NEET MDS Lessons
Pharmacology
Sedative-Hypnotic Drugs
Sedative drug is the drug that reduce anxiety (anxiolytic) and produce sedation and referred to as minor tranquillisers.
Hypnotic drug is the drug that induce sleep
Effects: make you sleepy; general CNS depressants
Uses: sedative-hypnotic (insomnia ), anxiolytic (anxiety, panic, obsessive compulsive, phobias), muscle relaxant (spasticity, dystonias), anticonvulsant (absence, status epilepticus, generalized seizures—rapid tolerance develops), others (pre-operative medication and endoscopic procedures, withdrawal from chronic use of ethanol or other CNS depressants)
1- For panic disorder alprazolam is effective.
2- muscle disorder: (reduction of muscle tone and coordination) diazepam is useful in treatment of skeletal muscle spasm e.g. muscle strain and spasticity of degenerative muscle diseases.
3-epilepsy: by increasing seizure threshold.
Clonazepam is useful in chronic treatment of epilepsy while diazepam is drug of choice in status epilepticus.
4-sleep disorder: Three BDZs are effective hypnotic agents; long acting flurazepam, intermediate acting temazepam and short
acting triazolam. They decrease the time taken to get to sleep They increase the total duration of sleep
5-control of alcohol withdrawals symptoms include diazepam, chlordiazepoxide, clorazepate and oxazepam.
6-in anesthesia: as preanesthetic amnesic agent (also in cardioversion) and as a component of balanced anesthesia
Flurazepam significantly reduce both sleep induction time and numbers of awakenings and increase duration of sleep and little rebound insomnia. It may cause daytime sedation.
Temazepam useful in patients who experience frequent awakening, peak sedative effect occur 2-3 hr. after an oral dose.
Triazolam used to induce sleep in recurring insomnia and in individuals have difficulty in going to sleep, tolerance develop within few days and withdrawals result in rebound insomnia therefore the drug used intermittently.
Drugs and their actions
1. Benzodiazepines: enhance the effect of gamma aminobutyric acid (GABA) at GABA receptors on chloride channels. This increases chloride channel conductance in the brain (GABA A A receptors are ion channel receptors).
2. Barbiturates: enhance the effect of GABA on the chloride channel but also increase chloride channel conductance independently of GABA, especially at high doses
3. Zolpidem and zaleplon: work in a similar manner to benzodiazepines but do so only at the benzodiazepine (BZ1) receptor type. (Both BZ1and BZ2 are located on chloride channels.)
4. Chloral hydrate: probably similar action to barbiturates.
5. Buspirone: partial agonist at a specific serotonin receptor (5-HT1A).
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine):
mechanisms not well-described. Several mechanisms may be involved.
7. Baclofen: stimulates GABA linked to the G protein, Gi , resulting in an increase in K + conductance and a decrease in Ca2+ conductance. (Other drugs mentioned above do not bind to the GABA B receptor.)
8. Antihistamines (e.g., diphenhydramine): block H1 histamine receptors. Doing so in the CNS leads to sedation.
9. Ethyl alcohol: its several actions include a likely effect on the chloride channel.
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.
NSAIDs: Classification by Plasma Elimination Half Lives
Short Half Life (< 6 hours):
more rapid effect and clearance
• Aspirin (0.25-0.33 hrs),
• Diclofenac (1.1 ± 0.2 hrs)
• Ketoprofen (1.8± 0.4 hrs),
• Ibuprofen (2.1 ± 0.3 hrs)
• Indomethacin (4.6 ± 0.7 hrs)
Long Half Life (> 10 hours):
slower onset of effect and slower clearance
• Naproxen (14 ± 2 hrs)
• Sulindac (14 ± 8 hrs),
• Piroxicam (57 ± 22 hrs)
Warfarin (Coumadin):
- The most common oral anticoagulant.
- It is only active in vivo.
- Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
- Warfarin is metabolized by the liver and excreted in the urine.
- Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
- Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.
- Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.
Oral anticoagulants are contraindicated in:
• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe
hepatic or renal disease, and where intensive salicylate therapy is required.
Inhalational Anesthetics
The depth of general anesthesia is directly proportional to the partial pressure of the anesthetic agent in the brain. These agents enter the body through the lungs, dissolve in alveolar blood and are transported to the brain and other tissues.
A. Rate of induction and rate of recovery from anesthesia:
1. The more soluble the agent is in blood, the more drug it takes to saturate the blood and the more time it takes to raise the partial pressure and the depth of anesthesia.
2. The less soluble the agent is in blood, the less drug it takes to saturate the blood and the less time it takes to raise the partial pressure and depth of anesthesia.
B. MAC (minimum alveolar concentration)
The MAC is the concentration of the anesthetic agent that represents the ED50 for these agents. It is the alveolar concentration in which 50% of the patients will respond to a surgical incision.
The lower the MAC the more potent the general anesthetic agent.
C. Inhalation Anesthetic Agents
- Nitrous Oxide
- Ether
- Halothane
- Enflurane
- Isoflurane
Paracetamol
Paracetamol or acetaminophen is analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains.
paracetamol acts by reducing production of prostaglandins, which are involved in the pain and fever processes, by inhibiting the cyclooxygenase (COX) enzyme.
Metabolism Paracetamol is metabolized primarily in the liver. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.
Carbonic anhydrase inhibitors
Acetazolamide, Dichlorphenamide, Methazolamide, Ethoxzolamide
Mechanism of Action
1. Carbonic anhydrase (CA) facilitates excretion of H+ and recovery of bicarbonate by the proximal renal tubule and ciliary epithelium of the eye. Sodium is recovered in exchange for H+.
2. Inhibitors block CA block sodium recovery. A very mild diuresis is produced (this is really a side effect of their use in glaucoma) because relatively unimportant mechanism for Na recovery and because proximal tubule site means that other sodium recovery mechansims continue to process their normal fraction of the sodium load.