What is an opiate?

What is an Opiate?

An opiate is a subclass of alkaloid opioids that are naturally extracted from the opium poppy plant, distinguished from the broader category of opioids which includes synthetic and semi-synthetic compounds. 1

Definition and Classification

The term "opiate" specifically refers to alkaloid compounds derived from the opium poppy, while "opioid" is the broader term encompassing natural opiates, synthetic compounds, and endogenous peptides. 1

Natural Opiates

• Morphine is one of the primary natural opiates extracted directly from the opium poppy 1
• Codeine is another naturally occurring opiate alkaloid from the same plant 1
• These compounds have been used for pain relief for thousands of years, with opium being the main remedy against pain since antiquity 2

Broader Opioid Classification

The opioid class extends beyond natural opiates to include:

• Synthetic opioids: heroin (diacetylmorphine), hydromorphone (Dilaudid), fentanyl (Sublimaze), methadone, oxycodone, and meperidine 1, 3
• Endogenous opioids: enkephalins, endorphins, and endomorphins produced naturally in the body 1
• Semi-synthetic derivatives: compounds like buprenorphine, derived from the opioid alkaloid thebaine 1

Mechanism of Action

Opiates and opioids work by activating opioid receptors in the central nervous system:

• They primarily bind to μ-opioid (mu) receptors, but also interact with κ-opioid (kappa) and δ-opioid (delta) receptors to produce analgesia 1, 4
• These receptors are highly expressed in brain regions regulating pain perception including the periaqueductal gray, thalamus, cingulate cortex, and insula 4
• Unlike other analgesics, opioids reduce pain perception rather than blocking pain signal transmission—sensory transmission remains intact while the subjective interpretation of pain is altered 4

Clinical Effects

Therapeutic Effects

• Supraspinal analgesia (pain relief originating from brain structures above the spinal cord) 1
• Sedation and euphoria 1
• Cough suppression 5

Acute Physiological Effects

• Miosis (pupil constriction), except with meperidine 3
• Respiratory depression 1, 3
• Decreased gastrointestinal motility 1
• Sphincter of Oddi spasm 3

Adverse Effects with Prolonged Use

• Physical and psychological dependence develops with chronic exposure 1, 6
• Tolerance requiring increasing doses to achieve the same therapeutic effect 4, 6
• Opioid-induced hyperalgesia: paradoxical increase in pain sensitivity that can develop even after a few administrations 4, 5
• Constipation (one of the most persistent side effects) 3, 7, 8
• Nausea and vomiting 3, 7
• Opioid-induced hypogonadism and adrenal suppression with chronic use 3

Important Clinical Distinctions

Narrow Therapeutic Index

Opiates demonstrate a narrow therapeutic index, meaning the difference between therapeutic and toxic doses is small. 1 However, the interpatient variability in dose requirements is wide due to genetic differences in pharmacokinetics and pharmacodynamics. 1

Tolerance vs. Dependence vs. Addiction

These are distinct phenomena that clinicians must differentiate:

• Tolerance: physiological adaptation requiring higher doses for the same effect 4, 6
• Physical dependence: physiological state causing withdrawal symptoms upon discontinuation 6
• Addiction: behavioral disorder characterized by compulsive drug-seeking despite harmful consequences 6

Importantly, tolerance to analgesia develops faster than tolerance to respiratory depression, increasing overdose risk over time. 4

Critical Safety Consideration

Opioid receptor re-sensitization typically occurs within 3-7 days after discontinuation, with complete resolution of tolerance, physical dependence, and hyperalgesia generally occurring within one week for most opioids. 4 However, the state of addiction does not resolve promptly like tolerance and physical dependence. 4