A Textbook of Clinical Pharmacology and Therapeutics

as a way of minimizing medical complications of opioid

dependence.

INTOXICATION AND OVERDOSE

For several seconds following intravenous injection, heroin

produces an intense euphoria (rush) which may be accom-

panied by nausea and vomiting, but is nevertheless pleasura-

ble. Over the next few hours the user may describe a warm

sensation in the abdomen and chest. However, chronic users

often state that the only effect they obtain is remission from

abstinence symptoms. On examination, the patient may appear

to be alternately dozing and waking. The patient may be hypo-

tensive with a slow respiratory rate, pin-point pupils and infre-

quent and slurred speech. These signs can be reversed with

naloxone. Opioids predispose to hypothermia.

Overdose is commonly accidental due to unexpectedly

potentheroinor waning tolerance (e.g. after release from

prison). Severe overdose may cause immediate apnoea, circu-

latory collapse, convulsions and cardiopulmonary arrest.

Alternatively, death may occur over a longer period of time,

usually due to hypoxia from direct respiratory centre depres-

sion with mechanical asphyxia (tongue and/or vomit block-

ing the airway).

A common complication of opioid poisoning is non-

cardiogenic pulmonary oedema. This is usually rapid in onset,

but may be delayed. Therefore, any patient who is admitted

followingheroinoverdose should usually be hospitalized for

approximately 24 hours. Naloxonereverses opioid poisoning

with a rapid increase in pupil diameter, respiratory rate and

depth of respiration. It may precipitate an acute abstinence

syndrome in addicts and (very rarely) convulsions. This does

not contraindicate its use in opioid overdoses in addicts.

Severe hypoxia causes mydriasis and some opioids (notably

pethidine) have an anti-muscarinic atropine-like mydriatic

effect, so absence of small pupils should not preclude a trial of

naloxonewhen the clinical situation suggests the possibility

of opioid overdose. Naloxoneis eliminated more rapidly than

morphine and may need to be administered repeatedly

(Chapter 25).

TOLERANCE AND WITHDRAWAL

Increasing doses of opioid must be administered in order to

obtain the effect of the original dose. Such tolerance affects the

euphoric and analgesic effects, so the addict requires more

and more opioid for his or her ‘buzz’. Changes in tolerance are

much less apparent in the therapeutic use of opioids for the

treatment of pain.

Withdrawal symptoms usually start at the time when the

next dose would normally be given, and their intensity is

related to the usual dose. For heroin, symptoms usually reach

a maximum at 36–72 hours and gradually subside over the

next five to ten days. Table 53.4 lists features of the opioid

abstinence syndrome.

OPIOID/NARCOTICANALGESICS 435

Table 53.2:Central nervous system effects of opioids

Analgesia

Euphoria

Drowsiness:sleep:coma

Decrease in sensitivity of respiratory centre to CO 2

Depression of cough centre

Stimulation of chemoreceptor trigger zone (vomiting in

15% of cases)

Release of antidiuretic hormone

Table 53.3:Medical complications of opioid addiction

Infection Endocarditis – bacterial, often tricuspid valve,

staphyloccocal, fungal (e.g. Candida)

HIV/hepatitis B virus (HBV)/hepatitis C virus

(HCV)

Abscesses

Tetanus

Septicaemia

Hepatitis

Pulmonary Pneumonia – bacterial, fungal, aspiration

Pulmonary oedema – ‘heroin lung’

Embolism

Atelectasis

Fibrosis/granulomas

Skin Injection scars

Abscesses

Cellulitis

Lymphangitis

Phlebitis

Gangrene

Neurological Cerebral oedema

Transverse myelitis

Horner’s syndrome

Polyneuritis

Crush injury

Myopathy

Hepatic Cirrhosis

Renal Nephrotic syndrome with proliferative

glomerulonephritis

Musculoskeletal Osteomyelitis (usually lumbar vertebrae,

Pseudomonas,Staphylococcus,Candida),

crush injury, myoglobinuria, rhabdomyolysis