2. NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of drugs
used to reduce pain, inflammation, and fever. They are commonly used
to treat conditions such as arthritis, menstrual cramps, and headaches.
3. Introduction
The inflammatory process is the response to an injurious stimulus. It can be evoked
by a wide variety of noxious agents (e.g., infections, antibodies, or physical
injuries). The ability to mount an inflammatory response is essential for survival in
the face of environmental pathogens and injury; in some situations and diseases,
the inflammatory response may be exaggerated and sustained without apparent
benefit and even with severe adverse consequences.
Phases of inflammation
Acute phase: characterized by transient local vasodilation and increased capillary
permeability;
Delayed phase: subacute phase characterized by infiltration of leukocytes and
phagocytic cells
Chronic phase: proliferative phase, in which tissue degeneration and fibrosis occur.
6. Pharmacological effects of NSAIDS
Analgesia: PGs induce hyperalgesia by affecting the transducing property of free nerve endings so that stimuli
that normally do not elicit pain are able to do so.
Antipyresis
NSAIDs reduce body temperature in fever, but do not cause hypothermia in normothermic individuals.
Anti-inflammatory
The most important mechanism of anti-inflammatory action of NSAIDs is considered to be inhibition of COX-2
mediated enhanced PG synthesis at the site of injury.
Dysmenorrhoea
NSAIDs lower uterine PG levels—afford excellent relief in 60–70% and partial relief in the remaining. Ancillary
symptoms of headache, muscle ache and nausea are also relieved. Excess flow may be normalized.
Antiplatelet aggregation
NSAIDs inhibit synthesis of both proaggregatory (TXA2) and antiaggregatory (PGI2) prostanoids, but effect on
platelet TXA2 (COX-1 generated) predominates → therapeutic doses of most NSAIDs inhibit platelet
aggregation: bleeding time is prolonged.
Gastric mucosal damage
Gastric pain, mucosal erosion/ulceration and blood loss are produced by all NSAIDs to varying extents
8. OVERVIEW
• Opioids are natural or synthetic compounds that produce morphine-like
effects. They are usually the drugs of choice for severe or chronic
malignant pain [The term opiate is reserved for drugs, such as morphine
and codeine, obtained from the juice of the opium poppy]
• All drugs in this category act by binding to specific opioid receptors in the
CNS to produce effects that mimic the action of endogenous peptide
neurotransmitters. Although the opioids have a broad range of effects,
their primary use is to relieve intense pain and the anxiety that
accompanies it, whether that pain is from surgery or a result of injury or
disease, such as cancer.
• However, their widespread availability has led to abuse of those opioids
with euphoric properties. Antagonists that can reverse the actions of
opioids are also very important clinically for use in cases of overdose.
11. MORPHINE cont’d….
• THERAPEUTIC USES:
• Analgesia: Despite intensive research, few other drugs have been developed that are
as effective as morphine in the relief of pain. Opioids induce sleep, and in clinical
situations when pain is present and sleep is necessary, opiates may be used to
supplement the sleep-inducing properties of benzodiazepines, such as temazepam.
[Note: The sedative-hypnotic drugs are not usually analgesic, and they may have
diminished sedative effect in the presence of pain.]
• Treatment of diarrhea: Morphine decreases the motility and increases the tone of
intestinal circular smooth muscle. [Note: This can cause constipation.]
• Relief of cough: Morphine suppresses the cough reflex; however, codeine or
dextromethorphan are more widely used for this purpose. Codeine has greater
antitussive action than morphine.
• Treatment of acute pulmonary edema: Intravenous (IV) morphine dramatically relieves
dyspnea (difficult breathing) caused by pulmonary edema associated with left
ventricular failure possibly by its vasodilatory effect.
12. Antimicrobials:
• Antimicrobials are a group of drugs used to treat infections caused by
bacteria, viruses, fungi, or parasites. They work by killing or inhibiting
the growth of microorganisms. Antimicrobials are commonly used to
treat conditions such as pneumonia, urinary tract infections, and
sexually transmitted infections.
13. Antimicrobial Agents Used In Vivo
• Antimicrobial drugs are classified on the basis of
• Molecular structure
• Mechanism of action
• Spectrum of antimicrobial activity
16. Synthetic Antimicrobial Drugs
• Nucleic acid base analogs have been formed by the
addition of bromine or fluorine
• Quinolones are antibacterial compounds that
interfere with DNA gyrase (e.g., ciprofloxacin)
17. Naturally Occurring Antimicrobial Drugs: Antibiotics
• Antibiotics are naturally produced antimicrobial agents
• Less than 1% of known antibiotics are clinically useful
• Can be modified to enhance efficacy (semisynthetic)
• The susceptibility of microbes to different antibiotics
varies greatly
• Gram-positive and gram-negative bacteria vary in their
sensitivity to antibiotics
• Broad-spectrum antibiotics are effective against both
groups of bacteria
18. -Lactam Antibiotics: Penicillins and Cephalosporins
• -Lactam antibiotics are one of the most important
groups of antibiotics of all time
• Include penicillins, cephalosporins, and cephamycins
• Over half of all antibiotics used worldwide
• Penicillins
• Discovered by Alexander Fleming
• Primarily effective against gram-positive bacteria
• Some synthetic forms are effective against some gram-
negative bacteria
• Target cell wall synthesis
19. -Lactam Antibiotics: Penicillins and Cephalosporins
• Cephalosporins
• Produced by fungus Cephalosporium
• Same mode of action as the penicillins
• Commonly used to treat gonorrhea
20. Antibiotics from Prokaryotes
• Many antibiotics effective against Bacteria are also
produced by Bacteria
• Aminoglycosides are antibiotics that contain amino sugars
bonded by glycosidic linkage
• Examples: kanamycin, neomycin, amikacin
• Not commonly used today
• Neurotoxicity and nephrotoxicity
• Considered reserve antibiotics for when other antibiotics fail
21. Antibiotics from Prokaryotes
• Macrolides contain lactone rings bonded to sugars
• Example: erythromycin
• Broad-spectrum antibiotic that targets the 50S subunit of
ribosome
• Tetracyclines contain four rings
• Widespread medical use in humans and animals
• Broad-spectrum inhibition of protein synthesis
• Inhibits functioning of 30S ribosomal subunit
22. Antiviral Drugs
• Most antiviral drugs also target host structures,
resulting in toxicity
• Most successful and commonly used antivirals are the
nucleoside analogs (e.g., AZT)
• Block reverse transcriptase and production of
viral DNA
• Also called nucleoside reverse transcriptase inhibitors
• Nonnucleoside reverse transcriptase inhibitors (NNRTI)
bind directly to RT and inhibit reverse transcription
23. Antiviral Drugs
• Protease inhibitors inhibit the processing of large viral
proteins into individual components
• Fusion inhibitors prevent viruses from successfully
fusing with the host cell
• Two categories of drugs successfully limit influenza
infection:
• Adamantanes
• Neuraminidase inhibitors
• Interferons are small proteins that prevent viral
multiplication by stimulating antiviral proteins in
uninfected cells
24. Antifungal Drugs
• Fungi pose special problems for chemotherapy
because they are eukaryotic
• Much of the cellular machinery is the same as that of
animals and humans
• As a result, many antifungals are topical
• A few drugs target unique metabolic processes unique to
fungi
25. Antiparasitics
• Antiparasitic drugs are medications used to treat infections caused by
parasites, which are organisms that live on or inside another organism
(host) and rely on the host for their nourishment. These drugs can be
classified based on their mechanism of action and the types of
parasites they target.
26. Antiparasitics
• Antimalarial Drugs:
• Example: Chloroquine, Artemisinin-based combination therapies (ACTs) like
artemether-lumefantrine, and mefloquine.
• Antiprotozoal Drugs:
• Nitroimidazoles:
• Example: Metronidazole (used for treating infections like giardiasis and amebiasis).
• Antimalarial Agents:
• Example: Atovaquone-proguanil combination (used for malaria prophylaxis and treatment).
• Antiamoebic Drugs:
• Example: Tinidazole (used for amebiasis).
• Antileishmanial Drugs:
• Example: Sodium stibogluconate (used for leishmaniasis).
27. Antiparasitics
• Anthelmintic Drugs:
• Benzimidazoles:
• Example: Albendazole (used for
treating a variety of helminthic
infections, including roundworm,
hookworm, and whipworm).
• Avermectins:
• Example: Ivermectin (used for treating
parasitic infections such as river
blindness and certain types of
roundworm infections).
• Praziquantel:
• Example: Praziquantel (effective
against tapeworms and flukes).
• Niclosamide:
• Example: Niclosamide (used for
treating tapeworm infections).
• Antifilarial Drugs:
• Example: Diethylcarbamazine (used
for treating filarial infections like
lymphatic filariasis).
• Antischistosomal Drugs:
• Example: Praziquantel (also
effective against schistosomiasis).
28. Ectoparasiticides
• Lindane (hexachlorocyclohexane) is used to treat infestations with
mites or lice and is also an agricultural insecticide. The agent can be
absorbed through the skin; if excessive amounts are applied, toxic
effects, including blood dyscrasias and convulsions, may occur.
• Crotamiton is a scabicide with some antipruritic effects, which can be
used as an alternative to lindane. Allergic contact hypersensitivity
may occur.
• Permethrin is used topically in pediculosis and scabies; adverse
effects include transient burning, stinging, and pruritus.
• The organophosphate cholinesterase inhibitor malathion is also used
topically in pediculosis (lice infestation)
Editor's Notes
Figure 26.12 Mode of action of some major antimicrobial agents.
