Download Old Drugs Forgotten uses.. Think outside the BOX PAIN PAIN

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 Your subscription to playboy has been replaced by the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
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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)
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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)
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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
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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
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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
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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
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Careful with chronic alcoholism,
alcoholism liver dx,
dx wasting chronic
Can cause hepatotoxicity
Avoid in G6
G6--PD deficiency patients
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This drug has a great effect with little if any side effects and should be
considered a first line oral analgesic
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Half life 1
1--4 hours; onset 30 minutes; 44-6 hours between dose
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WOW did we forget about this one—
one—USE THE IV FORM>>>>>>>>
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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
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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
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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
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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
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Some early psych research suggests it helps with refractory depression
form MOA withdrawal
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Currently some research also suggests that until you get to very high
doses there is no sympathetic response
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The only true single anesthetic drug
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Causes dissociative anesthesia; they only true anesthesia drug we have
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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
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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)
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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
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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
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We need to start moving towards aggressive treatments
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ASA retro study
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Nausea and vomiting is a complex mechanism and needs to involved a variety of
classes of drugs to treat
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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
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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
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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.
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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.
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Hence; we need a multi modal attack against nausea and vomiting
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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
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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
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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
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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
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Things we forget about:
Insensible losses; fever up to 500ml/degree Celsius/day
Increased perspiration; NE and nervousness
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Don’t forget about preps, drug therapy, wounds
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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
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Insensible loss: 2 ml/kg/hr
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Blood loss replacement 3:1 rule
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Intravascular life for crystalloid is 30 minutes
Intravascular life for colloid is 3
3--6 hrs
Hypotension
 What is your order for treating Hypotension????
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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
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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
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Nasal fentanyl with BMTs
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Toradol local at epidural/spinal site
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Ephedrine IM at epidural or spinal site for OB site
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Bicarb (remember the ionized and unionized lectures) with local
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propofol 20
20--30 mg nausea
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Magnesium for injection with propofol
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Neo and Ephedrine in Propofol injection
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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