Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin

Indications:

infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)

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.

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.

Factors affecting onset and duration of action of local anesthetics

pH of tissue

pKa of drug

Time of diffusion from needle tip to nerve

Time of diffusion away from nerve

Nerve morphology

Concentration of drug

Lipid solubility of drug

VITAMIN -K

• Group of lipophilic, hydrophobic vitamins.
• Needed for the post-translational modification of coagulation proteins.
• Phylloquinone (vitamin K1) is the major dietary form of vitamin K.

• Vitamin K2 (menaquinone, menatetrenone) is produced by bacteria in the intestines.

Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia. 
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.