Midterm - Pharmacodynamics & Pharmacokinetics Flashcards
NAPRA I drugs
- Prescription needed for sale by Pharmacist
- Includes prescription drugs (Pr), narcotics (N), controlled substances (C1, C2, C3), and targeted substances (TS)
- eg. Fentanyl patch
NAPRA II drugs
- Prescription not required
- Must be dispensed by pharmacist (ie. behind the counter)
- eg. insulin
NAPRA III drugs
- Client may obtain at pharmacy without need of pharmacist
- eg. ranitidine (Zantac)
Unscheduled drugs
- Client may obtain at retail stores as well as pharmacy
- eg. naproxen (Aleve)
Pharmacodynamics vs pharmacokinetics
Dynamics = drug’s actions on body
Kinetics = body’s actions on drug
Signal transduction pathway
- aka receptor-effector coupling mechanism
- consists of the receptor, its cellular target, and any intermediary molecules
Drug affinity
- Favourability of a drug-receptor binding interaction
- Sum total of forces imparts high affinity of the drug for receptor
What drugs are MORE selective for their receptors?
Drugs that bind through multiple weak bonds to their receptors (if a drug has a super strong bond, it can likely bond to lots of things and will be less selective)
Strength of bonds from greatest to least
Covalent (uncommon, irreversible) > ionic > hydrogen > Van Der Waals (common, reversible)
Enantiomer
- Same atomic structure but arranged spatially different (optical isomer)
- produce different effects
Racemic mixture
50:50 mix of both enantiomers
Cell-type distribution
The more restricted the cell-type distribution of the receptor targeted by a drug, the more selective the drug is likely to be
eg. restriction of H2 receptors in the
stomach means Ranitidine has limited effects on body beyond the stomach
Effector domain purpose
Message propagation = conformational change in receptor that is transduced intracellularly to effect downstream molecules to cause a response (activate, enhance, diminish, terminate)
Ligand activated (gated) channels
- found in the CNS
- binding of molecules induces a conformational change that opens the pore
- eg. nicotinic acetylcholine receptor
Types of ligand activated (gated) channels
- Excitatory (ACh or glutamate)
- Inhibitory (glycine or GABA)
Voltage-activated channels
- Initiate action potentials in the
axons of nerves and muscle cells - activated channel depolarizes the membrane to attract positive ions through open pore
- refractory period = “reset”
Sulfonylurea receptor
- aka SUR1
- Regulates ATP-dependent K+ channel in pancreatic β-cells
G-protein coupled receptors
- aka GPCRs
- sensory perception, nerve activity, etc.
- target of over half of all non-antibiotic
drugs
G-protein activation
1) Agonist binding
2) GTP-GDP exchange
3) G-protein activation
(terminated by GTP hydrolysis)
β-adrenergic receptor group
- group of G-proteins
- eg. epinephrine and norepinephrine (both are catecholamines that increase second messenger cAMP)
Transmembrane receptors with an intracellular linked enzymatic domain
- single membrane spanning
- add/remove phosphate groups from specific aa’s
Types of transmembrane receptors with an intracellular linked enzymatic domain
- Receptor Tyrosine Kinases
- Tyrosine Kinase-Associated Receptors (receptors have no intrinsic enzymatic activity, but dimerization allows for binding of an intracellular tyrosine kinase)
Nuclear hormone receptors
“lag on, lag off”
Nitric oxide (NO)
- binds N-terminal of soluble GC and enhances activation of cGMP (vasodilation)
Dissociation constant
- aka Kd
- most important for impacting the chance of binding (drives affinity)
- ligand concentration where 50% of receptors are bound by ligand (lower Kd = higher affinity)
[LR]/Ro
Fraction of all available receptors that are ligand bound
Types of D-R relationships:
- Graded = D-R of individual
- Quantal = D-R of population
Efficacy
Maximal response produced by the drug at that receptor
Potency
- drug concentration which elicits 50% of the maximal response
- considers both affinity and efficacy
Therapeutic Index
- Gives an estimate of relative safety margin of drug
- considers both toxic and effective doses
Effect of competitive ANTagonists
- increase Kd for agonist = decrease affinity = decreases potency
- no effect on efficacy since they can be outcompeted with higher doses
Non-competitive ANTagonists
irreversible binding can not be “washed out” or outcompeted by the agonist
- decrease efficacy (sometimes potency too)
Types of non-receptor ANTagonists
- Chemical = renders agonist inactive
- Physiologic = binds different receptor and produces opposite effect
Allosteric modulators
Indirectly influence the effects of an agonist at its receptor (alters Kd or conformational change)
Types of passive transport
- passive diffusion = unbound drug carried through cell membrane by bulk flow of water
- paracellular transport = passage of molecules through intercellular gaps
Passive flux formula
Flux = [concentration gradient (aka C1 - C2) x area x partition coefficient] / membrane thickness
Partition coefficient
- solubility of drug
- greater coefficient = faster diffusion
Un-ionized species vs ionized species
- Unionized = more lipid soluble, more readily diffuse cell membranes
- Ionized = less lipid soluble, less able to diffuse through cell membranes
pKa
pH at which 50% of drug is ionized and 50% is unionized
Ionized form of an acid
Deprotonated (negatively charged)
Ionized form of a base
Protonated (positively charged)
Henderson-Hasselbalch equation
log([protonated]/[deprotonated]) = pKa - pH