Pharm. Review Iv

Front 1

**Drugs which prolong the state of inactivation of Na channels:

Back 1

**PVC**

=Phenytoin
=Valproate
=Carbamazepine

Front 2

Phenytoin

Back 2

**DOC for generalized tonic-clonic seizures.

**Treatment of status epilepticus (=diazepam is DOC)

**Treatment of episodic clonic movements following severe head injury

Front 3

Side Effects:

Back 3

=gingival hyperplasia
=ataxia
=nystagmus
=diplopia
=psychological disturbances
=megaloblastic anemia (interferes w/ folate met.)
=osteomalacia

Front 4

Teratogenic?

Back 4

Yes--cleft lip/palate

Front 5

Carbamazepine

Back 5

**Treatment of temporal lobe seizures

**DOC for trigeminal neuralgia

Front 6

S/E's

Back 6

**Monitor LFT's especially in young patients or patients w/ treated w/ valproate + other seizure meds

**Can cause an increased release of AVP + potentiate antidiuretic effects of AVP
=dilutional hyponatremia

Front 7

Phenytoin and phenobarbital cause osteomalacia. How?

Back 7

**They induce CYP450 --> which increases metabolism of vitamin D and vitamin K
=decreased vitamin D lowers the GI absorption of calcium
=in order to maintain plasma Ca, bone is resorbed

Front 8

Primidone

Back 8

**Metabolized to phenobarbital but probably acts directly on Na channels like phenytoin

Front 9

Ethosuximide

Back 9

MOA:
=blocks T-type Ca channels in the thalamus

**DOC for absence seizures

Front 10

What is an absence seizure?

Back 10

Blank stare, eyelids flutter, 3/sec spike wave rhythms from the thalamus

Front 11

Baclofen MOA

Back 11

Interacts w/ GABA (B) receptors linked to K-channels
=enhanced K conductance hyperpolarizes glutaminergic neurons in sc --> prevents release of glutamate onto alpha-motor neurons
=decreased excitation of SPASTIC skeletal muscle

Front 12

Uses?

Back 12

Used to treat spasticity from sc injury, CP, or MS

Front 13

Dantrolene MOA

Back 13

**Inhibits release of "trigger" Ca from SR in skeletal muscle

Front 14

Uses:

Back 14

Treatment of spasticity from SC injury, malignant hyperthermia, NMS

Front 15

S/E's:

Back 15

Generalized muscle weakness

Front 16

What blocks NE reuptake?

Back 16

Desipramine (secondary amine)

Front 17

What blocks 5-HT uptake?

Back 17

SSRI's
=fluoxetine
=paroxetine
=citalopram
=fluvoxamine

Front 18

What blocks BOTH NE and 5-HT reuptake?

Back 18

=imipramine (tertiary amine)
=clomipramine
=venlafaxine

Front 19

S/E's of antidepressants:

Back 19

1) Confusion in the elderly
2) Postural hypotension
=alpha blockade
3) Sedation
=central antimuscarinic effect
4) Urinary retention and tachycardia
=atropine-like effect
5) Fine tremor and AV block

Front 20

MOA of MAO inhibitors:

Back 20

**inhibit MAO-A which degrades NE and 5-HT

recall: MAO-B degrades DA

Front 21

Schizophrenic patient w/ depression

Back 21

SSRI like fluoxetine

Front 22

Depressed patient w/ hypotension

Back 22

SSRI like fluoxetine

Front 23

Depressed patient being treated w/ an antidepressant suffers from sedation + hypotension

Back 23

**Could be an MAOI or TCA since BOTH cause sleepiness and hypotension, but pick the TCA because they cause greater orthostatic hypotension than do MAOI's

Front 24

Small child w/ nocturnal enuresis

Back 24

Treat w/ TCA for atropine-like effect in urinary bladder

Front 25

Which NT is involved in OCD?

Back 25

5-HT

**Treatment for OCD
=Clomipramine or
=SSRI

Front 26

Depressed patient w/ CHF is treated w/ digoxin. He is given a TCA.

Back 26

Inverts or flattens T-wave --> slows conduction in fast fibers so QRS is increased

Front 27

What are the usual effects when you OD w/ imipramine?

Back 27

1) Decreased BP
=alpha blockade
2) Increased HR from decreased BP and anticholinergic effects
3) Decreased AV conduction w/ increased Q-T interval

Front 28

What are the symptoms of serotonin syndrome?

Back 28

1) Increased BP, HR, and respiration
2) Increased muscle activity
=muscle twitchcing, shivering, myoclonus
=causes hyperthermia and sweating
3) Pupillary dilation
4) Confusion, agitation, hallucinations

Front 29

What causes the Serotonin Syndrome?

Back 29

**Results from excessive stimulation of central 5-HT receptors
=caused by an SSRI or a TCA which blocks BOTH NE and 5-HT uptake (i.e. impipramine) ESPECIALLY in patients taking an MAOI
=MAOIs can prevent the degradation of 5-HT in the CNS--> 5HT accumulates in central neurons

Front 30

MOA

Back 30

Block D2 receptors in the mesolimbic DA pathway

Front 31

Haloperidol

Back 31

**Least sedating
**Greatest liklihood of EPS

Front 32

DOC for Tourette's Syndrome

Back 32

Haloperidol

Front 33

Clozapine

Back 33

**Effective in treatment of negative symptoms

=must measure CBC weekly

Front 34

Chlorpromazine

Back 34

**Prevents emetic effects of D2-receptor stimulation in the CTZ

Front 35

S/E's:

Back 35

1) Alpha blockade
2) Muscarinic blockade
3) Central D2 blockade
4) Neuroleptic Malignant Syndrome

Front 36

What are the effects of an alpha blockade?

Back 36

=dizziness, orthostatic hypotenstion, increased HR, nasal stuffiness, impotence

Front 37

What are the effects of a muscarinic blockade?

Back 37

=dry skin and mouth, mydriasis, increased HR, urinary retion, sedation, hyperprolactinemia, galactorrhea, amenorrhea

Front 38

Lithium MOA

Back 38

=Inhibits enzymes important in recycling phosphoinostides

=SO, PIP2 is depleted

Front 39

What drugs enhance the reabsorption of lithium in the PT causing toxicity?

Back 39

=HCTZ
=Furosemide

Front 40

S/E's:

Back 40

=Tremor
=Motor and psychiatric distrubances

**Causes NEPHROGENIC DI by inhibiting adenyl cylcase cocupled to V2-ADH receptors in the CD

Front 41

In a female patient w/ bipolar disease, you must DISCHARGE lithium in the 1st trimester to prevent teratogenesis.

Back 41

**Called "Ebstein's Anomaly"
=leaflets of mitral valve displaced downward into right ventricle
=tricuspid regurgitation
=right ventricular dysfunction

Front 42

What are drugs that cause parkinson's-like side effects?

Back 42

=D2-receptor antagonists like haloperidol, chlorpromazine, trifluperazine

Front 43

Levodopa

Back 43

**Precursor of DA which is pumped into the brain via the aromatic amino acid pump

Front 44

What can interfere w/ the therapeutic action of L-dopa?

Back 44

**Treatment w/ vitamin B6
=increases peripheral decarboxylation of levodopa --> DOPA

Front 45

Carbidopa

Back 45

**inhibits DOPA decarboxylase outside the brain to ENHANCE the amount of DOPA taken up by the brain and converted to DA

Front 46

Benztropine

Back 46

=central muscarinic receptor blockade

Front 47

Bromocriptine

Back 47

=Central D2 dopamine receptor agonist

Front 48

Amantadine

Back 48

=antiviral drug which releases DA centrally

Front 49

Selegiline

Back 49

=selective MAO-B inhibitor --> blocks breakdown of DA in CNS

Front 50

Benefts of Carbidopa + Levodopa

Back 50

1) Can reduce the dose of DOPA
2) Prevents decarboxylation of DOPA outside of CNS
3) Carbidopa does NOT enter the CNS
4) Carbidopa does NOT attenutate the orthostatic hypotension caused by L-DOPA

Front 51

What about treatment of a schizophrenic patient w/ levodopa?

Back 51

=Levodopa can cause the reappearance of psychotic symptoms in a schizophrenic patient w/ parkinsonian symptoms caused by typical antipsychotic drugs (i.e. haloperidol)

Front 52

What are drugs that INCREASE plasma prolactin?

Back 52

1) D2-receptor blockers like haloperidol
2) Reserpine
3) Metoclopramide
4) alpha-methyldopa

Front 53

What are the effects of hyperprolactinemia?

Back 53

=galactorrhea
=amenorrhea
=anovulatory cycles and infertility
=decreased libido/impotence in men

Front 54

Bromocriptine

Back 54

**D2 receptor agonist
=used to treat PD AND
=inhibit prolactin release in hyperprolactinemia

**Reverses infertility caused by hyperprolactinemia

Front 55

Ethanol

Back 55

=Oxidized to acetaldehyde by alcohol dehydrogenase
=Acetaldehyde will be degraded to water + CO2 by acetaldehyde dehydrogenase

Front 56

Kinetics of Ethanol

Back 56

**Alcohol dehydrogenase is easily saturated w/ low concentrations of ethanol --> SO ethanol is removed by ZERO ORDER KINETICS
=a constant amount of drug/hour

Front 57

What inhibits acetaldehyde dehydrogenase?

Back 57

1) Disulfiram
2) Metronidazole

Front 58

Aldehyde Syndrome

Back 58

**Build up of aldehyde causes:
=red skin
=n/v
=pulsating headache
=sweating
=chest pain
=vertigo, syncope, blurred vision
=confusion

Front 59

EtOH and body heat

Back 59

EtOH enchances the loss of body heat by peripheral vasodilation

Front 60

A patient is being treated for Giardia and some other infection. They develop n/v and a headache after drinking a beer. Which drug causes this?

Back 60

Metronidazole.

Front 61

Alcoholism causes:

Back 61

1) Hyperlipidemia + fatty infiltration of the liver
2) Cardiomyopathy, portal HTN, gastric ulceration, esophageal varices
3) Wernicke-Korsakoff Syndrome

Front 62

What is Wernicke-Korsakoff Syndrome?

Back 62

**Associated w/ thiamine deficiency
=get paralysis of external eye muscles
=altered mentation
=ataxia

Front 63

Fetal Alcohol Syndrome

Back 63

*underdevelopment of mid-facial region
=Flattened face
=Short nose
=Short palpebral fissures

=microcephaly w/ low IQ
=retarded growth

Front 64

Methanol Toxicity

Back 64

**Severe visual disturbance
=like being in a snow storm
**Relatively clear sensorium
**Headache, dyspnea, cold digits, GI pain
**Breath smells of formaldehyde

Front 65

How do you treat this?

Back 65

**Treat w/ ETHANOL to saturate enzymes which degrade EtOH and MeOH because the TOXIC product of MeOH appears to be a FORMATE COMPOUND produced by the normal breakdown of alcohol and acetaldehyde dehydrogenases

Front 66

What is the toxic product of ethylene glycol (=antifreeze)?

Back 66

**Converted to OXALATE
=causes acute renal failure

Front 67

Amphetamine Toxicity

Back 67

=Nervousness, restlessness, insomnia
=HTN, tachycardia, hyperthermia
=Toxic psychosis --> paranoid schizophrenia
=weight loss + formication
=tonic-clonic seizures

Front 68

What about the EYES?

Back 68

**With early use, you get pupillary DILATION from the release of NE in the radial muscle.
**With PROLONGED use, you get MIOSIS due to depletion of NE

Front 69

Does amphetamine withdrawl cause delerium tremors (DT's)?

Back 69

NOOOOOOO

Front 70

Treatment of ADD and ADHD in children:

Back 70

Methylphenidate

Front 71

Side Effects:

Back 71

**Can cause:
=depression, insomnia
=loss of appetite + weight loss
=SLOWED GROWTH RATE

Front 72

Drugs for neonatal apnea

Back 72

=THEOPHYLLINE
=aminophylline
=caffeine

Front 73

What drug suppresses appetite via the release of NE in the hypothalamus?

Back 73

Phentermine

Front 74

What is the effect of MDMA = "ecstacy"?

Back 74

**can cause degeneration of central 5-HT neurons

Front 75

ALL SEDATIVE-HYPNOTIC drugs cause:

Back 75

**i.e.
=barbiturates, benzos

**Dependence
**Shortened sleep latency--suppression of REM sleep
**Rebound insomnia
**Respiratory depression

THEY ARE NOT ANALGESIC.

Front 76

Barbiturates

Back 76

=general CNS depressants with a LOW therapeutic indez

Front 77

MOA

Back 77

**Enhance GABA-A receptor-mediated increase in Cl conductance to HYPERPOLARIZE neurons
=enhances DURATION of channel opening

Front 78

What about in older patients?

Back 78

**Can cause a PARADOXICAL excitation.

Front 79

Which of the barbiturates is the LEAST sedating?

Back 79

Phenobarbital

Front 80

Thiopental

Back 80

**POOR analgesic activity
=used for the induction of anesthesia
=SHORT duration of action due to redistribution from blood/brain/visera --> skeletal muscle --> fat

Front 81

CV effects of thiopental:

Back 81

=Transient decrease in BP w/ reflex increase in HR and dp/dt

**SO, CO is NOT depressed.

Front 82

MOA

Back 82

=enhances GABA-A-receptor mediated increase in Cl conductance to hyperpolarize neurons
=enhances RATE/FREQUENCY of channel opening

Front 83

What about in older patients?

Back 83

**In older patients, drugs have a longer t1/2 due to decreased chlorine
=increased receptor sensitivity to BZ's
=INCREASED RISK OF FALLS AND HIP FRACTURE

Front 84

So, which benzos are preferred for older patients?

Back 84

**Lorazepam
**Oxazepam

=cleared by glucuronidation rather than CYP450 --> rate of glucuronidation does NOT decrease with age

Front 85

Which has the shortest t1/2?

Back 85

**Triazolam
=used to treat INSOMNIA

**Greatest risk of rebound insomnia

Front 86

BENZO Withdrawl Syndrome

Back 86

=Anxiety, agitation
=Dysphoria
=Insomnia
=Vomiting, sweating, muscle and abdominal cramps
=Myoclonic jerks and convulsions

**NO CV EFFECTS!!!!!

Front 87

BZ Receptor ANTAGONIST?

Back 87

**Flumazenil
=used to treat OD w/ Benzo's
=also can precipitate the withdrawl syndrome in patients addicted to benzos

Front 88

Zolpidem

Back 88

**a non-BZ hypnotic drug
=acts to increase chloride conductance

Front 89

Buspirone

Back 89

=NOT ADDICTIVE

Front 90

MOA

Back 90

**Partial agonist at 5-HT-Ia receptors linked to K channels
=causes HYPERPOLARIZATION to suppress neuronal acvitiy

Front 91

Effects:

Back 91

**Slow onset of action conpared to BZ's

**NO sedation or interaction w/ EtOH
=no hypnotic, anticonvulant, or muscle-relaxant effects

Front 92

Class I

=no medical uses

Back 92

=Heroin
=LSD
=Marijuana
=Mescaline
=PCP

Front 93

Class II

=no telephone scripts/refills

Back 93

=Opiates
=Amphetamines
=Cocaine

Front 94

Class III

=Rewrite script after 6 months or 5 refills

Back 94

=Codeine
=Opium
=Some barbiturates

Front 95

Class IV

=Rewrite script after 6 months or 5 refills

Back 95

=BZ's
=Phenobarbital

Front 96

Class V

Back 96

=Diphenoxylate

Front 97

Opiates

Back 97

Clinically useful opiates are relatively selective for MU receptors--but LARGER doses affect all opiate receptors (=mu, kappa, and delta)

Front 98

Mu Receptors

=What are the natural agonists?

Back 98

=Morphine
=Endorphins
=Enkephalins

Front 99

What causes analgesia?

Back 99

**Morphine causes analgesia in humans via stimulation of supraspinal mu1 and spinal mu2 receptors
=respiratory depression --> mu2
=decreased GI motility --> mu2

Front 100

Other Effects of Stimulation at mu receptors?

Back 100

1) Miosis
2) Euphoria
3) Physical dependence

Front 101

Kappa Receptors--natural agonists?

Back 101

=Dynorhins

Front 102

Analgesia caused by:

Back 102

Supraspinal kappa3 and spinal kappa1

Front 103

Other Effects of Stimulation at kappa Receptors?

Back 103

**Dysphoria
=disorientation
=depersonalized feelings
**Sedation

Front 104

Delta Receptors--agonists?

Back 104

=enkephalins

Front 105

Analgesia?

Back 105

**Supraspinal and spinal analgesia--SPINAL more important

(recall: at the mu receptors--supraspinal was the dominant effect)

Front 106

SO...how is the SUPRASPINAL effect established?

Back 106

**GABA neuron normally inhibits pain-inhibiting-neurons (PINs)

**Opiates inhibit the GABA neuron
=so no GABA is released onto the PINs = NO inhibition of PINs --> and we get a central descending inhibition of pain pathways

Front 107

How is the SPINAL effect achieved?

Back 107

**Opiates block nociceptive stimuli in ascending spinothalmic pathways
=mu2, kappa1, and delta2 stimulation DECREASES NT (glutamate) release

Front 108

SO, the mu, delta, and kappa receptors are coupled to G-proteins:

Back 108

**mu and delta --> increased K conductance = HYPERPOLARIZATION

**kappa = decreased Ca conductance

Front 109

SO, summary of actions of opiates:

Back 109

1) Analgesia
2) Respiratory Depression
=increase in the threshold CO2 which activates the medullary respiratory center
3) Constipation
4) Miosis
5) Sedation, euphoria, dysphoria, physical dependence

Front 110

Continued:

Back 110

6) Cough suppression
7) Emesis

**Not as much effect on BP or HR in the supine patient
=though, IV morphine can induce histamine release which can DECREASE BP + cause itching/hives

Front 111

Other adverse CV effect of morphine?

Back 111

**Can act centrally to cause orthostatic hypotension

Front 112

What 2 Symptoms does an addict NOT GAIN tolerance to?

Back 112

=Miosis
=Constipation

Front 113

TOXICITY TRIAD:

Back 113

1) Miosis
2) Depressed respiration
3) Coma

Front 114

Which drugs cause LESS depression of respiration?

Back 114

**Pentazocine
**Butorphanol
**Nalbuphine
**Buprenorphine

Front 115

Symptoms of Opiate Withdrawl:

Back 115

=Rhinorrhea
=Lacrimation
=Chills, hyperthermia, sweating, + piloerection ("goose flesh")
=n/v, diarrhea
=myalgia, tremor
=mydriasis
=anxiety, hostility

Front 116

Which opiate has the LONGEST DURATION of action?

Back 116

**Methadone
=active p.o.
=duration of 15-30 hours --> important for keeping addicts OFF morphine

Front 117

Which drug causes the GREATEST inhibition of respiration?

Back 117

Morphine

Front 118

Whihch has the LEAST POTENTIAL for addiction?

Back 118

Diphenoxylate

**used to treat diarrhea

Front 119

DOC for pain and pulmonary edema caused by acute MI

Back 119

Morphine
=bc it acts in the CNS to decreases SNS activity
=decreases preload and afterload

Front 120

A female w/ acute pain from gallstones is treated with morphine. She is in greater pain. WHY?

Back 120

Morphine contracts the SM of the GB.

recall: opiates can cause SM contraction in the biliary tract + GU tract

Front 121

Female on methadone has emergent surgery and is treated w/ butorphanol. The patient experiences S/S of opiate withdrawl. Why?

Back 121

**Butorphanol is a partial agonist at mu receptors--displaces the methadone.

Front 122

What are the other partial agonists?

Back 122

=Pentazocine
=Nalbuphine
=Buprenorphine
=Butorphanol

Front 123

Which opiate does NOT cause a dose-related inhibition of respiration?

Back 123

=the partial agonists pentazocine, butorphanol, and nalbuphine

Front 124

Newborn baby has respiratory distress depression--why?

Back 124

Mom recieved an opiate during labor.

Front 125

Patient w/ MI is treated w/ morphine. WHY?

Back 125

**Chest and arm pain INCREASE the activity of the sympathetic NS which constricts arterials + venules to increase the preload + afterload
=damaged heart cannot pump increased venous return
=SO, morphine acts centrally to decrease pain and DECREASE sympathetic outflow --> dec. pre/afterload --> improves CO

Front 126

MAC

Back 126

**The concentration of inspired air which is required to cause a surgical plane of anethesia in 50% of patients

**Measure of anesthetic potency and is INVERSELY related to the oil/gas partition coefficient

Front 127

Nitrous Oxide

Back 127

**CANNOT be used for anesthesia because its MAC is >100%
=even if it were 90%, you still couldn't use it --> patient has to breathe at least 20% oxygen to prevent hypoxia

Front 128

What are drugs that LOWER the MAC (=dose) of volatile anesthetic agents?

Back 128

1) NO
2) BZ's
3) Opiates
4) Ketamine
5) Barbiturates
6) EtOH

Front 129

Blood/Gas Partition Coefficient

Back 129

**Determines rate of onset (induction)/offset of anesthesia
=agents that are POORLY soluble in blood have a RAPID rate of onset/offset

Front 130

Review --> You are given a question regarding potency or MAC.

Back 130

**Most POTENT drug has the SMALLEST MAC

**Gas w/ the LOWEST MAC = gas w/ the HIGHEST oil/gas partition coefficeint

**Gas w/ the highest MAC = gas w/ the lowest oil/gas partition coefficient

Front 131

Continued:

Back 131

**An anesthetic gas w/ LOW lipid solubility = HIGH MAC and fast induction and recovery

**An anesthetic gas w/ HIGH lipid solublity = low MAC and SLOW induction and recovery

Front 132

Second-Gas Effect

Back 132

**A rapidly absorbed gas INCREASES the rate of uptake of a second gas
=i.e. give 70% nitrous oxide + .78% halothane + 29% oxygen
=the rapid uptake of NO pulls the halothane along w/ it!

Front 133

THUS, the arterial tension (partial pressure) of halothane rises MORE RAPIDLY when given w/ NO --> what is the NET effect?

Back 133

**Net effect is 2 fold:
=Steady-state alveolar concentration of halothane is increased
=the MAC of halothane is decreased

Front 134

What is diffusion hypoxia?

Back 134

**NO is VERY insoluble in blood
=when its administration is STOPPED, large volumes of NO pour out of the blood into the lungs --> dilutes O2 --> patient becomes hypoxic

Front 135

When does it occur?

Back 135

**Occurs in the first 10 minutes after discharge of NO

**Treat patient w/ 100% oxygen

Front 136

Other Complications of Using NO:

Back 136

**NO can easily leave the blood and enter ANY air-filled cavity in the body
=i.e. IF the air-filled cavity is non-compliant--sinuses, middle ear--cavity pressure increases --> can cause a RUPTURE of the tympanic membrane or cause n/v after surgery

Front 137

Factors Controlling the RATE of Induction of Anesthesia:

Back 137

1) Alveolar ventilation rate
2) Blood/gas partition coefficient
3) Partial pressure of gas in lungs
4) CO
5) Increase in FI = [ ] of gas in inspired air
6) Cerebral blood flow

Front 138

What does NOT affect this rate?

Back 138

MAC!!

Front 139

Factors Controlling the Rate of OFFSET of Anesthesia?

Back 139

=Blood/gas partition coefficent
=Hyperventilation
=CO
=Drug metabolism by the liver

Front 140

CV Effects of Halothane, Isoflurane, and Enflurane

Back 140

**Decrease MAP by decreasing either CO or TPR
=IF in the presence of NO, however, they will not decrease BP

**Isoflurane has little effect on CO

Front 141

Complications after use of Methoxyflurane:

Back 141

**Causes RENAL FAILURE after surgery via release of fluoride ions.

Front 142

Ketamine MOA

Back 142

**Blocks NMDA glutamate receptor coupled to Ca channel

Front 143

Effects:

Back 143

**Produces a dissociative state of consiousness + analgesia + postanesthetic hallucinations

**LEAST LIKELY to suppress respiration.
=all opiates, barbs, benzos, and gaseous anesthetics suppress respiration

Front 144

Etomidate MOA:

Back 144

**Enhances GABA-A-mediated chloride conductance to hyperpolarize neurons

Front 145

Effects:

Back 145

**Minimal effect on BP or respiration
**Causes myoclonic movements (=not epilepsy) which can be prevented by pretreatment w/ BENZO's
**Can cause adrenal suppression w/ decrease in plasma cortisol

Front 146

Opiates

Back 146

BP --> no change

Decreased respirations

Front 147

Ketamine

Back 147

Increased BP

NC in respirations

Front 148

Etomidate

Back 148

BP and respirations no change

Front 149

Thiopental

Back 149

DECREASED BP and respirations

Front 150

What does halothane predispose you to?

Back 150

**Epi-induced cardiac arrhythmias

**Treat w/ a B-blocker

Front 151

One more time...what does NO NOT cause?

Back 151

**NO produces analgesia, amnesia, and mental confusion but NOT anesthesia!