Narcotic analgesics and non-narcotic analgesics Flashcards
1
Q
What type of drugs are narcotic analgesics?
A
Opioids
2
Q
What group of drugs are non-narcotic analgesics?
A
NSAIDs
3
Q
What proportion of visits to the doctor are due to pain?
A
60-90%
4
Q
Should lecturers put weird philosophy stuff in their slides?
A
No
5
Q
In order, what are the phases of pain?
A
- Transduction
- Transmission
- Perception
- Modulation
6
Q
What are the two general systems by which pain reception happens?
A
The nociceptive system and the antinociceptive system
7
Q
What is the nociceptive system?
A
The system of pain reception and its physical appreciation with launching of some conditional and unconditional reflexes
8
Q
What is the antinociceptive system?
A
The system of excessive pain reception suppression
9
Q
Why does the antinociceptive system exist?
A
Excessive pain perception can lead to distress and shock, so this system prevents such excess
10
Q
What are first order pain afferents?
A
Neurones that, when triggered by a stimulus, conduct a pain signal to the spinal cord.
11
Q
What are second order pain afferents?
A
Neurones that conduct a pain signal up the spinal cord
12
Q
What are opiates and opioids?
A
OPIATE
Drugs derived from opium like morphine and codeine, and a wide variety of semi synthetic agents derived from them and from thebaine, another component of opium
OPIOID
A more inclusive term referring to all agonists and antagonists with morphine-like activity as well as to naturally occurring and synthetic opioid peptides
13
Q
What does the term endorphin refer to?
A
Three families of endogenous opioid peptides: the enkephalins, dynorphins and beta-endorphins
14
Q
What kind of receptors are opioid receptors?
A
G-protein coupled receptors
15
Q
Where in the synapse are opioid receptors located?
A
On the prejunctional neurones
16
Q
What is the outcome of the effect of activated opioid receptors?
A
Inhibition of release of neurotransmitters noradrenaline, dopamine, GABA, 5-HT ad glutamate
17
Q
Describe the molecular process between activation of opioid receptors and their final effect
A
Activation reduces intracellular cAMP formation
Opening of K+ channel via μ and δ
Suppression of N-type Ca++ channels
Ultimately hyperpolarisation and reduced intracellular Ca++
Reduced neurotransmitter release
18
Q
What are the three types of opioid receptor?
A
Delta, kappa and mu
19
Q
Where are delta, kappa and mu opioid receptors found in the body?
A
Delta - Brain
Kappa - Brain, spinal cord
Mu - Brain spinal cord
20
Q
What are the therapeutic effects of activation of the three types of opioid receptor?
A
DELTA - Analgesia, antidepressant effects, physical dependence
KAPPA - Spinal analgesia, sedation, miosis, inhibition of anti-diuretic hormone release
MU1 - Supraspinal analgesia, physical dependence
MU2 - Respiratory deression, miosis, euphoria, reduced GI motility, physical dependence
21
Q
How are narcotic agents traditionally classified?
A
STRONG - morphine, diamorphine, fentanyl
INTERMEDIATE - partial agonists, mixed agonist-antagonist
WEAK - codeine
22
Q
How are narcotic agents structurally classified?
A
MORPHINANS - morphine, codeine
PHENYLPERIDINES - meriperidine, fentanyl
DIPHENYLPROPHYLAMINES - methadone, dextropropoxyphene
ESTERS - remfentanil
23
Q
How are narcotic agents functionnally classified?
A
PURE AGONISTS - morphine, codeine
PARTIAL AGONISTS - buprenorphrine
MIXED ACTION - pentazocine, nalbupine, butorphanol
ANTAGONISTS - naxolone
24
Q
What side effects of narcotic analgesics does the mnemonic MORPHINE stand for?
A
M - miosis O - orthostatic hypotension R - respiratory depression P - physical dependency H - histamine release I - increased ICP N - nausea E - euphoria S - sedation
25
Describe the analgesic action of morphine
Two components: spinal and supraspinal
Inhibits release of excitatory transmitters from primary afferents - at substantia gelatinosa of dorsal horn
Exerted through interneurones - gating of pain
At supraspinal level in midbrain, cortex and medulla - alter processing and interpretation and send inhibitory impulses through descending pathway
26
Describe the sedation caused by morphine
Drowsiness and indifference to surroundings
Inability to concentrate and extravagant imagination - colourful daydream
Apparent excitement
Larger doses produce sleep - EEG resembles normal sleep
27
Describe the mood effects of morphine
In normal persons calming effect, mental clouding, feeling of detachment, lack of initiative etc - unpleasant in absence of pain
Sometimes dysphoria
But in persons with pain and addicts sense of wellbeing, pleasurable floating sensations - kick euphoria
28
Describe the depressive actions of morphine
Respiratory centre depression - both rate and depth of depression are diminished - dangerous in head injury and asthmatics
Cough centre depressed
Temperature centre regulation depressed
Vasomotor centre - high doses cause fall in blood pressure
29
Describe the stimulating effects of morphine
CTZ (cranioreceptor trigger zone) - sensitize CTZ to vestibular and other impulses
Edingher Westphal Nucleus - miosis
Vagal centre - bradycardia
Hippocampal cells - convulsions (inhibition of GABA release)
30
Describe the effect of morphine on the gastrointestinal tract
Constipation due to direct action on the intestine reducing propulsive movement, spasm of sphincters, decrease in all GIT secretions
31
Describe the effect of morphine on the smooth muscles
Biliary tract - biliary colic, closure of sphincter of Oddi
Bladder - urinary urgency but difficulty
Bronchi - bronchospasm
32
What are the therapeutic uses of morphine?
1. Long bone fracture
2. Myocardial infarction
3. Terminal stages of cancer
4. Burn patients
5. Visceral pains - pulmonary embolism, pleurisy, acute
pericarditis
6. Biliary colic and renal colic
7. obstetric analgesia
8. Segmental analgesia
33
What are the side effects of morphine?
1. Respiratory depression (infant and old)
2. Vomiting
3. Sedation, mental clouding - sometimes dysphoria
4. Hypotensive effect
5. Rise in intracranial pressure
6. Apnoea: new born
7. Urinary retention
8. Idiosyncrasy and allergy
9. Acute morphine poisoning
10. Tolerance and dependence
34
What dose of morphine causes acute poisoning?
>50mg
35
What dose of morphine is lethal?
>250mg
36
How is morphine overdose managed?
Gastric lavage with potassium permanganate (KMNO4)
Antidote is Naloxone 0.4-0.8mg every 2-3 minutes until respiration picks up
37
What is the danger of repeated morphine use?
Psychological dependence
Physiological dependence
Tolerance
Withdrawal syndrome
38
How long do short- and long- acting opiates have an effect?
Short - 6 to 12hrs
Long - 30hrs
39
What are the symptoms of opiate withdrawal?
```
Nausea
Vomiting
Stomach cramps
Diarrhoea
Goosebumps
Depression
Drug cravings
```
40
Where does Tramadol act?
Centrally acting
41
How strongly does Tramadol stimulate opioid receptors?
Very weakly
42
How does Tramadol reduce pain?
Other mechanisms involved in analgesic action
NA reuptake inhibition - spinal inhibition of pain
43
What routes of administration are effective for Tramadol?
Oral and IV
44
How do the side effects of tramadol compare to those of morphine?
Similar but less severe
45
How well tolerated is tramadol?
Well tolerated
46
How much abuse potential is there for tramadol?
Low abuse potential
47
How well does naloxone reverse the action of tramadol?
Only partially
48
What is tramadol used for?
Neuropathic pain and short diagnostic procedures
49
What is the normal dose of tramadol?
50-100mg IV/IM/oral
50
What receptors do pure opioid antagonists have affinity for?
All opioid receptors - delta, kappa and mu
51
What can opioid antagonists do to opioids bound to alpha-receptors?
Displace them
52
What is the effect of opioid antagonists on normal people, poisoned people and addicts?
Normal - no effect
Poisoned people - reverses poisoning
Addict - relieves withdrawal symptoms
53
What is the mechanism of action of pentazocine?
Weak alpha-receptor antagonist but agonist of kappa-receptor
54
How frequently is pentazocine used?
One of the commonly used agents
55
How is pentazocine administered?
Orally and IM
56
How liable is pentazocine to be abused?
Low abuse liability
57
Describe the pharmacokinetics of pentazocine
High first pass metabolism but effective orally
Metabolised in the liver by glucoronide conjugation
Half life = 3-4hrs
58
What is the normal dose of pentazocine?
Orally 50-100mg
IM 30-60mg
59
What is pentazocine used for?
Moderately severe pain in:
```
Injury
Burns
Fracture trauma
Cancer
Orthopaedic manoeuvres
```
60
What are the features of pentazocine compared to morphine?
Spinal analgesia via kappa receptor
Dose is 30mg vs 10mg and low ceiling effect
Sedation and respiratory depression at lower doses
Tachycardia and rise in BP - dangerous in MI
Lesser smooth muscle spasms
Vomiting and other side effects are less
Subjective effects - lower ceiling (psychomimetic
effects)
Tolerance develops on repeated use but less than morphine
Withdrawal symptoms - similar to morphine
Good analgesic in subjects not exposed to morphine
Precipitate withdrawal - in morphine addicts
61
What is the origin of Buprenorphine?
Synthetic thebaine cogener
62
Is Buprenorphine lipid or water soluble?
Highly lipid soluble
63
How is Buprenorphine administered and why?
Sublingually and parenterally but not orally because of its high first pass metabolism
64
What is the mechanism of action of Buprenorphine?
Selective mu receptor agonist
65
How does the potency of buprenorphine compare to morphine
20-30 times greater than morphine
66
How does the duration of action of buprenorphine compare to that of morphine?
Slower to take effect but lasts longer - up to 24hrs
67
Describe the pharmacological effects of buprenorphine
Similar to morphine
68
What is the ceiling effect?
The drug ceiling effect refers to a particular phenomenon in pharmacology where a drug's impact on the body plateaus. At this point, taking higher doses does not increase its effect. It has, in essence, hit a ceiling. This happens with many types of drugs, including aspirin and opioids.
69
Does buprenorphine have a ceiling effect?
Yes
70
What kind of patients is buprenorphine suitable for?
Patients who are new to opioids or don't take them regularly
Unsuitable for addicts - precipitates withdrawal symptoms
71
How does tolerance of buprenorphine compare to that of morphine?
Lower
72
How does the chance of physical dependence of buprenorphine compare to that of morphine?
Lower
73
How does the liability for abuse of buprenorphine compare to that of morphine?
Lower
74
Describe the withdrawal symptoms of buprenorphine
Similar to morphine
75
Give the adverse effects of buprenorphine
Postural hypotension
Respiratory depression (fatal in neonates and cannot be reversed by naloxone)
76
Give the uses of buprenorphine
Long-lasting painful conditions - cancer
Post-operative pain
Myocardial infarction
77
What preparations are available for buprenorphine?
Norphine, Tidigesic
0.3 mg/ml injections and 0.2 mg sublingual tablets
78
How does overdose of narcotics happen?
Tolerance develops and dose is gradually increased to compensate until there is an overdose
79
What are the symptoms of opioid poisoning?
CNS - coma, convulsions
CARDIAC - hypotension, bradycardia
RENAL - urinary retension
PULMONARY - bradypnoea, Cheyne-Stokes respiration
(hyperpnoea, hypopnoea, apnoea,
repeat)
EYES - miosis
80
Give the supportive measures in opioid poisoning
Maintain patent airway
Endotracheal intubation - ventilation
Activated charcoal
81
Give the antidotes to opioid poisoning
Naloxone - all opiates except buprenorphine
Naltrexone
Nalmefene
82
Give the mechanism of action of naloxone
Competitive antagonist of all opioid receptors
Inhibits mu receptors at a much smaller dose
83
How is naloxone administered?
Always IV
84
Which symptoms of morphine action does naloxone inhibit?
All of them
85
Compared to morphine what needs to be done with the dose of naloxone to antagonise the action of nalorphine and pentazocine?
Higher doses
86
Does naloxone antagonise all the actions of nalorphine and pentazocine?
No
Dysmorphic and psychomimetic effects are not suppressed (delta receptors)
87
What doses of naloxone need to be given to alleviate withdrawal symptoms of marphine, nalorphine and pentazocine?
0.4mg doses - morphine
4-5mg doses - nalorphine and pentazocine
88
What is the basic mechanism of action of all NSAIDs?
Inhibiting cyclooxygenase (COX1, COX2) and thus inhibiting formation of prostaglandins
89
Is the action of NSAIDs reversible?
Only for aspirin
90
What are the functions of prostaglandins?
```
Induce sleep
Reduce intraocular pressure
Vasodilation
Bronchodilation
Prevent arterial sclerosis
Production of gastric mucus
Maintain renal circulation
Promoting uterine contraction
Prevents arthritis
```
91
What are the mechanisms of action of COX1 and COX2?
COX1 is responsible for the production of physiological production of prostanoids
COX2 is responsible for the production of prostanoids in sites of disease and inflammation
92
What is the function of COX1
It is described as the housekeeping enzyme that regulates normal cellular processes such as gastric cytoprotection, vascular cytoprotection, platelet aggregation and kidney function
93
What is the function of COX2?
Expression is increased during states of inflammation
94
What s the function of COX3?
Increasing of pain impulse transmission through afferent pathways
Influence upon centre of thermoregulation (decreasing of warm eradiation)
95
In terms of effects, what are the two types of non-selective COX1 and COX2 inhibitors?
Those with equal analgesic, anti-inflammatory and anti-pyretic properties
Those with Mainly anti-inflammatory effect
96
What are the therapeutic effects of NSAIDs and how do they come about?
Anti-inflammatory
Analgesic
Antipyretic
Spasmolytic
Due to COX2 inhibition
97
What are the effects of NSAIDs that are therapeutic or adverse depending on the situation?
Anti-platelet
Tocolytic
Spasmolytic
98
What are the adverse effects of NSAIDs and how do they come about?
```
Ulcerative
Chondrotropic, osteotropic
Haematotoxic
Hepatotoxic
Nephrotoxic
Cardiotoxic
Cerebrotoxic
```
Mainly COX1 inhibition
99
How are NSAIDs thought to produce their analgesic effect?
Prostaglandins are thought to sensitise nerve endings to inflammatory mediators. Therefore by reducing prostaglandin formation through COX inhibition, NSAIDs reduce pain
100
What kind of pain are the salicylate NSAIDs used for?
Low to moderate severity arising from musculoskeletal disorders
101
Name conditions in which NSAIDs are used
Rheumatoid arthritis and osteoarthritis
102
How is fever related to the NSAIDs?
Fever is produced when an inflammatory process produces endogenous pyrogenic agents which stimulate the production of prostaglandins which increase the set point of the hypothalamus, thus causing fever.
By inhibiting prostaglandin production, NSAIDs reduce fever
103
How do NSAIDs reduce inflammation?
Inhibition of prostaglandin production reduces aspects of inflammation in which prostaglandins are mediators
104
Can aspirin arrest the progress of arthritis or induce remission?
No
105
How can NSAIDs be used for the treatment of patent ductus arteriosus?
It is the cessation of production of prostaglandins that normally closes the ductus arteriosus
Small doses of aspirin or indomethacin mimic this effect and cause closure in most cases
106
Give clinical uses of NSAIDs
For prevention of attack of MI (prevent platelet aggregation)
For relief of dysmenorrhea
For gout in high dose
107
Give the adverse GI effects of NSAIDs
```
Epigastric distress
Nausea
Vomiting
Erosions
Ulceration
GI bleeding
```
108
How do NSAIDs cause GI issues?
Reduced prostaglandins increase acid production, reduce bicarbonate production, reduce mucus production and reduce trophic effects on mucosal cells.
109
How can GI symptoms of NSAIDs be reduced?
Use COX2 specific NSAIDs
Limit duration of therapy as much as possible
Limit dose as much as possible
110
Give the renal disorders caused by NSAIDs
```
Salt and fluid retention
Hypertension
Interstitial nephritis
Nephrotic syndrome
Acute renal failure
Acute tubular necrosis
```
111
How do NSAIDs cause renal adverse effects?
Changes in renal haemodynamics cause by a reduction in prostaglandins which normally cause a widening of the afferent arterioles
112
What are the adverse effects of NSAIDs on blood?
Prolonged bleeding time due to reduced platelet aggregation
113
How should NSAIDs be managed if a patient requires surgery?
Aspirin should be stopped 1 week before surgery
114
What is the metabolic side effect of NSAIDs?
Hyperthermia?
115
How do NSAIDs cause hyperthermia?
In toxic quantities they cause energy that normally goes towards producing ATP to be dissipated as heat
116
What percentage of people given NSAIDs experience a hypersensitivity reaction?
15% (including me!)
117
What is Reye's syndrome?
Fulminating liver failure with cerebral oedema when aspirin or other salicylates are given during a viral infection, most commonly seen in children
118
In children what should be used to reduce fever in order to avoid risk of Reye's disease?
Acetaminophen
or
Ibuprofen
119
What are the symptoms of mild salicylism (salicylate poisoning)?
```
Nausea
Vomiting
Marked hyperventilation
Headache
Mental confusion
Dizziness
Tinnitus
```
120
How dangerous can salicylates be in children?
Ingestion of as little as 10mg can be lethal
