Lecture 12: Predicting Adverse Drug Effects Flashcards
Example of an agonist drug
Beta receptors are located in the airways where noradrenaline (and adrenaline) act as agonists to produce bronchodilation
How does salbutamol act as as agonist in asthma?
In asthma a drug called salbutamol acts as an agonist on Beta2 receptors to provide bronchodilation and provide relief
Example of an antagonist
Beta receptors are also located on the heart where noradrenaline (and adrenaline) act as agonists to increase force of contraction.
How does atenolol act as an antagonist for blood pressure?
In high blood pressure, a drug called atenolol blocks Beta1 receptors to reduce blood pressure: an antagonist effect.
What are receptor subtypes?
Molecules with the same overall structural patterns and associated signal transduction pathways, but slightly different structures and different functions.
What are the 4 mechanisms of loss of drug effect?
- Exhaustion of mediators
- Increased metabolic degradation
- Physiological adaptation
- Active extrusion of a drug from a cell
How does exhaustion of mediators cause loss of effect in drugs?
Constant drug activation causes one or more mediators to “run out”.
How does increased metabolic degradation cause loss of effect in drugs?
Induction of drug metabolising enzymes such as CYP450 leading to increased breakdown of drug.
What is refractoriness?
Loss of therapeutic efficacy
What is receptor desensitisation?
Loss of intrinsic activity of receptor complexes
How does physiological adaptation cause loss of effect in drugs?
Production of new cells which lack active receptors or induction of resistance genes.
How does extrusion of drugs cause loss of effect in drugs?
Bacteria and cancer cells are able to pump out drugs and leads to multiple drug resistance
What is meant by therapeutic effect?
Drug produces the intended biological effect
What is meant by side effect?
Nuisance effects of a drug which can become harmful
What is meant by adverse effects?
Undesired effects of a drug that can be harmful; eg. allergies
What is meant by toxic effects?
Drug poisoning which is harmful and may be life-threatening.
What is the autonomic nervous system (ANS)?
A division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of internal organs.
What is the role of the autonomic nervous system (ANS)?
Regulates bodily functions, such as the heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousal.
What are the 2 branches of the autonomic nervous system (ANS)?
- Sympathetic (“fight or flight”)
2. Parasympathetic (“rest and digest”)
What mediates the sympathetic nervous system?
Adrenaline
How can drugs be used to lower blood pressure (hypertension)?
(1) Decreasing cardiac output
(2) Decreasing peripheral resistance
How can we decrease cardiac output to lower blood pressure?
Decrease cardiac output by increasing parasympathetic nervous system activity.
What are the consequences of increasing PNS activity to decrease cardiac output?
No parasympathetic innervation of blood vessels, so no effect of peripheral resistance and an overall modest reduction in BP.
What drugs target PNS?
- Muscarinic agonist eg. acetylcholine
2. Anticholinesterase drugs (drugs that prevent breakdown of acetylcholine); eg. neostigmine
What are the side effects of PNS activation?
- Visual disturbances
- Lacrimation & salivation
- Bronchoconstriction
- Stomach cramps
- Constipation
- Incontinence
How can we decrease peripheral resistance to lower blood pressure?
Decrease blood pressure by decreasing sympathetic nervous system activity.
What are the consequences of decreasing SNS activity to decrease peripheral resistance?
Because noradrenaline acts on different subtypes of adrenoceptors (alpha and beta), it would produce opposing responses alongside beneficial responses.
What drugs can we use to decrease SNS activity?
- Give an adrenoceptor antagonist
2. Prevent release of noradrenaline
How do mixed alpha/beta antagonists work?
Decrease cardiac output, decrease blood flow to skeletal muscle, and increase blood flow to skin and gut.
Examples of mixed alpha/beta antagonists?
Carvedilol and labetalol
What are the side effects of mixed alpha/beta antagonists?
- Bronchoconstriction
- Postural hypotension
- Bradycardia
- Muscle weakness/fatigue
- Cold extremities
How do selective alpha antagonists work?
Increases blood flow to skin and gut, and decrease peripheral resistance, but no direct effect on heart.
Example of selective alpha antagonist?
Phentolamine
What are the side effects of selective alpha antagonists?
- Headaches
- Postural hypotension
- Reflex tachycardia
How do non-selective beta antagonists work?
Decrease cardiac output and decrease blood flow to skeletal muscle due to increased peripheral resistance.
Example of non-selective beta antagonists?
Propranolol
What are the side effects of non-selective beta antagonists?
- Bronchoconstriction
* Muscle weakness / fatigue
How do selective beta 1 antagonists work?
Decrease cardiac output and have no effect on blood flow to skeletal muscle.
Examples of selective beta 1 antagonists?
Atenolol
How can we treat asthma?
- Decreasing activity of the parasympathetic nervous system
- Increasing activity of the sympathetic nervous system
What drug can decrease PNS activity in asthma?
Muscarinic antagonist, e.g. ipratropium bromide or tiotropium bromide
Side effects: blurred vision, dry mouth, tachycardia, constipation and urinary retention.
What drug can increase SNS activity in asthma?
Beta(2) agonists e.g. salbutamol
Side effects: tremor and tachycardia.
How can we limit the adverse effects of salbutamol?
Limit adverse effects by local administration through an aerosol inhaler.
