minimize absorptionCholinesterase inhibitor*

Competitive antagonistsCompete with AChInhibit nerve transmission

Sites of actionAll systems except musculo-skeletal*

EXAMPLESBentyl (dicyclomine HCL) Antispasmotic used to decrease intestinal cramping in IBS

Atropine (Prototype)Acetylcholine antagonistAntidysrhythmicAntispasmoticAntisecretory

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USESDry oral secretionsIncrease heart rateTreat urethral colicDecrease GI motilityParkinsons diseaseDecrease upper respiratory secretions*

OXYBUTYNIN (DITROPAN)Synthetic antimuscarinicINCREASES BLADDER CAPACITYDECREASES FREQUENCY OF VOIDING

TOLTERODINE (DETROL, DETROL LA)Synthetic antimuscarinicDELAYS THE URGE TO VOIDINHIBITS BLADDER CONTRACTIONS*

Dose dependentLow dose

High dose

Glands: sweat, salivary, bronchialHeartEyeBladderIntestine motilityLungStomach*

Drugs with anti-muscarinic (anticholinergic) side effects effectsAntihistaminesPhenothiazine antipsychoticsTricyclic antidepressantsFurosemide (Lasix)*

Increase Acetylcholine at all receptors!Reversible (must know these agents)Neostigmine: myasthenia gravisPhysostigmine: anti-cholinergic antidoteIrreversible (do not need to know for test)Used as insecticidesDeveloped in WW2 as nerve gasOne is used for glaucoma (just trivia for you attorney types)*

Etiology: Antibodies against Nicotinic-M receptorsClinical manifestations: fatigue, muscular weakness, dyspneaTreatmentCholinesterase inhibitorsSide effects: can cause accumulation of acetylcholine and nicotinic-M and muscarinic receptors*

TreatmentSide effects contMuscarinic effectsNeuromuscular blockade (toxicity)*

Neuromuscular BlockersParalyze muscleUse to intubate so they dont fightAgentsNondepolarizing: tubocurarine, et al.Depolarizing: succinylcholineUsesSurgeryMechanical Ventilation, ET intubationAdjunct to ECT*

Phenylephrine and PseudoephedrineEpinephrine, Norepi, Dopamine, DobutamineAll lung beta-2 agonistsAlpha blockers: terazosin, phentolamineBeta blockers: propanolol, metoprolol, atenolol, carvedilolIndirect antagonists: Clonidine*

Catecholamines: Broken down by MAO and COMT in liver and intestineParenteral onlyCannot be given orally, short half-lifeColorless solutions; color is sign of oxidationNatural catecholamines: epi, norepi, dopamineSynthetic: dobutamine (others we dont need to know)Non-catecholaminesCan be given POLast longer in body

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NoncatecholaminesPhenylephrine: (alpha1) nasal congestion, inotropic support (rare now)Pseudoephedrine (all alpha and beta):Nasal congestionCan be used to make amphetamines*

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-1-2-1-2dopaEpinephrine++++Dopamine+++Dobutamine+Norepinephrine+++

Therapeutic effectsVasoconstriction BP (intensive care, last resort)Hemostasis local anesthesia absorptionNasal decongestionMydriasisAdverse effectsHypertensionNecrosisBradycardia*

Therapeutic UsesCardiac arrest (make heart beat again)Heart Failure: inotropic supportShock: inotropic and chronotropic supportA-V heart block (speed conductivity)Adverse effects HRAngina pectorisdysrhythmia*

Therapeutic useAsthma: bronchodilatePreterm labor: stop contractionAdverse effectsHyperglycemiaTremor*

Therapeutic uses: absorption of local anestheticsControl superficial bleeding BPMydriasisAV block, V. fib, AsystoleStatus AsthmaticusAnaphylactic shockReduce nasal congestionAdverse eventsHypertensive crisisDysrythmiasAngina pectorisNecrosisHyperglycemia*

AbsorptionInhalation: minimalInjectionPreparationsSC, IM, IV, Intracardiac, intraspinal, inhalation,Lidocaine with epiNo fingers, nose, penis, and toesInactivation: MAO and COMT in liver*

InteractionsMAO inhibitors (why oh why?)Alpha-adrenergic blocking agentsBeta-adrenergic blocking agents*

Receptor: dopamine, alpha1, (beta1 higher doses)Therapeutic UsesShock: HR and contractilityMaintain renal artery perfusionHeart failure: same as aboveARF: low dose (may not be effective)Adverse EffectsDysrhythmias, angina pectoris*

Short actingAlbuterolLevalbuterolLong actingSalmeterolFormoterol*

Dobutamine (beta1) usesShock (inotropic support)Stress EchoesTerbutaline: (beta2) usesStop preterm labor contractions*

Receptor: alpha 1 & 2, beta1Therapeutic usesHypotensive stateCardiac arrest (last resort)Brand: Levophed (Leave em dead!)*

Can be quite selective for receptors*

Therapeutic usesHypertensionBPHReverse toxicity of epinephrinePheochromocytoma (what is it?)Raynauds disease

Adverse effectsOrthostatic hypotensionReflex tachycardiaNasal CongestionInhibition of ejaculationNa+ & H2O retention*

Prazosin - HTNDoxazosin HTN, BPHTerazosin HTN, BPHTamsulosin BPHPhentolamine Pheochromocytoma, tissue necrosis*

Therapeutic UsesMIHFAngina PectorisDysrhythmiasHTNOtherHyperthyroidMigraineStage FrightPheochromocytomaGlaucomaAdverse Effects (1) HRCOAV heart blockPrecipitate HFRebound cardiac excitationAdverse Effects (2)BronchoconstrictionInhibition of glycogenolysis*

Beta1, Beta2Propanolol*NadololPindololSelectiveMetoprolol*Atenolol*Bisoprolol

* Means must knowBeta1,beta2, alpha1LabetalolCarvedilol*

Used for HFMetoprolol*Carvedilol**

Clonidineactivates alpha-2 receptors in CNS norepinephrine releaseUsesHypertensionPain relief in cancer (epdidural use only)Adverse effectsDrowsiness, dry mouth, rebound HTN, bradycardiaPreparationsOral: at least twice a dayTransdermal: seven days*

ReserpineSuppresses NE synthesis and promotes MAO-mediated destructionCrosses BBBEffectsHypotensionAdverse effectsDepression, sedation, apathyBradycardia, hypotensionGuanethidine: similar but fewer CNS effect*

Methyldopa, MethyldopateSimilar to clonidine, but are taken up in brain stem neurons and converted to active alpha2 agonistUse: HTNAdverse effects10 20% Positive Coombs test (5%) will go on to have hemolytic anemiaHepatotoxicityDrowsiness, dry mouth, hypotension, etc.*

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