Pharmacology Flashcards
What is pharmacodynamics?
Drug action on the body
What is pharmacokinetcs?
Body action on a drug
What does an agonist do?
Gains a response
What does an antagonist do?
Blocks a response
2 steps of receptor activation?
- Affinity (binding to receptor)
- Efficacy (change from bound and inactive to active)
Do agonists vs antagonist possess affinity and efficacy?
- Agonists possess both
- Antagonists only possess affinity
Affinity is determined by?
Binding and dissociation rates
A high affinity ligand will have a ….. binding rate compared to …. ?
High and low dissociation rate
Efficacy is determined by?
Forward beta activation rate vs backwards alpha inactivation rate
A ligand with high efficacy will have a … beta rate and … alpha rate?
High and low
An antagonist can be + an agonist can be?
Competitive or non-competitive + only competitive
Competitive antagonists + agonists bind to what?
Both to the active site/ orthosteric site
Non-competitive antagonists bind to what?
Allosteric site
2 shapes of agonist depending on graph + 2 key values?
- Hyperbolic curve on a linear graph or sigmoidal on a log graph
- EMAX is the highest level of response
- EC50 is half the maximal response
What are full agonists?
Can reach their EMAX
What is a partial agonist?
Cannot reach EMAX
Agonist + competitive antagonist effect on curve?
Shift to right as more agonist needed to reach EMAX
Agonist + non-competitive antagonist effect on curve?
No shift but depression of curve as EMAX/EC50 cannot be reached
Autocrine signalling?
Cell signal acts on itself
Paracrine signalling?
Cell signal acts on neighbour cells
Endocrine signalling?
Cell signal moves via blood to target areas of the body
4 main types of cell receptors?
Ligand-gated, GPCRs, kinase-linked and nuclear (all in the cell membrane except nuclear)
Ligand gated channel rate of action?
Fast action
GPCR rate of action + structure?
- Act slowly
- NH2 + COOH ends with 7 transmembrane domains
- Alpha, beta and gamma subunit
- Alpha subunit has a guanine nucleotide bonding site
GPCR signalling summary?
- GTP binds to guanine binding site on alpha unit
- Alpha unit dissociates from beta and gamma subunit to modify G-protein
- Signal turned off when GTP is hydrolysed
2 main types of GPCR alpha subunits and their actions?
- Gs via sympathetic innervation stimulates adenyl cyclase/ cAMP formation
- Gi via parasympathetic innervation inhibits adenyl cylase/ cAMP formation
Kinase-linked receptor rate of action + main molecule that targets it + relevance to cancer + 2 examples?
- Act slowly
- Targeted by growth factors
- Mutations lead to cancer
- ECGR and PI3K
Nuclear receptors mechanism + molecules that target it?
Combines with steroid and moves to nucleus to alter genes + steroid hormones
Where does drug metabolism occur?
In the liver
Phase I metabolism reaction + key proteins?
- Catabolic reaction that increases polarity of drug via hydrolysis, oxidation etc.
- P450 (CYP) monooxygenase proteins
Phase II metabolism reaction + common reaction?
- Chemical groups made in phase I are joined
- Glucuronidation is a common reaction
3 ways drugs are excreted + short summary + most common method?
- Glomerular filtration (for unbound proteins)
- Active tubular secretion (via OATs and OCTs) - MOST COMMON (90%)
- Tubular reabsorption (passive diffusion of reabsorbed drug)
2 receptors that parasympathetic fibres act on?
Nicotinic ligand-gated channels and muscarinic GPCR
What can also be released from parasympathetic fibres apart from ACH + whay they cause?
VIP and NO + SM relaxation
What can also be released from sympathetic fibres apart from NA?
ATP and NPY
SM contraction summary?
- GPCR activates PLC
- PLC produces IP3
- IP3 binds at SR and releases Ca
- Ca binds calmodulin
- Calmodulin activates MLCK
- MLCK activates mysoin cross bridge
SM relaxation summary?
- GPCR activates AC
- AC forms cAMP
- cAMP activates PKA
- PKA activates MLCK and MP
- Calcium dissociates from calmodulin and MP inactivates cross bridge
Skeletal/cardiac contraction summary?
- GPCR activates AC
- AC produces cAMP
- cAMP activates PKA
- PKA activates L-type Ca channels
- CICR occurs
- Ca binds tropomyosin C
- Tropomyosin shifts actin out of cleft
Skeletal/cardiac relaxation summary?
- PKA activates phoshoplamban
- Phospholamban increases CICR and relaxation rate
- L-type channels close
- Ca-ATPase reruits Ca back into SE
- Ca dissociated from tropomysoin C
How is cAMP inactivated?
Phosphodiesterase (PDE)
cAMP role in muscle?
Activates PKA
PKA action in SM vs skeletal/cardiac?
Relaxation vs contraction AND relaxation
First order kinetics relationship + curve shape?
Rate of elimination = drug concentration + hyperbolic curve
Zero order kinetics relationship + curve shape?
Cp > Km of enzyme that metabolises it + linear curve
Clearance of a drug definition + what is applies to?
Volume cleared from plasma over time + only applies to first order kinetics
How is Ach vs NA taken back into pre-synaptic neurons?
Ach = enzyme degradation vs NA = reuptake channels (U1 and U2)
Effects of cocaine and amphetamine?
Increases adrenoreceptor stimulation so vascontriction, increased heart rate etc.
Sympathetic vs parasympathetic receptors in the smooth muscle + heart + vasculature?
Beta 2 and M3 + beta 1 and M2 + alpha 1
