NEET MDS Lessons
Pharmacology
Nystatin
Candida spp. are sensitive to nystatin.
Uses: Cutaneous, vaginal, mucosal and esophageal infections.
Candida infections can be treated with nystatin.
Cryptococcus is also sensitive to nystatin.
Nystatin is often used as prophylaxis in patients who are at risk for fungal infections, such as AIDS patients with a low CD4+ count and patients receiving chemotherapy.
MOA
nystatin binds to ergosterol, the main component of the fungal cell membrane. When present in sufficient concentrations, it forms a pore in the membrane that leads to K+ leakage and death of the fungus.
DIAGNOSIS
Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania
Diagnosis is based on
At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate,
IX. Recurrent thoughts of death
Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters norepinephrine and/or serotonin in the brain.
Aspirin
Mechanism of Action
ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding
Uses of Aspirin
Dose-Dependent Effects:
Low: < 300mg blocks platelet aggregation
Intermediate: 300-2400mg/day antipyretic and analgesic effects
High: 2400-4000mg/day anti-inflammatory effects
Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks
Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks
Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.
Clavulanic acid is often combined with amoxicillin to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. It works by preventing bacterium that release beta-lactamases from destroying amoxicillin.
Antifungal
There are several classes of antifungal drugs.
The polyenes bind with sterols in the fungal cell wall, principally ergosterol. This causes the cell's contents to leak out and the cell dies. Human (and other animal) cells contain cholesterol rather than ergosterol so are much less suceptible.
Nystatin
Amphotericin B
Natamycin
The imidazole and triazole groups of antifungal drugs inhibit the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. These drugs also block steroid synthesis in humans.
Imidazoles:
Miconazole
Ketoconazole
Clotrimazole
The triazoles are newer, and are less toxic and more effective:
Fluconazole
Itraconazole
Allylamines inhibit the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis:
Terbinafine
Echinocandins inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-β glucan synthase:
Caspofungin
Micafungin
Others:
Flucytosine is an antimetabolite.
Griseofulvin binds to polymerized microtubules and inhibits fungal mitosis.
Ketorolac
Mechanism of action
primary action responsible for its anti-inflammatory/antipyretic/analgesic effects is inhibition of prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX). Ketorolac is not a selective inhibitor of COX enzymes
Indications: short-term management of pain
Contraindications
hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).
Lithium carbonate: 1st choice (controls mania in bipolar disorders); delay before onset of therapeutic benefit; no psychotropic effects in normal humans
i. Mechanism: blocks enzymes in inositol phosphate signaling pathway; no consistent effects of lithium on NE, 5-HT, and DA
ii. Side effects: severe CNS (ataxia, delirium, coma, convulsions) and CV (cardiac dysrhythmias)