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You Know you have reached middle age if? Old Drugs Forgotten uses.. There’s no need to run out and buy a home pregnancy kit Happy Hour with free Hors d’oeuvres no long constitutes a meal Major Peter Strube CRNA MSNA APNP ARNP Your subscription to playboy has been replaced by the Victoria’s Secret catalog You can’t eat a midnight snack anymore without staying up until 3 am Think outside the BOX www.crnatoday.com DO YOU REMEMBER WHEN ? We currently have in the our pharmacology knowledge a number of great drugs that we have forgotten about ZOFRAN EXAMPLE Or these old drugs have gotten new and different uses? I will bet you can think of several more that I missed????? PAIN No this is not another boring pain lecture Two types of pain Norciceptive pain (i.e. pain from somatic or visceral structures Somatic is bone, joint, skin and ……… Visceral pain example a tumor Just a review (for the students in the room – HINT HINT) Norciception works via the routes transduction transmission perception modulation MU narcotics work here!! (students AA-DELTA / C) PAIN What else have we forgotten? Pain is also – Neuropatic Neuropatic— — What kinds of agents can we use to work on the route and that can augment narcotics?? We will talk about: gabapentin; clonadine clonadine;; Tylenol; Ketamine; magnesium; toradol 1 Gabapentin Originally as a antiepileptic Analog of GABA but do not be fooled it does not have gabaergic action it does not block the uptake GABA but glutamate and asparate p release rather works on g Does not bind with plasma proteins and is excreted unchanged in by the kidneys What does this mean for us;;;;; Gabapentin Gabapentin Gabapentin mechanisms of action of anti anti--hyperalgesics work different than norciceptive agents (narcotics) IT does not have a affect on norciceptive pain but rather reduces the hyperexcitability of neurons that were stimulated by tissue damage How it reduces this NOBODY really KNOWS:::: there is a lot of speculation but no real reason Ketorolac (toradol) Gabapentin is typically well tolerated in the correct does: Doses range 300300-1200 mg single does for anesthesia Higher the dose (smaller the patient) more side effects (keep in mind excretion i.e. renal failure) T picall Typically: Somnolence Dizziness Fatigue Impaired concentration This is the only IV NSAID available for use in the US Inhibits prostaglandin synthesis (COX) Prostaglandin synthesis which sensitizes and amplifies norciceptive input The use is limited by the dose ? Higher the dose the worse it is. Temporary T effect ff t on platelets l t l t (36 h hours)) iinhibit hibit th thromboxane b ffrom A-2 Renal issues (Kidney patients, hypovolemia, HTN) Diabetes Elderly Typically single small does (300(300-600) little problems Keep in mind Half life of 5 5--7 hrs There is a increased movement to just give if we deem appropriate and not ask the surgeons about it Issues Contraindications: Allergy – nasal polyps – GI bleed – bronchospasm (careful with bronchospasm and asthma) Peds = 0.5 mg/ kg (keep less than 15 mg) Smaller dose is better – remember this is a adjunct GI upset Inhibit platelet function and impaired coagulation – this is most like clinical insignificant in most patients in the correct dose If you are worried of bleeding don’t do it Ortho has the strongest claim on not using is due to osteogenesis Ibuprofen OB anesthesia… great for post delivery uterine cramping. New injectable form coming out. Example: either a single one time dose OR NORMAL PATIENT (RARE) 15 15--30mg every 8 hours for no more than 5 days…. Do we need to do this ;; probably not; just a single dose Remember this can also be given IM and new Nasal route 2 Careful---JJ Careful--JJ announcement!!!! TYLENOL Normal dose = 500 – 1000 mg for an adult PEDS (KISS) 10 10--20 mg/kg (tell parents when given) Give early (i.e. PO Tylenol with PO versed for a BMT) ? IV FORM NOW MAX DOSE::::::::: 4 gm a day adult Careful with chronic alcoholism, alcoholism liver dx, dx wasting chronic Can cause hepatotoxicity Avoid in G6 G6--PD deficiency patients This drug has a great effect with little if any side effects and should be considered a first line oral analgesic Half life 1 1--4 hours; onset 30 minutes; 44-6 hours between dose WOW did we forget about this one— one—USE THE IV FORM>>>>>>>> This is a great electrolyte for pain control NMDA antagonist Need to be careful on dosing Some evidence suggests that 2mcg/kg also have mild activity as a antiemetic Hypermagnesemia can impair the release of acetylcholine and decrease motor end plate sensitivity of acetylcholine in the muscle Can be administered anytime Keep levels low; keep dosing low; Magnesium has a very narrow therapeutic index; Inhibits the release of substance P blocking pain reception Half life 99-12 hours Dose 11-2 grams in a normally healthy patient diluted in 5050-100 ccs given over 30 minutes Works great as a anxiolytic with minimal respiratory depression It is easily excreted in the kidneys so those with renal failure will be prone to hyper levels Side effects; Decrease BP; bradycardia; bradycardia; sedation; dry mouth; orthostatic Blocks bradykinin release in the local vasculature; works great as a predosing agent in small doses for propofol -- dose this in mmols WOW!! is this one we really forgot about Even comes in a IV form; PARACETAMOL (2g/6hr) NOW AVAILABLE IN THE US>>> OFIRMEV-OFIRMEV-- Cadence Very limited side effects (hepatic in high doses) NO antiplatelet effects NO gastric damage to the mucosa (high doses can get GI upset) NO effect on wound healing or bones Does not affect major organs in small doses NO real reason why it works?? Mechanism of action is poorly understood -- It may be working on a COX— COX—3 route This is a safe weak to moderate analgesic that is quickly absorbed Clonidine Alpha 2 agonist that works presynaptic centrally by inhibiting negative feedback and blocking neurotransmitter communication IT does have peripheral postsynaptic actions (decreased BP) Magnesium Decreased narcotic requirements and improved analgesia Ketamine IF we get over the stigma from the past and understand how to truly dose this drug; it is one of the best anesthetic drugs around Some early psych research suggests it helps with refractory depression form MOA withdrawal Currently some research also suggests that until you get to very high doses there is no sympathetic response The only true single anesthetic drug Causes dissociative anesthesia; they only true anesthesia drug we have NMDA receptor antagonist NMDA plays a important role in processing pain via glutamate Reduces the need for opioids May reduce PONV?? MH treatment = sequesters calcium Ketamine the secret agent Analgesia; 0.10.1-0.2 mg/kg IV At these low levels ; little if any side effects; (cardiovascular and psychological side effects) At amnesia and analgesia doses; proper pretreatment with a benzo will help eliminate the psychological effects if any…. Keeping doses less than 1 mg/kg with a benzo is the max benefit of both drugs Watch the eyes 3 YES ---- PONV Ketamine Ketamine and propofol mix for MAC cases Tourniquet pain IM Dart for patients: 4 4--8mg/kg – that is a lot (2 (2--4mg/kg) It is not a controlled substance at a lot of places and should be! Bronchodilator with asthma New concentrations Raises ICP; raises IOP; Increases mental outcome of psych patients Careful; some people are very prone to salivation; they may need a antimuscarinc agent Post operative delirium is associated with females; greater than 15; doses greater than 2mg/kg; and history of nightmares (PTSD?) not just another boring lecture There is a complex set of mechanisms that are involved in nausea and vomiting. So we really need to start considering a multi modal attack route to prevent this response WE need to leave behind to old school thoughts and embrace the idea that everyone should get something to prevent PONV/PDNV Number one reason for inpatient admissions post outpatient procedures Increased risk of dehydration, wound complications, aspiration .. . . . . . . . . Increased frustration of patients and staff and surgeon We need to start moving towards aggressive treatments ASA retro study Nausea and vomiting is a complex mechanism and needs to involved a variety of classes of drugs to treat Where and Why Two brain stem sites play key roles in the vomiting reflex pathway Chemoreceptor trigger zone in the postrema (this is a structure at the caudal end of the fourth ventricle, outside the blood brain barrier) This position allows it to respond directly to chemical stimuli in the bl d or CSF blood CSF. Multi Modal example Anticholinergic drugs (both scopolamine and robinul robinul)) (anti muscarinic receptor antagonists) and HH-1 antagonists such as dramamine and meclizine are very useful in motion sickness but are ineffective against substances that act directly on the chemoreceptor trigger zone A lot of drugs we use, then trigger nausea and vomiting in the chemoreceptor trigger zone --- thus making the above listed drugs useless in this regard. Antiemetic drugs should be combined to increase antiemetic activity while decreasing toxicity effects; for example, dexamethasone when given with 5HT--3 increases activity of both. Diphenylhydramine when given with 5HT metoclopramide increases the action of both while reducing the risk of EPS. Hence; we need a multi modal attack against nausea and vomiting Remember these of older drugs either forgotten or just not used anymore. You still have the mainstay drugs to use…. The vomiting center located in the lateral reticular formation of the medulla, medulla, this is the location that coordinates the motor mechanism of vomiting. The vomiting center also responds to the afferent input from the vestibular system, the periphery (pharynx and GI tract) and higher brainstem and cortical structures. The vestibular system functions mainly in motion sickness Oxygen Haloperidol Hypoxia triggers cortical afferents which triggers the vomiting center which leads to the act of vomiting Yes Haldol (not droperidol droperidol,, the black box warning is hog wash) One specific study showed a decreased rate of PONV Butyropherones are powerful antiemetic agents by virtue of their inhibition i hibiti off d dopaminergic i i receptors t iin th the CRTZ A second study trying to prove the first could not either prove or disprove the first study Increased O2 levels (less than 80%) in orthopedics have been shown to decrease infection rates in total joints 18 studies actually proved that low dose haldol haldol;; 11-2 mg IV decreased PONV Interesting thoughts? 4 Dramamine Diphenhydramine Antihistamines: Dramamine and Meclizine H-1 antihistamines act similarly to the anticholinergic agents suppressing transmission of neuronal impulses originating in the labyrinth. Used primarily to treat or prevent motion sickness Prevent or diminish vomiting and nausea mediated by both the chemoreceptor and vestibular pathways. The antiemetic action of these substances seems to be independent of their antihistaminic and other actions Motion sickness is a prime trigger for PONV Be aware of strong sedative properties in high doses Both agents are available orally PONV dose is 6.25 – 12.5 mg; clinical no sedative properties at these doses High dose range 2525-100mg either PO/IV/IM duration is 33-6 hrs Have antimuscarinic effects Dramamine is available IV Dose is 2525-50 MG IV (0.5mg/kg-(0.5mg/kg--Peds Peds)) 24hr coverage Should be given with induction or post cord clamping Works great with OB post C C--section; Remember sedative actions of this drug H2 Has nothing to do with nausea?? No antiemetic activity Four major players; tagamet tagamet,, zantac, zantac, pepcid, pepcid, axid Pepcid as the least effect on the PP-450 Tagament has the most profound effect on PP-450 Zantac is the cheapest H-2 receptors are located throughout the body; this class of drugs has the unique ability to bind to receptors on the gastric parietal cells. So why would we give it? Decrease gastric PH and decrease the risk of heart burn/GERD Great treatment to prevent acute stress ulcers associated with major physical trauma i.e. surgery Allergic reactions Caffeine Peds Dose: 0.50.5-1 mg/kg IV peds dose PO Peds dose 1mgkg -- be mindful of paradox reaction Anticholinergic Agents Anticholinergic agents inhibit nausea and vomiting by reducing the excitability of the labyrinth receptors thus depressing conduction via the vestibularvestibular-cerebellar pathways prone p position? robinul for p Transdermal scopolamine patch for motion sickness. 1.5 mg patch delivers 1 mg over 72 hrs apply minimum of 1 hour prior to anesthesia Tell patient of the side effects ---- very important Corrects the imbalance of acetylcholine in the CNS which is responsible for the motion sickness Metoclopramide Number one consumed psychoactive drug This is a substituted benzamided with antiemetic activity In the correct dose it has been shown to prevent 3030-40% of emesis and reducing emesis in a majority of patients receiving chemo PDE inhibitor WOW --- Why do we not use it more Withdrawal headache Via this action a secondary antiemetic; all subjective considering a few studies suggest it does not play a role Old school was only for RSI; why not more for nausea 10 mg IV or PO (give PO early) and dilute IV and give slow – Do not push this drug if you can avoid it (chest tightness/abdominal cramping) Awake sleep cycle Increased sensitivity to catacteolamines Spinal HA Risks; antidopaminergic side effects limit its high dose use This includes; sedation, diarrhea, EPS (mostly limited to the younger patients) Central Nervous stimulate 5 Fluids NO it is not another boring fluid lecture Did we forget about fluids?? NPO and 3rd spacing Insensible loss Maintenance rule: 4 – 2 – 1 EBL Fluids Adipose contains little water -- leaner greater body water ratio Total Body Water (50 (50--70% of ideal body weight) Fluid balance: Average adult intake is 2600ml a day IN; 1400 mls from liquids; 800mls in solid food; 400mls from metabolism Why choose LR or NS?? Colloids?>? OUT: 1500ml/urine; 400ml Respirations; (HME) 500ml skin evaporation; 200 ml stool Fluids Hypotensive Thought Pattern Things we forget about: Insensible losses; fever up to 500ml/degree Celsius/day Increased perspiration; NE and nervousness Don’t forget about preps, drug therapy, wounds THIRD space; Mi i l ttrauma (h Minimal (hernia) i )4 4ml/kg/hr l/k /h Moderate trauma (hip) 6ml/kg/hr Severe trauma (belly) 8 ml/kg/hr Insensible loss: 2 ml/kg/hr Blood loss replacement 3:1 rule Intravascular life for crystalloid is 30 minutes Intravascular life for colloid is 3 3--6 hrs Hypotension What is your order for treating Hypotension???? 0 fluids 1 and 2; Neo and ephedrine 3 methylene blue 4 epi chip shots (5(5-10mcg) 5 vasopressin What is 6 for you? ?? Glucagon Methylene Blue Glucagon?? Not just for blood sugars anymore This is a age old drug; Traditionally used for Methemoglobinemia and as a tissue marker Remember that boring lecture in school about how it relaxes the sphincter of oddiiiiiiiiii???? Recent evidence (mostly in cardiac surgery) shows that it may be a benefit for refractory hypotension Glucagon is a positive inotrope Increases CC-amp Actually treatment of choice for betabeta-blocker overdose Dose 1mg/IV Has been used with liver transplant for hypotension Reports of being used for patients on ACE inhibitors for refractory hypotension 6 Methylene Blue MOA: inhibits guanylate cyclase enzyme with then blocks nitric oxide synthase This action blunts Nitric Oxide Nitric oxide as a second messenger causes a relaxation of the smooth muscle and this action causes a decrease in peripheral vascular resistance Calcium for BP Renal patients The kidney converts VITVIT-D to is physiologically active form D D--3 The patient on chronic renal disease becomes hypocalcaemia because of calcium absorption from the intestine is impaired when there is a deficiency of vitamin D Calcium is a positive inotrope Replacement with Blood transfusions What about a patient on Nitro? Nipride? Hydralize? Monitor Ionized Calcium levels Methadone Synthetic Opioid developed in Germany in 1937 Not chemically related to morphine or heroin Cheap and long acting Traditionally used with narcotic abuse Half life 2424-36 hours -- fat soluble Mu--receptor with limited action on NMDA Mu 5 -10 mg single dose decreases the intra and post operative opioid requirements This may be a great adjunct to both the chronic pain patient and the short term surgical patient. Additionally this drug does not have the euphoric effects that other narcotics have and this may be of great benefit in those with addictive personalities. Nubain Nubain Hot then cold group of drugs Is this a great pain control drug for the morbid obese intraop intraop?? ?? Remember now…. IV ORMIFEV SemiSemi-Synthetic opioid agonist antagonist At low doses have been shown to be a better pain control choice for woman than men IN a small percentage of men may actually increase pain Dose range 5 5--20mg (go on the lower side first) every 33-6/ 6/hrs hrs Doxapram Respiratory Stimulate – stimulates the carotid receptors which in turn stimulate the respiratory center in the brain stem Nubain does possess narcotic antagonist activity, there is a pool of evidence that in nonnon-dependent patients it will not antagonize a narcotic analgesic admistered. When administered increase tidal volume and rate Try small doses first: Great for post operative pain in both the surgical and OB patient Side effects; sweaty and clammy; N/V; dizzy and vertigo; dry mouth; headache Do you use Nubain or Narcan for itching with spinal Morphine side effects include hypertension; tachycardia, panic attack, tremors and sweating Avoid in patients with CAD and epilepsy; Avoid in newborns and peds the base is benzyl alcohol Dose 0.5 0.5--1 mg/kg with max dose of 1.5mg/kg 7 Edrophonium Edrophonium Reversible competitive inhibitor of acetycholinesterase Did we forget there is another reversal agent?? Rapid acting; Onset 3030-60 seconds Duration: 55-10 minutes They started Making it again – called ENLON PLUS Monitor for recurarization Great rescue drug when you have maxed out your dose of neostigmine Dose 0.5 0.5--1 mg/kg IV straight enlon plus 14mcg of atropine for every 1 mg of enlon They took out all the math for us This is a great rescue drug to have that deep or prolonged block Only for use with non non--depolarizing agents Lidocaine Thoughts A early heads up!! There is a growing pool of evidence that lidocaine infusions…. During the operative course lead to better outcomes…… Different IDEAS Different IDEAS Nasal fentanyl with BMTs Toradol local at epidural/spinal site Ephedrine IM at epidural or spinal site for OB site Bicarb (remember the ionized and unionized lectures) with local propofol 20 20--30 mg nausea Magnesium for injection with propofol Neo and Ephedrine in Propofol injection Glass Vials --------------------------IV --------------------------IV OFIRMEV-----------------------OFIRMEV------------------------ Thank You LR and psych patients LR and Trauma LR and blood Writing on the IV bags Lido and/or bicarb in the ett cuff DID we also forget about COXCOX-2 agonists Indigo carmine 8 Questions Thank you 9