Top 100 drugs: Paracetamol, Penicillins.

What is the indication for paracetamol?

A first-line analgesic for most forms of acute and chronic pain.

An antipyretic that can reduce fever and associated symptoms.

MOA of paracetamol?

In the CNS - acts as a reducing co-substrate of cyclo-oxygenase 2 (cox-2). This reduces the availability of oxidised COX-2, which is necessary for conversion of arachidonic acid to an intermediate metabolite in the prostaglandin synthesis pathway.

This interferes with transmission of pain signals between the spinal cord and high centres, which reduces pain sensitivity.

It also reduces PGE2 conics in the thermoregulatory region of the hypothalamus, which reduces fever.

Important adverse effects with paracetamol?

In overdose, the CYP450 elimination pathway becomes oversaturated and NAPQI accumulates which causes hepatocellular necrosis.

Hepatotoxicity can be prevented by treatment with the glutathione precursor acetylcysteine.

Warnings with paracetamol?

-paracetamol dose should be reduced in people at increased risk of liver toxicity, either because of increased NAPQI production or reduced glutathione stores.

Important interactions with paracetamol?

-CYP inducers eg. Phenytoin and carbamazepine, increases the rate of NAPQI production and therefore increase the risk of liver damage in paracetamol toxicity.

How can paracetamol be purchased?

-oral paracetamol is a GSL - can be purchased from any retail outlet, although it is also available on prescription.

Monitoring with paracetamol?

-efficacy of paracetamol in pain control can be established by enquiry about symptoms or by using a pain score.

Antipseudomnoal penicillins indication?

-reserved for severe infections, particularly when there is a broad spectrum of potential pathogens if antibiotic resistance is likely or in people who have immune suppression.

Eg. LRTI, UTI, intra-abdominal infection, skin and soft tissue infection

Antipseudomonal penicillins spectrum of activity?

-broad spectrum of activity against a wide range of gram-positive and gram-negative bacteria and anaerobes.

-they are formulated with a b-lactamase inhibitor which confers anti-microbial activity against b-lactamase-producing bacteria.

MOA of antipseudomonal penicillins?

-penicillins inhibit enzymes responsible for cross-linking peptidoglycans.

-this weakens bacterial cell walls, reducing their ability to maintain an osmotic gradient and resulting in cell swelling, lysis and death.

-penicillins contain a B-lactam ring which is responsible for their bactericidal activity.

-side chains attached to the B-lactam ring can be modified to make semi-synthetic penicillins.

Important adverse effects with antipseudomonal penicillins?

-GI upset very common.

-antibiotic-associated colitis

-delayed or immediate hypersensitivity may occur

Warnings with antipseudomonal penicillins?

-use in caution in people at risk of C. Difficile infection, particularly older people and those in hospital

-main contraindication is penicillin allergy.

-dose of antipseudomonal penicillins should be reduced in moderate/severe renal impairment.

Important interactions with antipseudomonal penicillins?

Penicillins reduce renal excretion of methotrexate, which increases the risk of toxicity.

-they can also enhance the anticoagulant effect of warfarin by killing normal GI flora that synthesise vitamin K.

Common indications of broad spectrum penicillins?

-used in infections eg sinusitis, otitis media, CAP, and UTI

-to eradicate H. Pylori in peptic ulcer disease

-co-amoxiclav - common choice for severe, resistant and hospital acquired infections, including pneumonia, UTI , intraabdominal infection, cellulitis and bone and joint infections.

Spectrum of activity of broad spectrum penicillins?

-broad spectrum of activity against gram-positive and gram-negative cocci and bacilli

-however, it is inactivated by bacterial penicillin axes, and resistance is increasingly prevalent.

MOA of broad spectrum penicillins?

-penicillins inhibit enzymes responsible for cross-linking peptidoglycans. This weakens the bacterial cell walls, reducing their ability to maintain an osmotic gradient, causing cell swelling, lysis and death.

-penicillins contain a b-lactam ring which is responsible for their bactericidal activity. Broad spectrum penicillins are synthesised by addition of an amino group to the B-lactam ring side chains, broadening activity against aerobic gram-negative bacteria.

Important adverse effects with broad spectrum penicillins?

-GI upset common

-antibiotic-associated colitis

-acute liver injury may develop

Warnings with broad spectrum penicillins?

-main contraindication is severe allergy to beta lactam antibiotics.

-use in caution with older or hospitalised people at risk of C. Difficile infection and in those with a history of penicillin-associated liver injury

-dosage should be reduced in severe renal impairment

Important interactions with broad spectrum penicillins?

-reduced renal excretion of methotrexate increases the risk of toxicity. Broad spectrum penicillins can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K.

When are broad spectrum antibiotics started?

When the cause of infection is unknown - broad spectrum antibiotics are started to empirically cover a wide range of possible organisms.

Common indications of narrow spectrum penicillins ?

Benzylpenicillin/phenoxymethylpenicillin: streptococcal infections, including tonsillitis, pneumonia, endocarditis and meningococcal disease.

Penicillinase-resistant penicillin - staphylococcal infections including skin, soft tissue, bone and joint infections, otitis external and endocarditis.

Spectrum of activity of narrow-spectrum penicillins?

-active against gram-positive organisms and some anaerobes, as well as gram negative cocci.

-narrow spectrum antibiotics can reduce emergence of anti microbial resistance but often need to be combined with other antibiotics for optimal treatment.

MOA of narrow spectrum penicillins?

-penicillins inhibit enzymes responsible for cross-linking peptidoglycans. This weakens the bacterial cell wall, reducing its ability to maintain an osmotic gradient, causing cell swelling, lysis and death.

Important adverse effects with narrow spectrum penicillins?

-minor GI upset is common

-neurological toxicity can occur at very high doses or in toxic accumulation due to renal failure.

Warnings with narrow spectrum antibiotics?

-dose reduction is required in severe renal impairment

-the main contraindication is allergy to any penicillin