Define Kd. What’s the formula?
Kd is the equilibrium dissociation constant. Kd = K1/K2 = EC50 (in ideal conditions).
What is the difference b/t graded and quantal dose responses?
Graded dose responses occur as the dose amount increases so does the response.
Quantal dose responses are all or none responses.
What makes a drug an agonist vs. an antagonist?
agonists have high dissociation constants and thus dissociate from the receptor quickly allowing more drug to bind and have a greater effect. Antagonists have a low dissociation constant and remain in the drug receptor complex for a longer time, blocking other drugs that could increase the drugs effect.
Is a drug with a K3 of 1 an agonist or antagonist?
Agonist. Drugs with a K3 closer to 0 are antagonists.
Define threshold dose and ceiling dose.
Threshold dose is the lowest dose that produces a response.
Ceiling dose is the lowest dose at which Emax is observed.
If two drugs produce the same maximal effect (Emax) but one is more potent than the other (i.e. produces the same effect at a lower dose), is it a ‘better’ drug?
No. while the more potent drug may acheive the desired effect at a lower dose its side-affects may also be more potent and result in harsher negative affects at the lower dose than the less potent drug at its higher dose.
While APAP (acetaminophen = tylenol), is less potent and has a lower Emax than the opioids codeine and oxycodone, why might APAP be used instead of, or in combo with low doses of, these opioids?
To avoid the nasty side affects of opioids. A single dose of opioids will cause ~60% of patients to feel side affects…very nasty drugs.
What were the two changes to tylenol’s concentration that was intended to decrease the chance of liver failure due to acetaminophen overdose?
- Tylenol reduced the maximum daily dose of tylenol from 4,000 mg/day to 3,000 mg/day.
- All opioid-APAP combination drugs will no longer be allowed to contain greater than 325 mg acetaminophen per capsule.
Name an opiate receptor agonist and antagonist.
Oxycodone is an opiate receptor agonist; K3 = 1.
Naloxone is an opiate receptor antagonist with a K3 of 0. Naloxone binds tightly to the opiate receptor binding sight while not activating the active sight.
What is the major difference b/t competitive and non-competitive drugs?
Competitive drugs can reverse the affects of their counterparts
Non-competitive drugs can’t have their activities reversed
Why is succinylcholine, a drug used to induce paralysis by blocking acetylcholine at the NMJ, potentially dangerous? What drug provides a safer alternative?
succinylcholine is a non-competitive inhibitor of ACH, thus if the patient does not have the required enzymes to degrade succinylcholine, paralysis may last for a long period of time. A safer alternative is Curare, which is a competitive binder to ACH, therefore to reverse paralysis all that is required is to increase [ACH].
What receptor does ACH, curare, and succinylcholine bind to?
Nicotinic M cholinergic receptors
What receptor do the agonists, ACH, muscarine & pilocarpine and the antagonists, atropine and scopolamine, act upon?
Muscarinic Cholinergic receptors
What are the agonist and antagonistic affects upon muscarinic cholinergic receptors?
Agonist: Increased sweating and salivation. Decreased HR.
Antagonist: Decreased sweating and salivation. Increased HR.
What receptor do the agonists, ACH and nicotine, and the antagonists, curare and succinylcholine, act on?
Nicotinic m cholinergic
What receptor do the agonists, norepinephrine & epinephrine, and the antagonists , prazosin and phentolamine, act upon? Describe the affects of epinephrine and phentolamine and how they are used in dentistry.
Alpha-1 adrenergic receptors
Epinephrine causes vasoconstriction while phentolamine causes vasodilation. Phentolamine is used to dilute epinephrine at the site of an injection following a dental procedure to allow patient to recover from soft tissue numbness more quickly
What are the agonistic and antagonistic effects on nicotinic m cholinergic receptors?
Agonist: Muscle stimulation (ex ACH)
Antagonist: Muscular paralysis (ex curare)
What receptor does the agonist epinephrine and antagonists propanolol and metropolol act upon?
What are the agonistic and antagonistic effects upon Beta-1 adrenergic receptor activation?
Agonist: Increased HR and contraction force
Antagonist (beta-blockers): Decreased HR and Contraction force
Describe the difference b/t chemical and physiologic antagonism?
Chemical: Another molecule binds the substrate either inactivating it or blocking it from entering ion channels
Physiological: One substance does the exact opposite action but does so by binding a different receptor. Ex = Alcohol & caffeine.
Tetracycline is knocked down when taken with milk. What type of antagonism is this an example of?
What conservative index is used to assess a drugs safety? How is it calculated?
Safety Index = LD 1/ED 99