N509 Pharmacology

Front 1

4 Factors that determine intensity of drug responses

Back 1

1. Administration
2. Pharmacokinetics
3. Pharmacodynamics
4. Sources of individual variation

Front 2

4 major pharmacokinetic processes

Back 2

1. Drug absorbtion
2. Drug distribution
3. Drug metabolism
4. Drug excretion

Front 3

Individual variation: 4 main sources

Back 3

1. Physiologic variables
2. Pathologic variables
3. Genetic variables
4. Drug interactions

Front 4

3 ways for drugs to cross the cell membrane

Back 4

1. Channels and pores
2. Transport system
3. Direct penetration of the membrane

Front 5

4 factors affecting drug absorption

Back 5

1. Rate of dissolution
2. Surface area
3. Blood flow
4. Lipid soluability
5. pH partitioning

Front 6

4 most common routes of drug administration

Back 6

1. Intravenous
2. Intramuscular
3. Subcutaneous
4. Oral

Front 7

Drug excretion: 2 main routes

Back 7

1. Renal routes
a. glomerular filtration
b. passive tubular reabsorption
c. active tubular secretion

2. Non-renal routes

Front 8

4 primary receptor families

Back 8

1. cell membrane-embedded enzymes
a. span the entire cell membrane

2. ligand-gated ion channels
a. each channel is specific to one enzyme

3. g protein-coupled receptor systems
a. receptor activates g-protein which activates effector

4. transcription factors
a. found inside the cell
b. response is delayed

Front 9

Agonists and Antagonists: distinguish between these

Back 9

1. Agonists: drugs that mimic the body's own regulatory molecules, or the effects of a naturally-occurring compound
a. these are molecules that activate receptors

2. Antagonists: drugs that block the actions of endogenous regulators
a. no effect of their own on receptor function, they work by preventing receptor activation

Front 10

Non-competitive and competitive agonists: define difference

Back 10

1. Non-competitive agonists bind irreversibly to receptors, which reduces the number of receptors available to agonists.

2. Competitive antagonists bind reversibly to receptors. They compete with agonists for receptor binding, whichever is present at highest concentration wins the receptor

Front 11

Therapeutic Index

Back 11

Measure of a drug's safety

TI = LD/ED

LD: average lethal dose
ED: dose needed to achieve therapeutic response

Low TI: not much room between these two doses

High TI: plenty of room between the doses

Front 12

3 types of drug-drug ineractions

Back 12

1. intensification of effects
2. reduction of effects
3. creation of unique response

Front 13

Basic mechanisms of drug-drug interactions

Back 13

1. Direct chemical or physical interaction (medicine with herbs, vitamins, etc)

2. Pharmacokinetic interactions (altered ADME)
Absorbtion, Distribution, Metabolism, Excretion

Front 14

FDA Category A drugs

Back 14

Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.

Front 15

FDA Category B drugs

Back 15

Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Front 16

FDA category C drugs

Back 16

Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Front 17

FDA category D drugs

Back 17

There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Front 18

FDA category X drugs

Back 18

Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Front 19

3 ways the renal system regulates blood pressure

Back 19

1. Filtration
2. Reabsorption
3. Active tubular secretion

Front 20

Name the 4 drug classes

Back 20

1. Sodium Channel Blockers
2. Beta Blockers
3. Potassium Channel Blockers
4. Calcium Channel Blockers

Front 21

Diuretics: What do they do, and what 3 kinds are there?

Back 21

These block sodium & chloride reabsorbtion at the renal tubules.

1. Thiazide Diuretics
2. Loop Diuretics
3. Potassium-Sparing Diuretics

Front 22

Thiazide (give example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 22

Hydrochlorothiazide
1. Acts at early distal convoluted tubule
2. B
3. Hypokalemia, Hyponatremia, Hyperglacemia
4. None mentioned

Front 23

Loop Diuretics (give example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 23

Forosemide
1. Acts at ascending loop of henle to block reabsorbtion
2. B
3. Hypokalemia, Hyponatremia, Hyperglacemia
4. Digoxin, Potas-sparing, Lithium

Front 24

Potassium-Sparing Diuretics (give example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 24

Spironolactone
1. Blocks sodium/pot exchange in distal nephron
2. B
3. Hyperkalemia, tumors, irregular menses, deeper voice
4. ACE inhibitors, Pot supp.

Front 25

Drugs acting on RAAS:
4 categories

Back 25

1. Renin Inhibitors
2. ACE Inhibitors
3. Angiotensin II Receiver Blockers
4. Aldosterone Antagonists

Front 26

Renin Inhibitors (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 26

Aliskiren
1. Inhibits renin directly-interferes with conversion of angiotensinogen
2. C/D
3. Angioedema, Hyperkalemia, Hypotension, GI issues, increased BUN/Cr values
4. Interferes with substrate 3A4 which inhibits metabolism of the drug--does not break down well

Front 27

ACE Inhibitors (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 27

Captopril, Ramipril
1. Inhibits ACE enzyme
2. C/D
3. 1st dose hypotension, cough, hyperkalemia, renal failure, neutropenia, fetal harm
4. Lithium

Front 28

Angiotensin II receptor blockers (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 28

Losartan, Valsartan
1. prevent angio-mediated vasoconstriction and aldosterone mediated volume expansion
2. C/D/D
3. Angioedema, fetal harm, renal failure
4. Reacts with diuretics, anti-hypertanseive agents, ant-inflamataries, potassium raising drugs

Front 29

Aldosterone antagonists:

Give two main types, mechanism of action, adverse effects

Back 29

1. Spironolactone
2. Eplereone

Block aldosterone receptors and promote excretion of Na + H20.

Adverse: hyperkalemia

Front 30

Spironolactone
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 30

1. Blocks aldosterone in distal nephron, retention of K+, increases Na excretion, binds with steroid receptors
2. D
3. Hyperkalemia, tumors,
4. Interacts with thiazides, agents that increase K+ levels

Front 31

Eplereone
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 31

1. selective blockade of aldosterone receptors
2. B
3. Hyperkalemia
4. Interacts with inhibiotrs of CYP3A4, drugs that increase K+levels, lithium

Front 32

Calcium-Channel Blockers
Give 2 main types

1. Give mechanism of action
2. Pregnancy Category

Back 32

Dihydropyridines and Non-dihydropyridines

1. Relaction of vascular smooth muscle causes vasodilation by preventing Ca from entering cells. Reduces arterial pressure and increases coronary perfusion--acts primarily on arterioles
2. C

Front 33

Dihydropyridines (example)
1. Adverse effects
2. Other drug interactions

Back 33

Nifedipine, Amidopine
1. Flushing, dizziness, headache, peripheral edema, reflex tachycardia (greater risk than non-dihydropyridines)
2. Interacts with beta-blockers

Front 34

Non-Dihydropyridines
1. Mechanism of action
2. Adverse effects
3. Name the 4 sub-categories

Back 34

Phenylalkylamine, Benzothiazipine
1. suppression of SNS influence on heart and blood vessels
2. Constipation, dizziness, flushing, headache
3. Beta blockers, Alpha blockers, Alpha/Beta blockers, Andrenogeric Neuron blockers

Front 35

Beta Blockers (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 35

proranolol, metoprolol
1. blockagde of cardiac and juxtaglomerular beta 1 receptors, suppress reflex tachycardia caused by vasodilators
2. varries
3. brachycardia (decreased AV conduction as well) decreased atrioventricular conduction, reduced contractility, bronchoconstriction, asthma excaberator
4. other hypotensives, CCBs, Digoxin, hypoglycemic agents

Front 36

Alpha Blockers (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 36

doxazosin, tarazosin
1. prevents stimulation of alpha receptors on arterioles and veins
2. C
3. orthostatic hypotension (largest effect--also worst with first dose), reflex tachycardia, inhibition of ejaculation, nasal congestion
4. PDE-5 inhibitors (viagra, cialis, etc) and other hypotensives

Front 37

Alpha/Beta Blockers (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 37

Carvidalol, labetalol
1. promotes dilation of areterioles & veins, reduces heart rate and contractility, suppresses release of renin
2. C
3 &4: Combine effects and drug interactions of Apha and Beta-blockers

Front 38

Centrally-acting Alpha 2 antagonists:
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects

Back 38

Clonidine, methyldopa
1. Acts in brainstem to suppress sympathetic outflow to heart and blood vessels
2. C/D, B
3. dry mouth, sedation, hepatoxicity (liver disorders) **can cause hypotension if removed abruptly--works at brainstem

Front 39

Adrenergic Neuron Blockers (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 39

Reserpine
1. Decrease BP through acting in terminals of post-ganglionic symptomatic neurons
2. C
3. depression, nasal congstion, bradycardia, orthostatic hypotension, GI issues, erection killer
4. Digoxin, levodopa, other hypotensive agents

Front 40

Direct-acting vasodilators (example)
1. Give mechanism of action
2. Pregnancy Category
3. Adverse effects
4. Other drug interactions

Back 40

Hydralazine, minoxidil
1. promotes dilation of arterioles
2. C
3. reflex tachycardia, expansion of blood volume, Na/H20 retention, cardiac tamponade, hypertrichosis (excessive hair growth). Minoxidil = 1 more issue: pericardial effusion (fluid buildup)
4. Interacts with other hypotensives

Front 41

Cardiac Glycosides (example)
1. Give mechanism of action
2. Adverse Events

Back 41

Digoxin is the only drug of this class approved in US
1. Increases miocardial contractility, increasing cardiac output
2. Mechanism of action can also cause severe dysrhytmias, therefore these are 2nd-line agents. K+ and digoxin are antagonistic competitors for same binding sites--K+ high=reduced therapeutic benefit, K+low=hypokalemia

*this drug is distributed widely and crosses placenta, ultimately eleminated by renal system. Half-life of 1.5 days

Front 42

Heart Failure Management:

Four drugs to try

Three drugs to avoid

Back 42

GIVE: 1. ACE Inhibitors, ARMS 2. Aldosterone Antagonists 3. Beta Blockers 4. Digoxin

AVOID: 1. Antidysrhythmic agents 2. Calcium-channel blockers 3. NSAIDS

Front 43

4 Stages of Heart Failure

Back 43

A: Asymptomatic, but high risk (diabetes, hypertension, family) MGT: reduce risk

B: Asymptomatic, but structural issues. MGT: prevent symptomatic HF

C: Symptoms with structural heart disease. MGT: releave symptoms, improve funct capacity, slow card remodeling, prolong life. Give diuretics, ACE, B-block, Digoxin

D: Advanced structural issues. Repeated hospitalization necessary. MGT: New Heart!

Front 44

Angina Pectoris: Define

1. Give 2 goals of drug therapy

2. Give 3 types

Back 44

02 supply not enough to meet heart demand

1. Prevent MI, prevent M ischemia & pain

2. Variant, Stable, Unstable

Front 45

3 families of anti-anginal agents and their mechanism of action

Back 45

1. Organic Nitrates
decrease 02 demand by dilating veins, decreasing preload

2. Beta Blockers
decrease 02 demand by decreasing heart rate and contractility

3. Calcium-channel blockers
decrease 02 demand by dilating arterioles, decreasing afterload

Front 46

Antiarrythmics: name two types and two fundamental causes

Back 46

1. Tachydysrhythmias: HR increase, this one is most common and responds best to drug therapy.

2. Bradydysrhythmias

2 causes:
1. Disturbance in automaticity
2. Disturbance in conduction

Front 47

Vaughan Williams classification of antidysrhythmic drugs: Name all four

Back 47

1. Sodium: slow contraction in atria, ventricles

2. B-blockers: lower automasticity (SA) conduction (AV) contractility (A&V)

3. K-ch blockers: lower repolarization

4. C-ch blockers: lower automasticity (SA) conduction (AV) contraction (A&V)

Front 48

Class IA antiarrythmics:
1. Give Example
2. Give Method of Action
3. Adverse effects
4. Drug interactions

Back 48

1. Quinidine

2. Blocks Na channels, slows impulse conduction, delays repolarization, blocks vagral input to heart, widens QRS, prolongs QT, used against supraventricular and ventricular dysrythmias

3. diarrhea, cardiotoxicity, arterial embolism

4. Digoxin

Front 49

Class IB antiarrythmics:
1. Give Example
2. Give Method of Action
3. Adverse effects

Back 49

1. Lidocane

2. blocks cardiac sodium channels, slows conduction in atria, ventricles, HIS purkinje system, minimal EKG changes. Give to help ventricular dysrhythmias

3. CNS efects, drowsiness, confusion

Front 50

Class IC antiarrythmics:
1. Give Example
2. Give Method of Action
3. Adverse effects

Back 50

1. Flecainide or Propafenone
2. block Na channels and delay ventricular repolarization
3. Same as IA/IB

Front 51

Class II Antiarrythmics
1. Give Example
2. Give Method of Action
3. Adverse effects

Back 51

1. Propranadol, Acebutolol, Esneolol, Sotalol
2. Decreases automatacity of SA node, decreases myocardial contractility, slows ventricular rate
3. heart block, heart failure, AV block, hypotension, sinus arrest, bronchospasm

Front 52

Class III antiarrythmics:
1. Give Example
2. Give Method of Action
3. Adverse effects

Back 52

1. Bretylium
2. Delays repolarization of fast potentials, prolongs QT interval, used for V-fib and V-tach
3. Hypotension

Front 53

Aminodarane:
1. Class
2. Mechanism of action
3. Adverse Effects
4. Metabolization

Back 53

1. Class III antiarythmic
2. lowers contractility, conduction velocity.
3. Optic neuropathy, pulmonary toxicity, cardiotoxicity
4. Highly lipid soluble, metabolized in liver (CYP34A)

Front 54

Class IV Antiarythmics:
1. Give Example
2. Give Method of Action
3. Adverse effects
4. Drug interactions

Back 54

1. Verapamil, diltiazem
2. delay AV node conduction, lower myocardial toxicity, prolong PR interval, slows ventricle rate
3. Bradycardia, hypotension, AV block, HG, peripheral edema, constipation
4. Digoxin, b-blockers

Front 55

Anti-hyperlipidemics

Name 4

Back 55

1. HMG-CoA reductase inhibitors
2. Bile-acid sequestrants
3. Nicotinic acid (niacin)
4. Fibrates

Front 56

HMG-CoA reductase inhibitors

1. Give Example
2. Give Method of Action
3. Adverse effects
4. Contraindications

Back 56

1. STATINS!
2. treatment of hypercholesterolemia--reduces proceedures like CABG/PTCA. This is an inhibitor of HMG-CoA reductase, thereby reducing cholesterol synthesis, and increases LDL receptors on hepatocytes increasing removal of LDL from blood. Also promotes plaque stability and reduces inflamation at plaque site

3. Myopathy, increased liver enzymes. ** Must do liver and renal workup before giving this drug, as it is metabolized rapidly in the liver and secreted in bile. Significant amounts found in urine.

4. Pregnancy (X), liver disease

Front 57

Nicotinic Acid (Niacin)

1. Give Example
2. Give Method of Action
3. Adverse effects
4. Contraindications

Back 57

1. Niacin

2. Reduces major coronary events and total mortality. Can be given immediate, sustained, and extended release.

3. Flushing of skin, GI, hyperglycemia, hyperuremia

(PREG: C)

4. Liver disease or gout, perhaps diabetes

Front 58

Bile Acid Sequestriants

1. Give Example
2. Give Method of Action
3. Adverse effects
4. Contraindications

Back 58

1.

2. Reduce coronary events and CHD mortality

3. Decreases absorbtion of digoxin, warafin, antibiotics

(PREG: B)

4. Bowel obstructions, TG level >400

Front 59

Fibric Acid Derivatives

1. Give Example
2. Give Method of Action
3. Adverse effects
4. Contraindications

Back 59

1. Fibrates

2. Decreases plasma TG content, lowers VLDL levels, raises HDL levels

3. Rashes, GI, glalstones, myopathy, liver injury

(PREG: C)

4. Severe renal or hepatic disease, also reacts with warfarin, statins

Front 60

EXETIMIBE:

1. Give Example
2. Give Method of Action
3. Adverse effects
4. Contraindications

Back 60

1. Tradename: Zetia

2. Inhibits cholesterol absorption, lowers LDL, raises HDL, lowers TG

3. Myopathy, hepatitis, pancreatitis, thrombocytopenia

(PREG: C)

4. Statins, fibrates, warfarin, bile-acid sequestriants