Drug Abuse/ Dependence, Opiods, Ethanol, And Benzodiazepine, And Iv Anesthetics

Front 1

Naltrexone

Back 1

Long-lasting Opiod Antagonist.
Half-life = 48-72 hrs

Effective ORALLY or IM (extended release form)

Treats overdose of opiods. More longterm in duration than Naloxone.

Also used to reduce cravings for various addictons (alcohol smoking, opiods). Blocks most of the rewarding effects of ethanol, and may reduce craving in recovering alcoholics.

SE: Malaise (not popular because of this). Malaise caused by the antagonist blocking opoid receptors for reward centers.

Contraindications: Should not be given with disulfiram since both drugs are toxic to the liver.

Front 2

Naloxone

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Short Acting Opiod receptor ACTIVE Antagonist

NOT effective orally due to 1st pass effect.

Used to treat opoid overdose. May require repeated dosing in OD due to short halflife.

Intravenous injection of naloxone (Narcan) dramatically reverses coma due to opioid overdose but not other CNS depressants. (It is a competitive antagonist specifically at mu receptors.)

Provide respiratory support, maintain airway after giving until effect.

NOTE: Due to its short half-life, naloxone must be readministered every 2-4 h, as needed

SE: may cause HOTN and pulmonary edema at high doses d/t active effects at other receptors.

Front 3

Flumazenil

Back 3

Benzo antagonist to reduce the respiratory effects of benzo's.

Blocks actions of BDZ's, eszopiclone, zaleplon, and zolpidem.

Can precipitate BDZ w/d.

Short 1/2 life may require multiple dosing to reverse effects of long-acting BDZ.

Reverses sedative effects of BDZ's but reversal of respiratory depression is predictable.

Front 4

Methadone

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A long acting, strong opoid agonist.
4 x the potency of morphine when given orally. (same IV)

It's orally active and lasts longer than morphine or heroin.

USE: Heroin addiction tx: Has a cross tolerance effect with heroin addicts...can be used to pvt abrupt withdrawals with heroin addicts.

Methadone has an active metabolite (LAAM)..this is what gives it it's long duration.

Front 5

Diazepam

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Long-acting benzodiazepine (t1/2 > 24hrs). (low potency, long halflife).

ONSET: Rapid

Has a cross-tolerance effect with Ethanol.

Can be used to prevent abrupt withdrawals from alcohol. Can also be used to treat alcohol withdrawal.

Is metabolized by CYP450's into Oxazepam, which is then glucuronidated and excreted.

Complete and rapid oral absorption
Very high Vd
High tissue binding, especially to fat
Highly bound to plasma proteins

SE: Profound CNS depression. Venous irritation due to lipid solubility.

Teacher says DOA depends on metabolism and that the drug is NOT redistributed (distribution t1/2 = 30-66 min while Elimination t 1/2 = 24-57 hrs).

Front 6

Buprenorphine

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A partial opiod agonist.

Can be used to pvt abrupt withdrawals from Heroin. Avoid use with pts strongly addicted to heroin b/c can precipitate withdrawals (especially with increased doses.).

Partial agonist at mu receptors

Partial agonist at kappa3 receptors

Antagonist at kappa1 receptors

Lower efficacy analgesic than morphine.

NOTE: Buprenorphine dissociates slowly from its receptors; possibly less physical dependence and toxic effects are less easily reversed by naloxone. Odd pharmacodynamics…sits on opiod receptor for a long time and doesn’t leave. Harder to reverse with naloxone. So respiratory depression from OD of buprenophine is harder to overcome.

Physical dependence may occur more slowly due to prolonged action at the receptor.

Conversely to more diffcult reversal of resp depression, this drug doesn't really get resp depr that much anyway b/c it has a ceiling effect, where increased doses do not cause increased effect. (increased doses will only precipitate withdrawals in opiod addicted pts.).

Front 7

Acamprosate

Back 7

Reduces drug craving for Alcohol...prevents relapse.

MECHANISM OF ACTION:
1) Weak glutamate NMDA-receptor antagonist
2) Weak GABA-a receptor agonist (likely a partial agonist at both sites)
3) Also reduces Glutamate release.

CONTRAINDICATIONS: Pts with severe renal impairment.

Front 8

Baclofen

Back 8

High-Affinity GABAb-receptor agonist

Used to reduce drug craving

Front 9

Modafinil

Back 9

Stimulant drug used to treat cocaine addiction.

Reduces drug craving.

Front 10

Clonidine

Back 10

Alpha2 Agonist

Used to decrease SNS effects of withdrawal from drugs.

Used to reduce drug cravings.

Front 11

Nicotine

Back 11

Used to reduce drug cravings for smoking.

Front 12

Alprazolam

Back 12

This is Xanax.
The only Benzodiazepine that is used as an antidepressant.

USE: Long-term tx of anxiety. (Panic Disorders, Antidepressant).

HIgh Potency
Short Half-life

Front 13

Midazolam

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ULTRA-Short Acting Benzodiazepine.

Used in surgical anesthesia. (Can cause respiratory depression..must have airway control.) More potent and faster in onset than Lorazepam or diazepam.

Hepatic clearance is much faster than diazepam or lorazepam, hence it has a faster recovery

Can be given IV, Oral, IM, or rectal).

Oral form: 50% lost to 1st pass metabolism
IV form: Has a diazepine ring that is open at a pH of 4.0...making it water soluble in solution. At physiological pH, the diazepine ring closes and it becomes lipid soluble...this causes it to be RAPIDLY REDISTRIBUTED.
IM: 80-100% remains bioavaliable but slower kinetics.
Very high Vd
High tissue binding, especially to fat
Highly bound to plasma proteins

NOTE: Redistribution of lipid soluble BDZs from CNS to peripheral tissues accounts for short DOA after single dose

CNS Effects: Decreased CBF and CMRo2 due to sedation. This decreases ICP.

CV Effects: Minimal

Respiratory Effects: Slight respiratory depression. ..have airway equipment.

Front 14

Lorazepam

Back 14

Benzodiazepine with no metabolites...therefore, fewer potential drug interactions.

Drug of Choice for status epilepticus. (shorter duration than diazepam).
Slower onset of action (so not used for induction).

Glucuronidated and excreted. (e 1/2 is 11-22hrs while distribution 1/2 = 3-10 min).

Complete and rapid oral absorption
Very high Vd
High tissue binding, especially to fat
Highly bound to plasma proteins

NOTE: Redistribution of lipid soluble BDZs from CNS to peripheral tissues accounts for short DOA after single dose

Front 15

Eszopiclone

Back 15

Cyclopyrrolone: A "non-BDZ" Sedative/ hypnotic - Intermediate Acting

Rapid Onset. Mean 1/2 life = 6 hrs.
High Potency, Short Half-life

USE: Short-term tx of insomnia.

SE: Somnolence, migraine; possible abuse liability & w/d upon D/C.

Front 16

Zolpidem

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"Non-BDZ" sedative/ hypnotic

Short-term tx of insomnia

SE: Somnolence, migraine; possible abuse liability & w/d upon d/c. . Rarely severe anaphylactic reactions (angioedema).

Avaliable in biphasic controlled release formulation

Front 17

Ramelteon

Back 17

MT1, MT2 Melatonin Receptor Agonist

USE: Short term insomnia and Jet lag

BENEFITS: No rebound insomnia. No abuse liability.

Rarely severe anaphylactic reactions (angioedema)

Highly variable pharmacokinetics

Front 18

Buspirone

Back 18

Non-BDZ anxiolytic

*Partial agonist at 5HT1A receptors
*Much slower onset of anxiolysis than BDZ's WITHOUT the sedative, hypnotic, or euphoric effects.
* Therapeutic benefits are delayed 2-3 weeks.
* Minimal abuse liability

USE: Generalized Anxiety Disorder (lacks muscle relaxant or anti-convulsant effects).

SE: Minimal abuse liability; non-specific SE (dizziness, nausea, headache).

CONTRAINDICATIONS: MAOI's

Front 19

Phenobarbitol

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Long-Acting Barbituate

USE: Generalized Tonic/ Clonic Seizures (but not the drug of choice).

SE: Barb + ETOH = death. Can cause tolerance, dependence, and life-threatening w/d.

Many drug interactions due to CYP450 enzyme induction.

CONTRAINDICATIONS: pregnancy.

Front 20

Thiopenthal

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Barbituate
Highly lipid soluble. 61% unionized at normal pH.
Rapid onset of action. (max effect at 1 min). (Acidosis will slow the onset by making more of the ionized form.)

(Short duration (5-8 min) of action due to redistribution from CNS to muscle. Also, high uptake by fat tissue due to lipid solubility.)

USE: mainly used as induction agent to prior to GA. Binds GABA receptors in the RAS of the cerebral cortex to produce hypnosis (loss of conciousness). Also used as an anticonvulsant.

SE: Potentiates CNS depressants; high abuse liability.
CNS Effects: Sedation causes decr CMRO2, dec CBF, ICP...therfore neuroprotective. Also decr IOP d/t sedation. Increased outflow of aqueous humor (mydriasis), relaxation of extraocular muscles, peripheral VD.

CV Effects: Decr in capacitance of vessel tone, Venous pooling, Decr venous return/ CO, Decr Inotropy, decreased SNS tone, VD, HOTN, Reflex tachycardia.

Respiratory Effects: Dose dependent resp. dep via medullary and pontine centers. Decr CO2 and O2 drive to breathe.

SE: Hyperalgesic at low doses (ie during onset and emergence); (No analgesic properties.) Pain, Tissue necrosis/ gangrene, long halflife for elimination, histamine release when given rapid IV Push (careful in asthmatics). CYP450 inducers.

MUST have airway control.

Protein binding is competitive with ASA, Indomethacin, Naproxen, coumadin, sulfisoxazole...so it pt takes these...will have higher conc with same dose.

Metabolized by CYP450 (inducer) and renally excreted (long elimination half-life). Longer window of high plasma levels in the elderly.

CONTRAINDICATIONS: Porphoria and asthma d/t histmaine release

Front 21

Oxazepam

Back 21

Intermediate acting benzo

No metabolites...gluronidated and excreted.

Cumulative and residual effects (excessive drowsiness) are less of a problem.

Front 22

Antidepressants

SSRI's: Venlafaxine
Tricyclics: Imipramine

Back 22

Increase serotonergic tone.

Therapeutic benefits are delayed 2-3 weeks.

Gold standard for long term tx of GAD.

Front 23

Sapmazenil

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A Inverse agonist at the BDZ site that can reverse the acute and sedative effects of ethanol.

Can cause seizures in high doses.

Front 24

Flurazepam

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Long acting BDZ

USE:

SE: In the elderly it can have a half-life of days due to active metabolites. This will increase daytime sedation, ataxia, confusion. Rarely, it can cause severe anaphylactic reactions (angioedema)

NOT for long-term use.

Front 25

Pregablin (Lyrica)

Back 25

Anticonvulsant drug for neuropathic pain that can also be useful in GAD and social anxiety disorder.

Front 26

Extended Release Naltrexone

Back 26

Once a month IM injection for alcohol dependence. (Reduces cravings).

One injection provides medication over one month; patients do not need to make daily decision to take this medication. . Avoids the major problem of pt compliance.

Front 27

Flurazepam

Back 27

Long-acting BDZ (T1/2> 24 hrs) w/ very long-lived metabolites (ESPECIALLY IN ELDERLY PATIENTS).

*Low potency

USE: Insomnia

SE: Can cause daytime sedation, ataxia, confusion. Can cause angioedema and anaphylactic reactions.

Front 28

Oxazepam

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Benzodiazepine.

No metabolites.

USE: Anxiety

Low potency, Short halflife (short duration).

Front 29

Temezepam

Back 29

This is restoril. It's a BDZ

USE: Insomnia

Low Potency
Intermediate halflife.

Front 30

Pregablin

Back 30

USE: GAD and social anxiety disorder

Front 31

Propanolol

Back 31

Non-selective beta blocker

*Reduces the most sympathetic signs of anxiety.

USE: Stage fright

Front 32

Disulfram

Back 32

Antiabuse

IRREVERSIBLY Inhibits Aldehyde dehydrogenase - the enzyme that breaks down Acetaldehyde ( a byproduct or initial alcohol metabolism).
Leads to a buildup of acetaldehyde, which causes N/V, facial flushing, dizziness, and headache. This pvts further drinking. (B/c of this, pt compliance limits usefulness.)

Disulfram also inhibits the metabolism of many other drugs by inhibiting this enzyme.

Effects may last up to one week after administration.

Other drugs with disulfiram-like effects: chloramphenicol, metronidazole, sulfonylureas e.g., tolbutamide, and ketoconazole (rare).

Front 33

Fomepizole

Back 33

A Selective inhibitor of alcohol dehydrogenase.

USE: tx for Methanol Poisoning: Prevents the breakdown of methanol by alcohol dehydrogenase into poisonous crystals.

Front 34

Remifentanyl

Back 34

Strong Acting Synthetic Opiod

Ultra-short acting due to rapid metabolism by esterases

Effective biological half-life ~ 3-10 min

Allows precise intraoperative titration

Does NOT accumulate even after prolonged infusion

Good for methadone pts in surgery to pvt precipitated withdrawals because you can titrate to effect. ..

Front 35

Heroin

Back 35

Strong Opiod Agonist

Diacetyl-morphine: It's more lipid soluble than morphine so it is absorbed faster (crosses BBB faster) and is more addictive. This is converted to morphine in the body.

2-5x as potent as morphine

Short half-life...intense, short withdrawal that is lifethreatening.

Front 36

Butorphanol

Back 36

A mixed opoid agonist - antagonist.

Kappa Agonist
Mu Partial Agonist

Avaliable as a Nasal Spray

5 X more potent in women than men

Get both kappa mediated and mu mediated analgesia but with a high dose not as much respiratory depression (not life threatening.).

BUT…less effective as fentanyl or oxycodone for very severe pain.

Front 37

Capsaicin

Back 37

A substance found in hot peppers

Can alter substance P effects of pain transmission.

Works at the site of tissue injury and peripheral tissues.

If you use it too long, can end up with hyperalgesia

Front 38

Morphine

Back 38

Strong Opiod Agonist
Naturally occuring opiod from poppy exudate.
Precursor for heroin.

Effective over a wide dose range

Positive effects on mood
Sedation

Morphine can cause CNS excitation and prolonged duration in renal failure pts. Morphine conjugates to morphine-3-glucuronide (M3G) which can cause unwanted CNS excitation and to morphine-6-glucuronide (M6G) which retains agonist activity.

Teacher says opiod of choice in an epidural and spinal in parturients.

SE:
Sedation*
Mental Clouding
Dysphoria
Constipation*
Dizziness
Nausea and vomiting
Respiratory depression*
Cough reflex depression* (medulla)
Circulatory depression
Pinpoint pupils
Pruritus and rash
Biliary tract spasms
Ureter, vesical spasms
Urinary retention
Behavioral dependence
Physical dependence
Tolerance

Front 39

Codeine

Back 39

Naturally occurring opiod from poppy exudate.
A weak or partial opioid agonist
1/10th the potency of morphine (a prodrug)

Reduced first pass metabolism - can be administered orally.

10% of Codeine is demethylated to morphine (a strong agonist) via CYP2D6, which is responsible for much of its analgesic activity (i.e., codeine acts as a prodrug to morphine). 10% of people do not have this enzyme and codiene will not treat their pain.

Mixed with NSAIDS for additive or synergistic analgesia without concomitant increase in adverse effects.

Front 40

Meperidine (demerol)

Back 40

Strong Opiod Agonist
Synthetic Opiod made from precursor compounds. (Phenylpiperidine Opiod).
About 1/8th potency of morphine

SHORT DURATION.

Created to tx nazi soldiers that could not get morphine...had to make their own opiod drug.

An analogue to atropine that is a potent opiod analgesic. (Therefore you will not get pin point pupils due to d/t atropine-like effects. Seizures occur most with meperidine because it causes CNS excitation. It also has an active metabolite that produces CNS excitation. (Therefore CONTRAINDICATED in pts with renal failure, hepatic failure, elderly, and seizure pts).

Reduces shivering (unknown mechanism)
Less smooth muscle spasm than morphine.
Will increase HR due to antimusc. effects....good opiod if you don't want to cause cardiac depression.
Hepatic oxidative metabolism is the primary route of degradation

Front 41

Fentanyl

Back 41

Strong Opoid agonist
Synthetic Opiod made from precursor compounds. (Phenylpiperidine Opiod)
80-100x the potency of morphine.

Highly lipid soluble, so can get sequestered in fat tissue.

Hepatic oxidative metabolism is the primary route of degradation

Can cause truncal rigidity with epidural or spinals which makes it hard to ventilate the pt. Mechanism is unknown.

Fast onset, short duration

Used IV for anesthesia (heart surgery)

Available as transdermal patch and as oral slow release prep

Front 42

Oxycodone

Back 42

Strong Opiod Agonist
10x the potency of oral codeine

Reduced first pass metabolism - can be given orally. (Also metabolized by CYP2D6.

Controlled release formulation – subject to abuse (‘Hillbilly heroin’)…people grind it up and shoot it IV to get a hi. Abuse potential.

Front 43

Ketamine

Back 43

NMDA receptor antagonist (in the medial thalamic nuclei and spinal cord). Stimulates SNS pathways.
(Also decreases ACh in the caudate nucleus)

Structure similiar to PCP.

ONSET: 5 min
DURATION: 10-15 min

USE: Reduces development of tolerance to opioid analgesic effects by preventing NMDA from downregulating the Mu receptor.

Also used an an induction agent in anesthesia.

CNS effects: Dissociative amnesia: Cateleptic: eyes open, pupils reactive to light, corneal reflexes, lacrimation, eye blinking, airway reflexes, skeletal muscle tone increased. Increased CBF 60-80% d/t increased CMRO2, so increased ICP. PROVIDES ANALGESIA AND AMNESIA!!

CV Effects: Tachycardia, HTN, Increased CO.

Resp Effects: No effect on RR, Intact responses to hypercarbia. Maintains laryngeal reflexes and SM tone.

OTHER:Partially water soluble (no pain on injection), very lipid soluble, 12% protein bound,

METABOLISM/ ELIMINATION: Hepatic CYP450 metabolism. Two compartment kinetics (peripheral vs central). Rapid redistribution (t1/2 = 11=17 min). Cumulative effect can occur d/t large amt remaining in peripheral system.

INTERACTIONS: Halothane prolongs ketamine activity.

SE: Emergence can cause psychic disturbances. (15%).

Front 44

Methylnaltrexone

Back 44

USE: Constipation

An opiod competitive antagonist that is a variation of naltrexone that is not absorbed (charged..cannot cross BBB), so it stays right there in the GI tract. It can treat opiod induced constipation. (You have mu receptors on your GI tract.)

SE: abdominal pain, flatulence, diarrhea

Front 45

Loperamide ( Immodium AD).

Back 45

– combination of morphine(strong opiod agonist) and atropine used to treat diarrhea

Front 46

Pentazocine

Back 46

A mixed opioid Agonist/Antagonist:
Kappa and delta agonist
‘Weak’ µ antagonist – partial agonist

‘Ts and blues’ – pts used to grind up and shoot IV to get a prolonged hi…made them more aggressive.

Oral form now combined with naloxone as Talwin NX® to pvt this. . This allows naloxone to sit on opiod receptors, blocking the opiod. Antihistamine effects will still occur with no opiod hi. STILL Ca pts can still take it orally and it treats their pain b/c naloxone is ineffective orally. It has a tremendous first pass effect. So only the Pentazocine works. (But won’t work IV).

CONTRAINDICATIONS: B/C partial Mu agonist…cannot use in pts with strong opiod dependence because it will precipitate withdrawal by blocking sites from full Mu agonist.

Front 47

Tramadol

Back 47

A partial opiod agonist (Mu and Delta)

NE and 5-HT reuptake blocker (~ TCA antidepressants)

α-2 adrenergic agonist (leads to less NE release) (mimics descending pathway)

Mixed actions are synergistic for analgesia

Can cause seizures

Avoid use with TCAs, MAOIs or SSRIs (you might get serotonin syndrome or HTN crisis).

Front 48

Hydromorphone

Back 48

Strong Opiod agonist
(5-10X more potent than morphine when given orally) (when given IV they have equipotence).

Has no active metabolites;

Shorter duration of action than morphine

Mixed with NSAIDS for additive or synergistic analgesia without concomitant increase in adverse effects.

Front 49

Talwin NX®

Back 49

Oral form of pentazocine combined with naloxone as Talwin NX®.

Oral med designed to pvt IV abuse. Naloxone is ineffective orally due to 1st pass metabolism. This allows naloxone to sit on opiod receptors, blocking the opiod when injected IV. Antihistamine effects will still occur with no opiod hi. Therefore drug cannot be abused.

Cancer pts can still take it orally and it treats their pain b/c naloxone is ineffective orally.

Front 50

Methohexital

Back 50

Ultra-short acting Barbituate
2-5x more potent than thiopenthal

Not as popular due to: excitatory movements on induction, Pain on injection, cough, seizures, prolonged mental impairment

Similiar CV and respiratory effects as thiopenthal.

Front 51

Etomidate

Back 51

Induction agent.

* Direct CNS depressant and GABA agonist.
* Inducing Agent produces hypnosis
* No analgesic properties
* Lipid soluble, rapid rise in brain (< 1 min)
* 76% Protein Bound (Albumen)
* Rapid redistribution (t 1/2 = 2.6 min)
*Rapid clearance so can repeat and continuous dose
* Recovery 7-10 min after bolus.

CNS Effects: Decr CMRO2, CBF, ICP. Maintains responsiveness to CO2 levels (neuroprotective). Decreases ICP. Good for neuro pts.

CV Effects: NONE!!!

Resp Effects: Mild dose related resp depression.

* No histamine release.

SE: Pain on injection, Myoclonic activity, N/V, Adrenocortico suppression.

Front 52

Propofol

Back 52

Rapid onset and short duration. (Ideal for outpatient settings).

Rapid redistribution

98% Protein Bound

Rapid metabolic clearance: Lower doses in elderly, higher doses in children d/t increase clearance rate.

Rapid/ pleasant recovery.

CNS Effects: Decreased CMRO2, CBF, and ICP

CV Effects: Significant myocardial depression, VD, and suppressed baroreceptor reflex.

Resp effects: Sig depression including normal response to hypercarbia.

SE: Not water soluble so painful on injection. High risk of bacterial contamination.

CONTRAINDICATIONS: ELDERLY ADN CARDIAC COMPROMISED PTS.