1. Introduction to Pharmacology Flashcards
What is the difference between Pharmacodynamics and Pharmacokinetics?
Pharmacodynamics = what the drug does to the body
Pharmacokinetics = what the body does to the drug
What do drugs act on to achieve their therapeutic effects?
(4 things)
Mechanism of Drug Action
Drugs achieve their therapeutic effects by acting primarily on either:
- Receptors
- Enzymes
- Ion channels
- Carrier molecules
What are receptors?
What are 6 things that bind to receptors?
Receptors = proteins found on the surface of cell membranes, or inside the cell
- They are binding sites for chemicals which are produced naturally in the body
- Neurotransmitters
- Steroids
- Prostaglandins
- Hormones
- Cytokines
- Peptides
- These chemicals produce their effects in the body by binding to their specific receptors
What are 3 examples of receptors?
Examples of Receptors
- Adrenaline stimulates adrenergic receptors
- Endorphins and enkephalins stimulate opioid receptors
- Histamine stimulates histamine receptors
What are 3 examples of Adrenergic receptors and their effects?
Adrenaline stimulates adrenergic receptors
- alpha receptors (vasoconstriction)
- beta1 receptors (cardiac stimulation)
- beta2 receptors (bronchodilation)
What are 3 examples of opioid receptors and their effects?
Endorphins and enkephalins stimulate opioid receptors
- mu (analgesia, constipation)
- delta (analgesia, sedation, mood)
- kappa (sedation)
What are 3 examples of histamine receptors and their effects?
Histamine stimulates histamine receptors
- H1 (vasodilation, flushing increased vascular permeability, bronchoconstriction, itch, rash)
- H2 (gastric acid secretion)
- H3 receptors and H4 receptors also exist
How do many drugs exert their actions?
Many drugs exert their actions by combining with (binding to), and activating (stimulating), receptors normally stimulated by naturally occurring substance in the body
What is it called when a naturally occurring substance, or a drug combines with a receptor?
When a naturally occurring substance, or a drug combines with a receptor it produces a drug-receptor complex
What is Affinity?
Affinity = The ability of a natural substance, or a drug to form a drug-receptor complex.
(ability to bind to the receptor)
What drug Efficacy/Intrinsic activity?
- If a drug can form a drug-receptor complex (affinity), this does not on its own result in a response being produced
- The drug-receptor complex must also set up a series of actions within the cell which results in a response being produced
- When the formation of a drug-receptor complex activates the receptor, and an overt response occurs = efficacy or intrinsic activity
What is an agonist?
What are the 2 properties of agonists?
An Agonist = Any natural substance or drug which can combine with, and activate a receptor.
- An agonist thus exhibits (or has)
- Affinity
- Efficacy or Intrinsic Activity
What is the Key and lock analogy?
Mechanism of Drug Action - Key and lock analogy
- Key goes into the lock (affinity)
- Key is turned and door opens (efficacy or intrinsic activity)
What are some examples of agonists?
Examples of Agonists
- Adrenaline, acetylcholine, histamine, GABA, morphine, salbutamol, testosterone, oestrogen, endorphins prostaglandins, serotonin (5-hydroxytryptamine)
- Remember that each agonist only binds to its own specific receptor type(s)
Which bonds usually exist between an agonist and a receptor?
- In most instances the bond between an agonist and a receptor (drug receptor complex) is relatively weak and easily reversible
- It usually consists of
- Ionic bonds
- Hydrogen binding
- Van der Waals forces
Give 4 examples of agonists that act on Adrenergic receptors?
Adrenergic Receptor Agonists
- Adrenaline
- Noradrenaline
- Salbutamol
- Phenylephrine
Give 4 examples of agonists that act on Opioid mu receptors?
Opioid mu receptor Agonists
- Morphine
- Pethidine
- Tramadol
- Oxycodone
Give 3 examples of agonists that act on GABAA receptors?
GABAA receptor agonists
- Alprazolam
- Diazepam
- Nitrazepam
What does an Agonist Log Dose Response Curve measure?
The magnitude of the response is directly related to the number of receptors activated by the agonist (up to the maximum response)
The maximum response to an agonist is often obtained when the agonist is bound to less than 100% of the receptors
What is the difference between efficacy and potency?
Efficacy = the maximum response a drug can produce
Potency - the amount of drug needed to produce a given response
How do drugs with different potency appear on an agonist log dose response curve?
What is the result if:
- Drug A is more potent than Drug B
- Drug B exerts the same efficacy as Drug A
If:
- Drug A is more potent than Drug B
- Drug B exerts the same efficacy as Drug A
There is no response that can be achieved with Drug A that cannot be achieved with Drug B - you just need to take a larger dose of Drug B
Potency by itself does not infer superiority
What is a Partial Agonist?
Partial Agonist = a drug which binds to a receptor (has affinity) but even at full receptor occupancy it has less efficacy or intrinsic activity than a full agonist
What is a Competitive Antagonist?
A competitive antagonist = a drug which can combine with a receptor (has affinity), but does not activate the receptor (no efficacy or intrinsic activity)
Competes with the agonist to combine with a receptor, and blocks the action of the agonist
How can competitive antagonist be overcome?
Why?
Competitive Antagonists
The effects of a competitive antagonist can be overcome by increasing the concentration of the agonist
The inhibitory effect of the competitive antagonist is surmountable because the bonds between the competitive antagonist and the receptor, like the bonds between the agonist and the receptor, are relatively weak and easily broken
What does a competitive antagonist do to the log dose response curve?
Competitive Antagonists
A competitive antagonist shifts the agonist dose response curve to the right
What are 4 examples of Competitive Antagonists?
Competitive Antagonists - Examples
- Beta blockers inhibit beta adrenergic receptors
- Eg. propranolol
- Angiotensin 2 receptor antagonists inhibit angiotensin 2 type 1 receptors
- Eg. Irbesartan
- Opioid antagonists inhibit opioid mu receptors
- Eg. Naloxone
- Antihistamines inhibit histamine H1 receptors
- Eg. Loratadine
Give an example of a Full Agonist, Partial Agonist and Competitive Antagonist?
Full Agonist, Partial Agonist and Competitive Antagonist
- Methadone has affinity and maximum efficacy/intrinsic activity (full agonist)
- Buprenorphine has affinity and reduced efficacy or intrinsic activity (partial agonist)
- Naloxone has affinity but no efficacy or intrinsic activity (competitive antagonist)
