Drug effect is proportional to the number of receptors occupied
Maximal effect occurs when all receptors are occupied
Coupling
Overall transduction process that links drug occupancy of receptors and pharmacologic response
Relative efficiency of occupancy-response coupling depends on receptor state (active/inactive) and downstream biochemical events
Spare receptors
Receptor reserves that allows maximal response to be achieved at a ligand concentration that doesn't occupy all available receptors
Sensitivity of a cell or tissue to a particular concentration of agonist depends on affinity of the receptor for binding the agonist (Kd) and degree of spareness (total number of receptors present compared with the number actually needed to elicit a maximal biologic response)
Receptor subtypes (isoforms)
Different receptor isoforms or subtypes can have different pharmacological effects
Most tissues express multiple receptors but there can be differential distribution of different receptor subtypes at different tissues
Receptor selectivity
Preferential binding of a ligand to a certain receptor over other types of receptors
Drugs acting selectively with a specific receptor subtype causes less side effects
Differences in selectivity explain differential side effects of the same class of drugs
Selectivity depends on dose or concentration of drugs
Side effects
Undesired effect that occurs regardless of dose, usually due to off-target effects
Types of variability in drug response
Hyporeactive: causes reduced response
Hyperreactive: causes increased response
Tolerance: over the course of drug therapy, drug response is reduced
General mechanisms causing variation in drug response
Alteration of concentration of drug that reaches receptor: pharmacokinetic variability
Variation in concentration of an endogenous receptor ligand: relevant to effects of pharmacologic antagonists
Changes in the components of response distal to receptor (functional integrity of the biochemical processes, physiological regulation by interacting organ system)
Alterations in the number or function of receptors (could be due to agonist inducing down-regulation or antagonist increasing number of receptors)
Potential consequences of alterations in receptor number or function
Tolerance: progressive decrease in response to a given dose
Withdrawal effect if drug is stopped (elevated number of receptors can produce exaggerated response to physiologic concentrations of agonist, or too few receptors for endogenous agonist to produce effective stimulation)
Pharmacological targets in the autonomic nervous system
Cholinergic receptors (nicotinic, muscarinic)
Adrenoceptors (alpha, beta)
Neurotransmitters in the autonomic nervous system
Synthesis, storage and release processes can be modulated/altered to alter neurotransmitters activity/amount
Roles of autonomic nervous system targets
In charge of somatic efferent, sympathetic, parasympathetic, and systems of CNS
Types of cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
Direct-acting
Indirect-acting
Reversible
Irreversible
Reversible cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
Short acting
Long acting
Short acting reversible cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
Edrophonium
Long acting reversible cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
Carbamates
Neostigmine
Pyridostigmine
Physostigmine
donepezil
Irreversible very long acting cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
Organophosphates
Sarin
Parathion
malathion
Types of cholinoreceptor-blocking drugs/cholinergic antagonists/anti-cholinergic/parasympatholytic drugs
Antimuscarinic
Antinicotinic
Types of adrenoreceptor agonists and sympathomimetic drugs
Direct acting
Mixed acting
Indirect acting
Types of adrenoreceptor antagonists drugs
Alpha receptor antagonists
Beta receptor antagonists
Alkaloids and Choline esters: direct acting drugs on muscarinic and nicotinic receptors