NEET MDS Lessons
Pharmacology
Diclofenac
Short half life (1‐2 hrs), high 1stpass metab., accumulates in synovial fluid after oral admn., reduce inflammation, such as in arthritis or acute injury
Mechanism of action
inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). There is some evidence that diclofenac inhibits the lipooxygenase pathways, thus reducing formation of the
leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a molar basis.
Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac and other drugs that are not selective for the COX2-isoenzyme.
Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)
Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i. Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)
Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia
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.
EPHEDRINE
It act indirectly and directly on α and β receptors. It increases blood pressure both by peripheral vasoconstriction and by increasing the cardiac output. Ephedrine also relaxes the bronchial smooth muscles.
Ephedrine stimulates CNS and produces restlessness, insomnia, anxiety and tremors.
Ephedrine produces mydriasis on local as well as systemic administration.
Ephedrine is useful for the treatment of chronic and moderate type of bronchial asthma, used as nasal decongestant and as a mydriatic without cycloplegia. It is also useful in preventing ventricular asystole in Stokes Adams syndrome.
Glucocorticoids
Cortisol (hydrocortisone) and its synthetic derivatives
|
Drug |
Duration |
| Cortisol | Short |
| Prednisone | Medium |
| Triameinolone | Intermediate |
| Betamethasone | Long |
| Dexamethasone | Long |
Mechanism
↓ the production of leukotrienes and prostaglandins - inhibits phospholipase A2 , inhibits expression of COX-2 , will also stimulate the bone marrow to produce neutrophils resulting in leukocytosis
halts inflammatory cascade
↓ leukocyte migration
↓ capillary permeability
↓ phagocytosis
↓ platelet-activating factor
↓ interleukins (e.g. IL-2)
may trigger apoptosis in dividing and non-dividing cells
used in cancer chemotherapy
Clinical use
anti-inflammatory
immunosuppression
cancer chemotherapy (prednisone most common)
CLL
Hodgkin's lymphomas
part of MOPP regimen
Addison disease
asthma
Toxicity
1) must taper dose to avoid toxicity
2) suppression of ACTH → shock state if abrupt withdrawal - > cortical atrophy, malaise, myalgia, arthralgia, fever
3) iatrogenic Cushing syndrome ->buffalo hump, moon facies, truncal obesity, muscle weakness and atrophy, thin skin, easy bruising, acne
4) osteoporosis - vertebral fractures, aseptic hip necrosis, ↓ skeletal growth in children
5) hyperglycemia (diabetes) -due to ↑ gluconeogenesis , glaucoma, cataracts, and other complications can subsequently result
6) ↑ GI acid release -ulcers
7) Na+ retention -> edema, HTN, hypokalemia alkalosis, hypocalcemia
8)↓ wound healing
9) ↑ infections
10) mental status changes
11) cataracts
Clotrimazole: Clotrimazole is a potent, specific inhibitor of p450 enzymes.
It is used in some antifungal medications, and in the treatment of yeast infections.
Other sedatives: carisoprodol, cyclobenzaprine, and methocarbamol are used for muscle relaxation.
Baclofen
1. Used in spasticity states to relax skeletal muscle.
2. Occasionally used in trigeminal neuralgia.
Antihistamines (first-generation H1 receptor blockers)
1. Used for sedation (e.g., diphenhydramine).
Ethyl alcohol