BASIC SCIENCE CONCEPTS Flashcards
Substrate/ligand?
compound that binds to a receptor and starts a chain reaction that produces an effect, such as altering a second messenger system
Agonist?
drug that behaves in a similar manner to an endogenous (produced by the body) substrate.
Eg: Albuterol is a beta-2 agonist that behaves similarly to epinephrine. It binds to beta-2 receptors in the lungs, which activates several steps [e.g., increased cyclic adenine monophosphate (cAMP) production and decreased intracellular calcium] that result in bronchial smooth muscle relaxation.
Antagonist?
drug that blocks an endogenous substrate from binding to its receptor (also called a blocker).
Eg: beta-1 blockers prevent adrenergic neurotransmitters (e.g., epinephrine) from binding to beta-1 receptors in the heart. Epi normally increases heart rate & contractility when it binds to beta 1 receptors. Blocking it causes decreased HR & contractility, thereby decreasing BP
Enzymes?
Enzymes are compounds that speed up (catalyze) a reaction (e.g., creating a new compound or breaking down a compound into smaller parts).
Eg: theophylline blocks the phosphodiesterase (PDE) enzyme, which increases the second messenger cAMP, which in turn causes the smooth muscles of the bronchioles to relax
Competitive inhibition
Competitive inhibition occurs when a drug binds to the same active site of a receptor or enzyme as the endogenous substrate, preventing the activity.
Eg: cyclic guanosine monophosphate (cGMP), which is involved in smooth muscle relaxation is degraded by the PDE-5 enzyme. Sildenafil a PDE-5 inhibitor, which binds at the same active site as cGMP and prevents the breakdown of cGMP.
Non competitive inhibition
Drug binds to the enzyme or receptor at a site other than the active site & reduces the activity of the substrate
Nervous system
Central nervous system & peripheral nervous system
CNS - Brain & spinal cord
PNS - nerves which connect CNS to rest of the body. Autonomic & somatic NS
Autonomic - involuntary (digestion, CO, BP). Presynaptic & post synaptic neurons.
Somatic - voluntary
ANS
Sympathetic & parasympathetic NS
PSNS - rest & digest. muscarinic receptors. GI tract, bladder, eyes
SNS - fight or flight. epi or NE. smooth muscles, heart, lungs. alpha 1, beta 1 or beta 2 receptors. increase BP, HR & broncodilaton
PSNS –SLUDD
Increase salivation, lacrimation, urination (bladder contraction), defecation/diarrhea, digestion.
Ach - nicotinic (Nn) - Ach- Muscarinic
SNS
Increase HR, BP, pupil dilation, bronchodilation, glucose production
Decrease bladder contraction, saliva, peristalsis
Ach - nicotinic (Nn) - epi/NE (adrenergic receptors -a1, b1, b2
- Beta 2 agonist
- beta 1 & beta 2 agonist
- alfa 1 & beta 1 stimulator
- terbutaline (acute, severe asthma exacerbation)
- isoproterenol (used for bradycardia, but causes bronchodilation
- epinephrine & NE vasopressors) increased vasoconstriction, HR and BP
- alfa 1, beta 1 & beta 2 blocker
- beta 1 & beta 2 blockers
- Centrally acting alfa 2 agonist
- labetalol. used to increase vasodilation (which decreases BP) and decrease HR, but it can increase bronchoconstriction
- propranolol & nadolol (non selective)
- clonidine. alfa 2 adrenergic stimulation in brain leads to decreased sympathetic output. ie less Ach in Nn receptors, decreased release of epi/ne. less epi/ne binding to adrenergic receptors results in vasodilation, decreased BP, HR.
Alpha 1 agonist & antagonist
Alpha 1 agonist - Inc vasoconstriction & BP (phenylephrine, dopamine dd)
Alpha 1 antagonist - smooth muscle relaxation Inc vasodilation, dec BP (doxazosin, carvedilol, phentolamine)
Muscarinic agonist & antagonist
Musc agonist - Increase SLUDD (pilocarpine, bethanechol
Muc antagonist - dec SLUDD (atropine, oxybutynin)
Beta 1 agonist & antagonist
Beta 1 agonist - Inc contractility, CO, HR (dobutamine, isoproterenol, dopamine dd
Beta 1 antagonist - Dec CO, HR (metoprolol & non selective beta blockers)
Beta 2 agonist & antagonist
beta 2 agonist - inc bronchodilation (albuterol, terbutaline)
beta 2 antagonist - Inc bronchoconstriction (non selective beta blockers)
MAO INHIBITORS
phenelzine isocarboxazid rasagiline selegiline methylene blue liinezoliid
role of mao
role of maoi in catecholamine induced hypertensive crisis
sx of hypertensive crisis
Tyrosine - dopa - dopamine
dopamine - NE by COMT & MAO
NE - Epi by MAO
epi - metabolites by MAO
Additionally tyramine is converted to its metabolites by MAO
MAOI inhibits conversion of dopamine to ne, ne to epi & epi to it metabolites leading to excess catecholamines. this plus other additive effects (bupropion, pseudoephedrine, levodopa) - leading to hypertensive crisis
SXs - hypertension, hyperthermia ,tachycardia, agitation, coma, death
MAOI & serotonin syndrome
Sx of serotonin syndrome
tryptophan - serotonin - metabolites
serotonin to metabolites is by MAO
MAOI blocks the breakdown of serotonin
Inc serotonin + additive effects (SSRI, SNRI, tramadol, dextromethorphan) leading to Serotonin Syndrome
Sx-tremor, akathisia, clonus, hyperthermia, sweating
