Pharmacokinetics Metabolism and Excretion - 2

The drug metabolising capacity of the body, especially the liver, is subject to?

• Fluctuations in Activity

Environmental factors (drugs, natural products and chemicals) can modify the?

• The Basal Rate of Drug Metabolizing Enzymes

Many compounds can increase the enzyme activity of the ……. When administered…..?

• Cytochrome P450 monoxidase system

• When Administered Quickly

Enzyme induction is an?

• Adaptive increase in enzyme metabolising capacity (dynamic)

• as a result of repeated or prolonged exposure to an inducing agent over several days

Enzyme induction effects are generally….?

• Reversible

Enzyme induction is one of the causes of?

• Drug Interactions

Drugs can act as inducing?

• Inducing Agents

• and can increase the activity of Cytochrome P450 enzymes when administered repeatedly

Enzyme induction increases metabolism of all?

• Substrates of Enzymes

Enzyme induction increases metabolism of all substrates of the enzyme. As a result, drugs that are substrates for the induced enzyme?

• Will be metabolized faster

• Reduced Drug Action

• Loss of Efficacy

Following enzyme induction, drugs will be?

• Metabolized faster

• Increased Drug Clearance

• reduced drug plasma levels

• shorter drug action.   

  
  

After Enzyme Induction Prodrugs will be metabolised faster too and form more?

• Active Metabolize

• Thus providing Longer drug action and increased efficacy.

Carbamazepine, an inducer of?

• Hepatic microsomal enzymes

Carbamazepine can accelerate ?

• the metabolism of the other drugs

• such as oral contraceptives, warfarin and corticosteroids,

• leading to loss of therapeutic efficacy.

Enzyme induction can also increase drug toxicity in cases where metabolites formed by?

• Phase 1 Reactions are More toxic than the parent compound

The susceptibility to paracetamol-induced liver toxicity is increased in?

• People who consume Alcohol regularly 

Regular alcohol consumption induces the….?

• cytochrome P450 enzyme

• responsible for the formation of the reactive (toxic) metabolite of

• paracetamol ,

• N-acetyl-p-benzoquinone imine

Drug metabolism can be affected by compounds that inhibit?

• P450 Enzyme Activity.

Enzyme inhibition generally has a?

• Prompt onset,

• Within hours

Enzyme inhibition can occur by competition of?

• 2 or more drugs for the same binding site.

Enzyme Inhibition decreases metabolism of drug substrates by the…. and results in….?

• the enzyme and results in

• reduced drug clearance,

• elevated drug plasma levels and prolonged drug action.

drug plasma levels to rise above the upper limit of the therapeutic range, which may result in an?

• Augmented Biological Response

• and Adverse Effects

drugs that are substrates for the inhibited enzyme will be metabolised slower and will have?

• Metabolized Slower

• Elevated drug plasma levels

• Prolonged Drug Action 

Following Enzyme Inhibition, Prodrugs will be?

• Metabolised Slower

• Produce Less active Metabolites

• prodrugs will have an decreased drug action and efficacy following enzyme

Enzyme inhibition can be protective if the metabolite is?

• More toxic than the parent compound.

Methanol and ethylene glycol are metabolised to reactive (toxic) products by the enzyme?

• alcohol dehydrogenase

In general, drugs are metabolized more slowly in?

• Neonatal and Elderly Humans

Why are Drugs metabolized more slowly in babies?

• This is due to slower Phase 1 and 2 reactions in the first two weeks after birth

Why are Drugs metabolized more slowly in Elderly?

• fall-off in liver metabolism of drugs in the elderly

there are higher rates of oxidation of oestrogens and benzodiazepines in?

• Women compared to Men

Pharmacogenetic variations contribute to the individual response to?

• Drugs and could cause unwanted or adverse drug reactions or toxicity.

In poor metabolisers, drugs will be?

• Metabolized more slowly.

• Their drug plasma levels will be elevated and there will be an increase in drug action and efficacy

poor metabolizers, prodrugs will be?

• Metabolized slower

• Produce less active Metabolites.

Succinylcholine (suxamethonium) is a?

• Rapid Acting Muscle Relaxant.

• Usually lasts 2-6 Minutes

The kidneys are the most significant site?

• For Excretion

While lipophilic drugs are filtered just as?

• hydrophilic drugs

hydrophilic compounds will remain in the?

• Filtrate

he kidneys receive approximately one-…?

• 1/5 of Cardiac Output

the normal rate of plasma filtration in the glomeruli is?

• 125 mL per minute.

The glomerular filtration rate declines with?

• Normal Aging

• usually beginning around the age of 30 at a rate of 8% per decade

Other routes of drug elimination include excretion into the?

• Bile (For Larger Compounds).

• and via the lungs (for volatile compounds).

About 5% of alcohol is excreted by?

• Exhalation