LIDOCAINE

This anti-arrhythmic agent suppresses automaticity of conduction and spontaneous depolarisation of the ventricles during diastole. Clearance is related to both hepatic blood flow and hepatic function; it will be prolonged in liver disease, cardiac failure and the elderly. The effects after the initial bolus dose last about 20 min. An IV infusion is needed to maintain the anti-arrhythmic effect.

USES

Prevention of ventricular ectopic beats,VT and VF after MI

CONTRAINDICATIONS

• It is no longer the first-line drug in pulseless VT or VF during cardiac arrest

• Hypersensitivity to amide-type local anaesthetics (rare)

• Heart block (risk of asystole)

ADMINISTRATION

• Loading dose:

1.5 mg/kg IV over 2 min, repeat after 5 min to a total dose of

3 mg/kg if necessary. Reduce dose in the elderly

• Maintenance dose:

4 mg/min for 1st hour

2 mg/min for 2nd hour

1 mg/min thereafter

• Reduce infusion rates in patients with hepatic impairment, cardiac failure and in the elderly

• Undiluted 40 ml 2% solution (800 mg)

4 mg/min = 12 ml/h

2 mg/min = 6 ml/h

1 mg/min = 3 ml/h

Continuous ECG and BP monitoring

How not to use lidocaine

Do not give by rapid IV bolus (should not be given at >50 mg/min)

ADVERSE EFFECTS

• Paraesthesia,muscle twitching, tinnitus

• Anxiety, drowsiness, confusion, convulsions

• Hypotension, bradycardia, asystole

CAUTIONS

• Elderly (reduced volume of distribution, reduce dose by 50%)

• Hepatic impairment

• Cardiac failure

• Other class 1 anti-arrhythmics, e.g. phenytoin, may increase risk of toxicity

ORGAN FAILURE

Cardiac: reduce dose

Hepatic: reduce dose

OMEPRAZOLE

Omeprazole is a proton pump inhibitor (PPI) which inhibits gastric acid production by the gastric parietal cells.Following endoscopic treatment of bleeding peptic ulcers, omeprazole given intravenous for 72 hours has been shown to reduce the risk of rebleeding.

USES

• Bleeding peptic ulcers, after endoscopic treatment of bleeding (unlicensed)
• Continuation of PPI therapy when the PO/NG route is unavailable.
• Helicobacter pylori eradication.

ADMINISTRATION

• Bleeding peptic ulcers, after endoscopic treatment of bleeding

IV: Initial 80 mg IV loading dose given over 1 hour, followed by 8 mg/h
IV infusion for 72 hours
Reconstitute with either sodium chloride 0.9% or glucose 5%

• Continuation of PPI therapy when the PO/NG route is unavailable
IV bolus: 40 mg daily. Reconstitute 40 mg vial with the solvent provided and administer over 5 min
• Eradication of Helicobacter pylori

ADVERSE EFFECT

• GI disturbances (nausea, vomiting, abdominal pain, diarrhoea and constipation)
• Paraesthesia
• Agitation
• Liver dysfunction
• Hyponatraemia
• Leukopenia and thrombocytopenia rarely

CAUTIONS

• Severe hepatic disease (risk of encephalopathy)
• Pregnancy (toxic in animal studies)
• May mask symptoms of gastric cancer
• Omeprazole may enhance anticoagulant effect ofwarfarin – monitor INR and may increase phenytoin levels
• Omeprazole may reduce the effectiveness of clopidogrel

ORGAN FAILURE

Hepatic: reduce dose

Morphine

Morphine is the standard opioid with which others are compared and remains a valuable drug for the treatment of acute, severe pain.Peak effect after IV bolus is 15 min. Duration of action is between 2 and 3 hours. Both liver and kidney function are responsible for morphine elimination. The liver mainly metabolises it. One of the principal metabolites, morphine 6-glucuronide (M6G), is also a potent opioid agonist and may accumulate in renal failure.

USES

• Relief of severe pain
• To facilitate mechanical ventilation
• Acute left ventricular failure – by relieving anxiety and producing vasodilatation

CONTRAINDICATION

• Airway obstruction
• Pain caused by biliary colic

ADMINISTRATION

• IV bolus: 2.5 mg every 15 min PRN
• IV infusion rate: 1–5 mg/h

Dilute in glucose 5% or sodium chloride 0.9% 
Stop or reduce infusion each day and restart when first signs of discomfort appear. Failure to assess daily will result in overdosage and difficulty in weaning patient from ventilation

• If the patient is conscious the best method is to give an infusion pump they can control (PCAS): 50 mg made up to 50 ml with sodium chloride 0.9%; IV bolus: 1 mg; lockout: 3–10 min

How not to use morphine

In combination with an opioid partial agonist, e.g. buprenorphine (antagonises opioid effects)

ADVERSE EFFECTS

• Respiratory depression and apnoea
• Hypotension and tachycardia
• Nausea and vomiting
• Delayed gastric emptying
• Reduced intestinal mobility
• Biliary spasm
• Constipation
• Urinary retention
• Histamine release
• Tolerance
• Pulmonary oedema

CAUTIONS

Enhanced and prolonged effect when used in patients with renal failure, the elderly and in patients with hypovolaemia and hypothermia.
Enhanced sedative and respiratory depression from interaction with:
• benzodiazepines
• antidepressants
• anti-psychotics

Organ failure

• CNS: sedative effects increased
• Respiratory: respiratory depression
• Hepatic: can precipitate coma
• Renal: increased cerebral sensitivity. M6G accumulates

Renal replacement therapy

CVVH dialysed dose as in CC 10–20 ml/min, i.e. use smaller than usual dose, e.g. 2.5–5 mg. HD dialysed dose as in CC 10 ml/min, i.e. use smaller doses, e.g. 1.25–2.5 mg and extended dosing intervals. PD not dialysable, dose as per HD. Active metabolite M6G accumulates in renal failure.Titrate to response, such as pain/sedation scores.

Applied Clinical Pharmacokinetics By Larry A. Bauer

                                                


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Facts about Generic Drugs

Today, nearly 8 in 10 prescriptions filled in the United States are for generic drugs. The use of generic drugs is expected to grow over the next few years as a number of popular drugs come off patent through 2015. Here are some facts about generic drugs:	Click image to view larger graphic.

  

 

FACT: FDA requires generic drugs to have the same quality and performance as brand name drugs.  

• 
  When a generic drug product is approved, it has met rigorous standards established by the FDA with respect to identity, strength, quality, purity, and potency. However, some variability can and does occur during manufacturing, for both brand name and generic drugs. When a drug, generic or brand name, is mass-produced, very small variations in purity, size, strength, and other parameters are permitted. FDA limits how much variability is acceptable. 

• Generic drugs are required to have the same active ingredient, strength, dosage form, and route of administration as the brand name product. Generic drugs do not need to contain the same inactive ingredients as the brand name product.  

• The generic drug manufacturer must prove its drug is the same as (bioequivalent) the brand name drug. For example, after the patient takes the generic drug, the amount of drug in the bloodstream is measured.  If the levels of the drug in the bloodstream are the same as the levels found when the brand name product is used, the generic drug will work the same. 

• Through review of bioequivalence data, FDA ensures that the generic product performs the same as its respective brand name product. This standard applies to all generic drugs, whether immediate or controlled release. 

• All generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs, and the generic products must meet the same exacting specifications as any brand name product. In fact, many generic drugs are made in the same manufacturing plants as brand name drug products.

FACT:  Research shows that generics work just as well as brand name drugs.

• A study evaluated the results of 38 published clinical trials that compared cardiovascular generic drugs to their brand name counterparts. There was no evidence that brand name heart drugs worked any better than generic heart drugs.

FACT:    FDA does not allow a 45 percent difference in the effectiveness of the generic drug product. 

• FDA recently evaluated 2,070 human studies conducted between 1996 and 2007. These studies compared the absorption of brand name and generic drugs into a person’s body. These studies were submitted to FDA to support approval of generics. The average difference in absorption into the body between the generic and the brand name was 3.5 percent[2]. Some generics were absorbed slightly more, some slightly less. This amount of difference would be expected and acceptable, whether for one batch of brand name drug tested against another batch of the same brand, or for a generic tested against a brand name drug. In fact, there have been studies in which brand name drugs were compared with themselves as well as with a generic. As a rule, the difference for the generic-to-brand comparison was about the same as the brand-to-brand comparison.
• Any generic drug modeled after a single, brand name drug must perform approximately the same in the body as the brand name drug. There will always be a slight, but not medically important, level of natural variability – just as there is for one batch of brand name drug compared to the next batch of brand name product.

FACT: When it comes to price, there is a big difference between generic and brand name drugs. On average, the cost of a generic drug is 80 to 85 percent lower than the brand name product.

• In 2010 alone, the use of FDA-approved generics saved $158 billion, an average of $3 billion every week.

FACT: Cheaper does not mean lower quality. 

• Generic manufacturers are able to sell their products for lower prices because they are not required to repeat the costly clinical trials of new drugs and generally do not pay for costly advertising, marketing, and promotion. In addition, multiple generic companies are often approved to market a single product; this creates competition in the market place, often resulting in lower prices.

FACT: FDA monitors adverse events reports for generic drugs.

• The monitoring of adverse events for all drug products, including generic drugs, is one aspect of the overall FDA effort to evaluate the safety of drugs after approval. Many times, reports of adverse events describe a known reaction to the active drug ingredient. 

• Reports are monitored and investigated, when appropriate. The investigations may lead to changes in how a product (brand name and generic counterparts) is used or manufactured.  

FACT:  FDA is actively engaged in making all regulated products – including generic drugs – safer.

• FDA is aware that there are reports noting that some people may experience an undesired effect when switching from brand name drug to a generic formulation or from one generic drug to another generic drug. FDA wants to understand what may cause problems with certain formulations if, in fact, they are linked to specific generic products.  

• FDA is encouraging the generic industry to investigate whether, and under what circumstances, such problems occur. The Agency does not have the resources to perform independent clinical studies and lacks the regulatory authority to require industry to conduct such studies. FDA will continue to investigate these reports to ensure that it has all the facts about these treatment failures and will make recommendations to healthcare professionals and the public if the need arises.