Pharm Quiz #1 Flashcards
What are three components of anesthesia no 1 drug can deliver?
Analgesia(opioid)
Amnesia(volatile agent)
Skeletal muscle relaxation(paralytic)
What does a BIS monitor measure?
Awareness
What is the Myer-Overton Lipid theory?
because inhalation agents act through the central nervous system cells, anesthetic potency increases with lipid solubility.
What is pharmacology?
the processes by which a drug produces one or more measured physiologic responses
What is the mechanism of action of anesthetic agents?
No precisely known
On what receptor sites do anesthetic agents primarily work?
membrane receptors
Where is the primary receptors for injected and inhaled anesthetics?
GABA receptors(gamma amino-butyric acid);primary mechanism of action, where volatile agents are mediated
What are three important components related to the receptors of pharmacologic responses?
protein composition
site of drug binding
regulator of pharmacologic response
What are four additional influence that affect pharmacologic responses?
absorption
distribution
metabolism
excretion
What is a drug receptor?
protein that binds to drug or endogenous substance?
What are three properties related to drug receptors that affect how they work?
- sensitivity
- selectivity
- specificity
How does sensitivity affect drug receptors?
required drug concentration to elicit an effect; variable with previous exposure and or genotype(immune response and red head take more anesthetic)
How does selectivity affect drug receptors?
receptors respond to structurally similar drugs
How does specificity affect drug receptors?
receptor response always the same
What is a drug receptor subunit?
they are the primary regulator of onset-offset drug response(onset on drug action-termination of drug effects)
What are the four types of drug receptor bonds from weakest to strongest?
Van der Walls
hydrogen
Ionic
Covalent
What are four common regulatory protein types as related to drug receptor structure?
Cell surface proteins
Enzymes
Carrier proteins(transporters)
Ion channels
Where are three drug receptor protein locations?
Within luminal membranes
Ion channel surfaces
Intracellular
What is reflected from the time of drug administration to response?
reflects the time required for receptor conformational change & tissue response
What is the most frequent receptor site for IV anesthetic agents as well as Inhalation agents to bind too?
GABA receptor
Anesthetics attach to receptors using a 3 point attachment that causes conformational changes. Attachment binding with what?
Van der Waals
Ionic bonding
Non-specific hydrophobic bonding(inhalation agents)
What is the difference between drug receptor and a drug acceptor?
receptor elicits a pharmacological response but an accepter does not, acceptors also reduce the amount of drug available to bind to receptors
Name the two most common opioid receptors?
Mu
Kappa
Name two adrenergic receptors?
alpha
beta
Name two acetylcholine receptors?
nicotinic
muscarinic
What is an example of a histamine drug receptor?
5HT3(benadryl)
How many peptide subunits is associated with GABA?
5 peptide subunits arranged in a ring
What is the drug response equation?
drug + receptor binding {Drug Receptor Complex}= tissue response
What is the Drug Receptor Complex?
selective process where only a few drugs may bind to a receptor type to elicit a response
What are three that can make tissue response variable?
the individual receptor
genetic
physiology
What is the occupancy theory?
magnitude of a drug’s response is proportional to the number of receptors occupied—>typically the more drug=greater tissue response
What is the definition of the mean pharmacological dose?
its the arithmetic average of doses required to produce a given response
What is the definition of the median pharmacological dose?
the dose on either side of which half drug responses occur
What is the definition of the mode pharmacological dose?
dose most commonly given; dose representing the greatest percent of responses
What largely determines the drug administration as related to drug dose response?
it is largely determined by mean therapeutic dose per kg of body weight
What are two types of drug response curves that describe drug response and patient variability?
- graded dose response
2. quantal dose response
What is the graded drug response?
demonstrates change in response as dose is increased, more drug causes more response until the plateau
What type of shape is the response curve?
hyperbolic; greatest change in response occurs to left on small portion of x-axis, large doses result in plateau as maximal response is reached
What is the Log Graded Response Curve?
- its more detailed graded dose response cube
2. its useful in comparing potency of drugs with similar mechanisms of action
What information does Quantal Dose Response give?
Provides information on frequency of drug producing therapeutic response in patients.
Response is measured as all or nothing.
What three things is Quantal Dose Response useful in deterring?
effective dose(EF=D 50) toxic dose(TD 50) lethal dose(ED 50)
Using dose response curves, what information is obtained concerning drug actions?
It quantifies drug actions
What is meant by ED 99?
effective dose for 99% of patients
What is meant by LD 1?
lethal dose for 1% of patients
What is the safety margin equation?
LD1-ED99/ED99*100
The greater the therapeutic margin of safety the ____ the drug.
safer
What is the definition of the Therapeutic Index?
its the median therapeutic safety margin for a specific agent
How is the therapeutic index calculated?
LD50/ED50
What are some drugs with narrow therapeutic index?
volatile inhalation agents such as Isoflurane at 1.5% end tidal provides anesthesia
Isoflurane at 4% causes circulatory collapse
What is the symbol denoting Median Effective dose?
ED50
What is the definition of Median Effective dose?
the dose where 50% of patients respond as desired
What is median effective dosing used for?
For comparing drug potency within a drug class
What is the median effective dose derived from on the quantal dose response curve?
the linear portion
What is the fractional tissue response of a drug?
its the desired drug effect
What causes fractional tissue response?
drug+receptor=drug receptor complex causing fractional tissue response
When does desired tissue response occur?
When sufficient quantity of receptors are activated by a drug
What is described by Intrinsic Activity?
describes the degree of drug receptor interaction for a given drug and receptor population(tissue response reflects number of drug receptor complexes)
In what two ways is Intrinsic activity described?
Affinity
Efficacy
How is affinity defined/described as related to Intrinsic activity?
“Potency”
Used to differentiate between deferent agonists that activate the same receptor(the agonist that produces a maximal response aka ~efficacy~ with the lowest drug concentration has the greatest affinity or potency).
How is efficacy defined/described as related to Intrinsic activity?
“how efficiently a drug elicits a fractional tissue response”
its ability to produce a desired response by stimulation of a specific receptor…maximum effect that a drug may produce.
What is Fractional Tissue Response Time(desired drug effect) dependent upon?
- Delivery of drug to receptors(requires sufficient # of drug receptors activated by free drug)
- Pharmacokinetic analysis(onset of drug response)
- Drug elimination kinetic analysis(duration of tissue response)
- Time for conformational change of receptors
- Receptor up regulation(amplification of receptor sensitivity to a drug)
* for example when pt rebounds after abruptly stopping beta blockage, hypersensitivity* - Receptor down regulation(reduction of receptor sensitivity to a drug
What is a drug agonists?
a substance that binds to a SPECIFIC receptor and TRIGGERS a cellular response, it mimics the action of endogenous ligands that binds to the same receptor, agonists in sufficient concentrations elicit maximal receptor activation
What are LIGANDS?
molecules that bind and form a complex with a receptor to produce a biologic response, can be either an endogenous chemical or be exogenously administered
What are some characteristics of pure antagonist?
- Structurally similar to agonist
- Binds to receptor without causing a conformational change(does not cause a response)
- Receptor affinity but NO EFFICACY(still causes bonds)
- Blocks another drug’s ability to produce a physiological response
- Higher receptor affinity than agonists
How do competitive antagonist differ from noncompetitive antagonist?
- possess weak affinity
2. may be displaced from receptor by agonist(atropine, esmolol)
Three important characteristics of Noncompetitive antagonist.
- strong affinity for receptors
- covalent bonds
- not displaced by agonists
What are two examples of a noncompetitive antagonists?
ASA and phenoxybenzamine(BPH drug)
What is a partial agonists?
agent that activates receptor but cannot produce maximal response, may partially block effects of full agonist, has a lower efficacy than full agonist
Receptor affinity with intrinsic activity
- Intrinsic activity 2-10% of a pure agonist
- incomplete receptor conformational change(Nalbuphine, Butorphenol, Pentazocine)
What are inverse agonist?
Drug or endogenous chemical that binds to receptors resulting in opposite action of agonist, binds preferentially to inactivated receptor state
What is the efficacy of a full agonist?
100%
What is the efficacy of an inverse agonist?
Less than zero efficacy, decreases the activity below the basal levels
What are some examples of inverse agonists?
- Cimetindine and ranitidine on H2 receptors
- Yohimbine on alpha 2A adrenergic receptors
- Clozapine on D2 and %HT2c receptors
- Timolol on beta2 adrenergic receptors
- Prazosin on alpha1 adrenergic receptors
- Haloperidol on D2 receptors
What is physiologic antagonism?
Involves 2 agonist drugs biding to different receptors
What is the drug response with physiologic antagonism?
the two drug responses oppose each other and produce minimal physiologic responses(each drug binds to a different receptor…each drug elicits a conformational change)
What is an example of physiologic antagonism?
Isoproterenol and Norepi for vasoconstriction, would result in no change in SVR, Iso vasodilator, NE vasoconstrictor
What is chemical antagonism?
A drug’s action is blocked but no receptor is involved
What are two examples of chemical antagonism?
- Heparin/Protamine(protamine’s positive charge forms an ionic bond with negatively charged heparin)
- Sugammadex/rocuronium
What is receptor down-regulation?
- Exposure of constant concentration of drug leads to diminished effects(for example diminished response to beta agonist inhalers for asthma) from continued stimulation of cells by agonists
- Down regulation = tolerance or desensitization
What is receptor up-regulation?
- With chronic antagonist administration the number and sensitivity of receptors increases
- Tolerance occurs
- Requires larger doses of antagonist to counteract larger numbers of receptors(for example sudden stop of beta blockers can cause a rebound affect)
What is drug tolerance?
- Increasing concentration of drug required to produce a given response
- Results from chronic exposure to agonists
What are 5 causes of drug tolerance?
- Up and down regulation
- Enzyme induction
- Depleted neurotransmitters
- Protein conformational changes
- Changes in gene expression
What is Tachyphylaxis?
rapid development of tolerance due to acute drug exposure(for example…the first time an opioid agonist is given it will work the best for the patient)
What is the spare receptor concept?
- A maximal response can be produced by activation of a fraction of receptors.(neuromuscular blockers-occupation of >70% of nicotinic cholinergic muscle receptors required to reduce response-maximal skeletal muscle function achieved with only 30% receptor activity)
- Provides mechanism for obtaining drug response with low concentrations of drug
