Lecture 4 - Anlagesic and Gut Motility Drugs Flashcards
1
Q
Pain Assessment
Comment on difficulties
What the patient must address
No response to treatment??
A
- Pain is hard to describe
- Clinicians may underestimate pain
- NEED to listen to what and how tha patient is describing their pain
- Characterise the pain
- Identify the underlying mechanism/cause
- Assess the effect on the patient’s functioning and quality of life
*If the patient is not responding, re-evaluate the patient for any missed causes*
2
Q
What type of assesment can be used to help the patient describe the pain?
Give Examples.
A
Pain Assesment Scales
1) Simple Descriptive Pain Intensity Scale
2) Numeric Rating Scale
3) Visual Analogue Scale
3
Q
How is pain classified?
Give Examples
A
1) Nociceptive Pain
Tissue Damage
-
Somatic
- Well localised, throbbing, ache
- Metastatic bone pain
-
Visceral
- From the stretching or expansion of hollow organs
- Signals carried by the ANS
- NOT as well localised
- Often referred pain
- Ex. Left shoulder pain caused by irritation of the right diaphragm caused by enlarged liver
- Liver Capsule Pain
- Presents as continous aches, dull
- Malignant bowel obstruction
- Colic Pain
2) Neuropathic Pain
- Nerve Damage
- Central/Local
- Presents:
- Dysaesthetic (burning)
- Lancinating (sharp pain)
4
Q
Describe the WHO Pain ladder
Address the appropriate treatment for each step
A
1) Aceteminophen, NSAIDS, Asprin
2) Codeine, Percocet, Percodan
* Combinations of Oxycodone with acetaminophen or aspirin
3) Morphine, Hydromorphone, Oxycodone, Methadone, Fentanyl
* DO NOT USE Meperidine
5
Q
Draw the Analgesic Arrow
A
6
Q
Paracetemol
Classification
Mechanism
Mode of Action
Indications
Adverse Effects
A
- Classification
- Analgesic
- Antipyretic
- NOT an NSAID
2. Mechanism
- Inhibits PG synthesis via COX-3 (CNS)
- DOES NOT PROMOT
- GI ulcers
- Bleeding
- Renal Failure
- Peripherally blocks generation of pain impulses
- Inhibits hypothalamic heat-regulation centre
3. Mode of Action
- Analgesic
- Weak PG inhibitor
4. Indications
- Mild/Moderate pain w/o inflammation
5. AE
- Rare at normal dosage
- Caution in liver failure/underweight
- Liver/Renal toxicity with overdose
7
Q
Paracetmol
Modes of metabolism
A
8
Q
Opiate: Analgesics
1) Source
2) Principal Alkaloids
3) Classification
A
Source
- Seed pods of opium poppy
Prinicipal Alkaloids
- Morphine
- Codeine
Classification
- Full Agonist = High Efficacy
- Partial Agonist = Weaker analgesia
9
Q
Terminology
Opium
Opiate
Opiod
A
- Greek word meaning juice or exudate from the poppy
- A drug extracted from the exudate of a poppy
- Natural or synthetic drug that binds to opiod receptors producing agonist effect
10
Q
What are the 2 sources of Natural Opiods?
Where are the rest derived from?
A
Sources:
1) The juices of the opium poppy (morphine and codeine)
2) Endogenous Endorphins
Remainder
- Prepared from Morphine
- Semisynthetic drugs such as heroin
- Synthesised from Precursor compunds
- Fentanyl
11
Q
What are the Pharmacological Effecs of opiods?
A
1) Sedation and Anxiolytic
2) Depressed Respiration
- Main cause of death from opiod overdose
- Combination of OPIODS and ALCHOL = BAD
3) Cough Supression
4) Pupillary Constriction
5) Nausea and Vomitting
- Stimulation of receptors in an area of the medulla called the chemoreceptor trigger zone
- Causes nausea and vomitting
6) GI
- Can relieve diarrhoea
7) Other
- Opiods release histamines causing itching or more severe allergic reactions including bronchoconstriction
- Affect white blood cell function and immune function
12
Q
What is the mechanism of action of Opiods
A
- Activation of peripheral nociceptive fibers causes release of substance P and other pain-signaling neurotransmitters from nerve terminals in the dorsal horn of the spinal cord
- Release of pain-signaling neurotransmitters is regulated by endogenous endorphins or by exogenous opioid agonists by acting presynaptically to inhibit substance P release, causing analgesia
13
Q
What is the mode of action of Morphine?
Target
Action
Effect
Overall Effect
A
Target:
G- Protein coupled opioid mu receptors in the CNS or peripheral nervous system
Action:
Full Agonist
Effect:
- Closure of N-type, voltage dependent calcium channels
- Opening of calcium dependent inward;y rectifiying Potassium channels,
- Increased k+ conductance
- Also Inhibit the release of substance P
- Pain signalling neurotransmitter
Overall Effect:
- Membrane hyperpolarization
- Reduced neuronal excitabilty
- Reduction/Inhibition of pain NT signals
14
Q
What are the 3 of Opiod receptors?
Explain the differences
A
- mu
- Kappa
- Delta
15
Q
Describe the differences between the 3 subtypes of the mu receptor
A
Mu 1
- Central interpratation of pain
MU 2
- Respiratory Depression
- Spinal Analgesia
- Euphoria
- Dependence
MU 3
- Only Opiod alkaloids
16
Q
Further Explain the kappa receptor
A
- Only modest analgesia
- Little or no respiratory depression
- Little or no dependence
- Dysphoric effects
17
Q
Further explain the delta receptor
A
- It is unclear what delta’s responsible for
- Delta agonists show poor analgesia and little addictive potential
- May regulate mu receptor activity
18
Q
What is the expected response if an Opiod binds to a MU receptor
A
ANALGESIA
19
Q
What is the expected response if an opiod binds to a Mu2
A
- Analgesia
- Respiratory Depression
- Euphoria
- Decrease GI motility
- Physical Dependance
20
Q
What is the expected response if an opiod binds to a KAPPA receptor
A
- Analgesia
- Dysphoria
21
Q
Prescribing Opiods
- Weak Opiods
- Strong Opiods
- Do NOT use
A
1. Weak
- Dose often
- Codeine limited by presence of paracetmol and constipation
- Tramadol
- Caution in elderly and those on SSRI
2. Strong
- Morphine
- Oxycodone
- Fentanyl
- Diamorphine
- Hydromorphone
- Methadone
- Buprenorphine
3. DO NOT USE
- Pethidine
22
Q
What are the differences between opiods?
A
- Loads of inter and intra-individual variability in response to opiods
- Analgesic Response
- Side Effect responses
23
Q
Principles of Dosing Opiods
What is the goal?
A
The right dose is the one that achieves the best analgesia with the least side effects.
24
Q
Opiod Formulations
Discuss the options
Comment when to use either or
A
1) Short Acting
- Opiod-naïve patients
- Pain crisis
2) Long Acting
- For stable situations
- Can add a SA for breakthrough pain episodes
25
**Pharmackinetics of Opiods**
a) onset of pain relief
b) duration of pain relief
c) half life of transdermal fentanyl
**Onset of pain relief**
– Oral opioids 15 - 30 min
– SC opioids 5 - 10 min
– IV opioids 3 - 5 min
**Duration of pain relief**
– Short-acting oral opioids 3 - 5 hours
– Long-acting oral opioids 8 - 12 hours
– Fentanyl patches 48 - 72 hours
– IV or SC opioids 2 - 4 hours
– IV/SC fentanyl 40 minutes
**Half-life of transdermal fentanyl**
– 12 to 24 hours
26
How can one calculate the **breakthrough dose?**
* Equivalent to a 4 hourly dose
* May need to titrate dose according to patient needs: 5% to 25% of total daily opioid dose
* Generally use the same opioid as being used for regular regimen (except with fentanyl patches)
27
Contraindication of Opiods
Patients with...
* Impaired pulmonary function
* Impaired hepatic and/or renal function
* Hypothyroidism
* Recent head injury
28
Clincial Uses of Opiods
* Analgesia for severe visceral pain
* Acute pulmonary edema
* Cough suppression
* Diarrhoea
* Pre-medication
* Regional anaesthesia
29
**Tolearance in Opiods**
What is it?
Demonstrated by...
Physiological Tolerance...
Will it occur with Opiods?
* A **diminished responsiveness** to the drug’s action that is seen with many compounds
* Demonstrated by a decreased effect from a constant dose of drug or by an increase in the minimum drug dose required to produce a given level of effect
* Physiological tolerance involves changes in the binding of a drug to receptors or changes in receptor transductional processes related to the drug of action
* **This type of tolerance occurs in opioids**
30
**Physiological Dependance**
Withdrawl Reactions?
* Occurs when the drug is necessary for normal physiological functioning – this is demonstrated by the withdrawl reactions
* Withdrawl reactions are usually the opposite of the physiological effects produced by the drug
31
# Define Withdrawl
Give Examples of **Acute effects** and **Withdrawl Signs**
**Withdrawl** gives the opposite effect of the drugs physiological effect
**Acute**
Analgesia
Respiratory Depression
Euphoria
Relaxation and sleep
Tranquilization
Decreased blood pressure
Constipation
Pupillary constriction
Hypothermia
Drying of secretions
Reduced sex drive
Flushed and warm skin
**Withdrawl**
Pain and irritability
Hyperventilation
Dysphoria and depression
Restlessness and insomnia
Fearfulness and hostility
Increased blood pressure
Diarrhoea
Pupillary dilation
Hyperthermia
Lacrimation, runny nose
* Spontaneous ejaculation
* Chilliness and “gooseflesh”
32
Give an example of an opiod **antagonist**
Use?
Affinity?
MOA?
* Naloxone
* Opioid antagonists are used to treat opioid overdose
* Strong binding affinity for the Mu receptor
* Work by competitive inhibition site blocking agonist activity
33
**Management of Narcosis**
What is Narcosis?
How to recognise?
What to do if they ar uncoscious or in resp. depression?
**Narcosis**: Excess opiods
Suspect the diagnosis in any patient with **small pupils.**
\*If the patient is ***unconscious or has respiratory***
***depression:***
* Ensure a clear airway (ABCDE)
* Give naloxone iv every two minutes until the patient improves or until eight doses have been given.
* Check blood sugar
34
What to **remember** if the patient responds to Nalaxone
**RECAP:** Nalaxone = Opiod antagonist
* Relapse is likely after about **20 - 30 minutes.**
* Withdrawal effects can be precipitated .
* Infusion of naloxone may be required if relapse occurs.
35
Methods of Relieving Pain
**Remove peripheral stimulus**
* E.g. Treat infection / tooth extraction / NSAIDs
**Interrupt nociceptive input**
* NSAIDs / local anaesthetic / neurectomy
**Stimulate nociceptive inhibitory mechanisms**
* Electrical (TENS) / Heat
**Modulate central pain awareness**
* Opiates / General anaesthetics / Psychotropics
**Treat secondary factors contributing to pain**
* Muscle spasm (relaxants)
36
Summary #1
* There are different types of opioids with varying potencies
* They are very effective general pain relievers for moderate-severe pain but have a lot of adverse effects (some of which are serious)
* They don’t have any anti-inflammatory properties and therefore are less ideal in inflammatory pain
* If someone becomes narcosed (too much opioid) then this can be reversed by a competitive antagonist Naloxone – but care is needed due to shorter duration of action
37
Mechanisms of Nausea and Vomitting
**Brain Cortex**
* GABA
* Anxiety
* Anticipatory Nausea
**Vestibular Appartus**
* Histamine
* Motion Induced
**Vomitting Centre**
* AcH
* Dopamine
**GI tract**
* Dopamine
* 5HT3
* Tumors
* Obstruction
* Distension
**Chemoreceptor Trigger Zone**
* Dopamine, 5HT3
* Drugs (e.g. chemotherapy, opioids, SSRIs)
* Toxins (infections, etc)
* Biochemical (e.g. hypercalcemia, uremia, etc)
38
Management of Nausea
* Attempt to identify the underlying cause(s)
* Attempt to correct the underlying cause(s) if possible and if appropriate
* **Treat the symptoms**
* Anti-emetics selected according to the inferred underlying mechanisms
* **Prevent nausea**
* Employ a regular anti-emetic regimen if nausea is prolonged
* Prevent constipation
* If one agent not completely effective, review and add another or replace with another
39
Examples of Anti-emtics?
Caution
* **Anti-dopamine agents (CTZ)\***
* Metoclopramide
* **5HT3 antagonists**
* Ondansetron
* **Anti-Histamine**
* ****Cyclizine
**NOTE:**
\*Care in young people as can cause **_acute dystonia_**
40
What do Anti-emetics do?
Metclopramide SE?
**Pro-motility and anti-dopamine agents**
**1) Metoclopramide**
* Extrapyramidal side effects may occur
* Upper GI pro-motility
41
Which Anti-Emetics are appropriate for palliative care?
* **5-HT3 antagonists**
* Ondansetron
42
Causes of Constipation
**Other**
* Immobility
* poor diet
* poor fluid intake
* increased fluid loss (e.g. vomiting, diarrhoea, fever).
**Drugs**
* Opioids
* anti-muscarinics
**Local Pain**
* Anal fissure
* peri-anal abscess.
**Benign colorectal disease**
**Neuropathy**
**Malignancy** - Colorectal, ovarian, and uterine tumours
43
Treatment of Constipation
* Increase fluid intake
* Improve mobility
* Increased fibre intake (unless d/t opioids)
* Stopping constipating drugs
* Excluding underlying pathology
44
What is the MOA of laxatives
## Footnote
**Osmotic**
**Fecal Softener**
**Stimulant**
**Osmotic**
* Macrogols
* Lactulose
* Promote H20 out of cells into the gut lumen
* Large volume in bowel - enters and creates distension
* Purgation within an hour
**Fecal Softener**
* Docusate
* **Dulcolax** - Sodium Picosulfate
* Sofetenr and stimulant
* increases GI secretions into the lumen
**Stimulant laxatives**
* Bisacodyl
* Senna
* Stimulates eneteric nervous system to increase peristalsis and e- + H20 addition to the lumen
45
Management of Constipation
- Pre-empt constipation by putting everyone at risk (eg patients on opioids) on regular laxatives
- Treat reversible causes eg give analgesia if pain on defecation, alter diet, ↑ fluid intake
- Adjust any constipating medication, if possible.
- Advise the person about increasing dietary fibre, drinking an adequate fluid intake, and exercise.
**•Offer oral laxatives if dietary measures are ineffective, or while waiting for them to take effect.**
–Start treatment with a bulk-forming laxative (Fybogel)(adequate fluid intake is important).
–If stools remain hard, add or switch to an osmotic laxative (macrogols (Movicol))
– If stools are soft but the person still finds them difficult to pass or complains of inadequate emptying, add a stimulant laxative (Ducolax (sodium picosulfate)/ enema).
**If the person has opioid-induced constipation:**
– Avoid bulk-forming laxatives.
– Use an osmotic laxative (macrogols (Movicol))(or docusate which also softens stools) and a stimulant laxative (Ducolax (sodium picosulfate)/ enema).
• Laxatives can be stopped once the stools become soft and easily passed again.
46
Summary #2
* Nausea and vomiting often has multi-factorial influences – aim to treat cause
* Select anti-emetic based on likely cause baring in mind potential adverse effects
* Constipation also often has multiple influences – use practical measures to reduce these
* Different classes of laxative work synergistically
47
