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Theme 3: Molecular Cell Biology > Lecture 12: Predicting Adverse Drug Effects > Flashcards

Lecture 12: Predicting Adverse Drug Effects Flashcards

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1
Q

Example of an agonist drug

A

Beta receptors are located in the airways where noradrenaline (and adrenaline) act as agonists to produce bronchodilation

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2
Q

How does salbutamol act as as agonist in asthma?

A

In asthma a drug called salbutamol acts as an agonist on Beta2 receptors to provide bronchodilation and provide relief

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3
Q

Example of an antagonist

A

Beta receptors are also located on the heart where noradrenaline (and adrenaline) act as agonists to increase force of contraction.

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4
Q

How does atenolol act as an antagonist for blood pressure?

A

In high blood pressure, a drug called atenolol blocks Beta1 receptors to reduce blood pressure: an antagonist effect.

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5
Q

What are receptor subtypes?

A

Molecules with the same overall structural patterns and associated signal transduction pathways, but slightly different structures and different functions.

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6
Q

What are the 4 mechanisms of loss of drug effect?

A
  1. Exhaustion of mediators
  2. Increased metabolic degradation
  3. Physiological adaptation
  4. Active extrusion of a drug from a cell
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7
Q

How does exhaustion of mediators cause loss of effect in drugs?

A

Constant drug activation causes one or more mediators to “run out”.

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8
Q

How does increased metabolic degradation cause loss of effect in drugs?

A

Induction of drug metabolising enzymes such as CYP450 leading to increased breakdown of drug.

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9
Q

What is refractoriness?

A

Loss of therapeutic efficacy

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10
Q

What is receptor desensitisation?

A

Loss of intrinsic activity of receptor complexes

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11
Q

How does physiological adaptation cause loss of effect in drugs?

A

Production of new cells which lack active receptors or induction of resistance genes.

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12
Q

How does extrusion of drugs cause loss of effect in drugs?

A

Bacteria and cancer cells are able to pump out drugs and leads to multiple drug resistance

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13
Q

What is meant by therapeutic effect?

A

Drug produces the intended biological effect

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14
Q

What is meant by side effect?

A

Nuisance effects of a drug which can become harmful

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15
Q

What is meant by adverse effects?

A

Undesired effects of a drug that can be harmful; eg. allergies

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16
Q

What is meant by toxic effects?

A

Drug poisoning which is harmful and may be life-threatening.

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17
Q

What is the autonomic nervous system (ANS)?

A

A division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of internal organs.

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18
Q

What is the role of the autonomic nervous system (ANS)?

A

Regulates bodily functions, such as the heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousal.

19
Q

What are the 2 branches of the autonomic nervous system (ANS)?

A
  1. Sympathetic (“fight or flight”)

2. Parasympathetic (“rest and digest”)

20
Q

What mediates the sympathetic nervous system?

A

Adrenaline

21
Q

How can drugs be used to lower blood pressure (hypertension)?

A

(1) Decreasing cardiac output

(2) Decreasing peripheral resistance

22
Q

How can we decrease cardiac output to lower blood pressure?

A

Decrease cardiac output by increasing parasympathetic nervous system activity.

23
Q

What are the consequences of increasing PNS activity to decrease cardiac output?

A

No parasympathetic innervation of blood vessels, so no effect of peripheral resistance and an overall modest reduction in BP.

24
Q

What drugs target PNS?

A
  1. Muscarinic agonist eg. acetylcholine

2. Anticholinesterase drugs (drugs that prevent breakdown of acetylcholine); eg. neostigmine

25
Q

What are the side effects of PNS activation?

A
  • Visual disturbances
  • Lacrimation & salivation
  • Bronchoconstriction
  • Stomach cramps
  • Constipation
  • Incontinence
26
Q

How can we decrease peripheral resistance to lower blood pressure?

A

Decrease blood pressure by decreasing sympathetic nervous system activity.

27
Q

What are the consequences of decreasing SNS activity to decrease peripheral resistance?

A

Because noradrenaline acts on different subtypes of adrenoceptors (alpha and beta), it would produce opposing responses alongside beneficial responses.

28
Q

What drugs can we use to decrease SNS activity?

A
  1. Give an adrenoceptor antagonist

2. Prevent release of noradrenaline

29
Q

How do mixed alpha/beta antagonists work?

A

Decrease cardiac output, decrease blood flow to skeletal muscle, and increase blood flow to skin and gut.

30
Q

Examples of mixed alpha/beta antagonists?

A

Carvedilol and labetalol

31
Q

What are the side effects of mixed alpha/beta antagonists?

A
  • Bronchoconstriction
  • Postural hypotension
  • Bradycardia
  • Muscle weakness/fatigue
  • Cold extremities
32
Q

How do selective alpha antagonists work?

A

Increases blood flow to skin and gut, and decrease peripheral resistance, but no direct effect on heart.

33
Q

Example of selective alpha antagonist?

A

Phentolamine

34
Q

What are the side effects of selective alpha antagonists?

A
  • Headaches
  • Postural hypotension
  • Reflex tachycardia
35
Q

How do non-selective beta antagonists work?

A

Decrease cardiac output and decrease blood flow to skeletal muscle due to increased peripheral resistance.

36
Q

Example of non-selective beta antagonists?

A

Propranolol

37
Q

What are the side effects of non-selective beta antagonists?

A
  • Bronchoconstriction

* Muscle weakness / fatigue

38
Q

How do selective beta 1 antagonists work?

A

Decrease cardiac output and have no effect on blood flow to skeletal muscle.

39
Q

Examples of selective beta 1 antagonists?

A

Atenolol

40
Q

How can we treat asthma?

A
  1. Decreasing activity of the parasympathetic nervous system
  2. Increasing activity of the sympathetic nervous system
41
Q

What drug can decrease PNS activity in asthma?

A

Muscarinic antagonist, e.g. ipratropium bromide or tiotropium bromide

Side effects: blurred vision, dry mouth, tachycardia, constipation and urinary retention.

42
Q

What drug can increase SNS activity in asthma?

A

Beta(2) agonists e.g. salbutamol

Side effects: tremor and tachycardia.

43
Q

How can we limit the adverse effects of salbutamol?

A

Limit adverse effects by local administration through an aerosol inhaler.

Theme 3: Molecular Cell Biology (15 decks)

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