Toxicology Test3 Set1

Front 1

General Anticonvulsant Intoxication info (5)

Back 1

1)can give DONT b/c site of axn is CNS
2)if altered mental status consider CT, lumbar puncture and cultures to rule out infexn/trauma
3)if intentional OD get urine drug screen, 4h APAP lvl and pregnancy test
4)get EtOH level b/c can potentiate intoxication
5)get levels for mulitple anticonvulsants even if 1 med is known/suspected (ppl are usually on more than 1 drug)

Front 2

Phenytoin
a)normal level
b)normal free level
c)kinetics (3)
d)Fosphenytoin (3)

Back 2

a)10-20
b)1-2

c)MM kinetics
c)at therapeutic levels t1/2 if 6-24h (first order)
c)at toxic []s t1/2 is 20-60h (0 order)

d)prodrug
d)within 15min it is entirely converted to phenytoin
d)has NO PEG in it, so no ADRs like IV phenytoin

Front 3

Phenytoin lvl correction if HYPOALBUMEMIC (normal is 3.5-5)

Back 3

measured pheny lvl / (0.2 x measured albumin) + 0.1

Front 4

Phenytoin lvl correction if RENAL FAILURE (CrCl under 20)

Back 4

measured pheny lvl / (0.1 x measured albumin) + 0.1

Front 5

Phenytoin toxic effects
a)@ 20mcg/mL
b)@ 30mcg/mL (3)
c)@ 40mcg/mL (2)
d)@ 50mcg/mL (2)
e)IV phenytoin

Back 5

a)nystagmus

b)ataxia, slurred speech, n/v

c)mental status change (lethargy/coma)

d)coma, seizure

e)has PEG so if given over 50mg/min can cause hypotension and dysrhythmia

Front 6

Phenytoin OD tx (4)

Back 6

1)AC if presents within a reasonable time after exposure (but consider mental status due to aspiration in obtunded pt)
2)multidose AC may decr t1/2 of pheny, but not shown to sig affect pt outcome
3)NO hemodialysis

4)symptomatic/supprotive care mostly

Front 7

Tegretol
a)levels
b)t1/2
c)metabolism
d)has ____ properties meaning...

Back 7

a)4-12

b)10-20h, can get up to 25h after OD

c)enterohepatic recirculation = can use multidose AC

d)anticholinergic, peak lvls may be delayed up to 36-72h, and has potential to form concretions

Front 8

Tegretol toxic effects
a)over 12mcg/mL (2)
b)12-30
c)over 40 (4)
d)other (4)

Back 8

a)nystagums/ataxia

b)mild w/ incr CNS depression

c)incr coma, seizure, respiratory depression and cardiotoxicity

d)cardiotox only occurs in severe OD (tachycardia, hypotension, conduction abnormal)
d)see dystonic rxn, choreoathetosis in kids
d)chronic OD can lead to vasopressin release, leading to hyponatremia
d)can widen QRS and prolong QTc (as late as 20h after taken)

Front 9

Tegretol OD tx (8)

Back 9

a)protect airway if CNS or respiratory depressed

b)AC if presenting within reasonable amt of time from admin (consider neurologic status due to risk of aspiration)

c)multidose AC is useful

d)tx seizures w/ bzd's
e)tx dystonic w/ diphen
f)tx wide QRS (over 100ms) w/ Na bicarb

g)just monitor chorea, cardiac

h)NO hemodialysis

Front 10

VPA PK
a)lvl
b)peak plasma levels (2)
c)protein binding
d)decr ____ stores resulting in.... (2)

Back 10

a1)50-100

b1)occur in 1-4h for liquid/cap, 4-5h for EC
b)can be delayed 24h in OD w/ EC

c)90% normally, but can drop to 30% in OD pt

d)carnitine
d)hyperammonemia/hepatoxicity

Front 11

VPA toxic effects
a)mild OD
b)if level over 450 (major OD) (4)

Back 11

a)self-limiting CNS depression

b)hyperammonemia leading to encepalopathy
b)metabolic acidosis and incr lactic acidosis (bad sign)
b)leukopenia, thrombocytopenia, anemia 3-5d after severe OD
b)pancreatitis and hepatic/renal failure (rare)

Front 12

VPA OD
a)tx (4)
b)Carnitine (2 and doses for replacement/rescue)

Back 12

1)supportive care is mainstay (secure airway, provide ventilatory support)
2)AC (same inst. as tegretol/pheny), but NO multidose
3)WBI if pt ingests large quantities of EC tabs
4)hemodialysis IF levels is over 1000, hepatic dysfxn, rapid deterioration, lvls keep rising

b)supplemenation of it will reduce ammonia levels
b)use in pt w/ VPA induced hepatotoxicity, OD and high serum ammonia levels
b)PO 100mg/kg/d up to 2g, divided in 3 doses (po replacement)
b)IV 150-500mg/kg/d up to 3g, divided in 3 doses (rescue)

Front 13

With ALL other anticonvulsants....

Back 13

give AC if pt is NOT obtunded and if pt present within a reasonable amount of time

Front 14

Neurontin OD
a)effects (4)
b)tx

Back 14

a)drowsy/dizzy/fatigue
a)ataxia
a)nystagmus
a)HA

b)supportive care

Front 15

Felbamate OD
a)effects (5)
b)tx

Back 15

a)drowsy
a)ataxia
a)nystagmus
a)n/v
a)can see aplastic anemia and liver failure in chronic OD

b)symptomatic/supprotive care

Front 16

Lamotrigine OD
a)effects (4)
b)tx (3)

Back 16

a)lethargy/slurred speech
a)ataxia
a)nystagmus
a)seizure, EKG abnormal, QRS prolong in more severe OD

b)tx seizure w/ bzd
b)if EKG abnormal admit for minimum of 24h
b)bicarb to pt w/ QRS over 100ms

Front 17

Vigabatrin OD
a)effects (2)
b)tx

Back 17

a)drowsy/fatigue
a)delirum/psychosis

b)tx delirum/agitation w/ bzd

Front 18

Topiramate OD
a)effects (2)
b)tx (4)

Back 18

a)CNS depression (mild)
a)coma, seizure, metabolic acidosis (rarely)

b)symptomatic care
b)bzd for seizure
b)phenobarbital for refractory seizure
b)intubate pts w/ significant CNS depression

Front 19

Tiagabine OD
a)effects (3)
b)tx

Back 19

a)CNS depression
a)seizure
a)HTN, palpitations, tachyarrhymia w/ THERAPEUTIC USE

b)bzd for seizure tx (also of benefit in HTN, tachycardia)

Front 20

Oxcarbazepine
a)effects (3)
b)tx (3)

Back 20

a)CNS depression
a)hypotension, hyponatremia
a)bradycardia

b)hypotension resonds to fluid challenge
b)bradycardia may require atropine
b)monitor Na

Front 21

Levetiracetam OD
a)effects
b)tx

Back 21

a)drowsy

b)symptomatic/supportive care

Front 22

What to monitor in VPA OD (9)

Back 22

1)vpa levels
2)electrolytes
3)ammonia level
4)LFTs
5)SCr/BUN
6)lactic acid
7)CBC
8)ABGs if sig CNS depression
9)maybe blood carnitine level

Front 23

Cardiac glycoside sources
a)pharmaceutical (5)
b)plants (6)

Back 23

a)digoxin/digitoxin
a)ouabain
a)lanatoside C
a)deslanoside
a)gitalin

b)oleander
b)yellow oleander
b)foxglove
b)lily of the valley
b)dogbane
b)red squill

Front 24

Toxic effects of digoxin (7)

Back 24

1)sinus bradycardia
2)AV block
3)n/v
4)hyperkalemia****
5)halo/altered color perception
6)ventricular ectopy
7)CNS (fatigue, drowsy/dizzy)

Front 25

Digoxin Range of Toxicity (4)

Back 25

1)10mg dose in adult, 4mg dose in kids produce serious toxicity (including caridac arrest)
2)chronic use of digoxin is a common presentation of toxicity
3)ACUTE- present w/ more GI s/sx (n/v)
4)CHRONIC- more nonspecific s/sx (fatigue/weaK0

Front 26

Digoxin ranges
a)therapeutic
b)ways to detect (2)
c)other about these

Back 26

1)0.5-2 ng/mL

2)total digoxin by FPIA
2)free digoxin by ultrafiltration

3)dig levels and s/sx of toxicity do NOT necessarily correlate

Front 27

Digoxin OD tx (5)

Back 27

1)AC should be considered after acute digitalzing dose
2)tx bradycardia w/ atropine
3)tx dysrhythmia w/ antidote (digoxin immune fab)
4)tx hyperkalemia w/ insulin and bicarb (if antidote NOT available)- do NOT use kayexelate and Ca
5)monitor serum dig levels, serum K, and EKG

Front 28

Digoxin Antidote products
a)Digibind (4)
b)Digifab (4)

Back 28

Digibind
a)38mg/vial
a)1vial binds 0.5mg digoxin
a)Ovine makes it
a)$728/vial

Digifab
a)40mg/vial
b)1 vial binds 0.5mg digoxin
c)Ovine makes it
d)$600/vial

Front 29

Indications for Digoxin Antidote (5)

Back 29

1)ingestion over 10mg adults, over 4mg kids
2)digoxin levels over 6 post-distribution
3)K over 5.5 or refractory hyperkalemia
4)ventricular arrhythmias or bradycardia
5)AV block refractory to atropoine

Front 30

Digoxin Antidote dosing (3)

Back 30

1)in acute exposure (and ingested amt known) just administer twice as many vials as mg of dig ingested
2)if steady state dig level is NOT readily available, 20 vials of immune Fab can be admin

3)if SS is availabe use this calc:
SS level x kg / 100 (ROUND UP)

Front 31

Info in Digoxin levels (5)

Back 31

1)obtain level post-distribution phase
2)wait 6-8h from last dose (level will be accurate at this time)
3)immunoassay can over estimate free dig levels
4)ultrafiltration can under estimate free dig levels
5)dig levels will greatly incr w/ Fab use (so are useless after Fab is used)

Front 32

Endogenous Digoxinlike Immunoreactive Substance (DLIS)
a)what is it? (2)
b)how taken care of
c)conditions that cause it (just know first 3, look @ rest)

Back 32

a)pts not on dig can have elevated digoxin levels
a)result of DLIS (which is structure/fxnal similar to dig)

b)ultrafiltration to eliminate DLIS contribution

c)pregnancy
c)neonates
c)renal/liver insufficiency

c)subarachnoid hemorrhage
c)CHF
c)IDDM
c)acromegaly
c)hypothermia
c)stress

Front 33

Dig Drug interaxns
a)decr dig levels (4)
b)incr dig levels (5)

Back 33

a)cholestyramine
a)antacids
a)abx (neomycin, sulfa)
a)kaolin-pectin

b)quinine
b)amiodarone
b)verapamil
b)abx (erythromycin, TCN)
b)BB

Front 34

In chronic dig therapy pts may be HYPOkalemic due to: (6)

Back 34

1)loops
2)diarrhea
3)poor diet
4)use of K binding resins (kayexelate)
5)enhanced effects on heart
6)dysrhythmia can occur @ lower dig levels (toxicity @ normal levels)

Front 35

Dig levels in kids (3)

Back 35

1)kids taking dig tolerate higher doses and plasma levels
2)ped Vd is greater and half-life of dig is less
3)ped heart cells may be less sensitive to toxic effect of dig

Front 36

When to use Dig Antidote in kids (6)

Back 36

1)ingest 0.3mg/kg or more
2)dig lvl over 5 (in elimination phase)

AND also have:
a)life threatening arrhythmia
b)hemodynamic instability
c)hyperkalemia
d)rapidly progressive toxicity

Front 37

Clonidine OD effects
a)CV (4)
b)pulmonary

Back 37

a)initial HTN followed by significant hypotension
a)bradycardia common
a)AV block
a)cardiac ischemia may develop in hypotensive pts

b)respiratory depression leading to apnea

Front 38

Clonidine OD effects
a)neurologic (4)
b)others (3)

Back 38

a)CNS depression from lethargy to coma
a)ataxia
a)hyporeflexia/hypotonia
a)seizures (rare)

b)miosis and dry mucous membranes (characteristic)
b)pallor is common
b)toxic effects of clonidine often mistaken for an opioid OD

Front 39

Toxic dose of Clonidine (3)

Back 39

1)adults have survived doses over 10mg
2)kids can by symptomatic after 0.1mg
3)kids can die from sucking on discarded clonidine patches (may contain 75% of original content)

Front 40

Clonidine OD tx
a)tx (4)
b)decontamination (3)

Back 40

a)ABCs
a)focus on airway management and general supportive care
a)for apnea just stimulate pt (pinch, poke, stroke foot) to return breathing
a)pt will revert to hypoventilation/apnea if stim is dc

b)one dose AC if ingestion occurred recently and no CNS depression
b)consider WBI if patches have been ingested
b)emesis is CI b/c CNS depression may develop rapidly

Front 41

Clonidine OD antidote? (4)

Back 41

NONE, but
a)naloxone has been advocated for tx of clonidine toxicity
a)MAY tx clonidine's opioid like effects, BUT this may be due to stimulation during admin (needle stick)
a)if going to give it for respiratory/CNS depression give 2mg IV and watch for improvement
a)can double to 4mg if no improvement seen (over 4mg = no additional benefit)

Front 42

Clonidine OD supportive tx
a)hypotension (2)
b)HTN (2)
c)bradycardia (3)

Back 42

a)tx w/ isotonic fluid, trendelenburg position and maybe vasopressors
a)dopamine is vasopressor of choice (can add NE for refrac hypotension)

b)brief and minor, aggressive tx of it may result in prolonged and profound hypotension
b)nitroprusside is agent if choice if tx is reqd

c)respond to atropine if HR goes under 60
c)atropine will have no effect on respirations or mental status
c)consider pacing if refractory symptomatic bradycardia

Front 43

CCB's antagonize....

CCBs that are... (and characteristic of 1)
a)cardioselective
b)vascular selective
c)non-selective

Back 43

L-type Ca Channel

a)verapamil
b)DHP's (amlodipine, etc)
c)diltiazem (AV/SA node depression can be profound in OD)

Front 44

Desc effects of DHP's, Diltiazem, and Verapamil on:
a)vasodilation
b)myocardial depression
c)conduction delay

Back 44

DHP's
a)MAJOR
b)minor
c)minor

Diltiazem
a)minor
b)minor
c)MAJOR

Verapamil
a)moderate
b)MAJOR
c)MAJOR

Front 45

______ has its most major effects on..
a)Nifedipine (DHP) (2)
b)Diltiazem
c)Verapamil (4)

Back 45

a)peripheral dilation
a)decr BP

b)decr AV conduction

c)decr AV conduction
c)decr conduction
c)peripheral dilation
c)(-) inotropic

Front 46

CCB's comparative toxicity (4)

Back 46

1)all agents cause rhythm disturbances and conduction defects
2)DHP's lack effects on AV node conduction (more likely to have reflex tachycardia due to decr perfusion)
3)bradycardia 2x as likely w/ verapamil/diltazem
4)AV block greater than 1st degree predominant finding w/ verapamil

Front 47

CCB OD effects
a)CV (6)

Back 47

a)hypotension
a)bradycardia
a)AV node depression (1/2/3rd)
a)junctional, atrial and ventricular dysrhythmias
a)asystole
a)reflex tachycardia

Front 48

Other CCB OD effects
a)in severe OD (3)
b)metabolic (2)
c)neurologic disorders (2)
d)decr bowel motility (3)

Back 48

a)respiratory depression
a)noncardiogenic pulmonary edema
a)renal failure

b)hyperglycemic
b)lactic acid accumulation

c)CNS depression
c)seizures

d)ileus
d)bowel necrosis
d)mesenteric ischemia

Front 49

Onset/duration of CCB toxicity (5)

Back 49

1)hypotension/bradycardia within 1-5h after OD w/ IR CCB ingestions
2)hypotension can persist over 24h despite tx
3)cardiac rhythm disturbances can last up to 7d
4)s/sx may be delayed and prolonged following XR ingestion
5)XR CCB OD requires 24h ICU monitoring*****

Front 50

CCB OD Prehospital Management (5)

Back 50

1)aggressive airway management
2)ACLS/PALS protocol
3)no emesis
4)atropine (often not effective thou)
5)transcutaneous pacemaker (do NOT delay in symptomatic bradycardia)

Front 51

CCB OD Tx Overview (5)

Back 51

1)for hypotension give fluid, vasopressors, Ca
2)for bradydysrhythmias give atropine, glucagon, Ca, pacing
3)for seizures give bzd's

4)No AC/WBI
5)caution w/ lavage due to vagal stimulation that may cause emesis and bradydysrhythmias

Front 52

Traditional CCB OD Algorithm (6)

Back 52

Atorpine & 20mL/kg NS bolus -->
CaCl2 20mg/kg -->
Glucagon 3-5mg -->
Dopamine 5-20mcg/kg/min -->
NE 0.5-5mcg/min

possibly: pacing, aortic balloon pump, bypass

Front 53

Role of FLUIDS in CCB OD (4)

Back 53

1)crystalloid fluids (NS) incr intravascular volume (NO use D5W)
2)admin after first toxin-induced hypotension
3)admin 20mL/kg (if no CHF/PE)
4)repeat prn w/ consideration of pt's need and fluid status

Front 54

Role of ATORPINE in CCB OD (3)

Back 54

1)inhibits vagal nerve activity to incr HR
2)consider 1st in bradycardia that is caused by toxin depression of SA/AV node
3)many reported cases of failure of atropine to incr HR

Front 55

Role of Ca in CCB/BB OD (6)

Back 55

1)incr available intracellular Ca (good in both CCB and BB OD)
2)give Ca after glucagon admin IN BB OD
3)dose CaCl2 20mg/kg IV and up to 3g total (causes venous irritation so give centrally)
4)kids/pts w/ poor venous access use Ca gluconate (3x dose of CaCl2 but can give peripherally)
5)monitor for hypercalcemia
6)beware if digoxin OD

Front 56

Role of GLUCAGON in CCB/BB OD (5)

Back 56

1)incr cAMP = incr Ca release from SR thru non-B receptor mediated effect
2)used in BB and CCB OD but more effective in BB OD (BB decr cAMP)
3)slow IV bolus of up to 10mg (in divided doses) followed by cont. infusion of the effective initial dose given each hour
4)monitor blood glc
5)monitor airway (lower esophageal sphincter tone)

Front 57

Role of Vasopressors in CCB/BB OD (3)

Role of Pacing in CCB/BB OD (3)

Back 57

1)incr/maintain perfusion
2)if its needed using an agents that has alpha1 and beta1 agonist if best (NE/epinephrine)
3)hemodynamic monitoring w/ a pulmonary artery catheter advised to ensure optimal tx

1)aggressive care if pt remains unresponsive to previous tx
2)transcutaneous and transvenous pacing should be attempted
3)though there are cases of failure of pacing in the face of CCB/BB OD

Front 58

Other managment issues in CCB OD (4)

Back 58

1)small doses of CCB in kids can be lethal
2)seizures more likely in kids than adult
3)in kids consider heroic measures
4)no enhanced elimination in kids

Front 59

Monitoring parameters in CCB OD (6)

Back 59

1)hemodynamic status closely (HR, BP, EKG)
2)renal fxn/urinary output
3)electrolytes/glc
4)swan ganz monitoring in pts w/ severe hypotension
5)monitor respiratory fxn/oxygenation
6)CCB levels are useless

Front 60

CCB OD
a)observation (2)
b)when NOT to tx (3)

Back 60

a)symptomatic pts or any pt w/ hx of ingestion of SR, admit to ICU for atleast 24h of observation/tx (independent of dose ingested)
a)asympto pts w/ a hx of CCB ingestion get a baseline EKG and monitor for a min of 8h w/ repeat EKG b4 discharge

b)if more than 6h since IR ingestion
b)if more than 18h since XR release
b)if more than 24h since XR verapamil ingestion
AND no s/sx then toxicity unlikely

Front 61

Desc of 3rd degree heart block (7)

Back 61

1)complete failure of AV Node
2)no impulses from sinus node will pass thru ventricles
3)some part of conducting system will take over as pacemaker
4)P wave rate- normal
5)Ventricular rate- slow
6)ventricular complex may be broad idioventricular rhythm
7)complete dissociation b/w P waves and QRS

Front 62

Insulin/glc for CCB/BB toxicity (4)

Back 62

1)CCB OD causes diabetic like effects
2)myocardial cells normally rely on FFA for energy
3)in stress/shock they shift to glc as preferred substrate
4)CCB prevent adequate myocardial ultilization of CHO

Front 63

BB toxicity (2)

Results in ____ myocardium=....(3)

Back 63

a)also inhibits gluconeogenesis and glyconeogenesis (so will NOT see hyperglycemia like w/ BB OD*******)
a)results in impaired ability to recover from hypoglycemia

ATKINS
b)inhibition of Ca-mediated insulin release from pancreatic islet cells
b)CCB OD produces myocardial insulin resistance
b)poor tissue perfusion and severe acidosis impair carb delivery and glycolysis

Front 64

CCBs and
a)insulin release (2)
b)glc metabolism (2)

Back 64

a)volted Ca response for insulin (L-type receptor can block insulin release)
a)in shock pancreatic release of insulin is inhibited (= hyperglycemia and decr insulin)

b)Ca mediates to inhibit PDH
b)pyruvate shunted to lactate

Front 65

Myocardial starvation caused by what in BB/CCB OD (3)

Back 65

1)poor substrate availability
2)switch from substrate preference from FFA to CHO
3)insulin deficiency

Front 66

Little known fact, insulin is a _____, meaning.... (4)

Back 66

POSITIVE INOTROPE
1)support metabolic demands of the myocardium during stress
2)promotes glc utilization
3)activates PDH (lactate to pyruvate)
4)insulin incr coronary artery flow

Front 67

Recommendation of goals for BB/CCB OD (4)

Back 67

1)restore cardiac output/end organ perfusion
a)SBP over 90
b)urine output over 1mL/kg/hr
c)improved CNS

Front 68

Caveats for HIE (hyperinsulinemia-euglycemia) (CCB OD) (8)

Back 68

1)start early along w/ standard tx (onset is 30min)
2)works best in depressed myocardium
3)can give Ca and insulin simultaneously
4)monitor glc every 30min (most CCB OD pt's have altered mental status)
5)maintain glc @ 150 (will get insulin resistance early in course then incr dextrose demand later)
6)don't rush into K+ replacement (unless under 2.5 or ongoing K loss)
7)check Mg/PO4 (and replace as indicated)
8)must use insulin early NOT for rescue

Front 69

BB's
a)non-selective ones (4)
b)non-selective + non-selective alpha blocker (2)
c)highly lipophilic BB (=CNS depression/seizure) (2)
d)kind of lipophilic BB (=CNS/respriatory depression/seizure in SEVERE OD)
e)carioselective (4)

Back 69

a)nadolol
a)propanolol
a)sotalol
a)timolol

b)carvedilol
b)labetalol

c)propanolol
c)carvedilol

d)metoprolol

e)bisprolol
e)atenolol
e)metoprolol
e)esmolol (selectivity can be lost in OD for all these)

Front 70

BBs that have OD effect of QRS prolongation and hypotension (4) and also have....

Back 70

1)acebutolol
2)betaxolol
3)oxprenolol
4)propanolol

membrane stabilizing effects

Front 71

BB w/ _____ may be protective in OD (and 4ex)

Back 71

ISA
a)pindolol
b)penbutolol
c)oxprenolol
d)acebutolol

Front 72

Problems/desc of Sotalol (6)

Back 72

1)have K channel blockade
2)nonselective
3)low lipophilicity
4)no membrane stabilizing effect
5)NO ISA
6)can prolong QTc leading to Torsades

Front 73

BB OD
a)toxic dose
b)s/sx (6)
c)and when to always refer

Back 73

a)2-3x therapeutic dose

b)bradyarrhythmia
b)hypotension
b)decr LOC
b)respiratory depression
b)seizure
b)ventricular arrhythmia

c)if ingestion was intended w/ harm/suicide (this goes for CCB's too)

Front 74

BB OD Prehospital management (8)

Back 74

1)aggressive airway management
2)ACLS/PALS protocol
3)no emesis
4)atropine (may not work)
5)transcutaneous pacemaker (do NOT delay in symptomatic bradycardia)
6)glucagon IV bolus (incr cAMP)
7)fluid resuscitation (NS not D5W)
8)vasopressors prn (dopamine/epinephrine)

Front 75

Glucagon and BB (3)

Back 75

Relieves
a)hypotension
b)bradycardia
c)AV block

Front 76

Other management issues in BB OD (3)

Back 76

1)treat dysrhythmias
2)kids more likely to have hypoglycemia and seizures than adult, should consider heroic measures
3)insulin pump is option (experimental and only proven in dogs)

Front 77

MOA of opiates, alcohol, stimulants, nicotine to cause addiction

Back 77

stim the dopaminergic neurons in the nucleus accumbens ("brain reward pathway")

Front 78

Amphetamines MOA (5)

Back 78

1)incr DA []s in synapse
2)entry of amphetamine via DA transporters, which exchanges for cytosolic DA ("backward flow")
3)amphetamine in synapse compete w/ DA for uptake by DA transporter
4)alkalinization of DA storage vesicles w/ subsequent release of DA into the cytosol
5)inhibition of MAO, leading to incr DA

Front 79

Amphetamines/stimulants can cause mixed alpha/beta syndrome ("sympathetic storm"); what are s/sx (6)

Back 79

1)CNS excitation
2)mydriasis
3)hyperthermia
4)dry membranes
5)tachycardia/tachypnea
6)HTN

Front 80

OTHER effects of amphetamines (3)

Back 80

1)can block NE uptake by its transporter
2)high []s can incr serotonin release
3)MAO inhibition will further incr levels of NE/E

Front 81

Cocaine MOA (3)

Back 81

1)block reuptake of DA from synapse
2)also blocks uptake of NE/serotonin by their transporters
3)BOTH amphetamines and coke interfere w/ NT reuptake (DA, E/NE, serotonin)

Front 82

Amphetamine chemistry (3)

Back 82

1)basic part is phenylethylamine
2)has amino group on R end (ionized under acid conditions, but under body conditions its unionized so crosses membranes)
3)similar to catecholamines

Front 83

Amphetamine absorption and distribution (5)

Back 83

1)lipophilic
2)completely absorbed after po admin
3)Vd of 3-5L/kg
4)crosses BBB and placenta
5)extremely rapid transit from lung to brain

Front 84

Normal catecholamine metabolism and amphetamines (2)

Back 84

1)COMT can't metabolize amp's b/c aromatic rings lack OH groups
2)MAO can metabolize amp's b/c the alpha carbon is methylated

Front 85

Amphetamine metabolism (2)

Amphetamine excretion (2)

Back 85

1)usually by P450's; aromatic hydroxylation and N-demethylation
2)2D6 is major one (ppl w/ deficiency are sensitive to amp's)

1)urinary excretion of amp's is enhanced by acidic urine b/c amino group becomes protonated (HOWEVER not recommended to alkalinize or acidify the urine)
2)long t1/2 (8-30h)

Front 86

Amphetamine CNS ADRs (5 of many)

Back 86

1)anxiety/agitation
2)hyperthermia
3)intracebral hemorrhage
4)hallucinations/psychosis
5)seizures

Front 87

Amphetamines ADRs
1)blood vessels (3)
2)heart (3)

Back 87

a)vasospasm
a)vasoconstriction causing tissue anoxia
a)severe HTN due to vascular changes

b)tachycardia
b)dysrhythmias
b)myocardial ischemia

Front 88

Amphatamine ADRs
a)respiration
b)eye
c)body temp
d)glc

Back 88

a)incr RR

b)dilation of pupils

c)hyperthermia due to central effects, agitation, excessive movements/sizures

d)hyperglycemia initially (then hypo later after liver glc depleted)

Front 89

Amphetamine ADRs
a)musculature (2)
b)GI (2)

Back 89

a)rigidity/seizure
a)rhabdo

b)decr motility
b)colitis/perforated ulcers

Front 90

Causes of death in amphetamine ADRs (3)

Back 90

1)hyperthermia
2)dysrhythmias
3)intracebral hemorrhage (due to HTN)

Front 91

Routine labs to get for Amphetamine OD (4)

Back 91

1)Glc/electrolytes
2)BUN
3)CPK (rhabdo/cardiac damage)
4)EKG/cardiac monitor

Front 92

Basic management of amphetamine OD (5)

Back 92

1)supportive care
2)fluid hydration
3)lavage/charcoal considered early after po exposure (NO emesis)
4)tx hyperthermia aggressively
5)NO hemodialysis or hemoperfusion (b/c large Vd)

Front 93

Pharma management of amphetamine OD (5)

Back 93

1)Control HTN w/ NTG/nitroprusside, phentolamine, CCB
2)NO BB'S********* (unopposed alpha stim)
3)benzo's for agitation/seizures
4)for refractory seizures use barbiturates/propofol
5)lidocaine for dysrhythmias

Front 94

S/sx of CHRONIC amphetamine abuse (7)

Back 94

1)vasculitis
2)cardiomyopathy
3)pulmonary HTN
4)valvular heart disease
5)recurrent infexn
6)psychoses
7)nerve damage; death of neurons

Front 95

Unique effects of MDMA (4)

Back 95

1)an entactogen
2)1/10th the CNS stim of amphetamine
3)10x the inhibitory effect of amphetamine on serotonin reuptake transporter
4)high incidence of hyponatremia*********