Nitrous Oxide (N2O)

MAC 100%, blood/gas solubility ratio 0.47
- An inorganic gas., low solubility in blood, but greater solubility than N2
- Inflammable, but does support combustion.
- Excreted primarily unchanged through the lungs.
- It provides amnesia and analgesia when administered alone.
- Does not produce muscular relaxation.
- Less depressant to both the cardiovascular system and respiratory system than most of the other inhalational anesthetics.
- Lack of potency and tendency to produce anoxia are its primary limitations.
- The major benefit of nitrous oxide is its ability to reduce the amount of the secondary anesthetic agent that is necessary to reach a specified level of anesthesia.

Different Systems of the CNS & their functions

These systems are pathways formed of specific parts of the brain and the neurons connecting them. 

They include:
1.The pyramidal system 
2.The extrapyramidal system 
3.The limbic system 
4.The reticular formation 
5.The tuberohypophyseal system

The pyramidal system: 

It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”. 
It is responsible for the regulation of the fine voluntary movements.

The extrapyramidal system: 

It also controls the motor functionbut involves areas other than the corticospinal tract. 
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system. 

The “basal ganglia” constitute an essential part of this system. 

Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.

The limbic system: 

The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas. 

The limbic system is involved in the control of “behavior”& “emotions”.

The reticular formation:

It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards. 
It is important in the control of “consciousness” and “wakefulness”.

The tuberohypophyseal system: 

It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
 

Class II Beta Blockers 

Block SNS stimulation of beta receptors in the heart and decreasing risks of ventricular fibrillation
– Blockage of SA and ectopic pacemakers: decreases automaticity 
– Blockage of AV increases the refractory period
- Increase AV nodal conduction ´ 
- Increase PR interval
- Reduce adrenergic activity

Treatment: Supraventricular tachycardia (AF, flutter, paroxysmal supraventricular tachycardia 
– Acebutolol 
– Esmolol 
– Propanolol 

Contraindications and Cautions 

• Contraindicated in sinus bradycardia P < 45
• Cardiogenic shock,  asthma or respiratory depression which could be made worse by the blocking of Beta receptors. 
• Use cautiously in patients with diabetes and thyroid dysfunction, which could be altered by the blockade of Beta receptors 
• Renal and hepatic dysfunction could alter the metabolism and excretion of these drugs.
 

Meperidine (Demerol)

Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel

• Produces analgesia, sedation, euphoria and respiratory depression.
• Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
• Shorter duration of action than morphine (2-4 hrs).
• Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
• Meperidine appears to have some atropine-like activity.
• Does not constrict the pupils to the same extent as morphine.
• Does not cause as much constipation as morphine.
• Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
• Not an effective antitussive agent.
• In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
• Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
• It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)

 Adverse reactions to Meperidine

• Generally resemble a combination of opiate and atropine-like effects.

- respiratory depression, - tremors, - delirium and possible convulsions, - dry mouth

• The presentation of mixed symptoms (stupor and convulsions) is quite common in addicts taking large doses of meperidine.

Midazolam -Intravenous Anesthetics
 Midazolam is a benzodiazepine used for preoperative sedation, induction of anesthesia, or maintenance of anesthesia in short procedures.

Pharmacodynamic Effects of NSAIDs

A. Positive

analgesic - refers to the relief of pain by a mechanism other than the reduction of inflammation (for example, headache);

- produce a mild degree of analgesia which is much less than the analgesia produced by opioid analgesics such as morphine

anti-inflammatory - these drugs are used to treat inflammatory diseases and injuries, and with larger doses - rheumatoid disorders

antipyretic - reduce fever; lower elevated body temperature by their action on the hypothalamus; normal body temperature is not reduced

Anti-platelet - inhibit platelet aggregation, prolong bleeding time; have anticoagulant effects

B. Negative

Gastric irritant

Decreased renal perfusion

Bleeding

(CNS effects)

Adverse effects

The two main adverse drug reactions (ADRs) associated with NSAIDs relate to gastrointestinal (GI) effects and renal effects of the agents.

Gastrointestinal ADRs

The main ADRs associated with use of NSAIDs relate to direct and indirect irritation of the gastrointestinal tract (GIT). NSAIDs cause a dual insult on the GIT - the acidic molecules directly irritate the gastric mucosa; and inhibition of COX-1 reduces the levels of protective prostaglandins.

Common gastrointestinal ADRs include:

Nausea, dyspepsia, ulceration/bleeding, diarrhoea

Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time..

 Ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.

Commonly, gastrointestinal adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g. omeprazole

Renal ADRs

NSAIDs are also associated with a relatively high incidence of renal ADRs. The mechanism of these renal ADRs is probably due to changes in renal haemodynamics (bloodflow), ordinarily mediated by prostaglandins, which are affected by NSAIDs.

Common ADRs associated with altered renal function include:

salt and fluid retention,hypertension

These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor and a diuretic - the so-called "triple whammy" effect.

In rarer instances NSAIDs may also cause more severe renal conditions.

interstitial nephritis, nephrotic syndrome, acute renal failure

Photosensitivity

Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs. These antiinflammatory agents may themselves produce inflammation in combination with exposure to sunlight. The 2-arylpropionic acids have proven to be the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac and benzydamine.

ibuprofen having weak absorption, it has been reported to be a weak photosensitising agent.

Other ADRs

Common ADRs, other than listed above, include: raised liver enzymes, headache, dizziness.

Uncommon ADRs include: heart failure, hyperkalaemia, confusion, bronchospasm, rash.

The COX-2 paradigm

It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastroprotective prostaglandins.

The relatively selective COX-2 oxicam, meloxicam, was the first step towards developing a true COX-2 selective inhibitor. Coxibs, the newest class of NSAIDs, can be considered as true COX-2 selective inhibitors and include celecoxib, rofecoxib, valdecoxib, parecoxib and etoricoxib.