2. Mechanism of Drug Action Flashcards
The ability of a drug to form a drug- receptor complex is called
- Efficacy
- Intrinsic activity
- Potency
- Affinity
- Specificity
The ability of a drug to form a drug- receptor complex is called
- Efficacy
- Intrinsic activity
- Potency
- Affinity
- Specificity
An agonist is a drug which
- Has both affinity and intrinsic activity (efficacy)
- Must combine with 100% of receptors to produce a response
- Can combine with many different types of receptors
- Generally binds irreversibly with a receptor
- Has affinity but no intrinsic activity (efficacy)
An agonist is a drug which
- Has both affinity and intrinsic activity (efficacy)
- Must combine with 100% of receptors to produce a response
- Can combine with many different types of receptors
- Generally binds irreversibly with a receptor
- Has affinity but no intrinsic activity (efficacy)
Pharmacodynamics refers to
- What the body does to a drug
- The formation of a drug-receptor complex
- The maximum response a drug can produce
- What a drug does to the body
- The potency of a drug
Pharmacodynamics refers to
- What the body does to a drug
- The formation of a drug-receptor complex
- The maximum response a drug can produce
- What a drug does to the body
- The potency of a drug
The effect of a competitive antagonist on the log-dose response curve of an agonist is to
- Shift the curve to the left without affecting the maximum response
- Shift the curve to the right without affecting the maximum response
- Shift the curve to the left and reduce the maximum response
- Shift the curve to the right and reduce the maximum response
- A competitive antagonist has no effect on the log-dose response curve of an agonist
The effect of a competitive antagonist on the log-dose response curve of an agonist is to
- Shift the curve to the left without affecting the maximum response
- Shift the curve to the right without affecting the maximum response
- Shift the curve to the left and reduce the maximum response
- Shift the curve to the right and reduce the maximum response
- A competitive antagonist has no effect on the log-dose response curve of an agonist
Which of the following drugs is a competitive antagonist
- Morphine
- Salbutamol
- Naloxone
- Acetylcholine
- Histamine
Which of the following drugs is a competitive antagonist
- Morphine = μ-opioid receptor agonist
- Salbutamol = B2 receptor agonist
- Naloxone = opioid receptor antagonist
- Acetylcholine = Ach receptor agonists
- Histamine = histamine receptor agonists
Drugs achieve their therapeutic effects by acting primarily on what 4 things?
Drugs achieve their therapeutic effects by acting primarily on either:
- Receptors
- Enzymes
- Ion channels
- Carrier molecules
What are 4 Types of Drug Receptors?
Types of Drug Receptors
- Ligand gated ion channel receptors
- G-protein coupled receptors (GPCRs)
- Kinase linked receptors
- Nuclear receptors
How quickly do Ligand Gated Ion Channel Receptors produce a response?
Ligand gated ion channel receptors
- Stimulation of receptor
- Opening of ion channel
- Rapid response (msec)
What is an example of a Ligand gated ion channel receptor?
Ligand gated ion channel receptor - Example
Acetylcholine nicotinic receptors on skeletal muscle causing contraction
What is the structure of an Acetylcholine Nicotinic Receptor?
Acetylcholine Nicotinic Receptor
- Pentameric assembly of subunits
- There are four subunits - α, β, γ and δ
- There are two acetylcholine binding sites - acetylcholine must bind to both to activate the receptor
What is another example of a Ligand Gated Ion Channel Receptors?
Which drugs work on this receptor?
Ligand Gated Ion Channel Receptors - Example
= Gamma amino butyric acid GABAA receptors (CNS inhibition)
- GABAA receptor channel is selectively permeable to Cl ions
- Increasing the permeability and concentration of Cl- ions in the cell hyperpolarises the cell and reduces excitability
- BZ = Benzodiazepines → work on these receptors but at a different place
What is the structure of a G-Protein Coupled Receptor (GPCR)?
How are they identified?
G-Protein Coupled Receptors (GPCR)
- G-protein coupled receptors consist of a single polypeptide chain with seven transmembrane segments
- When the receptor is stimulated signals are transmitted to, and activate an attached G-protein (guanine nucleotide-binding protein)
- G-proteins are composed of alpha (α), beta (β) and gamma (γ) subunits
- G-proteins are identified by their G alpha subunits and are grouped into four families: Gs, Gi, Go, and Gq
What binds to the G-protein alpha subunit of a GPCR?
What happens next?
G-Protein Coupled Receptors (GPCR)
- G-protein alpha subunits bind either guanosine diphosphate (GDP) or guanosine triphosphate (GTP) depending on whether the G-protein is inactive (GDP) or active (GTP)
- When the receptor is stimulated GDP on the G-protein is replaced by GTP and the G-protein is activated
- When activated the alpha subunit splits from the beta and gamma subunits and moves from the receptor
- The alpha subunit, and the beta and gamma subunits, can then act on enzymes within the cell and cause the formation of a “second messenger” e.g. adenylyl cyclase and the formation of cyclic adenosine monophosphate (cAMP), or can have an action on ion channels in the cell membrane
- This results in a response being produced
Which receptors are the largest in the body?
What is their response time?
G-Protein Coupled Receptors (GPCR)
- G-protein coupled receptors are the largest and most diverse membrane receptors in the body
- It is estimated that around 50% of all drugs used today act on G-protein coupled receptors
- Response time is in seconds (slower than ligand gated)
What are 5 examples of GPCR agonists?
GPCR Agonists
- adrenaline and beta1 receptors (tachycardia), beta2 receptors (bronchodilation) and alpha receptors (vasoconstriction)
- acetylcholine and muscarinic M2 receptors (bradycardia)
- histamine and H1 receptors (bronchoconstriction)
- angiotensin II and angiotensin II type1 receptors (vasoconstriction)
- opioids e.g. morphine and mu receptors (analgesia)
What happens when beta1 adrenergic GPCRs are stimulated?
GPCRs - beta1 adrenergic receptors
- Stimulation of beta1 adrenergic G-protein coupled receptors in the heart increases heart rate (tachycardia)
- receptor stimulation, activation of G protein (Gs), stimulation of adenyl cyclase, increase in cAMP formation, activation of protein kinase and tachycardia
What happens when M2 muscarinic GPCRs are stimulated?
GPCRs - M2 muscarinic receptors
- Stimulation of M2 muscarinic G-protein coupled receptors in the heart decreases heart rate (bradycardia)
- receptor stimulation, activation of G protein (Gi), inhibition of adenyl cyclase, decrease in cAMP formation, reduced activation of protein kinase and bradycardia
What are 3 examples of competitive antagonists of GPCRs?
G-Protein Coupled Receptors (GPCR) - Examples of competitive antagonists include
- beta blockers (eg. propranolol) → inhibit beta adrenergic receptors
- angiotensin II receptor antagonists (eg. irbesartan) → inhibit angiotensin II type1 receptors
- narcotic antagonists (eg. naloxone) → inhibit opioid mu receptors
Where are Kinase linked receptors located?
What do they involve?
What are they activated by?
Response time?
Kinase linked receptors
- Located on the cell membrane
- Involve intracellular enzymes - e.g. protein kinase and gene transcription
- Activated by a number of agents including growth factor, cytokines and insulin
- Response in minutes to hours = slow
Where are Nuclear receptors located?
What do they involve?
What are they activated by?
Response time?
Nuclear Receptors
- Intracellular receptors within nucleus
- Involve gene transcription and DNA
- Activated by a number of agents including oestrogen, glucocorticoids, thyroid hormone and vitamin D
- Response in hours = slower
Give examples of a drug that works by inhibiting enzymes?
Mechanism of Action - Inhibiting Enzymes
- Nonsteroidal anti-inflammatory drugs (NSAIDS) such as diclofenac, ibuprofen and naproxen inhibit the enzyme cyclooxygenase and block the production of prostaglandins
Which prostaglandins are inhibited by NSAIDs?
NSAIDs
- Naproxen
- Diclofenac
- Ibuprofen
What is another example of a group of drugs that work by inhibiting enzymes?
ACE Inhibitors
Angiotensin converting enzyme (ACE) inhibitors such as perindopril and ramipril inhibit angiotensin converting enzyme and block the conversion of angiotensin I (1) to angiotensin II (2)
All ACE inhibitors end in -pril
What are Angiotensin II type 1 receptor antagonists and how do they work?
Examples?
Angiotensin II type 1 receptor antagonists
eg. Candesartan & Irbesartan
Give an example of a drug that achieves its therapeutic effects by inhibiting ion channels.
Mechanism of Action - Inhibiting Ion Channels
Calcium channel blocking agents such as amlodipine and verapamil which bind to the alpha1 subunit of the voltage- gated L type calcium channels and block the entry of calcium into the cell.
How do Calcium Channel Blocking Agents work?
Calcium Channel Blocking Agents
- Bind to the alpha1 subunit of the voltage-gated L type calcium channels and block the entry of calcium into the cell
- Block the entry, not the intracellular actions of calcium
- In blood vessels reduced calcium levels result in vascular smooth muscle relaxation (vasodilation), a reduction in peripheral vascular resistance and a drop in blood pressure
What is an example of a drug that works by inhibiting carrier molecules?
Mechanism of Drug Action - Inhibiting carrier molecules.
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline which inhibit the neuronal uptake (re-uptake) of serotonin (5HT)
