Fundamental of Pharmacology Flashcards
What are the 5 ways a cell can communicate with other cells?
1 - endocrine (in the blood, long distance)
2 - paracrine (close cells)
3 - juxtacrine (cells touching or via membrane rceptors)
4 - autocrine (cells signals itself)
5 - neuronal
In GPCRs, what determines its intracellular activity, for example, is the GPCR turned on or off?
- GTP = GPCR on
- GDP = GPCR off
Of the four intracellular signalling below, which has the quickest reaction?
1 - GPCR
2 - Iontrophic receptors (ion or ligand gated)
3 - Kinase linked receptors
4 - cytoplasmic/nuclear receptor
- iontrophic receptors (ion or ligand gated)
- almost immediate
In order rank the the four intracellular signalling below from quickest to slowest reaction?
1 - GPCR
2 - Iontrophic receptors (ion or ligand gated)
3 - Kinase linked receptors
4 - cytoplasmic/nuclear receptor
1 - Iontrophic receptors (ion or ligand gated)
2 - GPCRs
3 - kinase linked receptors
4 - cytoplasmic/nuclear receptor
If a drug is being developed that will decrease cAMP levels, which GPCR will this be?
- Gai
What is the definition of a side effect?
- undesirable secondary effect in addition to the desired therapeutic effect
- dose of drug is normal dose
What is the definition of an adverse effect?
- harmful effect on a patient
- dose of drug is normal dose
What is the definition of an adverse effect?
- deleterious, undesired effect
- dose of drug is higher than normal dose
What is the difference between allosteric and orthosteric binding sites?
- orthosteric = active site
- allosteric = non active site, but binding changes conformation so orthosteric site can not be accessed
When something binds to a receptor but the normal physiological or regulatory effect, what is this called?
- antagonist
If something is able to bind to the allosteric site of a receoptor and does not have the same regulatory effect, what is this called in terms of pharmacodynamics?
- non competitive antagonist
What is the difference between a competitive and non-competitive antagonist in terms of pharmacology?
- competitive antagonist = competes with agonist for orthosteric (active) binding site
- non-competitive antagonist = does no competes with agonist for orthosteric (active) binding site, rather it binds to allosteric binding site causing conformational changes in receptor
Does the figure below show a competitive reversible or non-competitive reversible antagonist?
- competitive reversible
- a larger concentration (1000 vs 1) would be required to reduce effect of the agonist
Does the figure below show a competitive reversible or non-competitive reversible antagonist?
- non-competitive reversible antagonist
- a larger concentration (10 vs 1) would significantly reduce the Cmax
In terms of pharmacodynamics, what does affinity mean?
- the ability of a drug to bind with a receptor
What is efficacy in relation to pharmacotherapy?
- the ability of an agonist to produce a biological effect
What is Rmax in relation to efficacy in pharmacotherapy?
- efficacy determines how effect an agonist is at eliciting a biological effect
- Rmax = maximal response
What is potency in relation to pharmacotherapy?
- which drug has the largest effect, i.e the most potent
What is EC50 in relation to potency in pharmacotherapy?
- effective concentration to elicit a response in 50% of population taking the drug
In the figure below which drug has the highest EC50, meaning it has the highest potency in pharmacotherapy, and why is this a good thing?
- drug A
- higher potentcy means lower EC50
- lower EC50 means lower drug dose required
How do we calculate therapeutic index?
- TD50 / ED50
- TD50 = toxic dose in 50% of population using the drug
- ED50 = effetive dose in 50% of population using the drug
What are the equilibrium potentials of Na+ and K+ in the cell?
- Na+ = +60mV
- K+ = -90mV
- helps maintain restint potential
What does the resting membrane potential of a cell normally sit at?
- between -90 to -70mV
Roughly what voltage needs to be reached for an action potential to occur?
- +20 - 40mV
In the image below of an action potential, which cation maintains the restin membrane?
- K+
Once a cell that is excitable and has recieved a stimulus, like a muscle cell, what cation is able to increase the resting membrane potential causing depolarisation?
- Na+
- positive charge increase the charge in the cell
In an action potential what is the threshold value?
- charge in cell increases about a certain value
- if this is reached the cell is commited to an action potential
In an action potential, once depolarisation has occured and Na+ channels begin to close, what cation is responsible for returning the membrane potential to resting or hyperrepolarisation?
- K+
- K+ channels open allowing positive charge to leave the cell
Once an action potential arrives the pre synapse and depolarises the pre synapse, what is released into the pre synapse and then what does this facilitate?
- Ca2+ channels open
- allows vesicles containing ACh to bind with pre synaptic membrane
In the autonomic system what is the neurotransmitter and receptor that is present between all pre and post ganglionic neurons?
- ACh
- all are nicotinic neurons (Nn) receptors
What is the definition of absorption in pharmacokinetics?
- transfer of a drug from the site of administration into the systematic circulation
- for example, a drug given orally then absorbed into the blood
What is the definition of distribution in pharmacokinetics?
- transfer of a drug from the genral circulation into other tissues around the body
What is the definition of metabolism in pharmacokinetics?
- process of a drug being altered
- alteration can enhance its action or enhance its elimination
What is the definition of excretion in pharmacokinetics?
- process where metabolites of a drug are removed from the body
The pH, enzymes, gut motility and first pass metabolism can all affect which of the A.D.M.E, which relates to pharmacokinetics?
- absorption
How do we calculate bioavailability in pharmacokinetics?
- area under the curve (AUC) for oral administration (OA) is divided by the AUC for IV administration
- AUC OA / AUC IV
If you are administering a drug at 25mg via IV, but the oral bioavailability is only 25%, what would you need to increase the dosage to, to ensure the same bioavailablity is provided?
- 25mg / 0.25% = 100mg
- 4 times more does needs to be given, but same bioavailability will be achieved
When considering bioavailability, what 2 factors from absorption, distribution, metabolism and excretion?
- absorption
- metabolism
Does a water or lipid soluble drug have a larger volume of distribution?
- lipid soluble
- able to cross membranes easier
When drugs are distributed they can be bound or unbound, which is able to have a therapeutic effect?
- unbound
Does the free or bound drug remain in the body for longer?
- bound drug
Bound drugs can remain in the body for longer, which 2 aspects from absorption, distribution, metabolism and excretion is bound drugs able to avoid once inside the body?
- metabolism (enzymes are unable to metabolise)
- excretion (too big to be filter in glomerulas)
Cytochrome P450 (CP450) is a superfamily of enzymes, responsible for the metabolism of most drugs. There are 2 phases of drug metabolism:
phase 1 = oxidation (gaining an oxygen and losing a electron ((H+) and reduction (gaining an electron (H+)
phase 2 = conjugation
Out of the 2 phases, which does CP450 work on?
- phase 1
Liver disease, other drugs, inducers or inhibitors are all able to influence one aspect of A.D.M.E?
- metabolism
If a patient is an ultrametaboliser of a drug, is this classed as an inducer or inhibitor?
- inducer
- drug is metabolised quickly and elimated from the body
If a patient is an poor metaboliser of a drug, is this classed as an inducer or inhibitor?
- inhibitor
- drug is metabolised slower and stay in the body for longer
If you are an ultra metaboliser, and you are given a pro-drug, would this increase or decrease:
- bioavailability
- therapeutic effect
- toxcitiy
- first pass metabolism
- metabolism rate
- bioavailability = increased (drug metabolised quickly and released into blood)
- therapeutic effect = increased (drug metabolised quickly and released into blood)
- toxcitiy = increased (drug metabolised quickly and released into blood)
- first pass metabolism = increased
- metabolism rate = increased
If you are an poor metaboliser, and you are given a pro-drug, would this increase or decrease:
- bioavailability
- therapeutic effect
- toxcitiy
- first pass metabolism
- metabolism rate
- bioavailability = decreased (drug metabolised slowly and released into blood)
- therapeutic effect = decreased (drug metabolised quickly and released into blood slowly reducing therapeutic effect)
- toxcitiy = decreased (drug metabolised quickly and released into blood slowly and reducing risk of toxicity)
- first pass metabolism = decreased
- metabolism rate = decreased
What is the mechanism of action of the antibiotic amoxicilin?
- able to pass through peptidoglycan layer of the bacteria
- can then bind and inhibit with transpeptidase
- reduces peptidoglycan production and bacterial cells lyse
What is the mechanism of action of vancomyosin?
- inhibits cell wall synthesis
- binds to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis meaning cell wall cannot form
What is the mechanism of action of clarithromycin?
- binds to 50S subunit of ribosome
- inhibits protein translation
What is the difference between bactercidal and bacteriostatic?
- bactercidal = kills bacteria
- bacteriostatic = inhibit the growth of bacteria
Tetracyclines, Aminoglycosides and Macrolids are classes of antibiotics, that share the method in how they are able to be effectibe at treating infections. What is the general mechanism of action of these classes of drugs?
- inhibit bacterial synthesis
- at ribosome
Ciprofloxacin is a a class of quinelone antibiotics, what is the mechanism of action?
- inhibit DNA synthesis
The Epstein-Barr virus (EBV), is a common viral infection, what type of virus is this?
- herpesvirus 4
- member of the herpes virus family
In drug treatment, empirical treatment describes what?
- antibiotic therapy commenced before the identification of the causative micro-organism is available
- local guidelines provide guide for this
Why does the gram negative staining not work on all bacteria?
- some strains posses special walls that staining cannot penetrate
- TB contains mycolic acid that Gram positive staining cannot penetrate
What is Ziehl–Neelsen staining?
- alternative staining used when gram positive staining cannot penetrate cell wall
- TB, which contains mycolic acid in its walls is an example
Acid fast staining, with the most common approach being the ziehl-neelsen stain, is an alternative staining used when gram positive staining cannot penetrate cell wall due to waxy surfaces such as mycolic acid on TB. What colour would TB and non TB stain when using the ziehl-neelsen stain?
- acid fast positive = pink/red such as TB
- non acid fast = blue/purple
Kirby Bauer Antibiotic Sensitivity Assay?
- antibiotic resistance to cultured bacteria can be tested
What is sensitivity and specificity?
- sensitivity = ability of a test to correctly identify patients with a disease
- specificity = the ability of a test to correctly identify people without the disease
What is the sellotape test?
- parasites can be seen visually generally
- sellotape on infected area will show eggs and potentially parasites under microscope
What does prophylactically mean in drug delivery?
- designed to prevent a disease
- vaccines
What is the mechanism of action of penicillin?
- penicillin specifically binds with a penicillin binding protein (PBB)
- PBB makes transpeptidoglycans for the bacterial cell wall
- penicillin inhibits transpeptidase and breaks transpeptidase bonds
- cell wall synthesis is stopped and cell lyses
What is the difference between vertical and horizontal gene transfer?
- vertical = genes are transferred down generations in offspring
- horizontal = genes are transferred across from an individual to others in the same generation, NOT inherited
If a gram + or gram - bacteria has been identified, which should recieve broad or narrow spectrum antibiotics?
- gram + bacteria = narrow spectrum
- gram - bacteria = broad spectrum
What is transpeptidase?
- bacterial enzyme responsible for cell wall synthesis
- needed to build bacterial cell walls
What are the 2 ways in which B-lactam antibiotics act on bacterial pathogens?
1 - breaking of transpeptide bonds in cell wall
2 - ⬇️ transpeptidase activity reducing cell wall turnover
β-lactamases are enzymes that are produced by bacteria. What do these enzymes do to antibiotics which contain B lactam rings?
- inhibit the B lactam antibiotics
- these bacteria are then resistant to B lactam antibiotics
Amoxicillin can sometimes be prescribed alongside clavulonic acid, why is this?
- clavulonic acid is able to inhibit B-lactamase
- Amoxicillin can function normally and inhibit transpeptidase
Vancomyosin can be used to treat bacterial infections. How are they able to break down bacterial cell walls?
- glycopeptide antibiotic
- means it targets the glycopeptide bonds in bacterial cell walls
What does ototoxic mean?
- toxicity of a drug to the ear lobe