This lecture discusses the following topics:

• General classification
• Cellular actions of opioid receptors
• Anatomical distribution and physiologic effects of mu, delta and kappa receptors
• Agonists and antagonists
• ORL-1 receptors

Outline:

• Facts about SSRIs adverse effects.
• Gastrointestinal adverse effects.
  5-HT3 and 5-HT4 receptors in the GI tract.
  5-HT3 receptors in the brainstem and hypothalamus.
• CNS adverse effects.
  5-HT2A receptor stimulation at the basal ganglia.
  5-HT2A and 2C receptors are hypothetically involved in agitation, anxiety and panic attacks.
• Sexual dysfunction

Article outline:

• Therapeutic index equation
• How therapeutic index is determined
• List of narrow therapeutic index drugs

Therapeutic index equation

The therapeutic index of a drug is the ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response in a population of individuals.

Where: TD50 is the dose of drug that causes a toxic response in 50% of the population and ED50 is the dose of drug that is therapeutically effective in 50% of the population.

How therapeutic index is determined

Therapeutic index and quantal dose response curves

Both ED50 and TD50 are calculated from quantal dose response curves, which represent the frequency with which each dose of drug elicits the desired response or toxic effect in the population.

There are some important characteristics of quantal dose-response curves (see image above) that are worth noting:

• Dose of drug in plasma is plotted in the horizontal axis while the percentage of individuals (animals or humans) that responds or shows a toxic effect is represented in the vertical axis.
• These curves measure all or none (positive or negative) responses. Some examples of positive responses include: relief of headache for an antimigraine drug, increase in heart rate of at least 20 bpm for a cardiac stimulant, or 10 mmHg fall in diastolic blood pressure for an antihypertensive.
• Data is obtained from a population. Unlike graded dose-response graphs, data for quantal dose-response curves is obtained from many individuals.

ED50

The graph below shows how ED50 is calculated.

The dose required to cause a therapeutic effect (positive response) in 50% of a population is the ED50.

TD50

The dose required to produce a toxic effect in 50% of the studied population is the TD50. For animal studies, LD50 is the dose that results in death of 50% of the population.

Narrow therapeutic index drugs

The list below mentions some examples of narrow therapeutic index drugs:

• Warfarin
• Lithium
• Digoxin
• Phenytoin
• Gentamycin
• Amphotericin B
• 5-fluorouracil
• AZT (zidovudine)

References and further reading

Craig, C. Modern Pharmacology With Clinical Applications. 6th ed. LWW, 2003

Golan, D. “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”. 2nd ed. LWW, 2008.

• Classification of heparins: Unfractioned heparin, Low Molecular Weight Heparin and Fondaparinux
• Chemical properties
• Fondaparinux
• Mechanism of action of heparin
• Heparin and the coagulation cascade
• Pharmacokinetics of unfractioned heparin
• Clinical uses and drawbacks

• Mechanism of Action
• Dosing/Target INRs
• Drug/Food Interactions
• Managing Elevated INRs
• Patient Counseling
• Other Considerations

“The European Medicines Agency has recommended restricting the use of modafinil-containing medicines. The medicine should only be used to treat sleepiness associated with narcolepsy. Doctors and patients should no longer use the medicine for the treatment of idiopathic hypersomnia, excessive sleepiness associated with obstructive sleep apnoea and chronic shift work sleep disorder.”

Click here to download the full press release.

Coagulation cascade: extrinsic, intrinsic and common pathways differentiation

Video animation contents:

• Intrinsic pathway
• Extrinsic pathway (endothelium exposure to VIIa factor).
• Common pathway

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This tutorial features interactive exercises and animations that help understand the role of coagulation cascade factors and physiological hemostatic processes.

It highlights clinical disorders on intrinsic and extrinsic pathways, with a special section overviewing Von Willebrand’s disease.

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Coagulation factors commented

This animation focuses exclusively on the coagulation cascade factors and its sequence of activation. It emphasises biochemical and laboratory aspects.

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