Dr Ilham Sayed
• An antifungal medication is a pharmaceutical
fungicide used to treat mycoses 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.
• Polyene antifungals
• The polyene antimycotics bind with sterols in the fungal
cell membrane, principally ergosterol.
• This changes the transition temperature (Tg) of the cell
membrane, thereby placing the membrane in a less fluid,
more crystalline state. (In ordinary circumstances
membrane sterols increase the packing of the phospholipid
bilayer making the plasma membrane more dense.)
• As a result, the cell's contents including monovalent ions
(K+, Na+, H+, and Cl-), small organic molecules leak and this
is regarded one of the primary ways cell dies.
Imidazole, triazole, and thiazole
• Azole antifungal drugs inhibit the enzyme
lanosterol 14 α-demethylase; the enzyme
necessary to convert lanosterol to ergosterol.
• Depletion of ergosterol in fungal membrane
disrupts the structure and many functions of
fungal membrane leading to inhibition of
• Echinocandins may be used for systemic fungal
infections in immunocompromised patients, they
inhibit the synthesis of glucan in the cell wall via the
enzyme 1,3-β glucan synthase:
• Echinocandins are poorly absorbed when administered
• When administered by injection they will reach most
tissues and organs with concentrations sufficient to
treat localized and systemic fungal infections.
• Benzoic acid – has antifugal properties, but must be combined with a
keratolytic agent such as in Whitfield's ointment
• Ciclopirox – (ciclopirox olamine) – is a hydroxypyridone antifungal which
interferes with active membrane transport, cell membrane integrity, and
fungal respiratory processes. It is most useful against tinea versicolour.
• Flucytosine or 5-fluorocytosine – an antimetabolite pyrimidine analog
• Griseofulvin – binds to polymerized microtubules and inhibits fungal
• Polygodial – strong and fast-acting in-vitroantifungal activity against
• Tolnaftate – a thiocarbamate antifungal, which inhibits fungal squalene
epoxidase (similar mechanism to allylamines like terbinafine)
• Undecylenic acid – an unsaturated fatty acid derived from natural castor
oil; fungistatic, antibacterial, antiviral, and inhibits Candida
• Crystal violet – a triarylmethane dye, it has antibacterial, antifungal, and
anthelmintic properties and was formerly important as a topical
Apart from side effects like liver damage or
affecting estrogen levels, many antifungal
medicines can cause allergic reactions in
For example, the azole group of drugs is known
to have caused anaphylaxis.
• There are also many drug interactions.
• 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.
• Azole antifungals also are both substrates and inhibitors of
the cytochrome P450 family CYP3A4, causing increased
concentration when administering, for example,
calcium channel blockers, immunosuppressants,
chemotherapeutic drugs, benzodiazepines, tricyclic
antidepressants, macrolides and SSRIs.
• Antiviral drugs are a class of medication used
specifically for treating viral infections.
• Unlike most antibiotics, antiviral drugs do not destroy
their target pathogen; instead they inhibit their
• Most of the antiviral drugs now available are designed
to help deal with HIV, herpes viruses (best known for
causing cold sores and genital herpes, but actually the
cause of a wide range of other diseases, such as
chicken pox), the hepatitis B and C viruses, which can
cause liver cancer, and influenza A and B viruses.
• Virus is a nucleic acid, either DNA or RNA which is
infectious in nature.
• Virus can infect all kind of organisms including plants,
animals and bacteria.
• This nucleic strand of the DNA is called genome.
Outside genome there is covering of proteinaceous
coat called capsid.
• Outside the capsid there presents a fatty envelope.
Capsid and genome together is known as nucleocapsid
and all the three capsid, genome and envelope
together is known as virion.
• Virus is an obligate parasite i.e. active only inside the
• Viruses are parasites that cannot reproduce on their
• They recognize specific molecules on the surface of
target cells and bind to them.
• After entering the cells, viruses take off their protein
coat'a process called un-coating'to release the genome
(DNA or RNA).
• They use the host cell's tools to reproduce themselves.
• Released viruses find new host cells to infect.
• Antiviral medications prevent viral entry, un-coating,
replication of viral genome (DNA or RNA), re-coating
and spread of viruses to new host cells.
• Antiviral drugs are classified into following classes:-
• a) Anti-herpes virus- Acyclovir, Gancyclovir,
• b) Anti-influenza virus- Amantadine & Rimantadine
• c) Broad spectrum antivral drugs- Vidabarine &
• d) Anti-HIV virus- Stavudine, Zidovudine, Carbovir &
• e) Anti-small pox virus- Methisazone & Anildone
• Nucleoside-Analog Reverse Transcriptase
Inhibitors (NRTI). These drugs inhibit viral RNA-
dependent DNA polymerase (reverse
transcriptase) and are incorporated into viral
DNA (they are chain-terminating drugs).
– Zidovudine (AZT = ZDV, Retrovir) first approved in
Transcriptase Inhibitors (NNRTIs)
• In contrast to NRTIs, NNRTIs are not incorporated into viral
DNA; they inhibit HIV replication directly by binding non-
competitively to reverse transcriptase.
• Protease Inhibitors. These drugs are specific for the HIV-1
protease and competitively inhibit the enzyme, preventing
the maturation of virions capable of infecting other cells.
– Saquinavir - first approved in 1995
• ii) Granulocytopenia
• iii) Thrombocytopenia
• GI upset and headache
• Renal dysfunction
Limitations of vaccines
• Vaccines bolster the body's immune system to better attack viruses
in the "complete particle" stage, outside of the organism's cells.
• They traditionally consist of an attenuated (a live weakened) or
inactivated (killed) version of the virus.
• These vaccines can, in rare cases, harm the host by inadvertently
infecting the host with a full-blown viral occupancy.
• Recently "subunit" vaccines have been devised that consist strictly
of protein targets from the pathogen. They stimulate the
immune system without doing serious harm to the host. In either
case, when the real pathogen attacks the subject, the immune
system responds to it quickly and blocks it.
• Vaccines are very effective on stable viruses, but are of limited use
in treating a patient who has already been infected. They are also
difficult to successfully deploy against rapidly mutating viruses,
such as influenza (the vaccine for which is updated every year) and
HIV. Antiviral drugs are particularly useful in these cases.
• Entry inhibitor
• A very early stage of viral infection is viral entry,
when the virus attaches to and enters the host cell. A
number of "entry-inhibiting" or "entry-blocking"
drugs are being developed to fight HIV.
• HIV most heavily targets the immune system's white
blood cells known as "helper T cells", and identifies
these target cells through T-cell surface receptors
designated "CD4" and "CCR5". Attempts to interfere
with the binding of HIV with the CD4 receptor have
failed to stop HIV from infecting helper T cells, but
research continues on trying to interfere with the
binding of HIV to the CCR5 receptor in hopes that it
will be more effective.
• Reverse transcription
• One way of doing this is to develop nucleotide or nucleoside
analogues that look like the building blocks of RNA or DNA,
but deactivate the enzymes that synthesize the RNA or DNA
once the analogue is incorporated. This approach is more
commonly associated with the inhibition of reverse
transcriptase (RNA to DNA) than with "normal" transcriptase
(DNA to RNA).
• The first antiviral drug to be approved for treating HIV,
zidovudine (AZT), is also a nucleoside analogue.
• An improved knowledge of the action of reverse transcriptase
has led to better nucleoside analogues to treat HIV infections.
• Researchers have gone further and developed inhibitors that
do not look like nucleosides, but can still block reverse
• Another target being considered for HIV antivirals include
RNase H – which is a component of reverse transcriptase that
splits the synthesized DNA from the original viral RNA .
• An analgesic, or painkiller, is any member of the
group of drugs used to achieve analgesia — relief
• Analgesic drugs act in various ways on the peripheral
and central nervous systems.
• They are distinct from anesthetics, which reversibly
• Classes: 1_ paracetamol (known in the US as
2_ The non-steroidal anti-inflammatory drugs (NSAIDs)
such as the salicylates, and
3_ Opioid drugs such as morphine and opium.
• Paracetamol and NSAIDs:
• The exact mechanism of action of
paracetamol/acetaminophen is uncertain but
appears to act centrally in the brain rather than
peripherally in nerve endings.
• Aspirin and the other non-steroidal anti-
inflammatory drugs (NSAIDs) inhibit
cyclooxygenases, leading to a decrease in
• In contrast to paracetamol and the opioids, this not
only reduces pain but inflammation as well.
• Paracetamol has few side effects and is regarded as
generally safe, although excess or sustained use can
lead to potentially life-threatening liver damage and
occasionally kidney damage.
• While paracetamol is usually taken orally or rectally,
an intravenous preparation introduced in 2002 has
been shown to improve pain relief and reduce opioid
consumption in the postoperative setting.
• NSAIDs predispose to peptic ulcers, renal
failure, allergic reactions, and
• Occasionally hearing loss, and they can
increase the risk of hemorrhage by affecting
• The use of aspirin in children under 16
suffering from viral illness has been linked to
Reye's syndrome, a rare but severe liver
• These drugs have been derived from NSAIDs.
• The cyclooxygenase enzyme inhibited by
NSAIDs was discovered to have at least 2
different versions: COX1 and COX2.
• Research suggested that most of the adverse
effects of NSAIDs were mediated by blocking
the COX1 enzyme, with the analgesic effects
being mediated by the COX2 enzyme.
• The COX2 inhibitors were thus developed to inhibit
only the COX2 enzyme (traditional NSAIDs block both
versions in general).
• These drugs (such as rofecoxib, celecoxib and
etoricoxib) are equally effective analgesics when
compared with NSAIDs, but cause less
gastrointestinal hemorrhage in particular.
• After widespread adoption of the COX-2 inhibitors, it
was discovered that most of the drugs in this class
increased the risk of cardiovascular events by 40% on
• This led to the withdrawal of rofecoxib and
valdecoxib, and warnings on others.
• Etoricoxib seems relatively safe, with the risk of
thrombotic events similar to that of non-coxib NSAID
Opioids and Opiates
• Morphine, and various other substances (e.g.
codeine, oxycodone, hydrocodone,
dihydromorphine, pethidine) all exert a similar
influence on the cerebral opioid receptor
• Buprenorphine is thought to be a partial
agonist of the opioid receptor, and tramadol is
an opiate agonist.
• Tramadol is delivers analgesia by not only
delivering "opiate-like" effects (through mild
agonism of the mu receptor) but also by
acting as a weak but fast-acting serotonin
releasing agent and norepinephrine reuptake
• Dosing of all opioids may be limited by opioid
toxicity (confusion, respiratory depression,
myoclonic jerks and pinpoint pupils), seizures (
tramadol), but there is no dose ceiling in
patients who accumulate tolerance.
• Opioids, while very effective analgesics, may
have some unpleasant side-effects.
• Patients starting morphine may experience
nausea and vomiting (generally relieved by a
short course of antiemetics such as
• Pruritus (itching) may require switching to a
• Constipation occurs in almost all patients on
opioids, and laxatives co-prescribed.
• When used appropriately, opioids and similar
narcotic analgesics are otherwise safe and
effective, however risks such as addiction and
the body becoming used to the drug
(tolerance) can occur.
• The effect of tolerance means that frequent
use of the drug may result in its diminished
effect so, when safe to do so, the dosage may
need to be increased to maintain
• This may be of particular concern regarding
patients suffering with chronic pain.
• In patients with chronic or neuropathic pain, various
other substances may have analgesic properties.
• Tricyclic antidepressants, especially amitriptyline,
have been shown to improve pain in what appears to
be a central manner.
• Nefopam is used in Europe for pain relief with
• The exact mechanism of carbamazepine, gabapentin
and pregabalin is similarly unclear, but these
anticonvulsants are used to treat neuropathic pain
with differing degrees of success.
• Anticonvulsants are most commonly used for
neuropathic pain as their mechanism of action tends
to inhibit pain sensation.
• Anti-inflammatory refers to the property of a
substance or treatment that reduces
• Anti-inflammatory drugs make up about half
of analgesics, remedying pain by reducing
inflammation as opposed to opioids, which
affect the central nervous system.
• Steroids Many steroids, to be specific
glucocorticoids, reduce inflammation or
swelling by binding to glucocorticoid
• These drugs are often referred to as
• Non-steroidal anti-inflammatory drugs (NSAIDs),
alleviate pain by counteracting the cyclooxygenase
• On its own, COX enzyme synthesizes prostaglandins,
creating inflammation. In whole, the NSAIDs prevent
the prostaglandins from ever being synthesized,
reducing or eliminating the pain.
• Some common examples of NSAIDs are: aspirin,
ibuprofen, and naproxen.
• The newer specific COX-inhibitors - it is presumed,
sharing a similar mode of action - are not classified
together with the traditional NSAIDs.
• On the other hand, there are analgesics that are
commonly associated with anti-inflammatory drugs
but that have no anti-inflammatory effects.
• An example is paracetamol, As opposed to NSAIDs,
which reduce pain and inflammation by inhibiting
COX enzymes, paracetamol has recently been shown
to block the reuptake of endocannabinoids, which
only reduces pain, likely explaining why it has
minimal effect on inflammation
• Antipyretics are drugs or herbs that reduce fever.
• Antipyretics cause the hypothalamus to override an
interleukin-induced increase in temperature.
• The body then works to lower the temperature,
resulting in a reduction in fever.
• Most antipyretic medications have other purposes.
• The most common antipyretics are ibuprofen and
aspirin, which are used primarily as pain relievers.
• Non-steroidal anti-inflammatory drugs (NSAIDs) are
antipyretic, anti-inflammatory, and pain relievers.