Pharmacology Flashcards
10 major sites of drug action in the CNS
action potential propogation synthesis storage metabolism release uptake degradation receptor ion conductance retrograde signaling (like glutamine to glutamate by glia)
monoamine transporters
VMAT- vesicle for monoamines
MAO- on mitochondria of nerves
COMT- in cytoplasm in liver. functions: breakdown dopamine/ Norepi/ Epi, etc.
Therapeutic applications of monoamine transporters as sites of drug action: ADHD: methylphenidate, amphetamine
Depression: SSRIs, SNRIs, TCAs
Glutamate: The Primary Excitatory NT
Localized throughout the CNS Glutamate accounts for most fast synaptic transmission in the CNS and spinal cord Pathophysiology Ischemic injury, stroke Migraine Alzheimer’s disease Lou Gehrig’s disease
GABA: The Primary Inhibitory NT
Localized throughout the CNS
Principal NT of interneurons
Neurons in striatum, globus pallidus, and Purkinje cells of cerebellum
Roles
Balances excitatory activity of glutamate
GABA dysfunction leads to hyperexcited states
GABA-mimetic drugs are used to induce sleep and control anxiety and seizures
Acetylcholine in the CNS
Functions
Wakefulness
Motor control
Memory
Drowsiness, sedation, and memory loss can occur when central ACh receptors are blocked
Many CNS drugs have significant affinity for muscarinic ACh receptors
Monoamine Regulation of Major Depressive Disorder Symptoms
Dopamine: Attention, motivation, pleasure, reward
norepinephrine: alertness, energy
Serotonin: obsessions and compulsions
Serotonin & norepinephrine together: anxiety
Dopamine Pathophysiology
SN → striatum regulates voluntary movement
- Striatal DA neurons degenerate in Parkinson’s disease
VTA “reward pathway” mediates
Drug addiction
- Cocaine blocks DA uptake
- Amphetamines increase DA release
Psychiatric disorders
- Schizophrenia involves increased DA activity
- Classical antipsychotics work (in part) by blocking dopamine D2 receptors
Serotonin (5-Hydroxytryptamine, 5-HT)
Mediates affective processes such as aggressive behavior and arousal
Descending pain pathways
Sensory enhancement
Depression is associated with decreased 5-HT function
Treated with SSRIs
Ectasy (MDMA), LSD and other hallucinogens probably act in part by interacting with 5-HT receptors
Norepinephrine
Modulates sleep, wakefulness, attention, and feeding behaviors
Roles in learning and memory, anxiety and pain, and mood
general wiring of the ANS (transmitters, receptors)
Parasympathetic
Neurotransmitter: ACh
Receptors: nAChR, mAChR
Sympathetic
Neurotransmitters: NE > Epi (DA); ACh
Receptors: α, β, (D), nAChR, mAChR
ionotropic vs metabotropic Ach receptors
Nicotinic is ionotropic, muscarinic is metabotropic
Rules of Thumb for Smooth Muscle and Autonomic Receptors
Alpha1 (α1) receptors
Stimulate contraction of all smooth muscle
Vascular smooth muscle – vasoconstriction
Beta2 (β2) receptors
Relax smooth muscle – vasodilation
Muscarinic receptors
Contract smooth muscle (different intracellular signal than α1 receptors)
Apparent discrepancy – ACh & muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
Norepinephrine happens with normal nerve stimulation ; does not have high affinity for B2 receptors. Most of the B2 relaxation will happen with epinephrine (stimulation of adrenal medulla)
Epinephrine is potent at all adrenergic receptors
Sympathetic vs. Parasympathetic Tone
Sympathetic Adrenergic (anticholinergic) Cutaneous vasodilation Pupil constriction (myosis) Increase in HR Reduction/elimination of the desire to urinate Decreased secretion and motility
Fight or flight
Smooth muscle relaxation
Parasympathetic Cholinergic Salivation, lacrimation Pupil constriction (myosis) Decrease in HR Urination, defecation Increased secretion and motility
Rest and digest
Smooth muscle contraction
High heart rate, pupillary dilation (not constricting the pupil anymore) comes from blocking
muscarinic receptors– inhibition of the parasympathetic system
AChE inhibitor acute intoxication
Parasympathetic effects
SLUDGE acronym – Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis
