Pharmacology Chapter on Angiotensin II and Toxicity

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Questions and Answers

What is the primary factor determining whether a substance has beneficial effects or becomes toxic?

Time period of exposure to the substance

Chemical structure of the substance

Concentration or dose of the substance (correct)

Rate of absorption in the body

What does the therapeutic index (TI) evaluate in drug administration?

The purity of the drug compound

The ratio of LD50 to ED50 or TD50 to ED50 (correct)

The duration of the drug's effects

The maximum effect of a drug on a target

At high concentrations, which receptor type does angiotensin II primarily bind to, leading to the inhibition of vasoconstriction?

ATR Type 1 Receptor

ATR Type 2 Receptor (correct)

ATR Type 3 Receptor

ATR Type 4 Receptor

What does the term LD50 represent in pharmacology?

The amount needed to kill 50% of test cells or organisms Signup and view all the answers

Which of the following substances can lead to toxicity at high concentrations, despite being beneficial at lower doses?

Insulin Signup and view all the answers

In the context of therapeutic index, what does a low TI indicate?

Close proximity of therapeutic and toxic dose ranges Signup and view all the answers

What is the consequence of a drug having a large therapeutic index?

Lower likelihood of toxicity occurring Signup and view all the answers

What type of antagonism can be directly defined as one substance acting to counteract the effects of another substance?

Physiological antagonism Signup and view all the answers

Which type of agonist can produce a maximum biological response at certain doses?

Full agonist Signup and view all the answers

What is the primary characteristic of a partial agonist?

It cannot elicit a complete response, regardless of dose. Signup and view all the answers

How is the therapeutic index defined in pharmacology?

The ratio of the toxic dose to the effective dose of a drug. Signup and view all the answers

Which scenario best describes pharmacokinetic antagonism?

One drug affects the metabolism of another drug. Signup and view all the answers

What does EC50 represent in pharmacological terms?

The concentration required to elicit 50% of the maximum biological response. Signup and view all the answers

What aspect of drug selectivity refers to the ability of a drug to produce a particular effect based on its molecular structure?

Specificity Signup and view all the answers

How does drug promiscuity potentially benefit pharmacology?

It allows drugs to interact with multiple targets for diverse therapeutic effects. Signup and view all the answers

What defines drug potency in relation to its effect?

The amount of drug required to elicit a specific effect. Signup and view all the answers

In what scenario might a drug with high selectivity cause unintended harmful effects?

When it interacts with non-target receptors due to promiscuity. Signup and view all the answers

What is indicated by a high therapeutic index of a drug?

There is a large margin between effective dose and toxic dose. Signup and view all the answers

Which statement exemplifies physiological antagonism in pharmacology?

Two drugs act at different receptor sites to produce opposing effects. Signup and view all the answers

What factor primarily influences the amount of a drug needed to achieve its effect?

The affinity of the drug for its target. Signup and view all the answers

Which of the following represents a potential toxic effect resulting from drug promiscuity?

Unintended receptor interactions leading to bronchospasm. Signup and view all the answers

Study Notes

Angiotensin II

At low concentrations, Angiotensin II binds to the Angiotensin II Type 1 receptor (ATR1), leading to vasoconstriction
At very high concentrations, it binds to the Angiotensin II Type 2 receptor (ATR2), negating the effects of ATR1 activation
Angiotensin II has a high affinity for ATR1 and a low affinity for ATR2, explaining why it only binds to ATR2 at very high concentrations

Toxicity

Everything is toxic, the dose determines if it has a beneficial or toxic effect
Insulin at high concentrations can lead to diabetic hypoglycemia and death
Paracetamol, an analgesic, at high concentrations can kill liver and kidney cells

LD50 and TD50

LD50: The amount of a drug needed to kill 50% of test cells or organisms
TD50: The amount of a drug needed to cause toxicity in 50% of test cells or organisms
Toxic effect can involve dysfunction or cell death

Therapeutic Index

Therapeutic index (TI) = LD50 or TD50/ED50, indicating the likelihood of side effects or toxicity
Drugs with a low TI (blue and red lines close together) require careful dosing as toxicity can occur at therapeutic doses, like Warfarin
Drugs with a large TI, therapeutic concentrations are much lower than toxic ones, reducing the likelihood of toxicity

Drug Properties

Three key drug properties determine if a drug works and works safely:
- Selectivity/Specificity
- Potency
- Efficacy

Selectivity/Specificity

Selectivity describes a drug's ability to produce a particular effect, relating to its molecular structure and receptor specificity
Receptor specificity is determined by the precise molecular interactions between a drug molecule and a receptor protein
Some drugs bind to one target (e.g., a receptor), while others interact with multiple targets
Binding to multiple targets (promiscuity) can be beneficial pharmacologically or lead to off-target/toxic effects

Drug Promiscuity

Example 1: Statins
- Inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver and circulating cholesterol levels
- Reported to modulate nitric oxide synthase gene expression in vascular endothelial cells (promoting vasodilation), reducing macrophage proliferation (anti-atherosclerosis effects), and inflammatory markers (anti-thrombus formation effects)
Example 2: Propranolol
- Blocks beta-adrenoceptor beta 1 in the heart, reducing heart rate and contractive force (clinical effect)
- Also blocks beta-adrenoceptor beta 2, inhibiting bronchial smooth muscle relaxation, potentially causing bronchospasm in asthmatic and COPD patients (toxic/harmful effect)

Drug Potency

Relates to the amount of drug needed to elicit an effect
Depends on the drug's affinity for its target
- Low affinity: Weak binding, readily dissociates, requires larger amounts of drug for effect
- High affinity: Strong binding, requires less drug for effect
Potency is often expressed as EC50, the concentration needed to elicit 50% of the maximum response
Time of exposure is crucial, especially in cell culture experiments

Drug Efficacy

Ability of a drug to induce a biological or physiological response
Drugs can be:
- Full agonists: Induce a full biological response at specific doses
- Partial agonists: Cannot induce a full biological response regardless of dose, but can still be effective drugs with reduced overdose risk
ED50: Dose of drug needed for a therapeutic effect in 50% of test cells or organisms

Agonists and Antagonists

Agonist: A compound that binds to a target molecule (e.g., a receptor) and activates it, eliciting a response.
Antagonist: A compound that binds to a target molecule and inhibits its activity.

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Description

This quiz explores the pharmacology of Angiotensin II, its receptors, and the principles of toxicity, including LD50 and TD50 values. Understand how different concentrations can lead to beneficial or harmful effects in various substances. Test your knowledge on the therapeutic index and its implications on drug safety.