Download FUN2: 10:00-11:00 Scribe: Joan

FUN2: 10:00-11:00
Scribe: Joan-Marie Manolakis
Monday, December 1, 2008
Proof: Teresa Kilborn
Dr. Pillion
Pharmacology
Page 1 of 5
Dental-Optometry Pharmacology
I. Introduction [S1]: He will use a Socratic method. We will be responsible to medicate people in the future and
everything that we do can interact with the drugs they’re taking. Sometimes changing a person’s medical therapy can
cause unexpected changes and that at first wouldn’t make much sense. Today, think about how the body is
introduced to and handles drugs. Someone once told him that pharmacology is just one big dose-response curve.
II. Concepts for you to learn: [S2]
a. What are drugs?
i. Response: things you take when you are sick.
ii. Professor asks: Is a glass of water a drug?
1. Why not? In a way it is because if you take much or too little there will be bad affects. This is a
common link with drugs. The right amount causes a favorable response.
iii. What are drugs?
1. Response: a synthetic.
2. Synthetics made by drug companies to mimic hormones or normal chemicals.
3. It mimics the drugs’ structure. Water does not mimic insulin because they have two different
functions.
4. There is a structure-function relationship.
5. For a drug to work, it’s a chemical with a certain structure. Two different structures do two different
things in the body.
6. Structure is determined by bonding properties.
7. Splenda is a drug. It is sugar that is altered. It’s a glucose molecule with chlorides in place of
hydrogens, and the body doesn’t handle it. It goes in your mouth and goes right through you. It
mimics the structure of sugar and fits on the same receptors on our taste buds.
8. A receptor is a binding site made of mostly proteins because they are big and can fold into certain
shapes. He relates receptors to a lock and key. The one that fits the lock will make it unlock and
work.
9. Sometimes drugs are made to go into the keyhole and not work on purpose because we want to
block a reaction from taking place. We use this to block bacterial or tumor cell growth.
10. Sometimes people don’t make enough thyroid hormone and have a hypothyroid problem. We
would give them thyroid hormone (or at least a drug that looks like it) so it’ll fit into the receptor and
does what thyroid hormone would do. Hyperthyroidism can be combated by an antagonist. Its
presence prevents thyroid hormone from binding to its receptor. You block the affect. It is a
competitive reaction. The more antagonist present, the more you can block the affect. If you have
too much antagonist, you become hypothyroid. You want to give the right amount of dose.
11. This is difficult because the body metabolizes the drugs throughout the day.
iv. Not all drugs are taken orally. Example: insulin. It is taken by injection not orally because it you want it to
get into the bloodstream. It’s different because it’s made of amino acids, it’s a protein or peptide. If eaten,
the body will digest it in the stomach.
v. If you eat a cheeseburger, your body must handle proteins, lipids, fats, and carbohydrates. If it can’t
handle it, it’ll leave the body. We eat them because we like them, and they provide nutrients.
vi. Respiration takes place every second every day. It gets out poisonous CO2 and allows for the intake of
oxygen. It goes to the lungs and exchanges on hemoglobin and is carried to the body.
1. The oxygen allows for energy production.
a. Oxygen plus organic compounds produces energy.
b. Example: campfire. You add oxygen and wood (carbohydrate) and get heat, CO2, and
water. The same thing happens in the body. The body produces heat and is continuously
losing oxygen and burning carbohydrates. This keeps our body at a constant temperature
(37 degrees). The energy produced is harvested in ATP molecules.
vii. In the mouth, we chew food to break it down. Saliva has enzymes. In the stomach the hydrochloric acid,
trypsin, and pepsin. Trypsin and pepsin break the proteins into amino acids so they may be used for
protein synthesis. In the small intestine, the amino acids are absorbed.
1. Starch molecule-made of hundreds of glucoses linked together. Break it down and absorb the
glucoses. They are now available for energy.
viii. Drugs taken orally: aspirin, penicillin, etc. Drugs not taken orally: preparation H, nasal decongestant,
asthma drug, poison ivy creme, etc.
1. Sometimes it’s better to put a drug into a certain route because it will work better in that route.
ix. Animals are necessary for testing drugs because sometimes it will do its function but may cause cancer or
other adverse effects.
III. Case #1 [S3]
FUN2: 10:00-11:00
Scribe: Joan-Marie Manolakis
Monday, December 1, 2008
Proof: Teresa Kilborn
Dr. Pillion
Pharmacology
Page 2 of 5
a. Five students in the class have a headache this morning after a late night of partying.
b. He proceeds with a dose response curve using Excedrin first. The active ingredient in Excedrin is aspirin. Dose
is on the x axis and response is on the y axis. He also uses ibuprofen and Aleve (Naproxen) as examples.
c.
d. Note: He points out, “You take the lowest amount that works.”
e. The cardinal rule of pharmacology: START LOW AND GO SLOW. Start with the lowest dose possible of a
drug and then increase.
f. Point of the curve:
i. Potency vs. efficacy
ii. Potency: what amount gives half the max response
iii. Efficacy: what is the maximum response you can achieve
iv. Our Graph: Efficacy of these drugs is the same because they have the same highest response. Potency is
different, in 3rd drug you need two pills to get the ½ max response and in the 1st drug you only need to take
one pill to get the ½ max response. It is not more efficacious, but it is more potent.
v. If a drug never gets to the 100% maximum relief, it’ll have lower efficacy but may be more potent.
vi. Saying a drug is more potent, really doesn’t say that much. Efficacy matters more
g. Dosing:
i. Two regular strength aspirin=650 mg (325 mg each). You take two every four hours =3900 mg through the
day
ii. Extra strength Tylenol: 500 mg each x 2=1000 mg every 6 hours so you take 4000 mg in a day
iii. They give the same amount of drugs in a bigger dose less frequently or a smaller dose more frequently.
iv. The level of the drug in the blood stream will look like a wave. It’ll jump rapidly and then fall.
v.
h. The level of the medication will fall below the threshold for it to work, so you must take another dose. Each time
you take another dose, it’ll go higher than the last dose. You can’t take too much too fast. If you take more
every six hours, the shape of the curve would go higher and last longer because there is more there.
i. The drug is being metabolized and eliminated. If not, the level would remain very high in the blood. However,
lead and DDT cause toxicity and stay in the body because they can’t be eliminated.
j. Alcohol produces a straight line, not a curved line. It is a steady rate of decline. They can see how much you
have metabolized and figure out your previous alcohol level.
k. Dose-response relationship [S2]
l. Toxicity
m. Therapeutic level of drug
n. Absorption
o. Distribution
p. Metabolism
q. Elimination
r. Potency
FUN2: 10:00-11:00
Scribe: Joan-Marie Manolakis
Monday, December 1, 2008
Proof: Teresa Kilborn
Dr. Pillion
Pharmacology
Page 3 of 5
a. Efficacy
II. SAMPLE CASE #2 [S6]
a. Mrs. N is a 72 y.o. female with the following medical problems:
i. Hypertension (HTN)
ii. Hyperlipidemia
iii. Diabetes mellitus (type 2), diet-controlled
iv. Chronic obstructive pulmonary disease (COPD)
v. Congestive heart failure
vi. Non-ulcer dyspepsia
vii. Insomnia
viii. Glaucoma
ix. Osteoarthritis
x. History of tobacco abuse
b. Consider: When selecting a drug, practitioners need to think about the full menu. There are several choices, but
you must understand which is the most appropriate for the patient.
III. The Menu Method [S8]
a. Selecting drug treatment is like selecting a meal from a menu
b. Kid’s Menu (only a few choices) vs. Full Menu (many choices)
IV. Kid’s menu: (one drug for one problem) [S9]
a.
PROBLEM
DRUG
i. For high blood glucose: Insulin
ii. For high cholesterol:
Atorvastatin
iii. For high blood pressure: Hydrochlorothiazide
iv. For moderate pain:
Aspirin
v. For severe pain:
Morphine
V. Adult menu: (Select from a variety of drugs, tailor the choices to best fit the patient) [S10]
a. Don’t memorize today. There are many drugs available, but you will be able to decide which is the right drug for
the patient.
b. For high blood glucose: Insulin
Lyspro-insulin
Glyburide
Apidra insulin
Metformin
Regular insulin
Rosiglitazone
NPH insulin
Pioglitazone
70:30 NPH:regular
Acarbose
70:30 NPH:lyspro
Avandamet
50:50 NPH:regular
Exenatide
Glargine insulin
Amylin
Levemir insulin
Note: Know the abbreviations for the drugs. You will hear more about this later in the week.
c. Some drugs may be taken only once a day (qam) because it may be metabolized more slowly or have a long
lasting affect at its target site. [S14]
A. Hydrochlorothiazide – thiazide diuretic – useful in the treatment of HTN (usually in combination with another
agent) and edema secondary to CHF. It inactivates a sodium chloride channel and lasts a long time. You try a
dose amount, and if it’s not affective then increase the dose. After raising the dose numerous times, you may
have to switch the drug or add another drug in addition.
B. Long-acting nifedipine – calcium-channel blocker – useful in the management of HTN
C. Atorvastatin – HMG co-A reductase inhibitor – statin that lowers cholesterol, powerful anti-lipidemic medication
D. Theophylline – a methylxanthine derivative – caffeine-like drugs used to open the lungs in a person with asthma
and is useful in the management of COPD
E. Combivent – contains albuterol (-adrenergic receptor agonist) and ipratropium (muscarinic cholinergic receptor
antagonist) – useful in the treatment of COPD as a bronchodilator. These are given at the same time because
they get a synergistic effect by working on two systems in opposite ways.
a. You can’t put all of her drugs in the inhalant spray because it may not be a direct route for some
of her maladies.
F. Prednisone – a corticosteroid – many uses – here utilized to treat the inflammation resultant from COPD and
osteoarthritis
G. Ranitidine – an H2 histamine receptor antagonist – useful for the treatment of non-ulcer dyspepsia
H. Pilocarpine – a muscarinic cholinergic receptor agonist – useful in the treatment of both narrow and wide-angle
glaucoma
FUN2: 10:00-11:00
Scribe: Joan-Marie Manolakis
Monday, December 1, 2008
Proof: Teresa Kilborn
Dr. Pillion
Pharmacology
Page 4 of 5
I. Timolol – a -adrenergic receptor antagonist – useful for the treatment of glaucoma
J. Mylanta – an antacid - useful for the treatment of non-ulcer dyspepsia
K. Diazepam – a benzodiazepine – useful in the treatment of insomnia
L. Interval History
M. Mrs. N falls [S12]
a. Mrs. N reports having a fall 2 days ago. The patient states that she was walking across her living room
when she slipped on a throw rug, fell to the ground and sustained an injury to her right ankle. There was
no associated chest pain, palpitations, worsening of her baseline shortness of breath, headache, double
vision, difficulty speaking, or loss of consciousness, and Ms. N injury to her eye or mouth. Anything here
that may indicate a medication problem?
N. Mrs. N is currently taking the following drugs: [S11, S14]
1.
Hydrochlorothiazide 25 mg qam-changes the sodium reabsorption and causes a diarrhesis (urinate a lot
which lowers blood pressure)
2.
Long-acting nifedipine 30 mg qd-blocks calcium channels in smooth muscles and causes dilation in the
blood vessels and falling blood pressure
3.
Atorvastatin 10 mg qhs-inhibits HMG co-A reductase
i. HMG co-A reductase is an enzyme involved in lipid synthesis and makes cholesterol. A drug inhibits an
enzyme rather than an ion channel.
ii. Aspirin-inhibitor of cyclo-oxygenase. Many drugs are enzyme inhibitors.
4.
Theophylline SR 400 mg bid- inhibits phosphodiesterase. Phosphodiesterase takes cAMP and makes it
AMP. cAMP is a second messenger (think fight or flight response). The lungs expand when the body has a fight
or flight response. If you inhibit the enzyme that breaks down cAMP, the lungs open up long term. If you have
COPD, the drug will cause a patient’s lungs to open up. Additionally, it will cause his/her heart rate to go up, and
if he/she starts to have difficulty breathing, he/she needs to take more. This can lead to other problems.
5.
Combivent (albuterol and ipratropium) metered dose inhaler 2 puffs qid.- contains albuterol (adrenergic receptor agonist) and ipratropium (muscarinic cholinergic receptor antagonist) – useful in the treatment
of COPD as a bronchodilator
i. A normal molecule that would bind to a beta-adrenergic receptor would be adrenaline (epinephrine). It
is an agonist. It binds and has an effect. It opens up the lung.
ii. Cholinergic and adrenergic (Acetylcholine and adrenaline) have opposite affects.
iii .Adrenaline speeds up heart rate and acetylcholine slows it down, etc.
iv. While sitting in class, acetylcholine is in control. Adrenaline may overtake the acetylcholine if you’re
nervous about being called on.
v. To open up the lungs, you can put in a molecule that looks like adrenaline or put in one that looks like
acetylcholine but doesn’t do what it does (a cholinergic antagonist or adrenergic agonist). Both will open up the
lungs.
vi. A beta-adrenergic receptor blocker (antagonist) will lower heart rate. You could also give a cholinergic
agonist.
6.
Prednisone 10 mg qam.- steroid, causes an anti-inflammatory effect. Asthma improved but they were
short and developed other complications. Now inhaled steroids are used for people with asthma because less
gets into the bloodstream.
7.
Ranitidine 150 mg qhs.-an antagonist of the histamine receptor.
i. Nose and stomach-antihistamines are active. The histamine in the nose causes nasal congestion.
ii. In the anti-histamines are a decongestant: H1 receptors.
iii. The antihistamine receptor in stomach blocks the secretion of acid. The histamine in the stomach
causes acid production.
iv. Histamine binds to both receptors.
v. The receptor in the nose can be blocked without affecting the one in the stomach.
vi. Two systems have multiple receptors: the two receptors that both bind histamine and the cholinergic
receptor (acetylcholine of different types) and the adrenergic receptors.
1. Adrenergic receptors are broken into alpha 1 and alpha 2 and beta 1 and beta 2 (others are
coming)
2. The receptors in the heart are beta 1 that bind adrenaline and increases heart rate.
3. In the lung they are beta 2 receptors. It binds adrenaline and makes the lungs dilate.
4. That’s why we can make drugs that work on our heart and not on our lungs or vice versa.
5. If a beta adrenergic agonist in for the lungs and have problems breathing, so it’s taken over and
over again, the level in the bloodstream goes up and starts to affect the heart because it looks
like adrenaline and will bind to the beta-1 receptor in the heart.
FUN2: 10:00-11:00
Scribe: Joan-Marie Manolakis
Monday, December 1, 2008
Proof: Teresa Kilborn
Dr. Pillion
Pharmacology
Page 5 of 5
6. When someone takes too much inhaler, their heart rate goes up because there is a receptor in
the heart for the same molecule, it just has higher affinity for the receptor in the lungs. If the dose
is very high, it’ll hit the lungs and the heart.
7. Side effect-what happens in other organs that you don’t want to happen.
8. When you think about side effects, you try to avoid them. You can make a therapeutic index and
do a dose-response.
a. When you take too many aspirins, you start to have more toxicity.
b. Amount that gives 50% of toxicity= TD 50 (toxic dose 50)
i. Measurement of toxicity: difference between affective dose and therapeutic dose.
c. Exception: chemotherapy for a patient with breast cancer. The effective and toxic dose
are very similar. The TD 50 for chemo may be lower than the effective dose. The
therapeutic or safety range may be nill. We would only use this in exception cases.
8. Pilocarpine HCL eye drops 4% 1 gtt ou qid.-treatment of glaucoma. We put in an adrenergic antagonist and a
cholinergic agonist. In the eye, the opposite is true from what was seen above.
9.Timolol eye drop 0.5% 1 gtt ou bid.
10. Mylanta 1 tablespoon, before meals, prn.-neutralizes acid
11. Diazepam 5 mg hs, prn, for sleep.-treats insomnia
12. Insulin 10 units 70:30 NPH: regular, bid
A. Concern: she is taking a lot of drugs, there is a chance she is not taking all of them everyday or can’t afford the drugs,
or have run out.
B. You have two choices in practice for a patient who hasn’t responded well to therapy: either up the dose or ask if it was
taken as directed
C. Many of these drugs bind to albumin. It serves as a sink that these drugs can stick to.
a. Example: Someone with epilepsy was given a pain reliever. Both the antiepileptic drug and pain medication
bind to albumin. Thus she may have too much or too little antiepileptic drug in her blood. It was not about the way the
drug worked, rather it was more about how it is carried in the blood stream.
b. Example: A lady on a blood thinner. You give her pain medication and she has a stroke because you’ve
displaced the blood thinner that’s bound to the albumin.
[end 60:33]