Kinetics, Dynamics, and G-Receptors Flashcards Preview

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Flashcards in Kinetics, Dynamics, and G-Receptors Deck (79)
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Pharmacokinetics involves these four processes

Absorption, distribution, metabolism, and exretion


What are pharmacodynamics

What the drug does to the body. nvolves mechanism of effect, sensitivity, and responsiveness


How do the two compartments interact?

Drug enters first central, distributes to peripheral compartment, and returns to central for clearance


The central compartment is made of ______

Highly perfused tissues, such as the kidney, liver, brain, heart, and lungs.


The central compartment receives _____% of the cardiac output despite only representing _____% of the bodymass

75% of CO
10% of bodymass


Peripheral compartmnet is composed of _____

Fat, musce, hair, bones, nails, etc.
Parts of the body with less blood supply.


Rate of compartment transfer decreases with _____

Aging and diminished cardiac function


Formula for calculating Vd

Vd = (Dose of IV drug) / (plasma concentration before elimination)


What does Vd tell you?

If the drug stays in plasma, follows TBW, or if it concentrates in the body tissues


What drug characteristics will affect Vd?

Lipid solubility (highly lipid soluble will directly enter the peripheral compartment)
Protein binding (more binding results in lower Vd. If protein bound - less able to cross membranes)
Molecular size (larger molecules less able to cross membranes)


Define elimination half-time

Time necessary for plasma concentration of a drug to decrease by 50% during the elimination phase


Elimination half-time is (dependent / independent) of the dose administered



Define elimination half-life

Time necessary for 50% of the drug to be eliminated from the body


How do most drugs cross cell membranes?

Simple diffusion


A high oil to water partition coefficient means the drug is

Highly lipid soluble


Can charged particles cross membranes by simple diffusion?



Weakly acidic drugs are best absorbed where?

Acidic environments


Weakly basic drugs are best absorbed where?

Basic environments


Benefits of sublingual / transmucosal medications

Bypass the first pass effect and avoids destruction by gastric enzymes


The rate limiting step of transdermal absorption involves crossing this layer of the epidermis

Stratum corneum - this is the outermost layer of the skin, consisting of dead skin cells that act as a barrier to infection, dehydration, chemicals and mechanical stress


Good location for medication patches

Chest - the skin is thin here


Why is rectal administration of drugs unpredictable?

Depending on how far the medication goes up dat butt, it may enter the portal system and undergo the first pass effect.


Effect of lungs on uptake and distribution

The lung uptakes lipophilic drugs (lidocaine, fentanyl, demerol), and acts as a reservoir to release the drug back into systemic circulation. Lots of the fentanyl we give will go to the lungs because it is vessel rich. This results in the double peak in plasma concentrations. This is also called the lung first pass effect.


How can the BBB be overcome?

Large drug doses, head injury, and hypoxia. Our drugs pass the BBB because they are lipophilic.


During neurosurgery, it is assumed that the _____ has been compromised



Why do many anesthetic agents have short onset and short duration of action?

The drugs we give are highly lipophilic. The brain has a high proportion of lipid and receives 15% of the CO! The duration is short because the drugs quickly exit to enter the body fat (where the drugs are more soluble)


When are acidic drugs highly ionized?

In basic environments. This is why acidic drugs are best absorbed in acidic environments.


What is ion trapping?

When a membranes divides two separate pH levels. The only practical scenario of this would be the placenta. The fetus is slightly more acidotic. For this reason, we decrease epidural dosing for parturients.


Most common plasma proteins involved in protein binding of drugs

Albumin (acids)
Alpha 1 Glycoproteins (bases)


Examples of drugs that are highly protein bound

Warfarin, propanolol, phenytoin, and diazepam


What patients would have decreased serum proteins?

Liver failure


Describe first order kinetics

Drugs administered in the therapeutic dose range are cleared at a rate proportional to the amount in the plasma.

Basically, clearance rate is proportional to the amount of drug given.


Describe zero order kinetics

Occurs when drug levels exceed metabolic or excretory capacity even at therapeutic doses. In this situation, drugs are cleared at a constant rate independent of dose.


Examples of drugs that undergo Zero Order kinetics

ASA, dilantin, and ETOH


Chronic drinkers will need (more/less) medication
Drunk patients will need ______
Acutely drunk alcoholics will need ____

Chronics need more
Drunks need less
Acutely drunk alcoholics need less


Asians metabolize drugs (faster/slower) than average



Germans metabolize drugs (faster/slower) than average



What is the extraction ratio?

An organ's ability to remove a drug from the systemic circulation over a single pass through the organ. This may be influenced by blood flower, protein binding, or intrinsic ability of the organ to eliminate the drug.


For drugs with a high extraction ratio (>.7), drug clearance depends highly on

Blood flow. This also means that low BP will result in slower metabolism of the drug.

This is "perfusion dependent elimination"!


For drugs with a low extraction ratio (<.3), drug clearance depends highly on

Protein binding. A decrease in protein binding or an increase in enzyme activity will result in an increase in hepatic clearance. Changes in blood flow won't really affect clearance.

This is "Capacity-Dependent Elimination"!


The extraction ratio for most drugs is between

.3-.7 meaning that most drugs rely on both capacity and perfusion dependent means


Most important organ for elimination



What happens to highly lipid soluble drugs in the kidney?

They are reabsorbed such that little or no unchanged drug is excreted in the urine. The liver has to metabolize the drug into a water soluble form before it can be excreted by the kidneys.


Main site of drug metabolism and biotransformation

The liver.

Other, less important, sites of dug metabolism include the lung, kidney, skin, and epithelial cells. Some reactions can also occur in the blood from plasma esterases and pseudocholinesterases.


Once a drug is metabolized, does that mean it is inactive?

Not always. Some drugs can have active metabolites. These metabolites tend not to be as strong as the parent drug. This can extend the life of the drug.


Examples of drugs with active metabolites

Morphine, versed, and ketamine


Phase I Metabolism

Oxidation, reduction, and hydrolysis through the Cytochrome P-450 System.


Phase II Metabolism

Conjugation. Large polar compounds are added to the molecule being metabolized, greatly increasing it's water solubility for renal or biliary excretion.


Cytochrome P-450 System

A family of more than 50 enzymes located on the smooth ER that are responsible for metabolizing certain drugs. Of these, only 6 are responsible for 90% of drug metabolism.


What is induction?

Increasing the ACTIVITY of CP-450 enzymes. This can be caused by ETOH and smoking. Induction will result in a reduced elimination half-life.


How is a person's P-450 system determined?

Genetics. We all have the 6 enzymes the contribute 90% of drug metabolism, but we may have them in different proportions.


NON-microsomal enzymes

Hydrolize drugs that contain ester bonds (esmolol and succhs). Metabolize drugs mostly by conjugation and hydrolysis and are located mostly in the liver, but also in the blood and GI tract. These enzymes are also determined genetically.


Do non-microsomal enzyme undergo indution?



Most common way that drugs exert their effects on the body

By binding to receptors


Receptor Activation Theory

Drugs convert non-activated receptors to their active form


Receptor Occupancy Theory

More receptors occupied by the drug results in more effect of the drug


Example of a drug that does not work by interacting with receptors



Chemical structure of a drug has major implications in

Affinity and intrinsic activity


Define being "hyper-reactive"

An unusually low dose of a drug causes it's expected pharmacologic effect. Similarly, a normal dose can have en exaggerated effect.


Define being "hypersensitive"


It is possible to have a delayed allergy, in that, the body made antibodies to the drug the first time they received it. Therefore, the next time they receive the drug, they may have an allergic reaction.


Example of medications with a synergistic effect

Benzos and narcotics have a synergistic effect on the respiratory system


Examples of cys-loop receptors

Nicotinic AChRs, GABAa receptors, glycine receptors


Examples of Ionotropic glutamate receptors

AMPA, NMDA, and kainate receptors


Examples of drugs that bind to Cys Loop receptors

Nicotine, varenicline (Chantix), muscle relaxants (Succ), barbiturates & diazepam (GABAa)


Drugs that work of ionotropic glutamate receptors

Aniracetam, "smart drugs," ketamine


Number of subunits that cys loop receptors have

5, each with 4 domains. There are also 5 different types of subunits that exist, but the receptor must have AT LEAST 2 alpha subunits.


# of subunits that glutamate receptors have

4, each with 4 domains


Ions that nAChRs pass

Mostly Na & K, but a little Ca


Glycine and GABAa receptors conduct this ion

Cl- (these are both hyperpolarizing/inhibitory receptors


Most synaptic transmission is mediated by these receptors



3 Classes of G-coupled protein receptors

Class A: Adrenergic, and muscarinic ACh
Class B: PTH receptor
Class C: Metabotropic glutamate receptors, GABAb receptors


How do NMDA receptors result in memory formation?

Mg+ is blocking NMDA receptors, but this is voltage dependent. When the neuron is depolarized, the Mg+ gets kicked out, allowing Ca++ to enter the cell, activating CaMKII, which results in the formation of more AMPA receptors. AMPA receptors are the main receptor in signal transduction. More AMPA receptors means the signal can now be passed more easily, resulting in a learned connection. The more the system is depolarized, the more Mg+ will be kicked out and eventually more AMPA receptors will be made.


Number of transmembrane domains that GPCRs have



Examples of drugs that work on GPCRs

Beta blockers, beta agonists, opioids (Mu receptors)


GPCRs. How da fuck do those things work?

When an agonist binds to the GPCR, a conformational change takes place that kicks out the beta-gamma subunit. The alpha subunit is now no-longer inhibited and can bind with GTP. Binding with GTP causes the alpha subunit to activate, and it goes off to do it's thang, activating other proteins n' shit. The alpha subunit eventually breaks down GTP into GDP, it inactivates, and the system resets.


How many types of G-alpha subunits are there?

G-alpha-s, G-alpha-i, G-alpha-q


What does the G-alpha-s subunit do?

Activates adenylyl cyclase, which causes an increase in cAMP, which activates protein kinase A, which then phosphorylates downstream proteins and transcription factors


What does the G-alpha-i subunit do?

Inhibits adenylyl cyclase (meaning that the increase in cAMP and proteins and transcription factors will not happen)


Transdermal absorption occurs how?

Through hair follicles and sweat glands that act as diffusion shunts