PCL 06- Opioids, Alan

l Relevant to the case

n Opioids for shingles

u Used when patient complained of severe pain (and antidepressent failed to work)

u Study conducted with 76 senior citizens

u Pain relief: 38% from opioids, 32% with antidepressants, 11% placebo

l Common forms

n Opium, codeine, Fentanyl, Heroin, Hydrocodone, Methadone, Morphine (strongest), Oxycodone, Paregoric, sufentanil

n Capsules, tablets, oral solution, injection…

l Mode of action

n Works at presynaptic region, inhibit release of neurotransmitters

n 3 types of opioid receptors (ultilises G proteins, opioids as ligands)

u Mu (μ)

u delta (δ)

u kappa (κ)

l Side-effects

n Allergy to the painkiller (rare)

n Addiction (rare if the course is monitored carefully)

n Common: drowsiness, sickness (goes away when body gets used to the drug)

n Others: constipation (take stool softener), dizziness, dry mouth, hallucinations

l Other Uses

n Pain relief in cancer patients

References:

http://www.australianprescriber.com/magazine/19/3/63/5/

http://www.cancerhelp.org.uk/help/default.asp?page=5976#opioids

The Essential Guide to Prescription Drugs 2006, James J. Rybacki, Pharm. D.

Shingles Definition

Shingles is caused by the varicella zoster virus (VZV). The virus initially presents in the form of the disease varicella (otherwise known as chickenpox), which then, following recovery, remains latent in dorsal root and cranial nerve ganglia. Hence only those who have had chickenpox are ever able to get shingles.
The disease predominately occurs in the elderly, although it can appear in people of any age. The virus usually reappears in immunocompromised individuals. Although the process is not completely understood, it is seen that the viral particles break away from the cell way in which they were dormant, travel down the axon, and cause inflammation and blisters to arise in the dermatome of the nerve.
The virus is transmittable to those without immunity to VZV. Until the rash forms a crust over the top, the person with shingles is highly contagious. Any newly-infected individual may develop chickenpox, but they will not immediately develop shingles.
In Australia, shingles in thought to affect up to 20% of the population in their lifetime. World statistics suggest incidence rate of herpes zoster every year ranges from 1.2 to 3.4 cases per 1,000 healthy individuals, increasing to 3.9–11.8 per year per 1,000 individuals among those older than 65 years.

‘Clinical Medicine,’ Kumar & Clark

Types of Pain - Nociceptive

Nociceptive pain occurs as a result of stimulation of sensory receptors (nociceptors).

Classified into two different types:
Somatic pain - well localised, sharp, aching or pressure-like
Visceral pain - poorly localised, aching, throbbing or colicky

Noxious stimuli (chemical, thermal or mechanical) is detected by nociceptors and transduced into electrical energy. When electrical energy reaches threshold, an action potential is generated.
There are two main classes of nociceptors:
High threshold mechanoreceptors - A-delta fibres which respond speficially to intense mechanical stimuli and mediate sharp pain.
Polymodal nociceptors - C fibres which mediate which slow, burning or throbbing pain. They are activated by algogenic (pain producing) chemicals that are released during tissue damage.

Sympathetic and Psychogenic Pain

Sympathetic pain
Related to dysfunction of the sympathetic part of autonomic nervous system (regulates heart rate, blood pressure, temperature, stomach acid secretions, sweating, etc.)

Complex Regional Pain Syndrome I (aka reflex sympathetic dystrophy, causalgia) – a chronic pain condition usually triggered by tissue injury (no nerve injury) in the extremities of the body/limbs. The pain is continuous and extreme in comparison to the severity of the injury. Symptoms include changes in skin temperature/colour (as a result of vasomotor instability), intense burning pain, sensitive skin/allodynia, sweating, swelling, motor disability.

Do not really understand the cause, just that the sympathetic nervous system has a large role in maintaining pain. Latest theories include pain receptors in the part of the body become responsive to catecholamines (NS messengers). Their release from sympathetic nerves could activate pain pathways after tissue/nerve injury.


Psychogenic pain
Pain disorder associated with psychological factors. Pain may be caused/increased/prolonged by mental or emotional problems. Diagnosed when there is no other basis for pain (biological/anatomical). Pain may increase/decrease with a change in psychogenic factors. Some of the most common types are headaches, muscle pains and back and stomach pains.

Can by acute or chronic. More common in people with anxiety disorders and mood disorders e.g. depression, bipolar

http://www.ninds.nih.gov/disorders/reflex_sympathetic_dystrophy/detail_reflex_sympathetic_dystrophy.htm
http://my.clevelandclinic.org/services/pain_management/hic_psychogenic_pain.aspx
http://www.bmhcc.org/health/library/ment3164.asp

PCL06 Shingles Treatment Myat

Pharmacological
Treatment has 3 main goals
1. Treatment of acute viral infection
2. Treatment of acute pain associated with herpes zoster
3. Prevention of postherpetic neuralgia

Antiviral Agents
· prevents the severity and duration of herpes zoster but does not reliably prevent postherpetic neuralgia
· Drugs can be used as prophylaxis and during acute phase
· Drugs should be administered 72 hours rashes appear
· Drugs :
o Acyclovir
- DNA polymerase inhibitor
- IV or Orally (low bioavailability)
- IV is given if patient is immunocompromised or if patient is unable to take it orally
- Dosing frequency – 5 times daily for 7-10 days
o Valacyclovir
- Better bioavailability than acyclovir
- Dosing frequency – 3 times daily for 7 days
o Famciclovir
- Better bioavailability than acyclovir and valacyclovir
- Long intracellular half life
- Dosing frequency – 3 time daily for 7 days

Corticosteroids
· Commonly used in conjunction with antiviral drugs
· Decreases neuritis and residual damage to nerves
· Debateable
· Recommended for patients above 50 years because they are of greater risk in dceloping postherpetic neuralgia
· Predinsone is most commonly administered

Analgesics
· Pain from virus may range from mild to severe
o Patients with mild to moderate pain may respond to OTC analgesics
o Patients with severe pain will require narcotic medication
· OTC Lotions
o Calamine – used on open lesions to reduce pain and pruritus (itch)
o Capsaicin cream – used for lesions that has crusted over
o Lidocaine – effective in reducing pain

Tricyclic Antidepressants for postherpetic neuralgia
· Reduce neuropathic pain by inhibiting reuptake of serotonin and noradrenaline NT
· Common drugs: amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil)
· Side effects: dry mouth, sedation, postural hypotension blurred vision, urinary retention

http://www.aafp.org/afp/20000415/2437.html

Cause of Shingles - Frank

PCL 6 – Cause of Shingles

Shingles, or Herpes Zoster, occurs as a result of reactivating the chickenpox virus. Those who have had Varicella Zoster Virus (VZV, the chicken pox virus) will retain the virus in a dormant state in nerve cells, and a variety of reasons such as stress, immunodeficiency, serious illness or trauma can reactivate this into Shingles. As such, Shingles itself is not contagious, although it can pass on chickenpox to anyone who has not had chickenpox before through fluids contained in the blisters. Thus, the virus responsible for shingles can be spread by direct contact with the lesions or by touching any dressings, sheets or clothes soiled with discharge from the spots.

So basically, if you’ve had chickenpox before, you can’t get shingles directly, only chickenpox.
If you’ve had chickenpox before, but not shingles, you may reactivate the VZV and develop shingles.
If you’ve had shingles before, you’re pretty much safe, as it is incredibly rare to have more than one attack of shingles.

Also, you can get immunisation against both shingles and chickenpox. The chickenpox one is free for babes at 18months, and again at 10-13 years. It can be prescribed for older patients, but costs money. Shingles is available on prescription for 50+ patients, but cost money.

http://www.betterhealth.vic.gov.au/BHCV2/bhcArticles.nsf/pages/Shingles?OpenDocument
http://www.blackmores.com.au/Conditions/Detail.aspx?ConditionId=1353

Risk Factors -- Shingles

1.Chicken pox (Varicella-Zoster virus)
- anyone who have chicken pox are at risk for shingles later in life

2.Age
- The risk for herpes zoster increases as people age
- The risk for postherpetic neuralgia (PHN) is also highest in older people with the infection and increases dramatically after age 50. PHN is persistent pain and is the most feared complication of shingles.

3.Immunosupressed
- People whose immune systems are impaired from diseases, such as AIDS or
childhood cancer, have a higher risk for herpes zoster than those with healthy
immune systems.
- Herpes zoster in people who are HIV positive may be a sign of full-blown AIDS. - -
The current drugs used for HIV, called protease inhibitors, may also increase the
risk for herpes zoster. But drug-associated herpes does not appear to be as
severe as it is in AIDS patients.

4.Cancer
- Cancer places people at risk for herpes zoster. At highest risk are those with
Hodgkin's disease (13% to 15% of these patients develop shingles). About 7%
to 9% of patients with lymphomas, and between 1% and 3% of patients with
other cancers, have herpes zoster.
- Chemotherapy also increases the risk for herpes zoster.

5.Immunosuppressant drugs
- Patients who take certain drugs that suppress the immune system are at risk for
shingles (as well as other infections). They include:
• Azathioprine (Imuran).
• Chlorambucil (Leukeran).
• Cyclophosphamide (Cytoxan).
• Cyclosporine (Sandimmune, Neoral).
• Cladribine.
These drugs can be used in patients who have undergone organ transplantation, but they are also often used for severe autoimmune diseases caused by the inflammatory process. Such disorders include rheumatoid arthritis, systemic lupus erythematosus, diabetes, multiple sclerosis, Crohn's disease, and ulcerative colitis.


http://www.cnn.com/HEALTH/library/DS/00098.html
http://nihseniorhealth.gov/shingles/causesandriskfactors/08.html
http://adam.about.com/reports/000082_2.htm

PCL 06 - Management of Neuropathic Pain

Generally, neuropathic pain responds to drugs which interfere with amine uptake or block Na+ channels.

• no evidence from controlled trials for paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), codeine, or opioid analgesics for treating the pain of acute shingles
• Opinion differs between reviews on the approach to simple analgesia, with some recommending paracetamol and a weak opioid and others suggesting paracetamol or NSAIDs (no evidence for either effectiveness or ineffectiveness of oral or topical NSAIDs)
• Tricyclic antidepressants
- have well-established efficacy in the treatment of post-herpetic neuralgia and other neuropathic pain syndromes and may therefore have an effect in treating pain in acute herpes zoster (Amitriptyline is common in UK)
- centrally inhibit NA uptake; action is independent of their antidepressant effects so SSRIs are ineffective
• Gabapentin (epilepsy drug)
- has not been extensively tested in randomized controlled trials for the relief of acute pain in shingles but is known to relieve chronic neuropathic pain
- acts on voltage gated Na+ channels
• Stronger opioids (e.g. dihydrocodeine, morphine) are thought to be useful for some people, but best to seek specialist opinion first
Not recommended:
• some evidence suggests that prednisolone may increase the rate of skin healing and relief of pain, and improve quality of life but evidence is insufficient to confirm the effectiveness and safety of corticosteroids to prevent post-herpetic neuralgia. There is also concern that corticosteroids may cause dissemination of herpes zoster and the adverse effect profile limits their use
• Pregabalin (anticonvulsant) is not recommended. It is licensed for neuropathic pain, but further post-marketing safety data are needed

Mostly quoted from http://cks.library.nhs.uk/shingles/management#-338097, also used Rang and Dale Pharmacology.

Complications & Prognosis for Shingles - Eunice

Complications
- more likely to occur in immunocompromised patients
- Posttherpetic neuralgia (PHN): Persistent pain in the same spot after blisters have healed; happens in one in five patients. Is due to damaged nerve fibres sending confused and exaggerated messages of pain from the skin to brain, so the affected area of skin is sensitive even to the slightest touch. Can persist for months of years after the lesions have disappeared, but does diminish over time. Incidence increases with age, and episodes in older individuals tend to last longer --> Most patients under 30 have no persistent pain
--> By age 40, the risk of prolonged pain lasting >1 month is 30%
--> By age 70, risk increases to 74%

- Encephalitis: inflammation of the brain
- Secondary bacterial infection
- Spread of infection throughout the body
- If shingles appears on the face: hearing problems and temporary or permanent blindness may result. Loss of facial movement (paralysis) is also possible.
- Bacterial skin infections: may occur if blisters aren’t properly treated

Prognosis
- Usually self-limiting; as the pain and rash usually go away within 3 to 5 weeks
- Usually resolves without complications
- Most people who have shingles have only one bout with the disease in their lifetime. However, individuals with impaired immune systems, i.e., people with AIDS or cancer, may suffer repeated episodes.
- The elderly or debilitated patient may have a prolonged and difficult course. For them, the eruption is typically more extensive and inflammatory, occasionally resulting in blisters that bleed, areas where the skin actually dies, secondary bacterial infection, or extensive and permanent scarring.
- Similarly, an immunocompromised patient usually has a more severe course that is frequently prolonged for weeks to months. They develop shingles frequently and the infection can spread to the skin, lungs, liver, gastrointestinal tract, brain, or other vital organs.
- Cases of chronic shingles have been reported in patients infected with AIDS, especially when they have a decreased CD4 count. Depletion of CD4 lymphocytes is associated with more severe, chronic, and recurrent varicella-zoster virus infections. These lesions are typical at the onset but may turn into ulcers that do not heal.

http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthatoz/Atoz/ency/shingles.jsp
http://www.wrongdiagnosis.com/artic/ninds_shingles_information_page_ninds.htm
http://www.wrongdiagnosis.com/s/shingles/prognosis.htm
http://www.mayoclinic.com/health/shingels/DS00098/DSECTION=complications

Neuropathic Pain - Bryn Thomas

Neuropathic pain is pain caused by a dysfunction in the nervous system.

Neuropathic pain may be caused by disorder of the central nervous system or the peripheral nervous system. Therefore the pain can be central, peripheral or mixed neuropathic pain.

Central neuropathic pain can be caused by spinal cord injuries, multiple sclerosis and sometimes in strokes.

Peripheral neuropathic pain can be caused by diabetes, herpes zoster or shingles, nutritional deficiencies, toxins, genetic and immunity disorders.

Neuropathic pain can be described as hot or cold, as a "pins and needles" sensation, numbness or itching. This is because neuropathic pain is caused by the firing of nerve fibres as well as other sensory fibres such as temperature and touch. Other signs include pain when pressure (touching or brushing) is applied to the area.

References:
Neuropathic pain : A practical guide for the clinician
http://www.cmaj.ca/cgi/content/full/175/3/265

http://www.virtualcancercentre.com/diseases.asp?did=797#Clinical_Examination

http://www.medicinenet.com/neuropathic_pain/article.htm

What are the side effects of NSAIDs?

What are the side effects of NSAIDs? - Sarah

NSAIDs are associated with a number of side effects. The frequency of side effects varies between the drugs. The most common side effects are nausea, vomiting, diarrhea, constipation, decreased appetite, rash, dizziness, headache, and drowsiness. NSAIDs may also cause fluid retention, leading to edema. The most serious side effects are kidney failure, liver failure, ulcers and prolonged bleeding after an injury or surgery. Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is administered. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID. Use of aspirin in children and teenagers with chicken pox or influenza has been associated with the development of Reye's syndrome. Therefore, aspirin and nonaspirin salicylates (e.g. salsalate) should not be used in children and teenagers with suspected or confirmed chicken pox or influenza.

References:
• http://www.medicinenet.com/nonsteroidal_antiinflammatory_drugs/article.htm