Pharm I Test Iii (Inhalation, Nmb, Barbs, Benzos)

Front 1

Mecamylamine (Inversine)

Back 1

Ganglionic Blocker Crosses CNS easily, and acts to block nicotinic receptors in the brain, as well as at the ganglia. In the brain, this blockade tends to decrease dopamine and norepinephrine release from specific neurons as well as modulating neuroendocrine responses.
Tourette’s syndrome

Front 2

ADVERSE REACTIONS OF MECAMYLAMINE (INVERSINE)

Back 2

N/V, anorexia, constipation, mydriasis, syncope, weakness and fatigue, among others.

Front 3

GANGLIONIC BLOCKERS

Back 3

*only nicotinic ganglionic blockers can completely block the transmission through ganglia.
Depolarizing type blockers initially stimulate the ganglia like ACh then block due to persistent depolarization

Front 4

HEXAMETHONIUM

Back 4

GANGLIONIC BLOCKER
doesn't stimulate the receptor, it acts by competing for ACh binding site only (non depolarizing)

Front 5

TRIMETHAPHAN

Back 5

mechanistically acts like curare does at the NMJ, competitively blocking ACh from getting to receptors on the ganglia

Front 6

Symptoms of ganglionic blockade

Back 6

: increased bloodflow to the skin (warm and pink), decreased sweating, inhibited lacrimation and salivation, mydriasis and cycloplegia, decreased GI tone and motility, hypotension, urinary retention, constipation, and hypoglycemia.
These symptoms are due to blockade of the predominant tone on each tissue, allowing the non-predominant autonomic effects to override and be expressed.

Front 7

Non-Depolarizing blockers

Back 7

Agents in this class act as (somewhat) competitive antagonists of ACh at the neuromuscular junction. This blocks the ability of ACh to stimulate the muscle at the motor end plate, resulting in muscle weakness (at lower doses) or paralysis (at higher doses).

Front 8

Succinylcholine

Back 8

Can cause transient sinus bradycardia accompanied by hypotension, cardiac arrhythmias, tachycardia, and possible cardiac arrest by increased vagal stimulation.
Can cause also cause hyperkalemia.
Pre-treatment with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias.
Also possesses significant histamine-releasing properties. Rxns at mast cells.

Front 9

potentiate neuromuscular blockade with the nondepolarizing agents.

Back 9

lithium, calcium salts, magnesium salts, inhalational anesthetics, local anesthetics, certain antibiotics, quinidine, procainamide, lidocaine, and others

Front 10

histamine-releasing properties

Back 10

atracurium, cisatracurium, and succinylcholine) have precautions for use in asthma or cardiac disease, and may be associated with increased cardiopulmonary adverse effects including flushing, hypotension, sinus tachycardia, urticaria, wheezing, and bronchospasm.

Front 11

Sugammadex (Bridion???)

Back 11

designed as a reversal agent for Rocuronium
also works fairly well with vecuronium and pancuronium
structure is a complex cyclodextrin ‘cage’ with high lipophilicity that binds the neuromuscular blocker and allows removal.

Front 12

AROMATIC GROUP

Back 12

lipophillic

Front 13

WHY ALKALINIZE A LOCAL ANESTHETIC PRIOR TO INJECTION?

Back 13

it will increase the onset time by increasing the pH of the solution, therefore increasing the number of unionized particles that will be able to cross the membranes better.

Front 14

DIAMINE

Back 14

two ionizable groups on the molecule each group has a different pka, you need to worry about the highest pka

Front 15

AMINE

Back 15

hydrophillic group

Front 16

INCREASING LIPID SOLUBILITY

Back 16

decreases onset time and increases duration

Front 17

LOCAL ANESTHETIC MOA

Back 17

All agents act to decrease the permeability of the membrane to sodium ions.
These agents bind to sites in the Na+ channel of the voltage gated Na+ channels, thus inhibiting Na+ inflow during depolarization.
Low conc. of LA's decreases both the rate of rise and the height of the action potential. Higher concentrations can abolish it totally.
Firing threshold is also increased, and total propagation time is increased.
In myelinated fibers, this occurs only at the Nodes of Ranvier.

Front 18

AT WHAT STAGE OF THE SODIUM CHANNELS DO LA BIND?

Back 18

The trick with the local anesthetics is to get them into the closed inactivated state and block them
. In the inactivated stage the beta subunit turns and plugs the channel causing it to become inactivated.

Front 19

NA CHANNELS MADE UP OF?

Back 19

Sodium channel made up of an alpha subunit comprised of 4 additional subunits, and additional beta subunits.
The alpha subunit contains the sodium pore
Local anesthetics bind to the closed, inactivated channel stabilizing it in that form.

Front 20

WHICH NERVES ARE AFFECTED FIRST IN LA?

Back 20

Small diameter nerves are affected first, then larger diameter nerves due to the number of channels to be blocked (greater in large fibers).
More rapidly stimulated fibers are also blocked first due to more frequent opening of Na+ channels, and the ability of the LA's to get into channel to bind (sensory fibers tend to be triggered more frequently than motor fibers, and so tend to be blocked first).
Usually, autonomic fibers are affected first, then sensory, then motor.

Front 21

LA RECOVERY

Back 21

Recovery is in reverse order
where motor neurons will come back first, then sensory, then autonomic.

Front 22

ONSET OF ANESTHESIA FASTEST WITH WHICH LA?

Back 22

lidocaine and prilocaine

Front 23

ONSET OF ANESTHESIA IS SLOWEST WITH WHICH LA?

Back 23

procaine and tetracaine

Front 24

SHORTEST DURATION OF ACTION OF THE LA?

Back 24

procaine and chloroprocaine (15-30 min)

Front 25

INTERMEDIATE DURATION OF ACTION OF LA'S?

Back 25

lidocaine and prilocaine 30-90 min

Front 26

LONG DURATION OF ACTION OF LA

Back 26

tetracaine 2-3 hours

Front 27

Local hypersensitivity reactions more common with

Back 27

ester type

Front 28

LA'S THAT CAN CAUSE METHEMOGLOBINEMIA

Back 28

oxidize hemoglobin
prilocaine, benzocaine, lidocaine, cetacaine

Front 29

Benzocaine (Oragel) (many other tradenames)

Back 29

Poorly water soluble, so topical use only.
Excessive absorption may lead to methemoglobinemia.
pKa ~ 3.5 sunburn after sunburn.

Front 30

Procaine (Novocaine)

Back 30

First synthetic local anesthetic.
Slower onset with short duration and weak potency.
Fairly low systemic toxicity.
Best for infiltration and nerve block.
Use superceded by better agents (amides).

Front 31

Chloroprocaine (Nesacaine)

Back 31

Rapid onset, short duration.
Low systemic toxicity.
Used in high concentration solutions (since toxicity is low).
For infiltration, nerve block, IV and epidural use.

Front 32

Tetracaine (Pontocaine)

Back 32

Ten times more potent than procaine, but also ten times more toxic.
Long duration with slow onset.
Major use is in spinal anesthesia, where the barriers decrease diffusion and decrease toxicity risk.
Also effective topically, but absorption across mucous membranes limits its use.

Front 33

Cocaine

Back 33

C-II controlled substance derived from the leaves of the coca plant.
Too toxic for uses other than topically. (cardiac toxicities)
Unique agent that has potent vasoconstrictive activity and addiction liability in addition to it’s LA effect.
Used topically on mucous membranes, such as nasal cavities or oropharyngeal cavities prior to surgery, and packed post-op to decrease bleeding and pain.

Front 34

Cetacaine (Cetylite)

Back 34

Topical agent for local skin disorders and is used on various mucous membranes (except the eye).
Cetacaine is a mixture of Benzocaine, Tetracaine, and Butyl Aminobenzoate used topically, rectally or as a spray to inhibit the gag reflex (during bronchoscope exam, etc).

Front 35

Lidocaine (Xylocaine)

Back 35

Most commonly used local anesthetic.
Rapid onset with intermediate duration.
Causes vasodilation, so many formulations include EPI.
Useful for most types of application

Front 36

Prilocaine (Citanest)

Back 36

Similar to lidocaine in properties, but less vasodilation.
Rapid onset, intermediate duration.
Least toxic of the amides, but can still cause methemoglobinemia.

Front 37

MORE LIKELY TO CAUSE METHEMOGLOBINEMIA

Back 37

amides

Front 38

Mepivacaine (Carbocaine)

Back 38

Uses Similar to lidocaine.
Used for infiltration, nerve block, epidural.
Not effective topically.
Not used in obstetrics because biotransformation in fetus is prolonged.
Racemic mixture, structurally similar to Bupivacaine and Ropivacaine

Front 39

Bupivacaine (Marcaine)

Back 39

Long duration, with slower onset.
High potency.
More toxic than Lidocaine (cardiotoxic).
Used for infiltration nerve block, epidural and spinal anesthesia.
Most likely to cause adverse effects.

Front 40

Articaine (Septocaine)

Back 40

Only available in U.S. in combination with EPI.
Similar to Lidocaine - short duration, rapid onset.
Used for dental and periodontal procedures.
Low systemic toxicity due to rapid breakdown (it has an ester group in addition to an amide).
Only used with epi b/c the drug is removed from the area so quickly. Articaine is BOTH an ester and an amide.

Front 41

Ropivacaine (Naropin)

Back 41

Long duration, similar to Bupivacaine, but less cardiotoxic.
Actually an S-isomer, whereas the structurally similar bupivacaine is racemic, with the more cardiotoxic R-isomer.
Less lipid soluble, and more rapidly metabolized than Bupivacaine.
Uses are similar to Bupivacaine (infiltration, nerve block, epidural, spinal).

Front 42

Pramoxine (Proctofoam)

Back 42

Topical agent for relief of hemorrhoids, rectal pain and itching of skin disorders (pruritus).
Weak potency (will not totally abolish gag reflex).
Mixed in combination with many products (ex. Hydrocortisone, calamine).

Front 43

SHIFTS OXYGEN DISSOCIATION CURVE TO THE LEFT

Back 43

decreased PaCO2, decreased temp, increased pH, decreased 2,3-dPG, fetal Hgb, CO, methemoglobinemia

Front 44

SHIFTS OXYGEN DISSOCIATION CURVE TO THE RIGHT

Back 44

increased PaCO2, increased temp, decreased pH, increased 2,3-dPG

Front 45

HYPOXIC EFFECTS

Back 45

Increased ventilation
sympathetic stimulation (tachycardia, but decreased peripheral vascular resistance – local effect)
pulmonary vasoconstriction to optimize V/Q
impaired CNS function
anerobic metabolism, increased lactic acid, decreased ionic gradients – increased cell H+, Ca++, Na+  cell death

Front 46

Hypocarbia (resp alkalosis)

Back 46

constrict cerebral vessels, and decrease brain size somewhat – used in neurosurgery
cardiac surgery uses to decrease air (insoluble N2) around heart
not normally used to increase respiration

Front 47

Nitric Oxide

Back 47

use can cause large pulmonary vasodilation with minimal systemic effects (binds and inactivates oxyhemoglobin)

Front 48

Paraldehyde

Back 48

, control DT’s in alcohol therapy

Front 49

GABA RECEPTOR COMPLEX

Back 49

pentameter, 5 proteins, chloride channel, benzos, steroids, barbs, picrotoxin

Front 50

Normal sleep characterized by at least 2 phases:

Back 50

Slow wave sleep (SWS) in which the EEG shows mainly high-voltage synchronous activity
Rapid eye movement sleep (REM) in which skeletal muscles are relaxed (inhibited) and the eyes move back and forth rapidly. Accounts for ~ 25% of sleep.

Front 51

Hypnotic sleep differs

Back 51

SWS patterns are altered and shortened
REM sleep is depressed
Total sleep time is prolonged

Front 52

The more lipid soluble agents (higher partition coefficient) of barbituates

Back 52

usually have the more rapid onset and shorter duration
Short duration because of redistribution.

Front 53

BARBS MOA

Back 53

Bind to GABAA receptor complex
Location is different from benzodiazepine binding site
Decreases the dissociation rate of GABA from its binding site, thus increasing the duration of action of GABA at the receptor, and increasing chloride conductance. (altering the affinity)
While Barbiturates have been reported to be able to mimic the action of GABA at the GABAA receptor, this is minimal, and major effects require GABA.
Also inhibits excitatory glutamate AMPA receptors

Front 54

Barbiturates
Chemistry and SAR

Back 54

Barbituric acid, which has no sedative powers is the parent compound
Exists in keto and enol forms (tautomers)
Addition of various functional groups onto position 5 alters sedative/hypnotic properties
Replacement of C-2 oxygen with sulfur results in the thiobarbiturates (greater lipid solubility)
Addition of a phenyl group at C-5 enhances anticonvulsant activity (ex.-Phenobarbital)
Addition of a methyl group to the ring N atom shortens duration of action (ex.- Methohexital

Front 55

LONG DURATION BARBS

Back 55

Phenobarbital (Luminal) (epileptic disorders)

Front 56

INTERMEDIATE DURATION BARBS

Back 56

Pentobarbital (Nembutal)
Secobarbital (Seconal)

Front 57

SHORT DURATION BARBS

Back 57

Methohexital (Brevital)
Thiopental (Pentothal)

Front 58

IONIZATION OF BARBS

Back 58

Barbiturates are weak acids
Usually packaged as sodium salt, which is the basic form
High pH of solution makes itself bacteriostatic
Stability of solutions limited to a couple weeks after opened and exposed to air due to precipitation of acid form caused by CO2 in air altering pH of solution

Front 59

BARBS METABOLISM

Back 59

. Potent enzyme inducers, induce their own metabolism.

Front 60

Barbiturates
Metabolism

Back 60

Most metabolized to a large extent
Primary metabolic pathway is hydroxylation to inactive metabolites
Some only slowly metabolized (ex.- phenobarbital, t1/2 = 86 hrs)
N-glucosylation also occurs (to a larger extent in oriental populations).
Potent inducers of the hepatic microsomal enzyme system.
Results in an increase metabolic rate of barbiturates as well as other drugs normally metabolized by this system (ie.- oral anticoagulants, phenytoin, TCA’s, etc.)
PHASE I REACTIONS

Front 61

Barbiturates
Use in Pregnancy

Back 61

Fetal blood levels usually well under maternal levels, but placental transfer does occur
Fetal elimination much slower than mother

Front 62

BARBS PRIMARY USES

Back 62

Therapeutic/diagnostic aids in psychiatry
Reduction of cerebral edema following surgery, head injury or cerebral ischema.
Antiepileptic use.

Front 63

Thiopental (Pentothal)

Back 63

-ultra short acting induction 10-15secs, metabolized P450, 1/2 life 6 hours, redistribution, repeated admin can lead to increased duration of action, lowers pain threshold thus increasing sensitivity to pain, very poor skeletal muscle relaxant effects, depresses myocardium and relaxes vascualr smooth muscle--> so decreases BP

Front 64

Methohexital (Brevital)

Back 64

Similar to thiopental, but three times as potent
metabolized faster (due to less lipid solubility) mainly via P-450 oxidation
loss of effect still mainly due to re-distribution
recovery is faster than thiopental with multiple doses

Front 65

INSOMNIA AGENTS

Back 65

Zaleplon (Sonata) – potency = 1
Zolpidem (Ambien) – potency = 1
Eszopiclone (Lunesta) – potency = 7X

similar to Benzodiazepines in action on GABAA receptor complex
bind to specific GABA receptor (alpha-1) subpopulations better and have greater effects on sleep (alpha-2 agonists anti-anxiety and anticonvulsant effects)
all have relatively short half-lives (< 8 hours) thus do not interfere with next day’s activities

Front 66

Propofol (Diprivan)

Back 66

Acts by interaction with GABAA receptor, decreasing the rate of GABA dissociation from the receptor.
Fairly selective with few perceivable effects at other receptors
Very low water solubility, so prepared in emulsion vehicle.
Vehicle contains soybean oil and egg lecithin
use care in patients with egg allergies
Reactions rare – due to proteins in egg white, not yolk
Diprivan contains disodium edenate as preservative (EDTA)
Generic formulation contains sodium metabisulfite and care should be observed in patients with sulfite allergies

Front 67

Fospropofol (Lusedra)

Back 67

propofol prodrug recently approved by the FDA which is cleaved to propofol on administration by endothelial alkaline phosphatases
Water soluble with little or no pain on injection
This will take a little longer than propofol

Front 68

PROPOFOL ANESTHESIA

Back 68

Induction in 15-30 seconds, but must be given more slowly than Thiopental due to vessel irritation at injection site.
To minimize pain on injection larger veins should be used
Pre-administration of 1% lidocaine also used to minimize pain
co-mixing with lidocaine may increase risk of pulmonary embolism due to breaking emulsion and the formation of soybean oil droplets
Awakening time faster than with other IV induction agents
Less occurrance of hang-over, in fact many reports of elevated post-op mood
Rapidly distributes to brain (high blood flow).
Also possesses antiemetic, antipruritic, and anticonvulsant actions.

Front 69

PROPOFOL METABOLISM

Back 69

Termination of anesthesia due to redistribution to fatty tissues and metabolism.
Hepatic and extrahepatic P-450 oxidative metabolism and phase II glucuronide and sulfate conjugation
High levels of lung cell uptake but released mainly unchanged
Duration of effect typically 5-10 minutes.
Half life of 2-3 hours, so it does not accumulate as much as Thiopental, and can be used for maintenance by continuous infusion.
Easily crosses placenta to fetus, but is rapidly metabolized by fetus.
Liver and renal disease do not appear to appreciably affect elimination.
Highly protein bound (95% - 99%)

Front 70

PROPOFOL EFFECT ON VITALS

Back 70

Does not increase pain sensitivity.
Blood pressure is decreased due to decreased cardiac output and vascular resistance.
Blood pressure is decreased more than seen with Thiopental by inhibition of sympathetic vasoconstriction
Increased risk of bradycardia-related death, due to inhibition of cardiac sarcolemmal calcium release
Depresses ventilation, with apnea reported in approximately 30% of patients.
This effect may be enhanced by opioids.
Does not trigger malignant hyperthermic crisis.

Front 71

PROPOVEN

Back 71

Propoven (different vehicle formulation – more lipids, but no preservative, so short vial life) approved by FDA

Front 72

PROPOFOL SIDE EFFECTS

Back 72

bradycardia, pain, hypertriglyceridemia all attributed to lipid emulsion vehicle
allergic reactions
lactic acidosis (more common with long term infusion)

Front 73

Etomidate (Amidate)

Back 73

Structure unlike any other anesthetics.
Mechanism believed to be via GABA-activity enhancement like barbiturates and benzodiazepines.
Exact site on GABAA receptors still not clear
More selective for GABAA receptors than the barbiturates
A weak base, it is 99% unionized at physiological pH
Mixed with propylene glycol for injection.
Approximately 75% protein bound
Vd is large (tissue distribution)
Reaches peak brain concentration within one minute following IV administration
Rapid recovery due to rapid lipid redistribution and partly due to metabolism
Metabolized rapidly mainly via hydrolysis of side chain ester group by plasma esterases and hepatic P-450 system

Front 74

ETOMIDATE EFFECTS ON VITALS

Back 74

Induction as rapid as Thiopental, with emergence in 5-10 minutes.
Elimination half-life of 2-5 hours
Minimal cardiovascular effects.
Better choice than barbiturates or propofol for patients with cardiac instabilities
Less ventilatory depression than with barbiturates or propofol
Occasional apnea on rapid administration
High incidence of myoclonus on rapid IV induction (>80%). If administered really fast.
Depresses steroid (cortisol) synthesis in adrenals, so is not recommended for long term use.
Increased risk in sepsis and hemmorrhage.

Front 75

Dexmedetomidine (Precedex)

Back 75

a novel agent for the control of stress, anxiety and pain
classed as an alpha-2 agonist
usually used in combination with agents such as propofol, opioids, and benzodiazepines
when used alone, it produces sedation with the ability to rouse the patient, allowing the medical staff to communicate with the patient if needed
negative feedback alpha 2 receptor

Front 76

Dexmedetomidine (Precedex)
METABOLISM

Back 76

Vd ~ 118 liters, t1/2 ~ 2 hrs, Cl ~ 39 L/hr
Approximately 95% protein bound
metabolism almost complete mainly via glucuronidation and P-450 hydroxylation
dosage adjustment may be required in hepatic disease
pharmacokinetics unaltered by age
administered via continuous IV infusion

Front 77

Midazolam (Versed)

Back 77

Usually used as an adjunct, but it can be used for induction (approximately 60 seconds) and maintenance.
Duration of effects approximately 15 minutes.
Usually used with opioid (i.e. fentanyl) for longer durations. Synergistic and pain relief
Minimal cardiovascular effects.
Good amnesic.
95% plasma protein bound (similar to other benzodiazepines)

Front 78

Ketamine (Ketalar)

Back 78

Similar to PCP (Phencyclidine).
Can be used IV or IM.
Rapid induction with IV duration of approximately 15 minutes.
Stimulates the cardiovascular system: increases heart rate, cardiac output, and blood pressure.
Good analgesic and amnesic.
Blocks glutamate excitatory NMDA receptors in CNS.
Highly lipid soluble but minimal protein binding
Triggers catalepsy (dissociative anesthesia), which is the appearance of being awake, even though they do not respond.
Recovery phase characterized by CNS stimulation, so keep patient in quiet area.
NMDA the only ones with ligand and gated receptors.

Front 79

Ketamine (Ketalar)
METABOLISM

Back 79

N-demethylated (P450) to Norketamine, which has approximately 25% of Ketamine’s activity
Further metabolized by hydroxylation (P450) to hydroxynorketamine (inactive)
Glucuronated and excreted in urine.

Front 80

Ketamine (Ketalar)
USES

Back 80

Used for induction and maintenance.
Potentially very dangerous, especially if unprepared and poorly trained.
Dangers presented with these are based on the potential of overdosing the patient and the irrevocable nature of IV administration.
Comes out of IM quicker than other drugs that are given IV

Front 81

Benzodiazepines
Pharmacokinetics

Back 81

Varying half-lives ranging from 1 hour for midazolam to more than 24 hours for diazepam.
Many metabolized via microsomal N-demethylation (diazepam), but some (oxazepam) eliminated rapidly primarily via glucuronide conjugation.
Midazolam is metabolized rapidly mainly via microsomal hydroxylation.
Due to liver metabolism, half-lives can be greatly altered in patients with liver disease or patients taking other drugs which induce or inhibit metabolism.
Diazepam not only has a long parent half-life, but is converted into several active metabolites which also increase the period of clinical effect.
Benzos are potent enzyme inducers. Decrease the half life.

Front 82

Benzodiazepines
Mechanism of Action

Back 82

Act on specific receptor sites located at the interface of the α and γ subunits of the GABA receptor in the CNS.
Enhance the ability of GABA to bind to its receptor, thus increasing the ability of the chloride ionophore to admit more chloride ions into the cell, resulting in hyperpolarization which makes them more resistant to excitation.
Receptors found almost exclusively on post-synaptic regions in the CNS, which explains their minimal effects in other areas of the body (except effects caused via CNS control).
Receptor density greatest in cerebal cortex and areas associated with memory formations.
Memory effects (amnesia) seen after use.
GABA either on pre or post synaptic neurons. Hippocampal region responsible for memory formation  lower part of the frontal cortex. NT for memory formation ACh. (usually cholinergic)
Ionophoric channels need to bind at two different places to open the channel.

Front 83

Benzodiazepines
Effects on other tissues

Back 83

Caused by action in the CNS
Mild cardiovascular effects, which are normally seen as a minor decrease in systemic blood pressure and vascular resistance.
Heart rate may decrease or increase somewhat, probably reflexively.
Transient apnea is a potential problem, especially with rapid IV infusion of diazepam, and respiratory support should be available.
Induces relaxation of spastic skeletal muscle activity via central inhibition.

Front 84

PRIMARY EXCITATORY AND INHIBITORY RECEPORS IN THE SPINAL CORD

Back 84

glycine – inhibitory, and aspartic acid – excitatory in the spinal cord)

Front 85

Benzodiazepines
Miscellaneous

Back 85

Crosses placenta well, and leads to fetal depression.
Not used as anesthetics, but adjunct to balanced anesthesia.
Use allows decrease in dose of other anesthetics.
Abuse potential relatively high, and long-acting agents (diazepam) can lead to true physical dependance.

Front 86

BENZOS THAT READILY LOOK LIKE BENZOS

Back 86

Chlordiazepoxide (Librium) - (oral)
Clorazepate (Tranxene) - (oral)

Front 87

Actions (Ethanol

Back 87

Locally cause dehydration of cell protoplasm (astringent).
Cooling effect on skin due to rapid evaporation.
Increases cutaneous blood flow when applied topically, and is used as a counterirritant and rubifacient.
This effect also partly responsible for the usefullness of alcohol rubs to lower body temperature.
Injections near nerves blocks conduction by decreasing Na+ and K+ conductance (high doses required).
Bactericidal effect by disruption of cell membranes.
Potent CNS depressant .

Front 88

CNS Actions (Ethanol)

Back 88

Decreases mental and physical abilities by a “top down” CNS depression, similar to other general anesthetics.
While effects are well correlated to plasma concentration, the effects are greatest of the “up-swing” of the plasma concentration curve.
Small therapeutic window as a general anesthetic, and so is not used for this purpose.
Raises pain threshold and causes euphoria.
Depresses medullary sensing of plasma CO2 levels, and thus may affect respiration.
Anticonvulsant activity, but only at concentrations that depress other CNS functions.

Front 89

Other Actions (Ethanol)
Cardiovascular

Back 89

Relatively minor in moderate amounts, however cutaneous vasodilation via central mechanism common.
Central temperature control mechanisms depressed in high doses, which causes a strong loss of body heat, and can be potentially fatal in cold weather.
High plasma concentration causes cardiac depression by both central and direct mechanisms

Front 90

Other Actions (Ethanol)
Skeletal Muscle

Back 90

Small doses increase total work ability via central mechanisms, but larger doses decrease work and are also damaging to the muscle directly.
Similar to rhabomylysis with large doses. Real hard core alcoholics

Front 91

Other Actions (Ethanol)
GI Tract

Back 91

Increases gastric blood flow and secretions (up to approx. 20% conc.) increases hunger.
High concentrations cause severe gastric irritation and erosion.
Vomiting due to large ingestions due to local irritant effect.

Front 92

Other Actions (Ethanol)
LIVER

Back 92

Increases synthesis of fat in liver, leading to “fatty liver” seen in alcoholics.
Cirrhosis seen in long-term abuse. Hallmark of liver cancer.
Ethanol helps solubility of lipid soluble drugs. Irritation also alters how compounds are dissolved.

Front 93

ETHANOL METABOLISM

Back 93

Ethanol is converted via alcohol dehydrogenase (a liver enzyme that contains zinc, and requires NAD as a cofactor) to acetaldehyde.
Acetaldehyde converted by another liver enzyme, aldehyde dehydrogenase, to acetic acid, which can then be used as an energy source.
Methanol converted via same enzymes to formaldehyde then formic acid.
Formaldehyde damages retinal cells and leads to blindness (15 ml dose of methanol).
Formic acid can not be utilized by body, and build-up leads to acidosis, which can be fatal.
Treatment of methanol toxicity with large doses of ethanol to ‘tie-up’ metabolizing enzymes until excreted in urine.
Newer agent (fomepizole, Antizol) is an inhibitor of alcohol dehydrogenase and may replace ethanol use.

Front 94

PANCURONIUM
METABOLISM

Back 94

-primarily renal, some biliary, may accumulate in renal failure
amino-steroidal
long acting

Front 95

ROC AND VEC
METABOLISM

Back 95

-primarily biliary, some renal
Roc no active metabolites
Vec metabolite 3-desacetyl has 1/2 the activity
both are amino steroidal
intermediate acting

Front 96

ATRACURIUM AND CISATRACURIUM
METABOLISM

Back 96

ester hydrolysis and Hoffman elimination
Laudanosine metabolite has CNS excitation
may accumulate in renal/hepatic failure

Front 97

INTERACTION WITH NMB
ANTIARRHYTHMIC
(QUINIDINE, PROCAINAMIDE, LIDOCAINE)

Back 97

ENHANCED NMB ACTIVITY
both non-dep and dep

Front 98

INTERACTION WITH NMB
ANTIBIOTIC

Back 98

prolonged resp depression, excessive blockade
both

Front 99

INTERACTION WITH NMB
ANTIEPILEPTICS
(CARBAMAZEPINE, FOSPHENYTOIN, PHENYTOIN)

Back 99

more rapid recovery time following NMB admin
NON DEP
may need higher/more freq doses of NMB agent

Front 100

INTERACTION WITH NMB
APROTININ
(TRASYLOL, BAYER)

Back 100

prolonged NMB activity
DEPOLARIZER
use lowest dose possible to achieve adequate blockade

Front 101

INTERACTION WITH NMB
AZATHIOPRINE

Back 101

DEP- enhanced NMB activity
NON DEP- reversal of NMB activity

Front 102

INTERACTION WITH NMB
CALCIUM CHANNEL BLOCKERS

Back 102

BOTH
enhanced NMB activity
use lowest possible dose

Front 103

INTERACTION WITH NMB
CORTICOSTEROIDS

Back 103

-NON DEP- muscle weakness, decreased NMB activity
DEP- prolonged NMB activity

Front 104

INTERACTION WITH NMB
CYCLOPHOSPHAMIDE

Back 104

DEP- enhanced or prolonged sux induced apnea

Front 105

INTERACTION WITH NMB
DIGOXIN

Back 105

BOTH- risk of cardiac arrhythmias
specifically with sux

Front 106

INTERACTION WITH NMB
INHALATION ANESTHETICS
(ENFLURANE, ISOFLURANE)

Back 106

BOTH- enhanced NMB activity

Front 107

INTERACTION WITH NMB
LITHIUM

Back 107

BOTH- prolonged NMB activity

Front 108

INTERACTION WITH NMB
MAG SALTS

Back 108

-BOTH- enhanced NMB activity

Front 109

INTERACTION WITH NMB
REGLAN

Back 109

BOTH- prolonged NMB activity
specifically with mivacurium

Front 110

INTERACTION WITH NMB
ORAL CONTRACEPTIVES

Back 110

-BOTH- prolonged NMB activity especially sux

Front 111

INTERACTION WITH NMB
OXYTOCIN

Back 111

BOTH- enhanced NMB activity

Front 112

INTERACTION WITH NMB
TACRINE

Back 112

DEP- prolonged NMB activity

Front 113

INTERACTION WITH NMB
TERBUTALINE

Back 113

DEP- enhanced NMB activity

Front 114

INTERACTION WITH NMB
TRICYCLIC ANTIDEPRESSENTS

Back 114

NON DEP- risk of ventricular arrhythmias

Front 115

POTENTIATION OF NMB

Back 115

NEURO DISEASE- myasthenia gravis, Eaton-Lambert syndrome
ELECTROLYTE-hypermag, hyponatremia, hypokalemia, hypocalcemia
ACIDOSIS- (conditions that prolong metabolism- atypical plasma cholinesterase, renal and hepatic disease)

Front 116

ANTAGONISM OF NMB

Back 116

NEURO DISEASE- hemiparesis or paraparesis, demyelinating lesions, peripheral neuropathies
OTHER- hypercalcemia, alkalosis, burn injury

Front 117

INCREASED RISK FOR CARDIAC ARRHYTHMIAS OR CARDIAC ARREST WITH SUX

Back 117

ACUTE PHASE OF INJURY FOLLOWING- major burns, multiple trauma, spinal cord injury, extensive denervation of skeletal muscle, upper motor neuron injury
OTHER- hyperkalemia, dig toxicity