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.
Monoamine oxidase inhibitors (MAOIs)
e.g. phenelzine, tranylcypromine, moclobemide
- Belong to first generation antidepressants with TCAs
- Most MAOIs irreversibly inhibit the intraneuronal catabolism of norepinephrine and serotonin by MAO-A and MAO-B
- increase brain levels of noradrenaline and 5-HT
- Moclobemide causes selective, reversible inhibition of MAO-A
DRUG INTERACTIONS
Hypertensive crises similar to cheese reaction with OTC cough/cold preparations containing indirect-sympathomimetics
e.g. ephedrine
- Other antidepressants should not be started at least 2 weeks after stopping MAOIs and vice versa due to risk of serotonin syndrome
- Similar interaction with pethidine
ADVERSE DRUG REACTIONS
- Antimuscarinic side effects (e.g. dry mouth, blurred vision, urinary retention)vision, urinary retention)
- Excessive central stimulation causes tremors, excitement and insomnia
- Postural hypotension
- Increased appetite with weight gain
Erythromycin
used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.
Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.
Mechanism of action Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.
Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.
Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine.
Erythromycin's half-life is 1.5 hours.
Side-effects. More serious side-effects, such as reversible deafness are rare. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrosis are some other rare side effects that may occur.
Contraindications Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem)
erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time.
Valproic acid: broad spectrum (for most seizure types)
Mechanism: blocks Ca T currents in thalamic neurons (prevents reverberating activity in absence seizures), ↓ reactivation of Na channels (in tonic/clonic seizures; prolongs refractory periods of neurons, prevents high frequency cell firing)
Side effects: very low toxicity; common = anorexia, N/V; at high doses inhibits platelet function (bruising and gingival bleeding); rarely see idiosyncratic hepatotoxicity
Drug interactions: induces hepatic microsomal enzymes (↓ effectiveness of other drugs), binds tightly to plasma proteins so displaces other drugs
Methyl salicylate
also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs
Dextromethorphan
O-methylated dextrorphan, Excellent oral antitussive, No analgesic effect, No GI effects, No respiratory depression
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.