Antifungal drug

Anti-Fungal Drugs are used to treat infections caused by a fungus. Though they are prescriprion drugs,
they also come under the category of non-prescription drugs, as you can get these drugs over the counter
without a doctor's prescription. Common fungal infections include athlete's foot, jock itch, yeast infection,
and ringworm.

An antifungal drug is a medication used to treat fungal infections such as athlete's

foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis,
and others. Such drugs are usually obtained by a doctor's prescription or purchased over-the-
counter

Mode of action
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal
organism without dangerous effects on the host.
Thus fungal and human cells are similar at the molecular level. This makes it more difficult to
find or design drugs that target fungi without affecting human cells.
As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be
life-threatening if the drugs are not used properly.

Types of Anti Fungal Drugs

• Systemic antifungal drugs: These medicnes are taken by mouth or by injection.

• Topical antifungal drugs: They are applied to the skin to treat skin infections.

• Purpose of Anti Fungal Drugs

• Anti-Fungal Drugs are used to treat infections in various parts of the body that are caused
by a fungus. A fungus is a one-celled form of life. A fungus survives by invading and living
off other living things. Fungi mostly live in moist, dark places, including some parts of the
body.

The areas in which fungal infections are formed are in the armpits, mouth, groin, and
genital areas, including scalp, neck, trunk, and other parts of the body. Topical
antifungaldrugs help in relieving the infection and also the associated problems like
itching, burning, and cracked skin. However, for internal fungal infection, systematic
antifungal drugs are required. They are used to treat a type of fungal infection called
candidiasis which can occur in the throat or in the vagina. Can also be used to treat fungal
infections such as histoplasmosis, blastomycosis, and aspergillosis, which can affect the
lungs and other organs.

Anti fungal drugs are available in the form of tablets, capsules, liquid, and injectable
forms, creams, ointments, sprays and powders

Popular Anti Fungal Drugs

o Fluconazole
o Itraconazole

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 o Ketoconazole
o Miconazole
o Miconazole
o Ciclopirox
o Clotrimazole
o Econazole
o Nystatin
o Oxiconazole
o Terconazole
o Tolnaftate.

Precaution
Apart from side-effects like liver-damage or affecting estrogen levels, many medicines can cause allergic
reactions in people. For example, the azole group of drugs is known to have caused anaphylaxis.

There are also many drug interactions. Patients must read in detail the enclosed data sheet(s) of the medicine.
For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors
of the P-glycoprotein, which (among other functions) excretes toxins and drugs into the intestines.[1] Azole
antifungals also are both substrates and inhibitors of the cytochrome P450 familyCYP3A4,[1] causing increased
concentration when administering, for example, calcium channel
blockers, immunosuppressants,chemotherapeutic drugs, benzodiazepines, tricyclic
antidepressants, macrolides and SSRIs.

Classes
Polyene antifungals
Amphotericin B

has been the mainstay of antifungal therapy for invasive and serious mycoses, but other antifungals
(eg, voriconazole , posaconazole , the echinocandins) are now considered first-line drugs for many of these
infections.

For chronic mycoses, conventional amphotericin B

is usually started at ≥ 0.3 mg/kg IV once/day, increased as tolerated to the desired dose (0.4 to 1.0 mg/kg;
generally not > 50 mg/day); many patients tolerate the target dose on the first day. If patients tolerate the target
dose, twice that dose can be given on a more convenient alternate-day schedule. Extended treatment courses
may be even less frequent (eg, 3 times/wk).

For acute, life-threatening mycoses, amphotericin B

is started at 0.6 to 1.0 mg/kg IV once/day. For certain rapidly progressive opportunistic mycoses (eg, invasive

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aspergillosis), daily doses as high as 1.5 mg/kg have been used, usually divided into 2 or 3 infusions. These
doses must be decreased to about 0.5 mg/kg/day as nephrotoxicity develops.

For chronic meningitis, intrathecal amphotericin B

Azole Antifungals
Azoles block the synthesis of ergosterol, an important component of the fungal cell membrane. They
can be given orally to treat chronic mycoses. The first such oral drug ,ketoconazole

has largely been supplanted by more effective, less toxic triazole derivatives, such as fluconazole
, itraconazole
, posaconazole
, and voriconazole
. Drug interactions can occur with all azoles but are less likely with fluconazole

Fluconazole: This water-soluble drug is absorbed almost completely after an oral dose. It is excreted
largely unchanged in urine and has a half-life of > 24 h, allowing single daily doses. It has high
penetration into CSF (≥ 70% of serum levels) and has been especially useful in treating cryptococcal
and coccidioidal meningitis. It is also one of the first-line drugs for treatment of candidemia in non-
neutropenic patients. Doses range from 200 to 400 mg po once/day to as high as 160 mg once/day in
some seriously ill patients and in patients infected with Candida glabrata or other Candida sp (not C.
albicans); daily doses of ≥ 1000 mg have been given and had acceptable toxicity.
Adverse effects that occur most commonly are GI discomfort and skin rash. More severe toxicity is unusual,
but the following have occurred: hepatic necrosis, Stevens-Johnson syndrome, anaphylaxis, alopecia, and,
when taken after the 1st trimester of pregnancy, congenital fetal anomalies.

Drug interactions occur less often with fluconazole than with other azoles. However,fluconazole
sometimes causes elevated serum levels of cyclosporine

Itraconazole: This drug has become the standard treatment for lymphocutaneous sporotrichosis as
well as for mild or moderately severe histoplasmosis, blastomycosis, and paracoccidioidomycosis. It
is also effective in mild cases of invasive aspergillosis, some cases of coccidioidomycosis, and
certain types of chromoblastomycosis.Itraconazole
can clear some types of fungal meningitis, but it is not the drug of choice. Because of its high

Adverse effects with doses of up to 400 mg/day most commonly are GI, but a few men have reported erectile

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dysfunction, and higher doses may cause hypokalemia, hypertension, and edema. Other reported adverse
effects include allergic rash, hepatitis, and hallucinations.

Drug and food interactions can be significant. Acidic drinks (eg, cola, acidic fruit juices) or food
(especially high-fat foods) improves absorption from the GI tract. However, absorption may be
reduced if itraconazole is taken with prescription or OTC drugs used to lower gastric acidity. Several
drugs, including rifampin

Voriconazole: This broad-spectrum triazole can be used as first-line therapy for seriousAspergillus infections;
most clinical mycologists consider it the treatment of choice forAspergillus infections in immunocompetent and
immunocompromised hosts.Voriconazole

can also be used to treat Scedosporium apiospermum and Fusariuminfections. Additionally, the drug is
effective in candidal esophagitis and other candidal infections; it has activity against a broader spectrum
of Candida sp than does fluconazole

Adverse effects that must be monitored for include hepatotoxicity, visual disturbances, hallucinations, and
dermatologic reactions. This drug can prolong the QT interval. Also, there are numerous drug-drug
interactions, notably with certain immunosuppressants used after organ transplantation.

Echinocandins
Echinocandins are water-soluble lipopeptides that inhibit glucan synthase. Their mechanism of action is unique
among antifungal drugs; echinocandins target the fungal cell wall, making them attractive because they lack
cross-resistance with other drugs and their target is fungal and has no mammalian counterpart. Echinocandins
available in the US are anidulafungin, caspofungin
and micafungin. There is little evidence to suggest that one is better than the other, but anidulafungin appears
to interact with fewer drugs than the other two.

These drugs can be used to treat various forms of candidiasis, aspergillosis, and other mycoses

Anti-dandruff shampoos
Antifungal drugs (such as ketoconazole) are often found in anti-dandruff shampoos. The antifungal drugs
inhibit the yeast Malassezia globosa which encourages seborrhoeic dermatitis and tinea versicolor.

Antihelminthic and Antiprotozoal Agents

"Antihelminthic and Antiprotozoal Agents". You can download the module from this page to put on your
computer. You can also launch the module straight off the web using the launch quiz link on the right-hand
side of this page. Another way to access this quiz is to install the Qedoc Quiz Player and bring up its directory
of downloadable quizzes. Whichever way you choose to use it, it's free.

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tiprotozoal drugs are used to treat a variety of diseases caused by protozoa. Protozoa are animal-like, one-
celled animals, such as amoebas. Some are parasites that cause infections in the body. African sleeping
sickness, giardiasis, amebiasis, Pneumocystis carinii pneumonia (PCP), and malaria are examples of diseases
caused by protozoa.

Description
Antiprotozoal drugs come in liquid, tablet, and injectable forms and are available only with a doctor's
prescription. Some commonly used antiprotozoal drugs are metronidazole (Flagyl), eflornithine (Ornidyl),
furazolidone (Furoxone), hydroxychloroquine (Plaquenil), iodoquinol (Diquinol, Yodoquinol, Yodoxin), and
pentamidine (Pentam 300).

Recommended dosage
The recommended dosage depends on the type of antiprotozoal drug, its strength, and the medical problem for
which it is being used. Check with the physician who prescribed the drug or the pharmacist who filled the
prescription for the correct dosage. Always take antiprotozoal drugs exactly as directed.

Precautions
Some people feel dizzy, confused, lightheaded, or less alert when using these drugs. The drugs may also
cause blurred vision and other vision problems. For these reasons, anyone who takes these drugs should not
drive, use machines or do anything else that might be dangerous until they have found out how the drugs
affect them.
The antiprotozoal drug furazolidone may cause very dangerous side effects when taken with certain foods or
beverages. Likewise, metronidazole (Flagyl) can cause serious liver damage if taken with alcohol. Check with
the physician who prescribed the drug or the pharmacist who filled the prescription for a list of products to
avoid while taking these medicines.
Anyone who has ever had unusual reactions to antiprotozoal drugs or related medicines should let his or her
physician know before taking the drugs again. The physician should also be told about any allergies to foods,
dyes, preservatives, or other substances.
Some antiprotozoal drugs may cause problems with the blood. This can increase the risk of infection or
excessive bleeding. Patients taking these drugs shouldbe careful not to injure their gums when brushing or
flossing their teeth or using a toothpick. They shouldcheck with the physician before having any dentalwork
done. Care should also be taken to avoidcuts from razors, nail clippers, or kitchen knives, orhousehold tools.
Anyone who has any of these symptoms while taking antiprotozoal drugs should call the physician
immediately:

• Fever or chills
• Signs of cold or flu
• Signs of infection, such as redness, swelling, or inflammation
• Unusual bruising or bleeding
• Black, tarry stools
• Blood in urine or stools
• Pinpoint red spots on the skin
• Unusual tiredness or weakness.

Anyone taking this medicine should also check with a physician immediately if any of these symptoms occur:

• Blurred vision or other vision changes

• Skin rash, hives, or itching
• Swelling of the neck
• Clumsiness or unsteadiness
• Numbness, tingling, pain, or weakness in the hands or feet
• Decrease in urination.

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Children are especially sensitive to the effects of some antiprotozoal drugs. Never give this medicine to a child
unless directed to do so by a physician, and always keep this medicine out of the reach of children. Use safety
vials.
The effects of antiprotozoal drugs on pregnant women have not been studied. However, in experiments with
pregnant laboratory animals, some antiprotozoal drugs cause birth defects or death of the fetus. Women who
are pregnant or who plan to become pregnant should check with their physicians before taking antiprotozoal
drugs. Mothers who are breastfeeding should also check with their physicians about the safety of taking these
drugs.

Key terms
Amebiasis — An infection caused by an ameba, which is a type of protozoan.
Fetus — A developing baby inside the womb.
Giardiasis — A condition in which the intestines are infected with Giardia lamblia, a type of protozoan.
Inflammation — Pain, redness, swelling, and heat that usually develop in response to injury or illness.
Parasite — An organism that lives and feeds in or on another organism (the host) and does nothing to benefit
the host.
Pneumocystis carinii pneumonia — A severe lung infection caused by a parasitic protozoan. The disease
mainly affects people with weakened immune systems, such as people with AIDS.
Before using antiprotozoal drugs, people with any of these medical problems should make sure their
physicians are aware of their conditions:

• Anemia or other blood problems

• Kidney disease
• Heart disease
• Low blood pressure
• Diabetes
• Hypoglycemia (low blood sugar)
• Liver disease
• Stomach or intestinal disease
• Nerve or brain disease or disorder, including convulsions (seizures)
• Psoriasis (a skin condition)
• Hearing loss
• Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD)
• Eye or vision problems
• Thyroid disease.

Side effects
The most common side effects are diarrhea, nausea, vomiting, and stomach pain. These problems usually go
away as the body adjusts to the drug and do not require medical treatment.
Other rare side effects may occur. Anyone who has unusual symptoms after taking an antiprotozoal drug
should get in touch with his or her physician.

Interactions
Antiprotozoal drugs may interact with other medicines. When this happens, the effects of one or both of the
drugs may change or the risk of side effects may be greater. Anyone who takes antiprotozoal drugs should let
the physician know all other medicines he or she is taking. Among the drugs that may interact with
antiprotozoal drugs are:

• Alcohol
• Anticancer drugs
• Medicine for overactive thyroid
• Antiviral drugs such as zidovudine (Retrovir)
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 • Antibiotics
• Medicine used to relieve pain or inflammation
• Amphetamine
• Diet pills (appetite suppressants)
• Monoamine oxidase inhibitors (MAO inhibitors) such as phenelzine (Nardil) and tranylcypromine
(Parnate), used to treat conditions including depression and Parkinson's disease.
• Tricyclic antidepressants such as amitriptyline (Elavil) and imipramine (Tofranil)
• Decongestants such as phenylephrine (Neo-Synephrine) and pseudoephedrine (Sudafed)
• Other antiprotozoal drugs.

The list above does not include every medicine that may interact with an antifungal drug. Be sure to check with
a physician or pharmacist before combining antifungal drugs with any other prescription or nonprescription
(over-the-counter) medicin
Anti-malarial drugs are medicines that prevent or treat malaria.

Purpose
Anti-malarial drugs treat or prevent malaria, a disease that occurs in tropical, subtropical, and some temperate
regions of the world. The disease is caused by a parasite, Plasmodium, which belongs to a group of one-celled
organisms known as protozoa. The only way to get malaria is to be bitten by a certain type of mosquito that
has bitten someone who has the disease.

Description
Anti-malarial Drugs are available only with a physician's prescription. They come in tablet, capsule, and
injectable forms. Among the commonly used Anti-malarial Drugs are Chloroquine, Mefloquine, Primaquine,
Pyrimethamine, and Quinine.

Malaria
Malaria is a female-mosquito-borne infectious disease caused by a eukaryotic protist of the
genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of theAmericas (22
countries), Asia, and Africa. After a period of between two weeks and several months (occasionally years)
spent in the liver, the malaria parasites start to multiply within red blood cells, causing symptoms that
include fever, and headache. In severe cases the disease worsens leading to hallucinations, coma, and
death.
Five species of the plasmodium parasite can infect humans: the most serious forms of the disease are
caused by Plasmodium falciparum. Malaria caused by Plasmodium vivax,Plasmodium
ovale and Plasmodium malariae causes milder disease in humans that is not generally fatal. A fifth
species, Plasmodium knowlesi, is a zoonosis that causes malaria inmacaques but can also infect humans.[1]
[2]

Malaria transmission can be reduced by preventing mosquito bites by distribution of inexpensivemosquito

nets and insect repellents, or by mosquito-control measures such as sprayinginsecticides inside houses
and draining standing water where mosquitoes lay their eggs. Although many are under development, the
challenge of producing a widely available vaccinethat provides a high level of protection for a sustained
period is still to be met.[3]
A variety of antimalarial medications are available. In the last 5 years, treatment of P. falciparuminfections
in endemic countries has been transformed by the use of combinations of drugs containing
an artemisinin derivative. Severe malaria is treated with intravenous or intramuscular quinine or,
increasingly, the artemisinin derivative artesunate.[4] Several drugs are

also available to prevent malaria in travellers to malaria-endemic countries (prophylaxis). Resistance has
developed to several antimalarial drugs, most notably chloroquine.[5]

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Each year, there are more than 250 million cases of malaria,[6] killing between one and three million people, the
majority of whom are young children in sub-Saharan Africa.[7] Ninety percent of malaria-related deaths occur in
sub-Saharan Africa. Malaria is commonly associated with poverty, and can indeed be a cause of poverty[8] and
a major hindrance to economic development

Chloroquine

Preparations available: Avloclor® (Zeneca) and Nivaquine® (Rhône-Poulenc Rorer). Adult dose is 2
tablets (each containing 150mg chloroquine as base) taken once a week. Nivaquine is available in
syrup form.

Consider a trial course before departure, if using this regime for the first time, to detect if you are
likely to get side effects (e.g. for two weeks). Otherwise, when possible, chloroquine should be
started one week before exposure (to ensure adequate blood levels), throughout exposure and for
4 weeks afterwards.

Nausea and sometimes diarrhoea can occur which may be reduced by taking tablets after food.

Headache, rashes, skin itch, disturbance of visual accommodation (often expressed as blurred
distance vision which may take up to 4 weeks to reverse) or hair loss may warrant changing to
alternative drugs.

Retinopathy (eye changes) which can be permanent is unlikely to occur until 100g have been
consumed (i.e. over 5 years treatment at prophylactic doses).

Caution in liver and renal disease.

Can aggravate psoriasis and very occasionally causes a convulsion so it should not normally be
used in those with epilepsy.

Chloroquine is very toxic in overdose - parents must take special care to store the tablets safely.

It is generally accepted, as a result of long usage, to be safe in pregnancy.

Proguanil
Preparations available: Paludrine® (Zeneca. Adult dose is 200mg daily.

Can normally be used continuously for a period of up to 5 years.

One or two doses should be taken before departure. It should be continued throughout exposure
and for 4 weeks afterwards.

Anorexia, nausea, diarrhea and aphthous (simple) mouth ulcers can occur.

Can delay the metabolism of the anticoagulant, warfarin, and result in bleeding. Those planning to
take warfarin must discuss this with their doctor before starting any treatment.

Caution in renal impairment.

Considered to be safe in pregnancy, but folate supplement is advised.

Mefloquine®
Preparations available: Lariam® (Roche). Adult dose is 250mg weekly.

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 One dose should be taken a week before departure and it should be continued throughout
exposure and for 4 weeks afterwards however three (3) doses at weekly intervals prior to
departure are advised if the drug has not been used before - this can often detect, in advance,
those likely to get side effects so that an alternative can be prescribed.

Not licensed in Britain for use for more than 1 year (in countries where it is licensed for more than
1 year, additional side-effects are rare).

Nausea, diarrhea, dizziness, abdominal pain, rashes and pruritis can occur.

Headache, dizziness, convulsions, sleep disturbances (insomnia, vivid dreams) and psychotic
reactions such as depression have been reported. These reactions most commonly begin within 2-3
weeks of starting the drug and may be worse if alcohol is taken around the same time as the
mefloquine.

Avoid in epilepsy, if there is a close family history of epilepsy (e.g. parents or siblings) or if there
is a history of psychiatric illness.

Caution, and avoid if alternatives are available, in severe renal or liver failure and those with heart
rhythm defects. Also caution in those taking digoxin, beta or calcium channel blockers when
arrhythmias and bradycardia can occur.

Although there is no evidence to suggest that mefloquine has caused harm to the foetus it should
normally be avoided during the first trimester of pregnancy or if pregnancy is considered possible
within 3 months of stopping prophylaxis.

Doxycycline

• Preparations available: Doxycycline (non-proprietary), Vibramycin® (Invicta). Adult dose is 100mg

daily.
• Can normally be used continuously for a period of at least 3 months - be guided by your doctor.
• Consider a trial course before departure, if you are using this regime for the first time, to detect if
you are likely to get side effects (e.g. for one week). Otherwise doxycycline need only be started
just before exposure (e.g. 2 days), continued through exposure and for 4 weeks afterwards.
• When other tetracyclines are being already used for acne this will provide protection against
malaria so long as an adequate dose is taken (you can change to 100mg doxycycline per day if
your doctor agrees).
• Erythema (sunburn) due to sunlight sensitivity can occur. Use of sunscreens is especially important
and if severe, alternative prophylaxis should be used.
• Heartburn is common so the capsule should be taken with a full glass of water and preferably while
standing upright.
• Contraindicated in pregnancy (including one week after completing the course), breast feeding, in
those with systemic lupus erythematosis, porphyria and children under 12 years because
permanent tooth discoloration can occur.
• It may reduce the effectiveness of the oral contraceptive pill, you should discuss this with your
family planning advisor.
• Occasionally anorexia, nausea, diarrhoea, candida infection and sore tongue (glossitis) have been
reported and rarely hepatitis, colitis and blood dyscrasias.

Malarone®
Adult dose is one tablet daily - each tablet contains 250mg atovaquone plus 100mg proguanil. Not
licensed in UK for children less than 40kg.

DO NOT confuse with Maloprim® which is not now advised for prophylaxis since more effective
alternatives are available.

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 Should be taken for 1 or 2 days before entering the malarious area, throughout exposure, and for
7 days after leaving the infected area. Can be used for trips of up to 28 days.

Consider a trial course before departure if you are using this regime for the first time so as to
detect if you are likely to get side effects (e.g. one week). Otherwise malarone need only be
commenced one or two days before exposure.

Abdominal pain, headache, anorexia, nausea, diarrhoea, coughing and aphthous (simple) mouth
ulcers can occur.

Absorption may be reduced in diarrhoea and vomiting, and blood levels are significantly reduced
with concomitant use of tetracyclines, metoclopramide and especially rifampicin or rifabutin

The proguanil component can delay the metabolism of the anticoagulant, warfarin, and result in
bleeding. Those planning to take warfarin must discuss this with their doctor before starting any
treatment.

Caution in renal impairment.

Lack of experience in pregnancy and during breast feeding means that it should be avoided in
these circumstances unless there is no suitable alternative.

No guidance is given yet on long term use by the manufacturers - the high cost makes it likely that
it will be mostly used for short trips.

NARCOTICS AND NON – NARCOTIC ANALGESICS:

Pain is something all of us feel; yet it is difficult for healthcare providers to accurately assess
because pain is whatever you say it is. You know it hurts when you twist an ankle or have a
pounding headache. All you want is fast relief.
You want a magic pill to make the pain go away.
The pill may be a narcotic agonist that blocks transmission of impulses from the site of the injury
to the area of the brain that interprets pain.

Defining Pain
Pain is whatever the patient who is experiencing pain says it is. Healthcare providers describe
pain in terms of intensity, duration, frequency, and type of pain. However, these terms are
subjective and characterized by the patient.

Components of Pain
There are two components of pain.
 physical sensation of pain and
 psychological component.

The physical sensation of pain occurs when nerve endings are stimulated causing it to send
an impulse along the nerve pathways to the brain, which transmits a pain response.

The psychological component is a person’s emotional response to pain based on a person’s

pain threshold.

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 The pain threshold is the level of nerve-ending stimulation that causes the person to have the
feeling of unbearable pain.

For example, applying heat to the skin will cause the sensation of pain.
However, the point beyond which pain becomes unbearable (pain tolerance) varies widely
among individuals.

Pain tolerance is also different for the same person depending on the circumstance in which
sensation is detected. For example, a toothache might hurt more when you’re home than at
work where you have a lot of distractions from the pain.

The Gate Control Theory

The gate control theory is an attempt to describe the mechanism of pain transmission.
The dorsal horn of the spinal cord contains a gate mechanism that alters
the transmission of painful sensations from peripheral nerve fiber to the thalamus and cortex of
the brain. The thalamus and the cortex is where painful sensations are recognized as pain.

Pain is classified in six ways.

1. Acute pain is the presence of severe discomfort or an uncomfortable sensation that has a
sudden onset and subsides with treatment.
For example, a fractured bone causes acute pain since the uncomfortable sensation occurs
suddenly when the bone is broken and subsides when the bone is immobilized in a cast.
Pain associated with myocardial infarction (heart attack), appendicitis, and kidney stones
are also examples of acute pain. Acute pain can be treated with NSAIDs or opioid analgesics.
2. Chronic pain is a persistent or recurring pain that continues for six months or more.
This is the pain from cancer and rheumatoid arthritis and other chronic conditions. Chronic pain
is treated with combinations of NSAIDs and opioid analgesics as well as medications to reduce
swelling and anxiety.
3. Visceral pain is the dull and aching pain caused by stimulating nerve endings in smooth
muscle or sympathetically innervated organs.
Visceral pain is referred pain. This makes it difficult to localize the source of the pain.

Pain of a myocardial infarction (MI) is an example of visceral pain.

MI can be described as crushing chest pain and also described as pain in the left arm or hand
and even the shoulder, left back, or the left ear.
Visceral pain is best treated with opioid analgesics.

4. Somatic pain is pain occurring from skeletal muscles, fascia, ligaments, vessels and
joint. Somatic pain is an aching, throbbing pain over the affected area. Somatic pain is
best treated with nonsteroidal anti-inflammatory agents.

5. Neuropathic pain is a burning, shooting, and sometimes tingling pain that is caused by
peripheral nerve injury.
This is caused by the invasion of a cancerous tumor or nerve damage.
Neuropathic pain is treated with a combination of medications such as anticonvulsants, tricyclic
antidepressants, and opioid analgesics.

6. Psychogenic pain is pain caused by psychiatric illness or psychosocial stimuli such as

anxiety, depression, and fear.
Drug therapy alone may bring brief relief. Psychotherapy may bring long-lasting relief from
psychogenic pain.

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 Agonists and antagonists:
Agonist drugs activate receptors to produce the desired response. Conventional agonists
increase the proportion of activated receptors. Inverse agonists stabilize the receptor in its
inactive conformation and act similarly to competitive antagonists
Many hormones, neurotransmitters (eg, acetylcholine, histamine, norepinephrine), and drugs
(eg, morphine

Antagonists prevent receptor activation. Preventing activation has many effects. Antagonist
drugs increase cellular function if they block the action of a substance that normally decreases
cellular function. Antagonist drugs decrease cellular function if they block the action of a
substance that normally increases cellular function.

Narcotic agonists

 are medications that relieve pain. These are safe and effective when properly
administered. These medications are opioid based and are used to treat acute or chronic
pain from trauma, tumor growth, and from surgical procedures.
They are also used to treat pain caused by the progression of diseases or complications from
other conditions.

NARCOTIC ANALGESICS

Narcotic analgesics are known as narcotic agonists, and act on the central nervous system
to provide relief from moderate and severe pain.

Narcotic analgesics are also used to suppress coughing by acting on the respiratory and cough
centers in the medulla of the brain stem.

Opioids are a category of narcotic analgesics. All relieve pain

Except meperidine (Demerol),
 have an antitussive (cough suppression) and antidiarrheal effect.

NARCOTIC ANTAGONISTS

Narcotic antagonists are antidotes for overdoses of narcotic analgesics.

They have a higher affinity to the opiate receptor site than the narcotic analgesic and block the
narcotic analgesic from binding to the opiate receptor site.
They also reverse the respiratory and CNS depression caused by the narcotics.

Naloxone (Narcan) is a narcotic antagonist and can be used to determine if an unconscious

patient has used an opioid narcotic drug. If the patient wakes up after Narcan is administered
intravenously, the patient is likely to have ingested or injected an opioid narcotic.

MIGRAINE HEADACHES
Migraines are a debilitating neurovascular disorder that affects 28 million people over the age of
11. The cause of migraines is not clearly understood although research indicates the expansion

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of blood vessels and the release of certain chemicals—such as dopamine and serotonin—causes
inflammation and pain.

Dopamine and serotonin are found normally in the brain. A migraine can occur
if an abnormal amount of these chemicals are present or if the blood vessels are unusually
sensitive to them.
Patients who have migraines experience intense, throbbing, headache pain which is often
accompanied by nausea, photophobia (sensitivity to light), phonophobia (sensitivity to sound),
and temporary disability.
Migraines are sometimes preceded by an aura such as a breeze, odor, a beam of light, or a
spectrum of colors. Migraines can occur on one side of the head (unilateral) and the pain is
frequently reported as pulsating or throbbing.

Treatment of migraine is divided into prevention and symptomatic relief.

There are six categories of medication used to prevent migraines. These are
blood-vessel constrictors and dilators (see Chapter 26), antiseizure drugs (discussed later in this
chapter), antidepressants (discussed later in this chapter), beta-blockers (see Chapter 26), and
analgesics (see Chapter 16).
Patients are given a selected combination of these medications to prevent migraines. The
prescriber determines the most effective combination for each patient based on the patient’s
response to these medications.

Commonly prescribed medications to prevent migraines are amitriptyline divaproex sodium,

propranol, timolol, topiramate, bupropion, cyproheptadine, diltiazem, doxepin, fluvoxamine,
ibuprofen, imipramine, and methysergide.
Methysergide is particularly effective. However, there are side effects that might
make this drug less tolerable.

Bringing about symptomatic relief from the pain associated with migraines
and other migraine symptoms is achieved by prescribing antiemetics (antinausea,
see Chapter 18), ergot alkaloids and related compounds, NSAIDS (see
Chapter 12), and other analgesic (nonopioids); opioids, and triptans (see

MIGRAINE HEADACHES

Migraines are a debilitating neurovascular disorder that affects 28 million people over the age of
11. The cause of migraines is not clearly understood although research indicates the expansion
of blood vessels and the release of certain chemicals—such as dopamine and serotonin—
causes inflammation and pain.

Dopamine and serotonin are found normally in the brain. A migraine can occur if an abnormal
amount of these chemicals are present or if the blood vessels are unusually sensitive to them.

Patients who have migraines experience intense, throbbing, headache pain which is often
accompanied by nausea, photophobia (sensitivity to light), phonophobia (sensitivity to sound),
and temporary disability.

 Migraines are sometimes preceded by an aura such as a breeze, odor, a beam of light, or
a spectrum of colors.
 Migraines can occur on one side of the head (unilateral) and the pain is frequently
reported as pulsating or throbbing.
Treatment of migraine is divided into prevention and symptomatic relief.

13
There are six categories of medication used to prevent migraines.
blood-vessel constrictors and dilators
antiseizure drugs
antidepressants
beta-blockers
analgesics

Patients are given a selected combination of these medications to prevent migraines. The
prescriber determines the most effective combination for each patient based on the patient’s
response to these medications.
Commonly prescribed medications to prevent migraines are amitriptyline, divaproex sodium,
propranol, timolol, topiramate, bupropion, cyproheptadine, diltiazem, doxepin, fluvoxamine,
ibuprofen, imipramine, and methysergide.

Methysergide is particularly effective.

However, there are side effects that might make this drug less tolerable.
Bringing about symptomatic relief from the pain associated with migraines and other migraine
symptoms is achieved by prescribing antiemetics (antinausea,
NSAIDS and other analgesic (nonopioids); opioids,

Centrally acting muscle relaxants

Carisoprodol (Soma), Cyclobenzaprine (Flexeril) and Methocarbamol (Robaxin).

These drugs decrease pain, increase range of motion and have a sedative effect on the patient.
Centrally acting muscle relaxants should not be taken concurrently with central nervous system
depressants such as barbiturates, narcotics, and alcohol.

Diazepam (Valium) and Baclofen (Lioresal)

These are used to treat acute spasms from muscle trauma and for treating spasms caused by
chronic neurologic disorders.

Dantrolene sodium (Dantrium)

This is a peripherally acting muscle relaxant. Peripherally acting muscle relaxants depress
neuron activity at the skeletal muscles and have a minimal effect on the central nervous system.
These are most effective for spasticity or muscle contractions caused by chronic neurologic
disorders. This is also used to treat malignant hypertension which is an allergic reaction to
anesthesia

Antispasmodic
Drugs
Definition
Antispasmodic drugs relieve cramps or spasms of the stomach, intestines, and bladder.

Purpose
Antispasmodic drugs have been used to treat stomach cramps. Traditionally, they were used to treat stomach
ulcers, but for this purpose they have largely been replaced by the acid inhibiting compoundsa, the H-2
receptor blockers such as cimetidine and ranitidine and the proton pump inhibtors such as omeprazole,
lansoprazole and rabetazole.

14
Most of the drugs used for this purpose as "anticholinergics", since they counteract the effects of the
neurohormone acetylcholine. Some of these drugs are derived from the plant belladonna, also known as
Deadly Nightshade. There is also a group of drugs with similar activity, but not taken from plant sources. The
anticholingergics decrease both the movements of the stomach and intestine, and also the secretions of
stomach acid and digestive enzymes. They may be used for other purposes including treatment of Parkinson's
Disease, and bladder urgency. Because these drugs inhibit secretions, they cause dry mouth and dry eyes
because of reduced salivation and tearing. Dicyclomine is an antispasmodic with very lettle effect on
secretions. It is used to treat irritable bowel syndrome.

Description
Dicyclomine is available only with a prescription and is sold as capsules, tablets (regular and extended-release
forms), and syrup.

Recommended dosage
The usual dosage for adults is 20 mg, four times a day. However, the physician may recommend starting at a
lower dosage and gradually increasing the dose to reduce the chance of unwanted side effects.

The dosage for children depends on the child's age. Check with the child's physician for the correct dosage.

Precautions
Dicyclomine makes some people sweat less, which allows the body to overheat and may lead to heat
prostration (fever and heat stroke). Anyone taking this drug should try to avoid extreme heat. If that is not
possible, check with the physician who prescribed the drug. If heat prostration occurs, stop taking the medicine
and call a physician immediately.

This medicine can cause drowsiness and blurred or double vision. People who take this drug should not drive,
use machines, or do anything else that might be dangerous until they have found out how the medicine affects
them.

Dicyclomine should not be given to infants or children unless the physician decides the use of this drug is
necessary. Diclyclomine should not be used by women who are breast feeding. Women who are pregnant or
plan to become pregnant should check with their physicians before using this drug.

Key terms
Heat stroke — A serious condition that results from exposure to extreme heat. The body loses its ability to
cool itself. Severe headache, high fever, and hot, dry skin may result. In severe cases, a person with heat
stroke may collapse or go into a coma.

Hiatal hernia — A condition in which part of the stomach protrudes through the diaphragm.

Hyperthyroidism — Secretion of excess thyroid hormones by the thyroid gland.

Inflammation — Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Myasthenia gravis — A condition in which certain muscles weaken and may become paralyzed.

Reflux esophagitis — Inflammation of the lower esophagus caused by the backflow of stomach contents.

Spasm — Sudden, involuntary tensing of a muscle or a group of muscles

Ulcerative colitis — Long-lasting and repeated inflammation of the colon with the development of sores.

15
Anyone with the following medical conditions should not take dicyclomine unless directed to do so by a
physician:

• Previous sensitivity or allergic reaction to dicyclomine

• Glaucoma
• Myasthenia gravis
• Blockage of the urinary tract, stomach, or intestines
• Severe ulcerative colitis
• Reflux esophagitis.

In addition, patients with these conditions should check with their physicians before using dicyclomine:

• Liver disease
• Kidney disease
• High blood pressure
• Heart problems
• Enlarged prostate gland
• Hiatal hernia
• Autonomic neuropathy (a nerve disorder)
• Hyperthyroidism.

Side effects
The most common side effects are dizziness, drowsiness, lightheadedness, nausea, nervousness, blurred
vision, dry mouth, and weakness. Other side effects may occur. Anyone who has unusual symptoms after
taking dicyclomine should get in touch with his or her physician.

Interactions
Dicyclomine may interact with other medicines. When this happens, the effects of one or both of the drugs may
change or the risk of side effects may be greater. Among the drugs that may interact with Dicyclomine are:

• Antacids such as Maalox

• Antihistamines such as clemastine fumarate (Tavist)
• Bronchodilators (airway opening drugs) such as albuterol (Proventil, Ventolin)
• Corticosteroids such as prednisone (Deltasone)
• Monoamine oxidase inhibitors (MAO inhibitors) such as phenelzine (Nardil) and tranylcypromine
(Parnate)
• Tranquilizers such as diazepam (Valium) and alprazolam (Xanax).

Antispasmodic drugs relieve cramps or spasms of the stomach, intestines, andbladder. The drug
described here, dicyclomine (Bentyl), is prescribed to treat a condition called irritable bowel
syndrome. In some people, the main symptom is abdominal pain. In others, it is diarrhea or
alternating bouts of diarrhea and constipation.

Dicyclomine is available only with a prescription and is sold as capsules, tablets (regular and
extended-release forms), and syrup. The usual dosage for adults is 20 mg, four times a day.
However, the physician may recommend starting at a lower dosage and gradually increasing the
dose to reduce the chance of unwanted side effects. The dosage for children depends on the
child's age.Check with the child's physician for the correct dosage.

Dicyclomine makes some people sweat less, which allows the body to overheat and may lead to
heat prostration (fever and heat stroke). Anyone taking this drug should try to avoid extreme
heat. If that is not possible, check with thephysician who prescribed the drug. This medicine can
16
cause drowsiness and blurred or double vision. People who take this drug should not drive, use
machines, or do anything else that might be dangerous until they have found out how the
medicine affects them.

Dicyclomine should not be given to infants or children unless the physician decides the use of
this drug is necessary. Diclyclomine should not be used bywomen who are breast feeding.
Women who are pregnant or plan to become pregnant should check with their physicians before
using this drug.

Anyone with the following medical conditions should not take dicyclomine unless directed to do
so by a physician:

• Previous sensitivity or allergicreaction to dicyclomine

• Glaucoma
• Myasthenia gravis
• Blockage of the urinary tract, stomach, or intestines
• Severe ulcerative colitis
• Reflux esophagitis.

In addition, patients with these conditions should check with their physicians before using
dicyclomine:

• Liver disease
• Kidney disease
• High blood pressure
• Heart problems
• Enlarged prostate gland
• Hiatal hernia
• Autonomic neuropathy (a nerve disorder)
• Hyperthyroidism.

Dicyclomine may interact with other medicines. When this happens, the effectsof one or both of
the drugs may change or the risk of side effects may be greater. The most common side effects
are dizziness, drowsiness, lightheadedness, nausea, nervousness, blurred vision, dry mouth, and
weakness. Other side effects may occur. Anyone who has unusual symptoms after taking
dicyclomine should get in touch with his or her physician. Be sure to check with a physician or
pharmacist before combining dicyclomine with any other prescription or nonprescription (over-
the-counter) medicine

Opioid analgesics
Opioid analgesics relieve pain caused by tissue damage.

Opioids include: morphine, diamorphine, pethidine/meperidine, meptazinol, dihydrocodeine(

df118), codeine, buprenorphine, tramadol, fentanyl, remifentanil, methadone, and
the “morphine antagonist or blocker”, naloxone.

Actions: Opioids are analgesic and anxiolytic: this dual action is helpful in some clinical
situations. They are similar to endorphins and enkephalins, which are the body’s natural
mood changers and analgesics in times of stress. They interact with dopamine in the areas of
the brain associated with ‘reward’. Prescribed opioids act on the different types of opioid
receptors of the spinal cord, brain stem, cerebral cortex and smooth muscle. Generally,
opioids (endogenous and pharmacological) depress the activity of nerve or smooth muscle
17
cells and have a calming effect. Sometimes, sedation, mental detachment or euphoria are
the predominant effects, and the patient may be able to tolerate pain, while still perceiving
the sensation.
Opioids regulate the endocrine, gastrointestinal, autonomic and immune systems, and
may trigger histamine release. They also act directly on the neurones of the chemoreceptor
trigger zone, which activates the vomiting centre

Indications:
_ pain and trauma.
_ severe pain in palliative care.
_ surgery.
_ myocardial infarction: slow intravenous diamorphine.
_ acute pulmonary oedema: slow intravenous diamorphine.
_ analgesia and suppression of respiratory activity in patients receiving intensive care and
assisted ventilation.
_ cough suppression in terminal care.
Specialists sometimes prescribe opioids for chronic non-malignant pain (Gutstein & Akil
2006). Such patients may need advice regarding driving.

Administration: Where pain is anticipated opioids should be administered regularly.

If pain has built-up, the dose needed to achieve analgesia may induce sedation. Less drug is
needed to prevent pain than to relieve it. Patients who are older, debilitated, malnourished,
or have impaired renal or hepatic function require lower or less frequent doses.
Morphine. Oral morphine is often the opioid of choice for pain control in palliative care. The
proportion absorbed is increased by food and varies between individuals. Extra doses may
be needed for painful procedures, such as dressing changes; these should be administered
30 minutes before the procedure. Morphine can be administered as modified release

capsules, which can be opened and added to soft food and swallowed without chewing
(BNF 2007 p. 229, Box 1.1).

Buprenorphine can be administered orally, sublingually, transdermally or by injection. Different

brands of transdermal patches deliver different doses. Times taken to achieve
analgesia and duration of action also differ. Buprenorphine may cause withdrawal reactions
a few days after discontinuation and in patients accustomed to opioid use. It is also prescribed
in substance misuse teams.
Codeine, dihydrocodeine and dextropropoxyphene are included in some compound
preparations
with paracetamol. At these low doses, they often provide very little analgesia, but
can cause unpleasant side effects: codeine is very constipating and dihydrocodeine causes
nausea, particularly in older people.

Diamorphine/heroin is highly lipid-soluble therefore:

_ It readily crosses the blood-brain barrier and rapidly relieves pain and distress.
_ Enough diamorphine for 24 hours can be placed in small patient-controlled analgesia
devices or syringe drivers. Low volume subcutaneous infusions cause less oedema and
induration at the syringe driver site (Fonzo-Christe et al. 2005).

Fentanyl is twice as lipid-soluble as diamorphine. It can be absorbed through the lining of

the mouth. It acts within 5 minutes and lasts 80–90 minutes. Lozenges may be administered
5 minutes before wound dressings or for breakthrough pain. Single and multiple doses of
fentanyl buccal tablets may not be bioequivalent (glossary) (Darwish et al. 2006).
In palliative care, skin patches may offer convenient alternatives to syringe drivers (Box
18
13.1). Patches are changed every 72 hours. The prolonged action of transdermal fentanyl
means that dose titration may be difficult. The full effects of a patch will not be experienced
for 24 hours, and monitoring should be continued for 24 hours after removal.

Box 13.1 Transdermal administration of medications

Gloves are worn when handling patches and skin preparations (Smith et al. 2008).
Gloves are not impermeable, and hand washing is important (Pratt et al. 2007).
Ensure that patches are applied to:

_ Hairless, unshaved areas. Shaving disrupts hair follicles, increasing absorption.

_ Dry skin, free of irritants, including soap.
_ Upper arms, chest or back (usually). The upper back is often the best site for
patients who may be confused or inclined to interfere with the patch. The thin skin
behind the ear is a popular site for hyoscine patches.
_ Sites which have not been used for several days, longer if advised by manufacturers
(some buprenorphine patches, should not be re-applied for 3 weeks (BNF 2007)).
Advise that:
_ Palm pressure for 30 seconds should ensure closure of patch edges.
_ On removal, patches should be folded. Used patches contain sufficient medication
to warrant disposal in ‘biohazard’ containers, rather than general waste (Smith et
al. 2008).

Increased absorption may occur if the patient or patch becomes hot, due to a fever,
hot bath, electric blanket or environmental conditions.
_ Inflammation may occur at the patch site. This should be reported. Particular care
over possible delayed reactions to buprenorphine patches.
_ Should a patch fall off, medication should be removed from the skin and a new
patch may be applied on a new site.

Hydromorphone capsules may be swallowed whole or the contents sprinkled onto food.
Modified release capsules and the 4-hourly capsules contain different quantities of the drug.

Pethidine/meperidine accumulates with prolonged administration. To avoid irritation, scarring

or fibrosis at injection sites, ensure sites are documented and not re-used.

Tramadol. In addition to its opioid actions, tramadol enhances the actions of serotonin and
noradrenaline/norepinephrine. Therefore, it has additional adverse effects, such as hypertension,
diarrhoea, confusion.

Naloxone reverses the effects of other opioids, including: respiratory depression, sedation,
itching, myoclonus (glossary) and analgesia. The half-life (glossary) and duration of action of
naloxone are much shorter than those of morphine, diamorphine, pethidine, fentanyl and
other opioids (1 hour versus 2–5 hours). Therefore, the effects of naloxone wear off before
those of the other opioid, allowing problems to re-emerge. Following administration, close
observation is required to identify any recurrence of respiratory depression.

Adverse effects:
_ Central nervous system depression and sedation. Opioids act directly on the respiratory
centre in the brain stem to depress respiration. They reduce the sensitivity of the respiratory
centre to carbon dioxide, thus reducing the normal drive to
respiration. Rate, depth and regularity of respirations are decreased, reducing the amount of air
reaching the alveoli, and oxygenation of the body. Depression of the carbon dioxide respiratory
drive means that the patient’s breathing depends on the hypoxic respiratory drive.
19
Administration of a high concentration of oxygen to a patient whose respirations are depressed
due to opioids can remove the remaining respiratory drive and precipitate a sudden respiratory
arrest.
This may be difficult to reverse, due to a sharp rise in carbon dioxide concentration (Gutstein &
Akil 2006). Respiratory problems are compounded by the depression of the cough reflex and
inhibition of the cilia lining the respiratory tract. These problems may continue after pain relief
has ceased. More rarely, the cardiovascular centres in the brain stem are depressed.

_ Stimulation of excitable tissues. Opioids reduce the availability of the neurotransmitter

responsible for inhibiting the nervous system, GABA. This can cause
excitability.

_ Gastrointestinal disturbances. Opioids act on the smooth muscle of the gut to

inhibit peristalsis, causing gastric stasis, delayed transit and constipation. At the
same time, they intensify sphincter contractions and the segmental contractions of
the gut or the common bile duct. This can cause spasms and colic.

_ Genito-urinary disturbances. Opioids act in the hypothalamus to increase secretion

of prolactin and reduce secretion of luteinizing hormone. This reduces secretion of

testosterone and inhibits ovulation. Opioids can cause spasm of the urethral
sphincter.

_ Impaired immunity. Opioids cause histamine release, unrelated to hypersensitivity

responses. There are opioid receptors on the cells of the immune system. Both pain
and opioids suppress the immune system. Overall, opioids boost the immune
system by relieving pain (Gutstein & Akil 2006).

Adverse effects: implications for practice: OPIOIDS

The commonest side effects of opioids are nausea, vomiting, constipation, drowsiness. Large
doses produce respiratory depression and hypotension.

Cautions and contra-indications:

_ Increased intra-cranial pressure (stroke, head injury). Opioids may increase intracranial
pressure and obscure vital signs/pupil reflexes.
_ Decreased respiratory reserve, including obesity and kyphosis; contra-indicated if pCO2
(carbon dioxide partial pressure or concentration) is increased.
_ Pregnancy and breastfeeding (Jordan 2002b).
_ Dependence (unimportant in palliative care).
_ Known allergy to opioids.
_ Renal insufficiency.
_ Dextropropoxyphene should be avoided where overdose is possible as it induces heart failure.
_ Neonates and premature babies require proportionately lower doses, due to the high
permeability of the blood-brain barrier. Fentanyl may cause jaundice.
Conditions which may be worsened include:
_ asthma.
_ acute alcohol intoxication.

20
Rare adverse effects reported with epidural, intrathecal or intravenous administration
_ Neonates and premature babies require proportionately lower doses, due to the high
permeability of the blood-brain barrier. Fentanyl may cause jaundice.
Conditions which may be worsened include:
_ asthma.
_ acute alcohol intoxication.
_ liver failure.
_ convulsive disorders (particularly tramadol, pethidine).
_ biliary colic, pancreatitis.
_ conditions where there is a possibility of paralytic ileus.
_ pre-existing hypotension, for example due to haemorrhage.
_ hypothyroidism or Addison’s disease.
_ phaeochromocytoma (glossary).
_ enlarged prostate.
_ myasthenia gravis.
Opioids are no longer recommended for:
_ cough suppression in children.
_ management of diarrhoea.

Interactions (summary):
21
Hypotension, sedation and respiratory depression may be intensified by: alcohol,
antihistamines, barbiturates, anaesthetics (nitrous oxide), benzodiazepines, metoclopramide,
phenothiazines, tricyclic antidepressants, and other non-opioid sedatives.
Protease inhibitors, cimetidine, and occasionally ranitidine, may have this effect.

Central nervous system toxicity may occur if: pethidine (possibly also fentanyl and
dextropropoxyphene) are administered within two weeks of any MAOI (including
moclobemide and (possibly) linezolid) or selegiline or rasagiline (for Parkinson’s);
tramadol is co-administered with most antidepressants; dextromethorphan is
co-administered with memantine (for dementia).

Myoclonus is more likely with co-administration of: chlorpromazine, haloperidol,

amitriptyline and some NSAIDs (but not diclofenac).

Drying of secretions, and therefore need for mouth care, is intensified by coadministration
of hyoscine, cyclizine or related drugs, see anti-emetics.
Oestrogens (including oral contraceptives), phenytoin, carbamazepine and rifampicin
decrease the effectiveness of some opioids. Phenytoin increases the risk of toxicity
with pethidine. Antiviral and antifungal drugs may affect opioid concentrations.
Dextropropoxyphene intensifies the effects of warfarin and carbamazepine.
Opioid-induced gastric stasis may delay or impair absorption of other drugs, for
example paracetamol.
Drugs are often mixed in syringe drivers, but compatibilities may be complicated

ANESTHETIC AGENTS

Anesthetic agents depress the central nervous system causing a loss of consciousness.
They are classified as general and local.

Anesthetic agents were introduced in surgery in the early 1800s in the form of nitrous oxide
which continues to be used today for dental procedures.

 General anesthetics are used for general surgery, cardiac surgery, neurosurgery,
 and pediatric surgery.
 They are administered by an anesthesiologist or a nurse anesthetist. They are inhaled
through a mask or breathing tube.
 A general anesthetic can consist of one medication or a combination of medications—
called balanced anesthesia—depending on the patient’s age, weight, medical history,
general health, and allergies.

This balanced approach is used when administering general anesthetics to patients in phases to
minimize cardiovascular problems, decrease the amount of general anesthetic needed, reduce
possible post-anesthetic nausea and vomiting, minimize the disturbance of organ function, and
increase recovery from anesthesia with fewer adverse reactions.

The night before the surgery, the patient is given a hypnotic to assist with a good night’s sleep.
On the day of the surgery, premedication may be given to the patient about one hour before
surgery.

Premedication typically consists of two medications.

One is a benzodiazepine such as lorazepan (Ativan). This medication sedates and decreases
anxiety.
The other is an anticholinergic such as atropine to decrease secretions.
22
A short-acting barbiturate such as thiopental sodium (Pentothal) is then administered in
the operating room to induce anesthesia.

The patient is then given inhaled gas and oxygen to maintain anesthesia.

Sometimes the anesthetic is administered IV. Depending on the nature of the

operation, the patient may also receive a muscle relaxant.

The patient experiences four stages of anesthesia,

. These stages are:
Stage one: analgesia
The patient experiences analgesia (a loss of pain sensation) but remains conscious and can carry
on a conversation.

Stage two: excitement

The patient may experience delirium or become violent. Blood pressure rises and becomes
irregular, and breathing rate increases.

Stage three: surgical anesthesia

Skeletal muscles relax. Breathing becomes regular. Eye movement slows then stops. It is at this
point when surgery begins.

Stage four: medullary paralysis

Breathing and other vital functions cease to function because the respiratory center
(medulla oblongata) is paralyzed.
Death results if the patient is not revived quickly.
Careful administration of the anesthesia prevents reaching this stage.

TOPICAL ANESTHETIC AGENTS

Topical anesthetic agents are solutions, liquid sprays, ointments, creams, and gels that are
applied to mucous membranes, broken or unbroken skin surfaces, and burns to decrease the
sensitivity of nerve endings in the affected area.

The first topical anesthetic agent was TAC,

which is a combination of tetracaine, adrenaline (epinephrine), and cocaine, and was used
for face and scalp lacerations.

A version of TAC called LET is used today.

LET is a combination of lidocaine, epinephrine, and tetracaine. Lidocaine replaced
cocaine.

LOCAL ANESTHESIA
A local anesthetic blocks pain at the site where the medication is administered without affecting
the patient’s consciousness.
It is commonly used for dental procedures, suturing of skin lacerations, short-term surgery at a
localized area, and diagnostic procedures such as lumbar punctures.

SPINAL ANESTHESIA

23
Spinal anesthesia is a local anesthetic injected into the spinal column in the third or fourth
lumbar space to produce a regional neural block.

If it is given too high, the respiratory muscles could be affected and respiratory distress or
failure could result.

There are 4 types of spinal anesthesia:

subarachnoid block, epidural block, the saddle block, and a caudal block.

A subarachnoid block is the injection into the subarachnoid space in the third
or fourth lumbar space to produce anesthesia.

The epidural block occurs when the anesthetic is injected into the outer covering (dura mater)
of the spinal cord near the sacrum.

The saddle block is given at the lower end of the spinal column to block the perineal area for
procedures such as childbirth.

The caudal block is placed near the sacrum.

The patient may experience headaches and hypotension as a result of these procedures because
of a change in cerebrospinal fluid pressure when the needle is inserted into the spine.

Antidepressants
Antidepressants are prescribed to elevate mood. They can be Grouped

_ Selective serotonin re-uptake inhibitors (SSRIs): fluoxetine, paroxetine, sertraline,

fluvoxamine, citalopram, escitalopram, duloxetine.
_ Tricyclic antidepressants (TCAs): amitriptyline, imipramine, doxepin, dosulepin
(dothiepin) and tricyclic-related: trazodone. Amitriptyline and nortriptyline are
prescribed in low doses for neuropathic pain (unlicensed).
_ Monoamine oxidase inhibitors (MAOIs): traditional e.g. tranylcypromine and reversible
e.g. moclobemide.
_ Others, including mirtazapine, duloxetine, reboxetine, venlafaxine, tryptophan. Compared to
TCAs, SSRIs are better tolerated (less cardiotoxic, less sedative) and safer
following overdose (NICE 2004b), but may be less effective for seriously ill clients (Barbui &
Hotopf 2001). MAOIs, tryptophan and venlafaxine are usually reserved for specialist use.

Actions:
 Antidepressants may affect mood and behavior by adjusting the operation of
key neurotransmitters (glossary):
 serotonin and noradrenaline. SSRIs increase the quantity of serotonin available in key
synapses by blocking its reuptake into neurones and removal.
 TCAs act similarly on noradrenaline. This alters the functioning of receptors and neurones,
and tends to normalise circadian (24 hour) rhythms.
 Increase in serotonin availability is thought to be responsible for mood elevation, anxiety,
anorexia, analgesia, and change in libido.
 However, excess may disturb CNS functioning; rarely, extreme excess can produce
fever and the ‘serotonin syndrome’ (below).

Indications:

24
  Antidepressants may be an important component of therapy for people with moderate or
severe depression (NICE 2004b).
 Some antidepressants are also prescribed for other conditions, including obsessive
compulsive disorders (OCD), bulimia nervosa, impulse disorders.
 Duloxetine is also prescribed for stress incontinence and diabetic neuropathy, usually
under specialist supervision.

Administration:
 A routine for administration is advisable, for example, paroxetine is best taken once daily,
in the morning, with food. Fluoxetine and its main metabolite have unusually long half-
lives of up to 10 days (glossary).
 Therefore, effects may be delayed and fluoxetine will remain in the body several weeks
after discontinuation.
 Most SSRIs are available as tablets or capsules and liquids. Citalopram oral drops can be
mixed with water or orange juice. Different brands and formulations may not be
bioequivalent.

Adverse effects:
_ Neurological. Increase in available serotonin or noradrenaline, either alone or by
antagonising dopamine, may:
❖ over-elevate mood
❖ alter behaviour
❖ affect posture and movement
❖ interfere with melatonin release, disturbing sleep patterns
❖ affect ion movements and neurone functioning.

_ Other systems. Serotonin acts on most body systems:

❖ Gastrointestinal motility is increased, causing diarrhoea.

❖ Arterioles are dilated, reducing peripheral resistance and blood pressure.
❖ Platelet activity is decreased, promoting bleeding. SSRIs reduce serotonin entry into platelets;
without serotonin, platelets cannot form clots.
❖ Antidepressants, to varying degrees, affect other receptors and neurotransmitters, including
the autonomic nervous system and dopamine. The skin and the genito-urinary system may be
affected.

_ The serotonin syndrome. This is a disturbance of the monoamine neurotransmitters of the

CNS, probably caused by raised concentrations of serotonin in both the CNS and peripheral
tissues. Recognition may not be easy (below).

Adverse effects: implications for practice: SSRIs

More than 80% of people prescribed SSRIs in the community experienced at least one
‘bothersome’ adverse drug reaction (Hu et al. 2004). Less than 1% of inpatients experienced a
serious adverse reaction, mainly psychotic and neurological disturbances (Degner et al.
2004). Some 10% of the population may be genetically vulnerable to adverse effects, at
normal doses

Antiepileptic drugs
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Antiepileptic drugs are prescribed to eliminate, minimise or control
seizures, while avoiding serious adverse drug reactions.

Actions: Antiepileptic drugs (listed below) reduce the activity of neurones in the central
nervous system. This is achieved by either direct action on the neurones or augmenting the
inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). While this reduces the
number of seizures, it also suppresses the normal functions of the CNS. This may lead to
sedation, inco-ordination or even depression of vital signs.
Each neurone’s (nerve cell’s) activity depends on the balance between positive and negative
ions entering the cell (Figure 14.1). This balance may be disturbed in epilepsy. Epilepsy
and over-activity (or repetitive firing) of neurones are associated with excess sodium ion or
calcium ion entry. Entry of these ions is blocked by some antiepileptics (carbamazepine,
phenytoin, lamotrigine). Since these ions are required by many cells, these drugs affect most
body systems. Other drugs restore the balance or ‘calm down’ the neurones by increasing
the number of negative ions entering the cells. Benzodiazepines and barbiturates increase
the number of negative chloride ions entering the neurones, by acting on the GABA

Indications and administration: Specialists select appropriate anti-epileptic

agents, in accordance with type of epilepsy or pattern of seizures, and individuals’ lifestyles
or preferences. Where possible, epilepsy is controlled by a single drug (NICE 2004c). There is
often a very narrow therapeutic range between seizures and sedation. For some people,
even a delayed dose can allow seizure breakthrough.

_ Carbamazepine: taken 2–3 times/day, with meals to reduce gastric irritation. Modified
release preparations are taken 1–2 times/day. Concentration peaks 4–24 hours after
ingestion. Dosage may need to be increased within the first few weeks’ of therapy. For
patients taking up to 1g/day, suppositories can be substituted for up to 7 days, but
careful dose adjustments are needed, because suppositories are not bioequivalent
(glossary) to oral medicines. Rectal irritation may occur. Oxcarbazepine is similar.

_ Gabapentin: usually as adjunct treatment, 3 doses/day, 2 hours apart from antacids.

_ Lamotrigine: taken once or twice each day. Only dispersible tablets can be chewed.
_ Levetiracetam tablets are swallowed whole, twice daily.
_ Phenytoin is taken 1–3 times/day with food and water to reduce gastric irritation. Mixing
with food or enteral feeds is not advised. In status epilepticus intravenous fosphenytoin is
an alternative.
_ Tiagabine: 2–4 doses/day with food.
_ Topiramate: broken tablets give a bitter taste – avoid. Swallow ‘sprinkle capsules’
immediately after adding to food.
_ Valproate: taken 2–3 times/day, with food to reduce nausea. Modified release preparations
taken once or twice daily. Maintain consistent relation to meals.
_ Vigabatrin is prescribed on specialist advice (see vision, below).
_ Benzodiazepines become less effective with regular use over 1–6 months. They are
important in emergency treatment:
❖ Status epilepticus: usual management is intravenous lorazepam
❖ Recurrent seizures, premonitary stage:
• diazepam as rectal solution, or
• midazolam, as buccal liquid (Walker 2005), following training (NICE 2004c), intramuscular
or intravenous injections (unlicensed).

Pregabelin and zonisamide have been introduced as adjunct therapy.

Barbiturates, ethosuximide, acetazolamide, corticosteroids, paraldehyde are occasionally
prescribed.
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Some antiepileptics are also prescribed for neuropathic pain (carbamazepine, gabapentin,
valproate) and mood disorders (carbamazepine, valproate). In older patients, doses are
lower and intravenous administration is slower.

Different brands and formulations may not be bioequivalent. Patients whose epilepsy is
controlled may suffer recurrence of seizures if brands or formulations are interchanged
(Chappell 1993). Seek advice from prescribers and/or pharmacists before undertaking any
substitutions.

Adverse effects:
_ Nervous system depression and dysfunction. Neuronal inhibition can affect all
functions of the central nervous system, particularly those controlling balance.
Both excitatory and inhibitory neurones may be depressed, resulting in either
sedation or over-activity.

_ Alteration of body-image
❖ Prolactin production may be increased by carbamazepine, phenytoin or polypharmacy
(see antipsychotics).
❖ Valproate is associated with weight gain and secretion of excess androgens,
which can affect the ovaries and the skin.
❖ Men taking carbamazepine may have reduced androgen secretion (Aronson
2006).
_ The cardiovascular and gastrointestinal systems may also be affected.

_ Nutrition and electrolyte imbalance. Some anti-epileptics speed-up metabolism,

increasing the elimination of vital nutrients, such as folates and vitamin D.

Adverse effects: implications for practice: ANTIEPILEPTICS

Many adverse effects appear days or weeks after initiation of therapy. The full effects of
valproate are not experienced for 3–4 days after initiation, and those of carbamazepine for
1–2 weeks. Doses are not usually incremented during these periods. Adverse events are
particularly
likely during illness or regimen change, including switching to chewable tablets.

Cautions and contra-indications:

_ Previous adverse reactions to the drug or related drug, e.g. carbamazepine is closely
related to tricyclics, oxcarbazepine and phenytoin.
_ Liver/kidney impairment: lower doses prescribed, choice of therapy will be
restricted; measurements of plasma drug concentrations may be requested.
_ Pregnancy. Specialist advice should be sought, preferably before conception. Medication
requirements often change during pregnancy, and this requires monitoring by specialists. Folate
supplements may be prescribed pre-conception to reduce the risk of neural tube defects (1%
carbamazepine, 2–3% valproate) (Aronson 2006).
Women should be advised that the fetus is more likely to be harmed by seizures
than prescribed medication, and abrupt discontinuation of antiepileptics is
hazardous. The risk of fetal malformations may be less with single-drug regimens
(Morrell 2003). Mothers and neonates taking some antiepileptics (including carbamazepine,
phenytoin) may be prescribed prophylactic vitamin K. Neonatal withdrawal problems (irritability,
feeding problems, seizures) have occurred: delivery should be in specialist centres (Clerk &
Emery 2002). Longterm follow up of infants may be advised.
_ Breastfeeding of healthy infants may be possible with some antiepileptics. Infants
must be carefully monitored for possible adverse effects, as problems can occur.
_ Children: see manufacturers’ guidelines.
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_ Diabetes. Urinalysis: valproate may cause false positives for ketones.
Gabapentin and phenytoin may affect control of diabetes.
_ Further caveats are related to the adverse effect profiles of individual drugs, for
example:
❖ heart disease, particularly heart block: carbamazepine
❖ history of bone marrow suppression: carbamazepine
❖ bleeding tendencies: valproate
❖ glaucoma: carbamazepine, topiramate
❖ neurological disorders: tiagabine
❖ history of psychosis: gabapentin
❖ porphyria (glossary): carbamazepine, oxcarbazepine, ethosuximide, phenytoin,
valproate, some benzodiazepines
❖ thalassaemia: lamotrigine
❖ lupus: valproate
❖ congenital enzyme deficiencies, neurological disorders in children: valproate
Interactions (summary): Advise patients to inform prescribers and pharmacists
of their anti-epileptic medication. Maintain detailed records on the effectiveness
and adverse effects of both the anti-epileptic and the drug co-administered. Some
drugs, including some antidepressants, antipsychotics, quinolones, antimalarials,
amphetamines, high doses of caffeine, increase the risks of seizures. Anti-epileptic
drugs interact with each other and special care is needed during addition or substitution
of new drugs.

Alcohol may worsen drowsiness and incoordination, and intensify difficulties with
driving.
Carbamazepine, phenytoin, topiramate, oxcarbazepine, barbiturates, and possibly
lamotrigine, reduce the efficiency of oral contraceptives (including emergency
hormonal contraceptives), necessitating higher doses. Advise women to seek advice
should breakthrough bleeding occur (Fairgrieve et al. 2000). Women prescribed lamotrigine
should discuss with prescribers before stopping the COC (dose of lamotrigine
needs to be reduced).

Sedation, tremor and ataxia may be increased by benzodiazepines, other sedatives

(see opioids), erythromycin, most SSRIs, clozapine, haloperidol, risperidone, paracetamol,
omeprazole, amioradone, digoxin, nifedipine, and other drugs.
Bleeding and liver dysfunction due to valproate may be intensified by aspirin,
salicylates, warfarin.
Grapefruit juice, influenza vaccine, caffeine may interact with carbamazepine.
Interactions may occur with folic acid, St. John’s wort anti-cancer drugs, immunosuppressants,
some corticosteroids, many anti-microbials e.g. aciclovir, metronidazole,
doxycycline, azole antifungals

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