Pharmacology.block 1

Front 1

What is the definition of drug bioavailability?

Back 1

proportion of unchanged drug that reaches the systemic circulation.
In IV administration, it is 1, or 100%

Front 2

What factors influence drug bioavailability?

Back 2

Drug Solubility, Chemical Instability (pH in stomach), and drug formulation (size, salt form, etc)

Front 3

A particular drug has an f value of 1. A different drug has an f value of .2. What's the difference?

Back 3

f is the bioavailability of the due, and is = AUC oral/AUC injected x 100.

A f value of 1 means that the drug has been given intravenously, low f values indicate it is an orally given drug

Front 4

T/F Half lifes of drugs are always constant

Back 4

False.

A half life will remain constant as long as the dose administered does not exceed the capacity of the elimination systems

Front 5

90% to steady state takes how many half lives?

Back 5

3.3

Front 6

3.3 half lives will take you how far to steady state?

Back 6

90%

Front 7

How many half lives will it take to reach steady state?

Back 7

4

Front 8

Any drug with a Therapeutic index less than 10 is considered _

Back 8

high toxicity

Front 9

If the pH of a solution is below the pKa,,,then acids will remain _and bases will remain _

Back 9

unionized

ionized

Front 10

Only the (non/ionized) form is absorbed.

The (non/ionized) form is renally excreted

Back 10

non -ionized are absorbed

ionized are excreted

Front 11

In the case of aspirin, which has a pKa of 3.3, what conditions are required to ensure absorption?

Back 11

Aspirin is a weak acid, and Only nonionized form is absorbed, therefore the pH must be lower than the pKa inorder for aspirin to be absorbed.....ie you need a pH of less than 3.3

Front 12

Why are antacids so important when talking about drug absorption?

Back 12

Antacids will increase the pH of the GI.

Anytime you alter the pH, you change the ionized and nonionized forms of other drugs, which will alter their absorption rate

Front 13

_ are contraindicated in neonates due to displacement of bilirubin, which will enter the CNS of the neonate.

Back 13

Sulfonamides

This has to do with drug distribution, the drug competes with bilirubin for protein binding, replaces it, and unconjugated bilirubin levels shoot up

Front 14

Vd=

Back 14

dose/Co (concentration in plasma at time 0)

The volume of distribution relates the amount of drug in the body to the concentration of drug in the plasma

Front 15

What is the standard size and volume distributions you should assume when given a calculation?

Back 15

70 kg Male total extracellular fluid volume is 42 L, Blood volume 5L, plasma volume 2 L

Front 16

What are the 4 drugs that compete the most for albumin binding sites?

Back 16

NSAID's, Sulfonamides, Digoxin, Warfarin

Front 17

(T/F) Drug elimination and drug excretion are synonyms

Back 17

False

Front 18

What is the major mechanism for drug elimination?

Back 18

Biotransformation

Front 19

Phase 1 biotransformation involves _ and _ reactions

Back 19

microsomal and nonmicrosomal

Microsomal enzymes include cytochrome P450, and are dependent on the ER

Front 20

Inhibition of _ may result in reduced metabolism of other drugs causing toxicity, while inducers of it will increase drug metabolism leading to treatment failure

Back 20

cytochrome P450

Front 21

What are some examples of CYP 450 Inhibitors? What will this lead to?

Back 21

grapefruit juice, cimetidine, omeprazole antibiotics, azole antifungals.

Inhibition of P450 will inhibit the metabolism of drugs, leading to drug toxicity

Front 22

Patients who are on statins are forbidden from taking _. What is the science behind this?

Back 22

Grapefruit juice,

Grapefruit juice inhibits CYP 450, preventing the breakdown of the drug, and leading to statin toxicity (Renal failure, rhabomylosis)

Front 23

A patient who has been taking diazepam for 2 years suddenly presents to the ER with diazepam toxicity shortly after having lunch at a Mexican restaurant and developing heartburn.His wife gave him a tablet she had in her purse to help with the burn. What is the science behind this?

Back 23

The pt probably took an OTC heartburn medication (Cimetidine), which is an H2 antagonist. This drug inhibits the P450 system 2C9, which is responsible for degrading diazepam. Now, the pt isn't degrading diazepam like normal and has toxicity.

Front 24

What are some examples of CYP 450 inducers? What will this cause?

Back 24

Barbiturates, all anticonvulsants, rifampin.

A 450 inducer will lead to treatment failure because of the increased metabolism of drugs

Front 25

Alcohol metabolism is considered a non-microsomal enzyme catalyzed reaction, or a microsomal enzyme catalyzed reaction?

Back 25

non microsomal (this is part of Phase 1 biotransformation)

Front 26

Phase II biotransformation is usually catalyzed by _, which _

Back 26

glucuronyl transferase, (there are other enzymes, but this is the most common)

enhances the excretion of the drug

Front 27

_ causes gray baby syndrome in neonates, and is completely contraindicated!

Back 27

Chloramphenicol

Front 28

Regarding biotransformation...any drug that is _ will move from phase I to Phase II

Back 28

lipid soluble

Front 29

Morphine undergoes _to form a highly active product, called morphine 6 beta glucoronide.

Back 29

phase II biotransformation (glucoronidation)

Front 30

(T/F) Neonates do not have the ability to undergo glucoronidation

Back 30

TRUE

Because of this inability, the anitmicrobial drug chloramphenicol is contraindicated in neonates. It will cause GRAY BABY SYNDROME

Front 31

What are some examples of Phase II biotransformation?

Back 31

Glucoronidation (acetaminophen, diazepam)
Sulfation (methyldopa, acetaminophen),
Acetylation (HIP drugs...common side effects!)

Front 32

What is the cause of gray baby syndrome?

Back 32

The drug chloramphenicol causes gray baby syndrome in neonates because they do not have the ability to undergo glucoronidation (phase II biotransformation), and therefore can not metabolize the drug

Front 33

_ drugs are notorious for causing side effects in people who are slow acetylators. What will happen if these patients receive any of the above drugs?

Back 33

HIP drugs - Hydralazine, Isoniazid, Procainamide

These pts will develop Lupus, - SLE butterfly rash

*Acetylation is a type of phase II biotransformation.

Front 34

Drug excretion is the result of separate processes, what are they?

Back 34

filtration, secretion, and reabsorption

Front 35

What is the normal GFR?

What is the normal creatinine clearance, for both women and men?

Back 35

120 ml/min

women - 87-104
men - 90-140 ml/min

Front 36

Rate of elimination =

Back 36

glomerular filtration rate (GFR) + active secretion – reabsorption

Front 37

Cl =

Back 37

free fraction × GFR

Assume a normal GFR of 120 ml/min
Say 60% is BOUND, then free fraction is .4

Front 38

Most drugs follow first order elimination rates, what does this mean?

Back 38

a constant FRACTION of the drug is eliminated per unit of time (half time)

Front 39

Ethanol, Phenytoin, and Salicylates follow _ elimination rates, meaning _

Back 39

0 order elimination rate

A constant AMOUNT of drug is eliminated per unit of time, elimination is independent of plasma concentration, and half life is variable

Front 40

Only the _ form of a drug will be excreted into the urine

Back 40

ionized, lipid INsoluble

Front 41

Acidifying urine will do what to Quinidine?

Back 41

Quinidine is a weak base, by acidifying the urine you are increasing ionization of quinidine and therefore increasing renal excretion of that drug

Front 42

How can you increase the renal excretion of Aspirin?

Back 42

Aspirin is a weak acid...to increase renal excretion of it, you can alkalinize the urine by adding in sodium bicarbonate, which will increase ionization of weak acids, therefore increasing excretion.

Front 43

What are a few ways to acidify the urine?

What will this do?

Back 43

Cranberry juice, vitamin C, NH4Cl

By acidifying the urine, you increase ionization of weak bases, which will increase renal excretion of any drugs that are weak bases (important in overdose)

Front 44

What are a few ways to alkalize the urine?

What will this do?

Back 44

Sodium bicarbonate, acetazolamine

This will increase ionization of weak acids, increasing renal excretion of drugs that are weak acids (such as aspirin)

This is extremely important in overdose situations

Front 45

LD (loading dose) =

Back 45

LD = Vd x Cp / f


Vd is volume of distribution, Cp - Plasma concentration, F is the bioavailability

Front 46

(T/F) A loading dose takes into account the clearance

Back 46

FALSE..

Loading dose does not take into account the clearance, whereas the maintenance dose does!

Front 47

Maintance dose =

Back 47

Cl x Cp / F


Clearance x plasma concentration / bioavailability

Front 48

4 ways the body handles drugs (pharmacokinetics):

Back 48

Absorption
Distribution (this is where drug interactions occur)
Biotransformation – Metabolism (mostly liver)
Excretion
(ADME)

Front 49

The concentration at the _ is responsible for the intensity of effect

Back 49

site of action

Front 50

Lipophilic or nonlipophilic drugs are more readily absorbed?

Back 50

Lipophilic

Front 51

Transdermal route usually has a _ absorption rate, and is used for _

Back 51

very slow absorption, used for lack of first pass effect prolonged duration of action

Front 52

LDOPA, used in treatment of parkinson's disease gets absorbed through the membrane via what mechanism?

Back 52

facilitated diffusion

Front 53

Only_ drug is available for action at target tissues

Back 53

free (unbound)

Front 54

2 month old presents to the ER with yellowing skin and failure to thrive. Mother states she was seen a few days earlier and prescribed sulfamethoxazole. What do you expect to find in the baby's lab work?

Back 54

High levels of unconjugated bilirubin

Sulfonamides are contraindicated in neonates, because it displaces bilirubin in the plasma

Front 55

Non microsomal enzyme catalyzed reactions include _ and _

Back 55

hydrolysis (succinylcholine)

Alcohol metabolism

Front 56

What is the biggest subtype of P 450?

Back 56

3A4

Front 57

Rifamin induces _, causing _

Back 57

P 450 3A4

oral contraceptive failure

Front 58

Cimetidine inhibits _, causing _

Back 58

P450 2C9
--its an H2 antagonist

diazepam toxicity

Front 59

Beta Adrenergic receptors are _

MOA?

Back 59

g alpha s (increase adeylyl cyclase leading to increased cAMP)

Front 60

Alpha1 adrenergic receptors are _

MOA?

Back 60

g alpha q/11, Increases phospholipase C leading to Increase protein kinase C, IP3, Ca.

Front 61

Alpha 2 adrenergic receptors are _, What is the MOA?

Back 61

G alpha i. Decreases adelylyl cyclase activity leading to decreased cAMP

Front 62

Gas has (stimulatory/inhibitory) actions primarily mediated through activation of _ and release of the second messenger _ leading to _

Back 62

stimulatory
adenylyl cyclase (AC)

cAMP leading to the activation of PKA

Front 63

The beta-gamma subunit of Gai has been found to open _ channels in cardiac myocytes leading to _ and _ heart rate when the M2 ACh receptor is activated by ACh

Back 63

K+

hyperpolarization

decreased

Front 64

Tyrosine kinase receptors effect _ and regulate _

Back 64

cellular function, and regulate transcription genes involved in growth and differentiation

Front 65

Examples of endogenous activators of the tyrosine kinase receptor?

Back 65

insulin, epidermal growth factor, ANF, PDGF

(growth factors and insulin)

Front 66

Give an example of a cytokine receptor. What do they do?

Back 66

JAK,
regulates genes involved in synthesis and release of many inflammatory mediators

Front 67

What is the pathway for JAK?

Back 67

JAK gets activated after ligand binding, activated JAK phosphorylates STAT, STAT molecules dimerize and travel to the nucleus to intiate transcription of specific genes

Front 68

The binding affinity, or KD is the _

Back 68

concentration of drug required to bind ½ of the receptors in a fixed population

the higher the KD of the drug the lower its affinity for the receptor

Front 69

the _the KD of the drug the lower its affinity for the receptor

Back 69

higher

Front 70

_ is a characteristic property of a ligand to induce the receptor

Back 70

Efficacy

Front 71

Partial agonists have _ and efficacy _

Back 71

affinity and varying degrees of efficacy (less than 1)

Compare to full agonist that has affinity, and efficacy =1.

Front 72

Where do indirect antagonists work?

Back 72

They inhibit a biological response by acting at a site beyond the receptor, for example: Gq receptor normally triggers IP3 which releases Ca. An indirect antagonist would prevent the release of intracellular calcium

Front 73

competitive antagonists have _ but no _

Back 73

affinity but no efficacy

Front 74

A nonequilibrium competitive antagonist binds _ to the receptor via a _ bond

Back 74

binds irreversibly to the receptor via a covalent bond

Front 75

Allosteric antagonists reduce the affinity or efficacy of agonists by _

Back 75

binding to and altering a receptors conformation, therefore reducing the affinity or efficacy of agonists

Front 76

Graphs for dose response theory: linear or log?

Back 76

log!

has a sigmoidal appearance and the concentration range of linear is too large to be useful

Front 77

There is a direct link between potency and efficacy (T/F)

Back 77

FALSE

potency compares ED50 values (slope of a curve). How quickly a response is generated,

Efficacy (KD) looks at the plateau. It is a property of the drug/receptor pair to trigger a response

Front 78

An equilibrium competitive, or reversible antagonism causes a _ shift in the dose-response curve

Back 78

rightward shift

It takes a little more agonist to have an effect (decreased affinity), but will still reach same efficacy

Front 79

A nonequilibrium competitve antagonism (irreversible antagonist), will _

Back 79

have an apparent decrease in efficacy, (plateau is much lower than control)

Front 80

A noncompetitive antagonist will show _ (with regards to a response/dose curve)

Back 80

decrease in efficacy,

the ligand still binds normally, but the effect will be decreased, because these antagonists block somewhere further on down the pathway

Front 81

Thermatory sweat glands are controlled by the _ nervous system, post ganglionic neurons release _ which acts on _ receptors

Back 81

SANS

acetylcholine, muscarinic

This is an Exception to the rule that SANS post ganglionic release NE and act on adrenergic receptors

Front 82

Odd Muscarinic receptors are _, they are coupled to _,

Back 82

Excitatory

Coupled to Gq11, activate PLC, increase IP3 and DAG

Front 83

Even muscarinic receptors are _, they are coupled to _

Back 83

Inhibitory

Gi, which inhibits adenylase cyclase, decreased cAMP, and increased K Efflux

Front 84

M3 receptors are found in _, _ and _

Back 84

smooth muscles and glands, endothelium, and vascular smooth muscle

Front 85

M2 receptors are found in _

Back 85

cardiac tissue (SA and AV), as well as presynaptic and post synaptic terminals

Front 86

M1 receptors are found in _

Back 86

autonomic ganlgia, presynaptic nerve terminal, and CNS neurons

Front 87

Alpha 1 adrenergic receptors mediate _

Alpha 2 do what?

Back 87

Alpha 1 : mediates vasoconstriction

Alpha2 : inhibits secretion of NE, found in postsynaptic tissues

Front 88

Alpha 1 receptors are found in _, They act through what pathway?

alpha 2 neurons are found in _. They act through what pathway?

Back 88

postjunctional smooth muscle (contracts). Gq, stimulation of PLC (increas IP3, DAG)

presynaptic neurons (inhibits NE secretion). Gi inhibits AC ( decreased cAMP)

Front 89

Beta 1 receptors are found on _

Beta 2 receptors are found on _. They act through what pathway?

Back 89

heart (stimulation) - Gs (increase cAMP)

bronchial, uterine and vascular smooth muscle (relaxes). Gs - stimulation of AC

Front 90

Beta 3 causes _

Back 90

lipolysis

There are NO drugs that activate B3

Front 91

Vasoconstriction.....what receptor should you be thinking of?

Back 91

Alpha1!

Front 92

PT HAS SWEATING,DIARRHEA, COMITING, SALIVATION, HEART DYSRRHYTHMIAS, MENTAL CONFUSION, SYMPTOMS ARE SIMILAR TO….

Back 92

CHOLINERGIC RESPONSE!

Front 93

Mydriasis is caused by an increase in _

Miosis is mediated by _ and what receptor?

Back 93

sympathetic tone


PANS, M3 (this is constriction of sphincter pupillae)

Front 94

Blurred vision is a side effect of many _

Back 94

muscarinic antagonists

Front 95

Aqueous humor secretion is predominately under the control of _. What receptors are involved?

Back 95

SANS (constriction of vascular bed via alpha receptors reduces humor secretion, while dilation (beta 2) increases

Front 96

_agonists & _inhibitors enhance aqueous humor drainage

Back 96

Muscarinic

Acetylcholine esterase

Front 97

_ antagonists and _ agonists reduce aqueous humor secretion

Back 97

beta antagonists

alpha agonists

Front 98

When you look from your computer screen to on the far end of the room, your ciliary muscle (relaxes/contracts). This is because the _ nervous system is stimulating _ receptors

Back 98

relaxes

SANS, beta 2

(The predominant pathway is contraction for near vision by the PANS and M3 receptors)

Front 99

Lacrimal secretions have only _ innervation and have a _ mediated effect

Back 99

PANS, M3 mediated effect

Front 100

_ agents cause dry eyes

Back 100

Anticholinergic, (anti muscarinic)

Front 101

Broncholes have both _ and _ receptors

Back 101

M3 and B2 receptors

M3 causes constriction
B2 dilation

Front 102

The heart is innervated mostly by _ receptors, and also _

Back 102

Beta 1 (little Beta 2), and M 2 (inhibitory)

Front 103

The detrusor muscle relaxes thanks to _ receptors

The spnicter contracts due to _

Back 103

beta 2

alpha 1 receptors

Front 104

The detrusor muscle contracts thanks to _ receptors

Sphincter relaxes thanks to _ receptors

Back 104

M3

M2 or M3

Front 105

Renin release is increased by _ due to _ receptors

Back 105

SANS, Beta 1

(activation of alpha 1 will decrease renin secretion)