Final Exam - Review Flashcards
Describe a non-competitve antagonist?
An allosteric receptor interaction that can never be overcome by the agonist.
Describe a partial agonist?
Competes with the full agonist and produces a lower response than full agonist when all receptors are bound.
In the prescene of a full agonist, it acts as an antagonist. In the abscence of a full agonist, it acts as an agonist.
Describe physiologic antagonism?
Drugs that inhibit the effect of another drug without binding to the same receptor.
Acetylcholine opposes the effects of epinephrine
Insulin opposes gluccocorticoid hormones
Explain active (Ra) and inactive (Ri) receptor congigurations?
Receptors switch between Ra and Ri on their own, even in the abscence of a drug - favors Ri.
Agonist favors Ra and Inverse Agonist favors Ri
Describe an inverse agonist?
An agonist that has a greater affinity for the Ri state, which inactivates the receptor site. Reduces constitutive activity which may producing an opposing physiologic effect.
In clinical practice it is just an antagonist.
Antagonistic activity (beta blockers, H1/H2 blockers)
Correlate stereoisomerism and differences in drug effects
One enantiomer is typically much more potent than the other, they can elicit differing respones from the receptor.
one enantiomer fits better into the receptor than the other
How can a partial agonist also behave as an antagonist?
Partial agonists compete for the same receptors as the full agonist, preventing the full agonist from binding.
Describe a physiologic antagonist?
A drug is given with an opposite charge that will bind and inhibit its effects.
Protamine (+) binds to and inhibits the effects of heparin (-)
What is the distribution coefficient (Kd)?
The concentration of a drug when 50% of the maximal binding is achieved
What would a high Kd indicate?
That the drug has a low affinity for the receptor.
What does albumin mostly bind to?
Acidic drugs
What does a1-acid glycoproptein mostly bind to?
Basic drugs
What does lipoprotein mostly bind to?
Neutral drugs.
Compare the efficacy and potency of these drugs.
Drug B is the most potent drug, but drugs A,C, and D are more and equally efficacious. Potency of the drugs is such that B>A>C>D.
How can you calculate therapeutic index?
TD50 divided by ED50.
What does the therapeutic index indicate?
The safety of a drug. A high Ti means the drug is safer than a low Ti.
What charge will a weak acid with a pKa of 3.5 favor at a pH of 1.5 and 6.5?
At pH 1.5 it will favor the uncharged (protonated) from and at pH 6.5 will favor the charged (unprotonated) form.
What is the charge on a weak acid when it become protonated and unprotonated?
When protonated it becomes uncharged, when unprotonated it becomes charged.
Acids have protons to give, so when protonated become neutral.
What is the charge on a weak base when it becomes protonated and unprotonated?
When protonated it becomes charged, when unprotonated it becomes uncharged.
Bases readily accept protons, and take on their charge when protonated.
What does the henderson hasselbach equation tell us?
The pH at which the protonated and unprotonated forms are in equilibrium (or the pKa)
What is Volume of Distubution (Vd)? How is derived?
The space available in the body to contain a drug. The higher the Vd the less it says in the blood and more it disturbutes into the tissues and vice versa.
Vd= dose / initial drug concentration
Describe first order elimination?
Applies to most drugs, rate of elimination varies with concentration. **Clearance remains constant. **
Describe Zero order elimination?
Rate of elimination is constant. Clearance varies with concentration.
Occurs when ability to eliminate drugs is at max capacity.
All transporters are being used.
What is half life (T1/2)?
The time it takes to get drug in body to 1/2 of its concentration.
How many half lives does it take to acheive full drug effect and full drug elimination?
4 1/2 lives to reach both full effect and full elimination.
What is steady state dosing?
Dosing the drug in a way that replaces the eliminated amount and still keeps therapetic effects.
What are the 4 transmembrane signaling methods by drug-receptor interations?
- Lipid soluble molecule crosses and attaches intracellularly.
- Enzyme activation (RTK’s)
- Ligand gated ion channels
- GPCR’s
Describe how GCPRs cause desensitization?
Drug activates GPCR. The carboxyl tail becomes phosphorlated by G protein kinases. This promotes binding of beta arestin and prevents further interactions with G proteins. This complex binds with a clatherin coated pit which internalizes the receptor. Then the drug unbinds form the receptor causing dephosphorylation and detachment of beta arestin. Then either 1. the receptor can be returned to the plasma membrane and bound again or 2. be taken to a lysosome for destruction.
##Footnote
This causes desensitization because the receptor cannot be bound during this period
Desribe the role and location of drug efflux transporters?
What are the major drug efflux transporters?
- They pump drugs out of the cell. Most are ATP Binding Cassette (ABC) transporters.
- Can be on apical or basalar membrane
- ABCB - broadest substrate specificity
- ABCC - antineoplastics
- ABCG - antineoplastics
Describe drug transporters in the BBB?
The vascular epithelium is primary site of exclusion due to tight junctions and multiple transporters. Most transporters efflux drugs back into the blood.
What are the components of an intact brain barrier?
Vascular space, vascular epithelium (tight junctions, primary site of exclusion), astrocyte, podocyte.
Describe ionotropic ligand gated ion channels?
The protein has a ligand binding site and channel. Ligand binding opens the gate and allows ions to cross.
Describe metabotropic ligand gated ion channels?
The ligand activates a GPCR which activates and EP that releases second messengers that open the ion channel.
Describe PY450 induction?
A drug may induce CYP450, increasing its activity. If a drug becomes inactive by P450 then it will be inactivated faster.
If a drug is activated by P450 (prodrug), it will taken to its active form faster.
Describe P450 inhibition?
A drug may inhibit P450, decreasing its activity. For a drug that is inactivated by P450 it may be active longer or have less inactivation.
For a drug that is activated by P450 (Prodrug), much less of the the drug will be activated.
Describe the nerve fibers in the sympathetic nervous system?
The preganglionc fibers are short while the postganglionic fibers are long. The fibers form a chain so that activation will activate the entire pathway. The ganglia are close to the spinal cord.
Describe the pathway of norepinephrine activated alpha 1 receptors?
Describe the pathway of B1/B2 stimulation in a cardiac myocyte?
Alpha 2 is inhibitory and prevents the release of norepinephrine
Describe the pathway of Beta 2 stimulation in peripheral smooth muscle?
cAMP inhibts MLCK (myosin light chain kinase) and leads to relaxation
alpha 1 consticts in vascular smooth muscle and beta 2 dilates peripheral smooth muscle = more blood flow to muscles during fight or flight
Describe the pathway of the different muscarinic and nicotinic cholinergic receptors when bound by ACh?
- M1,M2, M3 - activate Gq and activate phospholipase
- M2, M4 - activate Gi and inhibit adenylate cyclase
- Nicotinc- Bind to ion channels
Describe the autonomic and hormonal feedback loops that regulate changes in MAP?
What is the structure of a neuron?
- Information is recieved in the dendrites
- The cell body decides whether or not to send a signal
- The axon hillock generates the action potential
- The signal reaches the telondendrion
- The neurotransmitter is relased from the synaptic bouton
What is the sympathetic and parasympathetic effects on the heart?
What is the sympathetic and parasympathetic effects on the blood vessels?
What is the sympathetic and parasympathetic effects on the bronchioles?
What is the sympathetic and parasympathetic effects on the GI tract?
What is the sympathetic and parasympathetic effects on the kidney and liver?
