Sympatholytics And Alpha Adrenergic Blockers 

Types 
1.    Alpha 1-receptor blockers: prazocin,doxazocin. 
2.    Centrally acting alpha 2- agonists: methyldopa, clonidine. 
3.    Peripherally acting adrenergic antagonists: reserpine. 
4.    Imidazoline receptor agonists: rilmenidine, moxonidine. 
 
Advantages 

- Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. 
- Methyldopa: increases renal blood flow. Drug of choice during pregnancy. 
- Reserpine: neutral metabolic effects and cheap. 

Indications: 

- Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists. 
- Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists. 
- Prostatic hypertrophy: alpha 1- receptor blockers. 
- When there is a need for rapid reduction in blood pressure: clonidine. 

Side Effects 

- Prazocin: postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention). 
- Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance. 
- Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence
- Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly. 

Considerations 
- Prazocin, methyldopa, and reserpine should be combined with a diuretic because of fluid retention. 

Direct Arterial Vasodilators 

Types: hydralazine, diazoxide, nitroprusside, and minoxidil

DOBUTAMINE

It is a derivative of dopamine and has relatively β1 -selective action and it also activates α1 receptors and do not have D1  receptor agonistic property. It increases the force of myocardial contraction and cardiac output without significant change in heart rate, blood pressure and peripheral resistance. It is used as inotropic agent and for short term management of CHF and also in patients who are unresponsive to digitalis.

TCI -Target Controlled Infusion

TCI is an infusion system which allows the anaesthetist to select the target blood concentration required for a particular effect and then to control depth of anaesthesia by adjusting the requested target concentration

Mechanism

Instead of setting ml/h or a dose rate (mg/kg/h), the pump can be programmed to target a required blood concentration.

• Effect site concentration targeting is now included for certain pharmacokinetic models.

• The pump will automatically calculate how much is needed as induction and maintenance to maintain that concentration.

Methicillin

Methicillin is an antibiotic related to penicillin and other beta-lactam containing antibiotics. It is often used to treat infections caused by bacteria carrying an antibiotic resistance, e.g., staphylococci. As methicillin is deactivated by gastric acid, it has to be administered by injection.

Uses Methicillin serves a purpose in the laboratory to determine antibiotic sensitivity in microbiological culture.

Ether (diethylether)

Ether (diethylether) MAC 2.0%, Blood/gas solubility ratio 15
- Ether is generally mixed with 3% ethanol to retard oxidation. Peroxides form on exposure to air and can enhance the danger of an explosion.
- Slow rate of induction and recovery due to its high blood/gas solubility ratio.
- Produces profound muscular relaxation.
- Both the rate and the minute volume of ventilation tend to be elevated during the inhalation of ether.
- Ether maintains good circulatory stability and does not sensitize the heart to the arrhythmogenic action of catecholamines.
- More than 90% of the absorbed ether can be recovered unchanged in the expired air. Metabolism is not extensive and the metabolites are not hepatotoxic.
- Ether is a versatile anesthetic of unexcelled safety, but it is flammable and irritating to breathe. Secretions can be blocked with anticholinergics.

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.