Heroin and Other Opioids Flashcards
Pharmacodynamics-Opioid Mechanism of Action
3 types of opioid receptor types identified: mu, kappa, delta; in various nervous system sites in many tissues.
G protein coupled receptors.
The receptor types have different mechanisms of action, but the net effect of receptor stimulation is the inhibition of neurotransmission.
Effects of opioid receptor activation: affects ion channel gating, modulates intracellular calcium disposition, alters protein phosphorylation.
Two well established direct G protein coupled actions in neurons: close voltage gated calcium channels on presynaptic nerve terminals, which reduced transmitter release.
Opening K channels on postsynaptic neurons: hyper polarize and inhibit postsynaptic neurons by opening K channels.
Opium and Heroin Production
Opium is a natural product containing morphine as its main active ingredient.
Made by drying the exudate from the incised seed capsule of the opium poppy.
Initial processing of Opium Poppy: raw opium first dissolved in water and simmered over a low heat; solution then filtered and evaporated; the result is a smokable form of opium with a considerable higher morphine content percentage wise than the raw product; about 10-15%.
Pressed into bricks and either converted to heroin or used as is by smoking or eating.
Heroin Processing: produced by acetylation of the morphine extracted from opium; main abused opioid for about 100 years.
Heroin
Street names: Smack and junk are the most common; heroin, diacetylmorphine, H, horse, girl, tar, junk, scag.
IV use provides a better euphoria and is cheaper than snorting or smoking.
All routes of administration can produce a “high,” but only IV injection and perhaps smoking can produce a “rush.”
Available on the street as a powder or lumpy mass which ranges in color from white through various shades of brown to black.
Also available as a black tar-like substance.
The purity of heroin has increased dramatically during the last decade; was on the order of 4% and now averages 35% and is often in the 75-95% range.
Epidemiology of Abuse
Older IV junkies; many US users are not in their 40s or 50s and first started using during the heroin epidemic of the 1970s. Characteristics of the surviving groups: disadvantaged lower class youth, large group of mainly inner city lower SES youths; middle class "chippers"; increasing use of heroin by middle class persons in the teens and 20s; they chip the drug usually by smoking or snorting; many of these will eventually become addicted and move on to IV use.
The “rush”
Occurs with IV injection which is the most common route.
Short lasting “rush” or “flash” of extremely intense pleasure often likened to sexual orgasm but much better-lasts only a minute or two BUT it is powerfully reinforcing.
This “rush” is often the effect most sought after.
Heroin is preferred to morphine and most other opioids; it produces a better rush due to its rapid transit across the BBB.
The “high”
The rush is followed by the high; this is a period of mellow euphoria lasting several hours.
Characteristics: drowsiness and feelings of relaxation, contentment, peace and tranquility; near total lack of concern regarding existing or potential problems.
Narcotics are the ultimate tranquilizers.
User may drift back and forth between wakefulness and sleep; “on the nod” they can be easily aroused and can function in a fairly normal fashion.
Characterics NOT present: slurred speech, major physical incoordination, major mental impairment.
Persons on a heroin high are usually passive, quiet, and non-aggressive.
Diluents and Adulterants
Diluents: Mannitol, lactose, amorphous material, starch, dextrose, baby powder, fructose, sucrose, inositol, cellulose, calcium carbonate, citric acid, sodium bicarbonate, flour, salt; substance used to dilute something.
Adulterants: Quinine, Diphenhydramine, caffeine, acetaminophen, hydromorphone, ephedrine, benzocaine, cocaine, amitriptyline, phenobarbital, butabarbital, diazepam, aspirin, salicyclic acid, procaine, lidocaine ;a substance used to taint another substance.
IV Injection
Heroin is most often injected, usually IV.
Can also be injected subQ (“skin popping”) or intramuscularly.
Most street heroin is “free base heroin” and this product can be smoked or snorted as is.
However, for injection, it must be acidified with a little vinegar or lemon juice and then heated to get it into solution.
Smoking and Snorting
In past street preparations, heroin was so weak that injection was the only route which reliably produced a good effect.
However, due to the higher purity of recent product, heroin is now often snorted or smoked.
Ways to smoke the drug: dip the tip of a cigarette or joint into heroin powder, sprinkle heroin powder on tobacco or marijuana and smoke it as a joint or in a pipe, smoke the power directly in a glass pipe similar to a crack pipe, “chasing the dragon” (heating heroin on a metal foil and inhaling the rising vapors).
Orally
Heroin is rarely taken orally because of EXTENSIVE FIRST PASS METABOLISM in the liver.
Onset and Duration of Heroin
IV or smoked
Onset is less than 30 seconds, peak intensity occurs in a few minutes, and the duration is 3-5 hours.
Snorted
Onset occurs in a few minutes, peak intensity occurs at 10-15 minutes and the duration is 3-5 hours.
In all cases, the duration of euphoria after a usual dose is 3-5 hours.
Opiates and Reward
Main receptors: mu, kappa, and delta; drugs of abuse act as agents at these receptors, primarily the mu receptors.
Site of action: opiate neurons of the arcuate nucleus project to the VTA (site of dopamine cell bodies and where many neurotransmitters project) and to the nucleus accumbens (where dopaminergic neurons project).
Action: primarily produce euphoria through mu receptors which is the main reinforcing action.
Tolerance
Repeated daily use of heroin leads to the development of tolerance to the euphoric, sedative, analgesic, respiratory depressant and emetic effects of the drug but not to the constipating and miotic effects. Intermittent use such as on weekend (chippers) only may not lead to tolerance. Tolerance is totally pharmcodynamic (no changing rate of metabolism that makes someone tolerant). Degree of tolerance which can be quite large; novice users may start out injecting as low as 2 or 3 mg a day; highly tolerant users may inject 200-300 mg daily; abusers may reach a state of tolerance where no dose will produce the desired euphoria. Cross tolerance: extensive cross tolerance occurs within the opioid class of drugs but NOT between classes; may cause problems in addicts seeking relief of pain in a medical setting-may have a huge tolerance to medically acceptable opioid analgesics.
Physical Dependence
Physical dependence can develop by any route of administration; smoking and snorting are not safe.
Requires repeated exposure.
Heroin and many other opioids have a strong tendency to produce physical dependence.
More important than the route of administration is the DOSE and the FREQUENCY of use.
Morphine: use of a full therapeutic dose of 10 mg qid i.m. for 7-10 days produce only a very mild abstinence syndrome after abrupt discontinuation; probably true of heroin (equivalent dose would be about 3-5 mg qid).
Recreational user: one or twice a week, probably never develop a significant physical dependence; occasional users often get sucked into more frequent use.
Abstinence Syndrome
The abstinence syndrome associated with strong heroin physical dependence is highly unpleasant, but is less severe in several respects than that associated with alcohol, barbiturates, and other sedative agents; there are generally no convulsions, no delirium and death is extremely rare.
Some users go cold turkey voluntarily to decrease their tolerance to heroin- they can then get high again and the expense goes way down.
