IC12

• Receptor occupancy


  • 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
  • Can have excitatory or inhibitory effects
• Classes of cholinergic modulators

  • Cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs (direct-acting, indirect-acting, reversible, irreversible)
  • Cholinoreceptor-blocking drugs/cholinergic antagonists/anti-cholinergic/parasympatholytic drugs (antimuscarinic, antinicotinic)
• Classes of adrenergic modulators

  • Adrenoreceptor agonists and sympathomimetic drugs (direct acting, mixed acting, indirect acting)
  • Adrenoreceptor antagonists drugs (alpha receptor antagonists, beta receptor antagonists)
• Double dose of a drug with linear kinetics


  Double concentration/AUC (total systemic exposure)
• Double dose of a drug

  Linear change in response
• Different classes of cholinergic and adrenergic modulators

  • Cholinoreceptor-activating/cholinergic agonist/cholinomimetics/parasympathomimetic drugs and acetylcholinesterase-inhibiting/anti-cholinesterase drugs
  • Cholinoreceptor-blocking drugs/cholinergic antagonists/anti-cholinergic/parasympatholytic drugs
  • Adrenoreceptor agonists and sympathomimetic drugs
  • Adrenoreceptor antagonists drugs
• 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