Pharmacology Flashcards
(27 cards)
What are the definitions of a receptor and a ligand?
Receptor: biological macromolecule or complex that binds another molecule and initiates or modulates signalling of effector activity within a cell.
Ligand: a molecule that binds to a receptor
What are the definitions of an agonist and an antagonist?
Agonist: a ligand that binds to a receptor and activates it
Antagonist: a ligand that binds to a receptor and doesn’t activate it.
What are the 4 categories of receptors?
- Ligand-gated ion channel receptors (ionotropic) - signal rapidly e.g. nicotinic R binding ACh
- GPCRs (metabotropic) - most common receptor, 7 transmembrane segments, bind GTP, activate effector molecules
- Kinase-linked receptor - phosphorylate proteins, many are GF receptors
- Nuclear receptor - lead to changes in DNA transcription
How do receptor classes affect drug selectivity?
- receptor classes e.g. muscarinic/ nicotinic respond to ACh vs. adrenoceptors respond to A/NA
- receptor sub-classes e.g. β1 in heart and β2 in bronchi,
What is the dose-response curve and what is its clinical relevance?
Increasing dose gives a larger response until it hits a ‘ceiling’ where no more benefit is gained from increasing dose. Want a wide ‘therapeutic window’ to maximise benefit and keep side effects to a minimum, slope of the curve determines sensible dose increments
What are the steps of drug activation?
- bind to receptor
- activation (stimulus)
- transduction (response)
What is the difference between a full and partial agonist?
Full agonists (e.g. isoprenaline) bind and activate a receptor, producing full efficacy at that receptor
Partial agonists (such as salbutamol, buprenorphine) also bind and activate a given receptor, but have only partial efficacy/activation at the receptor relative to a full agonist, even at maximal receptor occupancy
What is the difference between pharmacological efficacy and clinical efficacy?
Pharmacological: the strength of receptor activation
Clinical: strength of the beneficial effect (may be full or partial, impacted by side effects)
what is a receptor reserve?
The extra or spare receptors present on a cell, in excess of those necessary to produce a maximum response when occupied by an agonist.
Full agonists usually have a reserve, important in disease (e.g Heart failure) which may induce receptor downregulation and need for more stimulation.
in heart failure, full agonists can bind more receptors from their reserve to still elicit maximal response, but partial agonists who dont have a receptor reserve and couldn’t even respond maximally in a healthy state are much more affected by receptor desensitisation in diseased state.
What are the 3 ways antagonists work?
- binding inhibition: e.g. competitive inhibition
- pathway inhibition: e.g. blocking of an element(s) in a certain pathway
- Functional antagonism: i.e. non-competitive inhibition e.g. ACh antagonism of adrenaline @ heart
What is an allostearic modulator?
binding of a molecule on an alternative (allostearic) binding site regulates the function of the ligand acting at the orthostatic site, modulating the ligands affinity or modulating receptor activity level. e.g. benzodiazipenes increase the affinity of the receptor for GABA and increases Chloride flow through ion channel.
Antagonist potency is mainly determined by…?
affinity to receptor
What are the advantages of allostearic modulators?
- selectivity b/w receptor subtypes because allostearic receptor doesn’t affect conserved orthostatic binding site
- Incomplete antagonism: ceiling effect so giving more does nothing more and maximal effect you get from the modulator can be ‘tuned’ so physiological function can continue
What factors influence drug distribution?
- molecular size - small to cross endothelium
- ability to bind plasma proteins - unbound to plasma proteins to cross endothelium
- lipid solubility - some lipid solubility to cross cell membranes
What is the apparent volume of distribution?
Theoretical volume of fluid into which the total drug administered would have to be diluted to produce the plasma conc.
V of distribution = X (amount in tissues)/ C (conc. in plasma)
What are the different routes a drug can be administered?
Oral: tablets or capsules
skin: nicotine patches
lungs: gaseous general anaesthetic
nose: cocaine
rectum: antibiotics
injectable: subcutaneous, intramuscular, invtravenous
What factors affect drug distribution?
Molecular size: small to cross vascular endothelium
Binding of plasma proteins: unbound to cross vascular endothelium
lipid solubility: some solubility to cross cell membranes
How does the kidney affect drug excretion?
- Glomerular filtration: takes drugs out, passive filtration through leaky glomerulus, not for drugs bound to plasma proteins
- Tubular secretion: takes drugs out, active process, can remove protein-bound drug, can be competitively inhibited
- Tubular reabsorption: puts drugs back in, passive movement, pH dependent
What is Phase I and II metabolism?
Phase I: create chemical functional group = more water-soluble and easier to excrete
Phase II: conjugation of water-soluble molecule onto functional group on drug = more water soluble
describe the major neurotransmitters and receptors involved in chemical transmission within the ANS and somatic NS
- Acetylcholine (ACh)
- Nicotinic Receptors (ligand-gated ion-channel)
- Muscarinic Receptors (GPCR) - Noradrenaline (NA)
- a-adrenoceptors (GPCR)
- ß - adrenoceptors (GPCR)
How does Botox work and what is a therapeutic use?
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Botox cleaves SNARE proteins and prevents adhesion and fusion of the vesicle membrane with the terminal membrane and no NT is released.
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How do anticholinesterases work and what are its therpeutic uses?
Anticholinesterases stop the breakdown of ACh into Choline via the AChE molecule and keep ACh in the synaptic cleft.
e. g. 1. Neostigmine, Pyridostigmine used to inhibit AChE to treat Myaesthenia Gravis
e. g. 2. Donezepil eneters CNS well and used to treat Alzheimer’s Disease
What are the effects and uses of muscarinic antagonists?
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- Reduced Salivation, Lacrimation, Urination, Defecation
- Reduced Sweating
- Tachycardia
- Bronchodilation
uses:
Atropine - reduce secretions, produce bronchodilation, pupil dilation
Ipratropium (inhaled) - COPD
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What are some clinical uses of nicotinic agonists and antagonists?
Agonists (CNS actions): Smoking cessation (nicotine patches)
Antagonists: pre-surgical muscle relaxant (non-depolarising e.g. tubocurarine, vecuronium)
