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.

Laxatives and cathartics (purgatives)

Constipation is a common problem in older adults and laxatives are often used or overused. Non drug measures to prevent constipation (e.g. increasing intake of fluid and high–fiber foods, exercise) are much preferred to laxatives.

Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel elimination (defecation). Both terms are used interchangeably because it is the dose that determines the effects rather than a particular drug. For example, Castor oil laxative effect = 4ml while Cathartic effect = 15-60ml

The term laxative implies mild effects, and eliminative of soft formed stool. The term cathartic implies strong effects and elimination of liquid or semi liquid stool. 

 Laxatives are randomly classified depending on mode of action as:
 
1. Bulk-forming laxatives: are substances that are largely unabsorbed from the intestine.
They include psyllium, bran, methylcellulose, etc. When water is added, the substances swell and become gel-like which increases the bulk of the faecal mass that stimulates peristalsis and defecation.

2. Osmotic laxatives such as magnesium sulphate, magnesium hydroxide, sodium phosphate, etc. These substances are not efficiently absorbed and cause water retention in the colon. The latter causes increase in volume and pressure which stimulates peristalsis and defecation.

Lactulose is a semisynthetic disaccharide sugar that also acts as an osmotic laxative. 
Electrolyte solutions containing polyethylene glycol(PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures

3. Stimulant (irritant) laxatives: these are irritant that stimulate elimination of large bowel contents. Individual drugs are castor oil, bisacodyl, phenolphthalein, cascara sagrada, glycerine, etc. The faeces are moved too rapidly and watery stool is eliminated. Glycerine can be administered rectally as suppositories.

4. Faecal softeners: they decrease the surface tension of the faecal mass to allow water to penetrate into the stool. They have detergent– like property e.g. docusate(docusate sodium, docusate calcium, and docusate spotassium. )

5. Lubricant laxatives e.g. liquid paraffin (mineral oil). It lubricates the intestine and is thought to soften stool by preventing colonic absorption of faecal water. They are used as retention enema. 

6. Chloride channel activators

Lubiprostone works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balances. Nausea is a relatively common side effect with lubiprostone.

Clinical indications of laxatives

1. To relieve constipation.
2. To prevent straining.
3. To empty the bowel in preparation for bowel surgery or diagnostic procedures.
4. To accelerate elimination of potentially toxic substances from the GI tract.
5. To accelerate excretion of parasite after anti-helmintic drugs have been administered. 

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.

Needle selection

Nerve blocks:

Inferior alveolar- 25 G short (LLU technique)

PSA- 25 G short

Mental/Incisive- 25 G short

Palatal- 27/30 G short/ultrashort

Gow-Gates/Akinosi- 25 G long

Infraorbital- 25 G long

Field Block:

ASA 25/27 short

Infiltration:

Infiltration/SP 25/27 short

PDL/Intraosseous

PDL 27/30 short

Intraosseous 30 short/ultrashort

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.

Antianginal Drugs

Organic Nitrates :
Short acting: Glyceryl trinitrate (Nitroglycerine, GTN), Amyl Nitrate
Long Acting: Isosrbide dinitrate (Short acting by sublingual route), Erythrityl tetranitrate, penta erythrityl tetranitrate

Beta-adrenergic blocking agents : Propanolol, Metoprolol
Calcium channel blockers Verapamil, Nifedipine, Dipyridamole
 
Mechanism of action 
– Decrease myocardial demand 
– increase blood supply to the myocardium