Clinical Pharmacology Intro and Drug Receptor Review

Pharmacokinetics

• What the body does to the drug

• ADMA: Absorption, distribution, metabolism, excretion

Pharmacodynamics

• What the drug does to the body

• Receptor, mechanism of action, physical results

Therapeutic Goals

Sedation/Anesthesia and/or analgesia, muscle relaxation, anxiolysis

Therapeutic Targets

A2-receptor - agonist, D2 receptor - antagonist, GABA receptor - agonist

Sedative

• drug that produces CNS depression accompanied by drowsiness

• Does NOT produce unconsciousness

• Patient Usually has normal autonomics functions (swallow, breathing, etc.)

Tranquilizer

• decreases anxiety/fear

• Patient is calmer and less reactive

  • Does not produce analgesia

General anesthetic

• Produce unconsciousness

• often effect autonomic functions

What is the mechanism of action of Benzodiazepines?

• GABA

• Secreted by neurons in brain and spinal cord

• facilitate GABA binding to the GABA receptor

• No analgesia

GABA

• Major INHIBITORY neurotransmitter

• Activation results in sedation/sleep

What do GABA receptor clinical drugs do?

• sedatives

• general anesthetics

• anticonvulsants

• alcohols

NMDA Receptor

• Tetramer ion channel

• co-activated by glutamate and glycine (need both to activate receptor)

• Channel specific for Na+ and Ca2+, which flow into cell

• Anesthetic drugs are ANTAGONISTS (block excitation of glutmate binding)

What is important about NMDA receptor antagonist: MOA?

• Ketamine /Tiletamine

• Block activation of NMDA receptor: decrease excitation (cause EEG dissociation between thalamocortical and limbic regions, provide analgesia, produce amnesia)

Opioids

Natural, semi-synthetic, or synthetic chemical that binds to opioid receptors on nerve cells in the brain and body to reduce pain or production

Opiates

natural

What are some clinical uses of opioids?

• treatment of pain

• sedation

• decrease need for other anesthetics/analgesics

• Antitussives

• Anti-diarrheal

• unrelieved pain is a major welfare issue

What are some locations of opioid receptors

• Supraspinal effects (Brain)

• Spinal cord (dorsal horn)

• Peripheral effects

Opioid effects on supraspinal effects:

Modulate descending antinociceptive pathways

Opioid effects on spinal cord

• Inhibit presynaptic release of neurotransmitters

  • Postsynaptic inhibition of nociceptive projection

Opioid effects on peripheral effects

Opioid receptors on nociceptive nerve terminal (permanent and induced receptos)

Opioid receptors

• Mu

• Kappa

• Delta

Dopamine

• Catecholamine neurotransmitter and hormone

• Complex neurotransmitter in CNS (brainstem)

  • Movement/motor contral

Parkinson’s disease

not enough dopamine/dopaminergic neurons

Dopamine-2 Receptor Antagonist

• Receptor antagonism (bind but don’t activate)

• Competitive inhibition with dopamine for D2 receptor

• Reduces hyperactive dopamine pathways in the limbic system

• less reliable with higher agitation/activation