Basics

Front 1

Papaverine (source and use)

Back 1

Opium extract, vasodilator and GI muscle relaxant (colics)

Front 2

Digoxin (source and use)

Back 2

Foxglove extract, increases cardiac contractility (manage heart failure)

Front 3

Atropine source and class

Back 3

Atropa belladona, cholinergic muscarinic antagonist

Front 4

Lovastatin and Simvastatin source and use

Back 4

Asperigillus terreus, lowers cholesterol

Front 5

Cyclosporine use

Back 5

Immunosuppressant

Front 6

to filter through normal renal capillaries, how small must the object be?

Back 6

below 59-69 kDa. Albumin is around 67,000 Da, should not cross in healthy individuals

Front 7

To undergo passive diffusion (water soluble) through aquaporins, how small must the object be?

Back 7

Under 150-200 Da, or less than 8-10 A (0.8-1nm). Note connexins are like two aquaporins

Front 8

Which allows more passage of liposoluble products- stomach or intestine?

Back 8

Stomach. Intestine is lined with hydrophilic sugars

Front 9

In the stomach milieu, are acidic drugs or basic drugs more easily absorbed into blood stream?

Back 9

Acidic drugs, like COO- which are protonated in stomach acid to COOH and are now neutral and lipid soluble

Front 10

In the intestinal milieu, are acidic drugs or basic drugs more easily absorbed into blood stream?

Back 10

Basic drugs, which are non protonated/neutral

Front 11

pKa =

Back 11

pH at which 50% of ionization occurs

Front 12

T/F: Protein-bound drug fraction depends on the concentration of drug

Back 12

F

Front 13

T/F Acidic and neutral drugs bind to albumin or lipoproteins

Back 13

T

Front 14

T/F Basic drugs bind to Alpha-1 acidic glycoprotein

Back 14

T

Front 15

Intravascular body water percentage

Back 15

4%

Front 16

Most body water found in...

Back 16

intracellular water (40-44%)

Front 17

Extracellular water made up of...

Back 17

Intravascular (4%) and Interstitial (12-16%)

Front 18

What is volume of distribution?

Back 18

Mass (amount of drug / concentration drug in plasma)

Front 19

High Vd indicates....

Back 19

highly distributed to tissues. Thus, higher lipid solubility, lower rates of ionization, or low plasma binding

Front 20

Assumptions made in apparent Vd

Back 20

Assumes drug distributed uniformly throughout body, distributed uniformly in a single compartment, concentration in plasma is representative

Front 21

Drugs that reach the brain have a high or low Vd?

Back 21

High

Front 22

Clearance =

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Biotransformation + Excretion

Front 23

Phase 1 drug biotransformation

Back 23

Usually transforms drug into polar metabolite (water soluble). Unmasks functional group through oxidation/reduction/hydrolysis. Inserts OH. The enzymes that regulate this are CYP450 family. Substrate specific. Metabolites usually inactive, but sometimes active or even toxic! CYP3A4/5 most abundant- takes care of 50% of drugs.

Front 24

CYP2D6 metabolizes what?

Back 24

Codeine, Fluoxetine. Codeine is transformed in the body into morphine (10%). Codeine is a prodrug. St. John's Wort is an inducer of 2D6, which means more codeine will be transformed to morphine.

Front 25

CYP2E1 metabolizes what?

Back 25

Ethanol, acetaminophen. Ethanol is also an inducer of 2E1, which can result in more Acetaminophen being broken down and releasing metabolite NAPQI (toxic).

Front 26

What biotransformation process does alcohol deplete

Back 26

Alcohol depletes glucoronidation and sulfation (Phase II). This shunts acetaminophen into Phase II, which produces NAPQI! PLUS, alcohol inhibits gluthione, which neutralizes NAPQI.

Front 27

Infants have higher/lower body water

Back 27

Higher body water. Less lipophilic drug in in fatty tissue.

Front 28

Liver metabolism of drug capability highest in what age group

Back 28

Young adults

Front 29

Renal drug elimination capability highest in what age group

Back 29

Young adults

Front 30

How is clearance measured

Back 30

Volume of body fluid from which compound is removed, per unit of time (mL/min)

Front 31

What do we use to measure GFR?

Back 31

Measure creatinine (small) in urine or blood. 6000 Da. Eliminated very easily. Should be same in urine as in blood.

Front 32

What drugs are eliminated by tubular secretion?

Back 32

Penicillin, PAH. Higher in urine than in blood.

Front 33

What compound is reabsorbed in the tubules?

Back 33

Glucose. Should be lower in urine than in blood.

Front 34

IV sodium bicarb (alkalize urine) will help eliminate what kind of drugs?

Back 34

Acidic drugs, like herbicides, fluoride, phenobarbital, salicylates. DECREASES their half life

Front 35

Ammonium chloride accelerates elimination of what drugs?

Back 35

Weak basic drugs- amphetamine, morphine, propanolol, atropine

Front 36

Zero order kinetics, rate of elimination is saturable/not saturable

Back 36

saturable. Prototypical example- alcohol

Front 37

T/F. Most drugs fall into first order kinetics

Back 37

True, because given at low doses

Front 38

Drug half life usually follows what order kinetics?

Back 38

First order, and drugs decreases exponentially over time

Front 39

What is an allosteric activator (noncompetitive activator)?

Back 39

Drug that doesn't do anything by itself, but potentiates agonist effect. Binds to other site on receptor.

Front 40

What is an allosteric inhibitor (noncompetitive inhibitor)?

Back 40

Drug that doesn't do anything by itself, but decreases the agonist effect. Binds to other site on receptor.

Front 41

Benzodiazepines (Diazepam, Valium) and barbiturates (Phenobarbital) are non competitive agonists (allosteric activators) where?

Back 41

At GABA-A receptors.

Increase GABA activity. GABA slows down neurons.

Front 42

Memantine (Ebixa) is an allosteric inhibitor at what site?

Back 42

Glutamate NMDA receptors.

Inhibits glutamate's excitatory effect, so prescribed to prevent epilepsy, in dementia.

Binds to a different site on the NMDA receptor than glutamate does.

Front 43

Opening of ion channels does what to the cell?

Back 43

Depolarize it (ion go from high concentration to low concentration)

Front 44

How many subunits does ion channel have?

Back 44

2 alpha and 2 beta units (4). Each is one long coiled chain of AA with 6 transmembrane units.

Front 45

Lidocaine blocks what channels?

Back 45

Sodium channels. Prevents depolarization of neurons (no pain felt)

Front 46

Dihydropyridine mechanism?

Back 46

Allosteric antagonist to decrease opening of Ca++ channels. Slows heart and decreased contraction. Dilates vessels. For CV disease

Front 47

Fluoxetine (Prozac) and Loop diuretics (furosemide) both work how?

Back 47

Block symport

Front 48

Digoxin and ouabain both work how?

Back 48

Inhibit antiport (Na+/Ca++ exchange inhibitors).

Manage heart failure

Front 49

Difference between pump and transporter?

Back 49

Transporter and energy independent.

Front 50

Examples of energy dependent transporters (pumps)

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ATP-binding cassette (ABC) transporters, Na+-K+ ATPase (sodium pump inhibitors), MDR transporters

Front 51

What do false substrates do?

Back 51

Keeps enzyme busy. Produces abnormal metabolite.

Front 52

Why do azoles and penicillins interact ith Warfarin?

Back 52

CYP2C9 is supposed to break down Warfarin. Penicillin and azoles inhibit CYP2C9. Too much free warfarin, risk of bleeding out.

Front 53

Why do Phenytoin, Alcohol, and Ginseng interact with Warfarin?

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Those three induce CYP2C9, which breaks down warfarin. Too much warfarin broken down -> not enough warfarin, risk of stroke.

Front 54

How does Viagara work

Back 54

?

Front 55

What are the 4 types of receptors?

Back 55

Ligand gates channels (ionotropic- ex. nicotinic)

GPCRs (adrenergic, muscarinic)

enzyme-linked receptors

intracellular receptors (bind steroid hormones)

Front 56

What unit has the binding site in a ligand-gated channel?

Back 56

The alpha subunit. There are two of them (5 units altogether) so you really need two of the same molecule to bind at the same time to open the receptor.

Front 57

Where is the binding site on the alpha subunits of an ROC?

Back 57

The amino terminus

Front 58

What kind of receptor is a GABA-A receptor?

Back 58

ROC (ligand gated channel). Lets in Cl- through channel, to hyperpolarize neuron and decrease activity.

Front 59

Where is the binding site in a GPCR

Back 59

inside the pore (not outside). Ligand must be very small. In 3rd transmembrane unit (counting from n-term)

Front 60

Which receptor type is most abundant in humans?

Back 60

GPCRs

Front 61

What kind of receptor are adrenergic receptors?

Back 61

GPCR

Front 62

A stimulatory G protein (Gs) sets off what transduction pathway?

Back 62

When agonist binds receptor, G protein UNCOUPLES and activate AC in membrane. More cAMP, which activate kinases. Those kinases can either activate proteins, or activate an ion channel. It's more complex than potential-regulated ion channels.

Front 63

Describe the G(q) protein transduction pathway

Back 63

PLC cleaves the membrane phospholipid PIP2 into DAG and IP3. DAG diffuses in membrane to activate PKC which phosphorylates proteins. IP3 stimulates the release of Ca++ from ER. Calcium release also stimulates protein phosphorylation events.

Front 64

What are enzyme linked receptors?

Back 64

One transmembrane domain. N-term is ligand recognition site (external, so accomodates large ligands), catalytic domain at C-term.

Example: Tyrosine kinase receptors (RTKs), which bind large hormones such as GFs and insulin

Front 65

What is unique about isulin receptor dimerization?

Back 65

It occurs even before ligand binding, unlike other RTKs

Front 66

Example of serine-threonine receptor?

Back 66

Cytokine receptors

Front 67

Example of Guanylyl receptor cyclase?

Back 67

nitric oxide receptors (blood vessels)

Front 68

Differences between Class I and Class II intracellular receptors?

Back 68

Class I are in cytosol at rest (need chaperone); Class II are bound to DNA.

CLass I are homodimers; Class II are heterodimers.

Class I examples: estrogen, corticosteroid receptors

Class II examples: Vitamin D3, thyroid hormone receptors

Front 69

Difference between efficacy and potency

Back 69

Efficacy has to do with effect of drug; potency with the amount.

Front 70

How do we measure potency?

Back 70

EC50. On a dose-response curve, find 50% of max response, report what drug concentration was at that point

Less potent = higher EC50 = line shifted to the right (higher drug concentration needed)

Front 71

How do you measure efficacy

Back 71

Emax- find the highest response on the dose-response curve, report drug concentration

Front 72

Describe a partial agonist in terms of efficacy and potency

Back 72

Efficacy- the dose response curve with be short, because Emax cannot reach 100% response.

Potency- the EC50 will not be 50% response, but half of whatever the maximum response is (Emax)

Front 73

How do you measure therapeutic index (ratio)?

Back 73

TD50/ED50 (

Front 74

What is considered a low therapeutic index (ratio)?

Back 74

if TI <= 2. If taking double the median effective concentration (ED50) is the median toxic concentration (TD50)

Front 75

What does a graph of agonist + increasing doses of irreversible antagonist look like?

Back 75

With each increase in irreversible antagonist, Emax (efficacy) decreases

Front 76

List 3 mechanisms of decreased response to drug action NOT targeting receptors (pharmacokinetics)

Back 76

Increased metabolism of drug (barbiturates)

decreased biotransformation of prodrug (nitrates)

physiological adaptation (which do not change [drug] in plasma. Ex: thiazides- diuretics)

Front 77

List 3 mechanisms of decreased response to drug action targetting receptors? (Pharmacodynamics)

Back 77

Desensitization: phosphorylation (seconds or minutes)

Internalization- fewer receptors available (minutes)

Downregulation- destruction of receptors- absolute decrease in receptor # (hours/days). This is relevant to opioid, amphetamine, THC tolerance.

Front 78

How is bioavailability calculated?

Back 78

Fraction of unchanged drug (fu = fraction unbound) reaching systemic circulation, after administration by any route. (Unchanged circulating dose / administered dose)