Acceptors

Non-functional drug binding sites on cells or tissues

Analgesic

A drug used to relieve pain. May be narcotic (e.g. codeine) or non-narcotic (e.g. aspirin)

Anesthetic

An agent which produces loss of sensation. May be general (e.g. halothane) or local (e.g. xylocaine)

Anticholinergic

Inhibits ACh action at all cholinergic sites

Anticonvulsant

A drug which depresses the CNS or motor activity and is used to control convulsions (e.g. barbiturates, phenytoin)

Ataractic

A drug used to produce sedation (e.g. major and minor tranquilizers)

Cholinomimetic

acts like ACh at all cholinergic sites (compare with parasympathomimetic)

Direct-acting

Modulation by binding to and stimulating receptor

Indirect-acting

Promotes or inhibits release or reuptake of neurotransmitter (pre-synaptic alpha-2 agonists binding to presynaptic receptors are direct0acting, even though the effect is to inhibit NT release)

Dissociative

An anesthetic agent which acts in the CNS to produce a state of unawareness, without sleep (e.g. ketamine)

Hypnotic

An agent used to induce sleep (e.g. pentobarbital)

Narcotic

An agent (usually related to opium alkaloids) which produces insensibility or stupor (e.g. morphine)

Neuroleptanalgesic

A combination of a neuroleptic and an analgesic (e.g. fentanyl-droperidol)

Neuroleptic

A CNS depressant which acts selectively to decrease dopaminergic activity in the mesolimbic system. Includes phenothiazines, butyrophenones, and Rauwolfia alkaloids (e.g. reserpine)

Parasympatholytic

An agent which inhibits the activity or fxns of the parasympathetic NS (e.g. atropine)

Parasympathomimetic

An agent that mimics the effects of parasympathetic nervous stimulation (e.g. muscarine). All of these are cholinergics, but not vice cersa.

Plasticity

Change in number of receptors (changes B_max not K_d). In general, agonists promote desensitization (decrease Bmax); antagonists promote supersentization (increase Bmax)

Receptor

A discrete cellular binding site which must be occupied for a drug to exert its effect

Sedative

An agent that produces sedation at low dosages; includes ataractics, hypnotics, and narcotics

Sympatholytic

An agent which inhibits the activity or fxns of the sympathtetic NS (e.g. phentolamine)

Sympathomimetic

An agent which mimics the action of the sympathetic nervous system (e.g. epinephrine)

Cholinergic effects on cardiovascular system

• decreased HR
• decreased atrial contractility
• decreased AV conduction (AV block)
• decreased ventricular contractility?

Cholinergic actions on the Respiratory System

• Produce bronchoconstriction
• Increase bronchial secretions

Cholinergic effects on GI tract

• Increased motility
• Increased secretions
• Relax sphincters

Cholinergic actions on bladder

• contract detrusor muscle
• relax internal sphincter

Cholinergic effects on eye

• Contract iris and sphincter mm (miosis)
• Contract ciliary mm (accomodation)

Cholinergic Effects on

Skeletal and Smooth mm

Contraction

M1 Cholinergic receptor site/action

• Stimulatory to the autonomic ganglion
• Undefined in the CNS

M2 Cholinergic Receptor Site/Action

Inhibitory to heart

M3 Cholinergic Receptor Site/Action

• Relaxation of sphincters
• Contraction of bronchial smooth muslces
• Stimulation of secretory glands

Nn Cholinergic Receptor Site/Action

Excitatory to autonomic ganglia and adrenal medulla

Nm Cholinergic receptor site/action

Contraction of skeletal mm

Mechanism of Nm Receptors

• Receptor made of 5 subunits (2a, 1 each of b, g, d), where ACh binds to the alpha subunits.
• When bound, central transmembrane Na+ channel is formed and allows Na+ to enter cell

Mechanism of M1 + M3 Receptors

• Single subunit protein with several transmembrane domains.
• ACh binds, and through G-protein cascade, phospholipase C is activated, resulting in PIP2 being cleaved into IP3 and DAG
• DAG activates protein kinase C, resulting in closing of K+ channel resulting in excitation (M1)
• IP3 increases intracellular Ca2+ resulting in sm mm contraction/exocrine secretion (M3)

M2 Receptor Mechanism

• ACh binds to single subunit receptor and activates G-protein, which opens K+ channels (hyperpolarization and thus bradycardia), and inhibits cAMP (decreased cAMP)

Natural Nm blockers

• Tetrodotoxin from puffer fish
• Saxitoxin from Gonyaulax during Red Tide

Natural Cholinergic Antagonists

• Atropine = muscarinic
• Curare = nicotinic

Conditions that will Inhibit ACh release

• Low calcium/Excess magnesium
• Botulinum toxin
• Aminoglycosides
• Local anesthetics

ACE Inhibitors

• Physostigmine (Reversible)
• Organophosphates (Irreversible)

Indirect Acting Drugs

Increase [ACh] in the vicinity of ACh-receptors and do not distinguish between muscarinic and nicotinic receptors (can be reversible or irreversible)