Pain and Opiods Flashcards Preview

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Flashcards in Pain and Opiods Deck (21)
1

codeine

Opioid Agonist

Pro-drug converted to MORPHINE (demethylated)
- IN combination with ACETAMINOPHEN (Tylenol #3)

Liver Enzyme: CYP2D6

- Effectiveness linked to high or slow metabolizer, genetic variability for this enzyme

Has ACTIVE METABOLITE

Phase 1 metabolism

2

fentanyl

Opioid Agonist

Opioid/narcotic

Mu Opioid Receptor Agonist

Can be used as Patch, for patients who can't swalow

Perioperative Use

Oral and Sublingual forms

IV: extremely rapid onset
- Same for Epidural, Intrathecal/subarachnoid

Liver Enzyme: CYP3A family

Phase 1 pharmacokinetics

NO ACTIVE METABOLITES

3

heroin

Opioid Agonist
- Mu Opioid Receptor

Pro-drug converted to Monoacetyl Morphine (deacetylated) and Morphine in the brain

Rapid onset pharmacokinetics (immediate)

More lipophilic than morphine

Has ACTIVE METABOLITES
- M-6-Glucoronide: 10 x more potent than morphine

4

hydrocodone

Opioid agonist
Mu Receptor

Combination with Acetaminophen

Metabolized to Hydromorphone
- Active METABOLITE (5X more potent than Morphine)
- Hydromorphone-6-glucoronide: less agonist activity than morphine-6-glucoronide

Liver Enzyme: CYP2D6
- Huge variability

Combination with acetaminophen gives pain relief without severe opioid side effects

Rarely use opioids with NSAIDs/Aspirin

Sustained Released Agonist
- Provide pain relief for 12 hour dosing by producing stable plasma levels

5

hydromorphone

Opioid Agonist
Mu Receptor

More lipid soluble than Morphine, faster onset

More potent: 5X, less dosage for same effect

Glucoronidation:
- Hydromorphone-6-glucoronide: less agonist activity than morphine-6-glucoronide
- hydromorphone-3-glucoronide (inactive metabolite)

Pretty safe in renal failure

Extended sustained release formula, provide relief in 12 hour dosing regimens

6

Meperidine

Opioid Agonist
Mu Receptor

More lipid soluble than morphine: faster onset

Less potent: 1/10X

Converted by Liver to NOR-MEPERIDINE (CNS stim, convulsions)

Nor-meperidine has a longer half life in patients that have renal failure due to decreased elimination

Use of drug has decreased

Used as serotonin reuptake inhibitor
- Can produce Serotonin Syndrome (excessive synaptic serotonin), when combined with SSRIs or MAOIs

Active Metabolite: Nor-meperidine


7

morphine

Opioid Agonist
Mu Receptor

Produces Analgesic via Brain
- Mu agonists influence motivatoinal affective component of pain

Neutral pH: 80% charged so only 20% allowed to cross
- Low lipid solubility so slowly crosses the BBB

Clinical duration of action: 4 hrs

Metabolism: Glucoronidation

Excretion: Glucoronide metabolites via kidney
- morphine-6-glucoronide (10x more potent) 5-10% of morphine
- morphine-3-glucoronide (inactive)

Half life: 2 hours

Liver disease little effect on action of morphine (need severe liver disease)

RENAL DISEASE: greatly affects morphine influence
- morphine-6-glucoronide secreted by organic ion transporters,
- Elimination impaired in RENAL DISEASE

If patient receiving morphine goes into renal Failure has dangerous consequences\

Inexpensive, widely used, measure of familiarity (widely studied)

MS Contin/ Morphine SR: continued release for managing cancer pain

Need to adjust from IV to PO form and vice versa because decreased oral bioavailability

Can be administered spinally (intrathecal/subarachnoid/epidural)

Intrathecally: Chronic
Epidural: Acute

Side Effects: Repiratory Depression, N/V, Sedation, Itching

8

methadone

Opioid Agonist
Mu Receptor

Oral

Ultra Long Acting
t1/2: 15 to 60 hours

Methadone mainteance used for Opioid Drug Addiction

Highly Variable Metabolism

Pain management

Liver Enzyme: CYP3A

9

oxycodone

Opioid Agonist
Mu Receptor

In combination with acetaminophen (percocet)

Metabolized: CYP2D6
- Genetic variability not clinically significant

Active Metabolite: Oxymorphone

Caused abuse problems: Not widely used as a result

Extended Release formula (Oxycontin) 12 hour dosing by producing stable plasma level

10

oxymorphone

Opioid Agonist
Mu Receptor

Major metabolite of oxycodone

Metabolized from CYP2D6

Sustained Release Form: OPANA

11

buprenorphine

Mixed Agonist/antagonist

Partial Mu agonist and Kappa agonist (associated euphoria)

Higher affinity for the mu receptor, difficult to reverse its mu agonist effect

Difficult to provide analgesia if patient has surgery because mu bound more tightly to this drug

Has utility in Drug Addicition and Abuse

Buprenorphine 7 day patch, must remove before surgery and wean off effects

Metabolized by CYP3A

12

nalbuphine

Agonist for K receptor

Mu receptor partial agonist

Mu antagonist

Used for management of acute, short term pain, not for management of chronic pain

Used for control of itching

13

Pentazocine

Agonist for K receptor

Mu receptor partial agonist

Mu antagonist

Used for management of acute, short term pain, not for management of chronic pain

14

tramadol

Partial Agonist
Mu agonist and monoamine reuptake inhibitor activity (contributes to analgesic activity)

Ultracet (tramadol + acetaminophen)

Metabolized by: CYP2D6 and CYP3A4

CYP2D6 produces active metabolite

15

tapentadol

Partial Mu agonist

Less pharamacogenetic variability compared to tramadol

Metabolized by CYP2C9, CYP2C19, CYP2D6

CYP2D6 produces active metabolite

Greater mu receptor efficacy

Used for mild to moderate acute/chronic pain

16

alvimopan

Opioid Receptor Antagonist

Poorly absorbed orally, active opioid antagonist

Antagonizes GI side effects of opiods

17

methylnaltrexone

Opioid receptor Antagonist

Quaternary ammonium derivative that is positively charged

IV peripherally restricted opioid antagonist for constipation

18

naloxone

Opioid Receptor Antagonist

parenteral

Pure Mu activity

Prevent/antagonize effect of opioid agonist

Oxycodone-naloxone: targets abuse by not allowing oxycodone effects when naloxone is released when abused

19

naltrexone

Opioid Receptor Antagonist

Oral

Pure Mu activity

Prevent/antagonize effect of opioid agonist

Morphine with sequestered naltrexone is an abuse resistant opioid

20

diphenoxylate

Opioid agonist

Antidiarrheal: poor or not absorbed after oral administration

21

loperamide

Opioid agonist

Antidiarrheal: poor or not absorbed after oral administration