Opiates Flashcards
Narcotic
Older term initially used to describe a drug that caused “narcosis” or sleep, but then became a loosely applied universal term for many illegal drugs, primarily for legislative purposes. Not a pharmacologically accurate term
Opiate
Any drug that is derived from the opium poppy, including natural and synesthetics
Opioid
General term for any drug(or endogenous peptide) that acts on the opiate receptor
Opium
Coagulated juice of the poppy pod that contains various opiates
Endorphine
Endogenous opiate like peptide that modifies the actions of other transmitters
Opiate Receptor Subtypes
mu
kappa
delta
nociception
Mu
Analgesia, physical dependence, respiratory depression, miosis, euphoria, reduced GI motility
Kappa
Analgesia, sedation, physical dependence
Delta
analgesia, anti depressant, physical dependence
Nociception
Anxiety, depression, appetite, develop tolerance to mu agonists
Endogenous Opiates
Enkephalins were first discovered, very potent (delta)
Beta endorphin (mu) and dynorphin (kappa)
Rapidly inactivated
Located in hypothalmus, forebrain, limbic medial thalamus, locus coeruleus to mediate pain perception and mood and released from pituitary during stress
Medical Use for Opiates
Pain
Cough
Diarrhea
Pain
Most common human experiences in which people seek medical treatment
Chronic pain is defined as that which lasts at least 3 months
It is difficult to measure because subjective
Types of Pain
Nociceptive- Physiological process of transmitting pain producing stimuli that emerge from tissue damage
Neuropathic- caused by lesion of the nervous system as a result of trauma, injury, or infection
Opiate Induced Analgesia
Blocks both perception and emotional components of pain
Does not impair conciousness
Reduces dull chronic pain
Patient Controlled Analgesia
- Patients control their pain by activating a pump on demand
Receives immediate dose, does not need to wait for nursing staff and physicians to administer the dose
Typically patient lets staff know, it takes 30-60 minutes
Faster alleviation of pain = less medication used
Euphoria
Intense sense of well-being and contentment, with a complete lack of concern for anything
Ecstatic- with sexual connotations
Primary reason for abuse
Physiological Effects
Histamine release- itching, red eye, sweating, fall in BP
Reduces gastric motility- constipation
Respiratory Depression- cause of death in overdose
Pupillary Constriction
Side Effects/Toxicity
Respiratory Depression
Opiates inhibit brainstem ability to detect buildup in CO2
Most important cause of death during overdose
Physiological Tolerance
Develops to everything, except for pupils and GI tract
Accounts for the increase in dose
Rate of development not the same- slow for respiratory rate
Lethal effects require 4-8 times the dose
Cross tolerance to all opiates
Physical Dependence
Withdrawal or abstinence signs
craving, anxiety
yawn, sweating, pupil dilation
tremors, flashes, insomnia
Heroin
Conversion of morphine to heroin is preferred by drug traffickers because
- 10 times more potent
Less space to hide
more lipid soluble
enters the brain more quickly
rapidly converted to morphine in bloodstream
Oxycodone
Developed in 1996 as timed release formulation
Abusers avoid the delay by crushing the tablets and snort or mix with water and inject in IV
Immediately delivers entire dose, sometimes combined with ecstasy
FDA released black box warning, prescription instructions
Reformulation- pills cannot be crushed, turned into a gel when mixed with water
- Decreased abuse by a little, more people turned to heroin
Public Heath
53 million Americans used prescription drugs for non-medical reasons
70% obtain from relatives and friends
DISPOSE OF ALL PRESCRIPTION DRUGS WHEN FINISHED
Signs of Opiate Overdose
Loss of Conciousness
Unresponsive
Unable to talk
Breathing very slow, erratic
Fetanyl
Synthetic opioid with potency 80-100 times that of morphine
Highly lipid soluble, immediate rise in plasma levels followed by an immediate fall
Rapid offset of action is due to redistribution
Fetanyl Abuse
Use needle to remove fetanyl gel from transdermal patch
Drug/gel is put in a syringe, and injected
High doses absorbed in short period
Results in thrombophelebitis, deep venous and abscesses
Revised formulation eliminates gel, reduced incidence of abuse
Mylan Fentanyl Transdermal System- Comes in a variety of doses to make it easier for patients
Opiates Toxicity
Generally non-toxic, as tolerance develops Overdoses from combination or pure batch Coma, respiratory depression, pinpoint pupils ER treatment with naloxone Related to IV use AIDS unsterile technique Adulterants Infections, abscesses in skin poppers
Methadone Maintenance
Developed in 1964
Dose was higher than used on street
Prevents withdrawal, but produces significant amount of cross tolerance, so prevents heroin or other opiates from binding to receptors, preventing acute effects– leads to extinction
Converts to less risky route- oral vs IV
Use of pure medication with known potency
Slower onset of action avoids the rush
Improved general heath status
Reduced use of healthcare services
Stabilization may take days or weeks
Patients must be educated to expect this delay
Withdrawal and craving suppressed slowly
Cross tolerance at 5-20 mg
After a few weeks- pool of methadone is established
Patient can miss a daily dose and not feel withdrawal
Does not assist analgesia, no need for additional analgesics for pain medication
Positive Results of Methadone Maintenance
Death rate is 10 times lower than in untreated individuals
Needle sharing is 14% vs 47 %
Slower progression to AIDS in HIV infected individuals
Decreased incidence of ER visits
Fewer upper respiratory infections
Improved immune function
Improved nutritional status
Reduced incidence of criminal convictions
Reduced incidence of selling drugs
Long-acting (24-36 hours)
Methadone Side effects
Constipation Sweating Nonmalignant edema Loss of libido Relatively safe, true methadone related deaths in maintenance are rare
Methadone Efficacy
1/3 get better, 1/3 vacillate, 1/3 get worse
Methadone does not treat antisocial behavior
Methadone decreases needle sharing, decreases HIV/AIDS
Methadone controversy
Switch to use methadone as primary medication for treating chronic pain
Developed after OxyContin crisis
But methadone pharmacokinetics are more complicated so OD is more common
Buprenorphine
Partial agonist at mu receptor
Similar effects to morphine at receptor but at a lower dose range
.3 mg buprenorphine = 10 mg morphine
Subutex
Sublingual buprenorphine formulation that does not contain naloxone
Management of pain in low risk patients
Buprenorphine Maintenance
Slow release off receptor will delay appearance of withdrawal, even after abrupt termination
Suboxone
Sublingual formulation that contains naloxone HCl
Naloxone not absorbed orally or sublingually, so has no effect on buprenorphine
If preparation is injected, naloxone blocks buprenorphine access to opiate receptor
Buprenorpine Delivery of Therapy
Office-based prescribing of buprenorphine, allows private physicians to manage
Physician training is available from a variety of source
Strategy opens opiate dependence treatment options to many more individuals
Naltrexone
Orally absorbed
Use only after detoxification- with patients who are highly motivated
Prevents heroin or morphine from getting into receptor
Injectable formulation vivitrol has been approved for use as a treatment
Naloxone
Opiate receptor antagonist Not orally absorbed- IV Sometimes used to asses dependence Not useful in maintenance-- too short acting Reverses opiate overdose in emergency Must put on slow drip after bolus
Naloxone Controversy
Giving naloxone injectors to the public
Given to ambulance drivers, police officers, first responders
Treatment Plan Heroine Users
use short acting opiates to engage Gradually shift to longer acting drugs Increase drug-taking interval Survey urine for illicit opiates Switch to antagonists after they have been detoxified
ALTERNATE
Some period may need maintenance for an extended period of time
Very low dose methadone may be all that is needed
Heroin Use
Troops had very little dependence once they returned to the US
Speedball
IV combination of heroine and cocaine
sometimes norted
often co-administered, but can also give one after the other in a short time period
Heroine allows a parachute from the intense high of cocaine
Cheese Heroine
Black tar mexican heroin mixed with crushed OTC that contain antihistamine diphenhydramine
Sedative effects of the heroin and sleep aids make it very dangerous
Targeted to middle school children
Krokodil
Desomorphine- 8-10 X more potent
Homemade from codeine, iodine, red phosphorous, gasoline, lighter fluid, and industrial clearners
Sensationalized as flesh eating heroin- causes skin necrosis and gangrene
Popular in Russia and Ukraine
Kratom
Made from the leaves of Mitragyna speciosa, southeast asian tree related to coffee, and has been consumed in Asia for Millenia, typically as tea or powder
Herb contains alkaloids that activate opioid receptors in the brain and reduce pain
Although most opioids have sedative qualities, low to moderate doses of kratom serve as a mild stimulant
Led advocated to claim kratom can be used as a maintenance drug to help recovering opiate dependents
DEA planning to place it on schedule 1
Mitragynine and 7hydroxymitragynine active ingredients in kratom, bind to opiate receptors in the brain
