that are not derived from opium. It refers particularly to opioid peptides, i.e. endogenous compounds that bind to opioid receptors and mimic the effect of morphine-like compounds.
genital system
(1) Gastrointestinal tract
GIT tone GIT motility delays passage
absorption of water
secretion of digestive gland central inhibition indigestion
nociceptor
Spinal cord
Pain transmission pathway
Drug treatment of pain
severe pain inflammatory pain local anaesthesia smooth muscle colic Opioids (eg. Morphine) NSAIDs (eg. Aspirin)
(3) Respiratory depression
respiratory rate ，tidal volume the most common cause of death from acute poisoning influenced by stimulus Mechanisms: the sensitivity of respiratory center
1975
1973
1962
Opioid receptors
NH2 Extracellular


Cytoplasmic

HOOC
G protein-coupled receptors

Opioid receptors
•: supraspinal analgesia, sedation, euphoria, dependence, respiratory depression, miosis •: spinal analgesia, sedation •: spinal analgesia, sedation, euphoria, dependence, respiratory depression •: dysphoria (烦躁不安), hallucination
drowsiness and Sedation: clouding of mentation sleep induced and aroused easily
a sense of contentment and well-being
Euphoria
the main reason for drug abuse Site: limbic system and locus ceruleus
抑制冲动传导
The cellular mechanisms
• Presynaptic inhibition: activation of opioid receptors on presynaptic nerve terminals. Close Ca2+ channel, decrease Ca2+ input, and thereby reduce transmitter release (Ach, NA, Glu, 5-HT, P). • Postsynaptic inhibition: activation of postsynaptic opioid receptors. Open K+ channels on postsynaptic neurons, increase K+ output , and thereby cause hyperpolarization and thus reduce postsynaptic neuronal excitability.
1. CNS
(1) Analgesia
insensitive: muscle spasms pain, deafferentation pain partially sensitive: nerve pain, CNS compression injury, bone cancer sensitive: myocardial infarction, other types of cancers relieve anxiety and distress, tolerance of pain
Opium (阿片) is the dried exudate obtained from unripe
seedpods of the poppy Papaver somniferum, containing morphine, codeine, and other alkaloid substances.
Limbic system
Somatosensory cortex
the sensory aspect of pain
Primary afferent fibres Noxious stimuli
PGs
BK 5-HT K+、H+
神经肽类 （如Ｐ物质）
Dorsal horn
谷氨酸 突触前膜 Ca2+突触后神经元Lo来自al anaesthetics
cholinoceptor-blocking drugs
vasodilator drugs (eg. Nitroglycerin) Carbamazepine
angina pectoris induced by coronary artery spasm
trigeminal pain
•Endogenous opioid peptides
Descending pain inhibitory pathways
Ascending pain transmission pathways
Pain
Local inhibitory interneuron in spinal cord
Pharmacological actions
Opiate (阿片剂) means that a substance is extracted from
opium or is similar in structure to natural substances present in opium.
Opioid (阿片样物质) is a term that designates substances
a call of nature
defecation reflex
constipation
(2) Biliary tract
constrict biliary smooth muscle constrict Oddi's sphincter
pressure in the biliary tract
Cortex
Opioids
NSAIDs PGs
BK 5-HT K+、H＋
Dorsal horn
Spinal cord
Sites of action of different drugs
opioid analgesics
(narcotic analgesic, addictive analgesics)
•灼性神经痛(causalgia)系指在明确的神经损伤后，与损伤神经支配范围相 一致的区域内出现的以剧烈灼样疼痛主要症状，表现为痛觉异常、痛觉过 敏、交感神经机能障碍、血流障碍、出汗异常、骨、肌肉萎缩，有时表现 出水肿性改变的慢性顽固性疼痛综合征。
(2) Sedation and euphoria
Widely use term
Opium (阿片)
Opium
The flower of papaver
Opiate (阿片剂)
• Morphine • Codeine • Papaverine (罂粟碱) ……
•structure-activity relationship
•海洛因
•吗 啡
•OH
(1) peripheral arterial and venous dilatation orthostatic hypotension Mechanisms:
release of histamine
vasomotor center
(2) intracranial pressure
to increased CO2 tension
(4) Cough suppression
codeine
• antitussive effect by inhibiting cough center
(5) Other CNS effects
Miosis: pinpoint pupils Nausea and vomiting: CTZ
Analgesics
Zhang, Bin
somatic sensation
affective (emotion)
two components
a. Acute pain (sharp pain) b. Chronic pain (dull pain)
mood effect, the affective aspect of pain
1. CNS
2. Smooth muscles
3. Cardiovascular system
S effects: principal effects
Analgesia Sedation & euphoria Respiratory depression Cough suppression Others: miosis, nausea, hormone