Download Document

Prof Graeme Henderson
Department of Pharmacology
C32 Medical Sciences Building
[email protected]
Anticholinergics
Opioids
Benzodiazepines and related agents
Issues
• multiple agents and ‘me too drugs’
• receptor selectivity
• ‘natural’ products and synthetic agents
• pharmacokinetics
Anticholinergic drugs/cholinergic antagonists
Muscarinic antagonists (not nicotinic antagonists)
Muscarinic receptor subtypes
M1 – CNS
M2 – heart
M3 – smooth muscle and secretory glands
M4 & M5
Most current drugs are not selective e.g. atropine
pirenzepine M1/M3
benztropine M1 (less peripheral side effects)
Muscarinic antagonists
Tertiary amines (CNS penetrant)
atropine, scopolamine, benztropine, procyclidine
Quaternary amines (not CNS penetrant)
propantheline, ipratropium, dicyclomine
(low absorption into blood stream after oral
administration – use in GI spasticity disorders)
Use of muscarinic antagonists
Smooth muscle relaxation (GI disorders - IBS)
bronchodilation (exercise induced asthma,
obstructive pulmonary disease)
decrease secretions in surgery
Parkinson’s disease
Drugs exhibiting anticholinergic side effects
tricyclic antidepressants (less with SSRIs)
antipsychotics
antihistamines (sedating)
dopaminergics (e.g. amantidine)
Side effects of anticholinergics
Constipation
Transient bradycardia followed by tachycardia
and increased BP
Palpitations and arrythmias
Decreased bronchial secretions
Dry mouth and thirst
Blurred vision, pupilary dilation, loss of accommodation
Urinary urgency and retention
Photophobia
Confusion (elderly)
Nausea and vomitting
Giddiness
Opioid analgesics
Receptors
m
(MOR)
euphoria
d
(DOR)
k
(KOR)
dysphoria
ORL1
(NOR)
Partial agonist at m receptor – buprenorphine
Mixed agonist and antagonist – k agonist and m antagonist
(pentazocine)
Major therapeutic effects
Unwanted effects
Analgesia
Sedation
Euphoria
Antitussive
Constipation
Euphoria
Constipation
Nausea and vomitting
Respiratory depression
Decreased gastric acid
secretion
Histamine release (itch)
Raised intracranial pressure
hypotension
Other effects
Miosis – pin point pupils (no tolerance)
Contentious issues in pain therapy
Is the patient receiving adequate pain relief?
choice of drug, dose of drug
• Does tolerance occur?
• Does psychological dependence occur (craving)?
•Does physical dependence occur?
• Is respiration depressed?
Individual agents (>20 listed in BNF)
Powerful agonists
Morphine
Heroin
Fentanyl
Tramadol
Anti diarrhoeal
Diphenoxylate (low CNS penetration)
Partial agonist
Buprenorphine
Treatment of opioid dependence
Methadone (orally active, long t1/2)
Antitussive
Dextromethorphan
(bell shaped response curve)
Weak agonists
Codeine
Pethidine
Pentazocine
Dextropopoxyphene
Antagonist
Naloxone (short t1/2)
Naltrexone
Antianxiety, sedative and hypnotic agents
Benzodiazepines
BZ receptor agonists
Zopiclone/zolpidem
BZ receptor agonists
Buspirone
5HT1A receptor agonist
Role of pharmacokinetics in choice of drug
Hypnotic
Short t1/2 - temazepam, nitrazepam, zopiclone
Antianxiety
Long t1/2 - chlordiazepoxide, lorazepam, diazepam
Benzodiazepines
Clinical Uses
• anti anxiety
• sedative
• hypnotic
• anticonvulsant
• muscle relaxant
Side effects
• drowsiness
• confusion
• amnesia
• impaired motor coordination
• lack of depth perception
• reduced REM sleep
Benzodiazepines
Tolerance
greater to anxiolytic and anticonvulsant actions
than to hypnotic actions
Physical dependence
withdrawal induces
anxiety
dizziness
tremor
sleep disturbances
No Psychological dependence
Buspirone
• long t1/2
Side effects (less than with benzodiazepines)
nausea
dizziness
headache
restlessness
No reports of tolerance and physical dependence