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Pharmacology > Intro To pharmacology > Flashcards

Intro To pharmacology Flashcards

1
Q

Define Pharmacology

A

The branch of medical science that deals with the interaction of drugs, diagnostic agents, environmental agents and toxic substances within the body.

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2
Q

Medicine in the 1800s

A

Allopathy - fatal or poisonous treatments

Homeopathy- activity enhanced by dilution Sam H

Osteopathy - manipulation of musculoskeletal system surgery less drugs ATStill

Chiropractic- diagnosis and treatment skeletal system spine D Palmer

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3
Q

Revolutionary Developments

A 
Natural product Isolation: Morphine cocaine
Ether: Revolutionized surgery
Fundamental drug receptor theory
synthetic chemistry
Penicillin 40s anibioticd
Thorazine : Mental illness
Barbiturates: 
SSRI Fluoxetine: drugs could help people feel better even if they weren’t ill
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4
Q

Major Branches of Pharmacology

A

Pharmacodynamics

Pharmacokinetics

Pharmacotherapeutics

Pharmaceutics

Toxicology

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5
Q

Pharmacodynamics

A

Actions of drugs on the body

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6
Q

Pharmacokinetics

A

Actions of Body on the drugs

ADME

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7
Q

Pharmacotherapeutics

A

Use of drugs to treat disease

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8
Q

Pharmaceutics

A

Toxicology

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9
Q

Pharmacokinetics

A

The qualitative description of the time course for absorption distribution, metabolism and excretion of drugs

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10
Q

Pharmacodynamics

A

The quantitative description of the biochemical and physiological effects of drugs and the mechanisms underlying these effects.

Therapeutics, side effects, toxic effects

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11
Q

See slide 16 -20

A

Know Slide 16-20

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12
Q

What is the importance of the blood level of the drug?

A

For most drugs the duration of action is related to the time the blood level is above Minimal Effective Concentration.

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13
Q

Explain how Pharmacokinetics and Pharmacodynamics intersect.

A

Too high of a concentration of drugs can have toxic effects

But the minimal effective concentration keeps you in the therapeutic range.

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14
Q

What are the factors in determining blood levels of a drug? (4)

A 
Absorption
-Amount of given Dose
-Route of Administration
-Rate and Extent of Absorption 
Distribution to Tissues
-Sites if action
-Sites or Loss
Metabolism Rate
Excretion Rate
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15
Q

What are the common routes of drug administration:

A

Oral
Parenteral
Other

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16
Q

What is the most common route of drug Administration

A

Oral ( low bioavailability)

Sublingual ( bypass portal circulation) nitroglycerin

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17
Q

Parenteral routes of drug administration ( high bioavailability)

A

Intravenous: must be water soluable

subcutaneous: must be non irritating

Solid pellets: hormones contraceptives

Intramuscular: deltoid Bastia lateralis better than glutes

Intra-arterial: localize cancer treatment

Intrathecal: epidural bypass blood brain barrier

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18
Q

Other routes of drug administrations

A

Transdermal: patch

rectal: 50% drug bypass liver

Pulmonary: Inhaler

Topical: Skin cream

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19
Q

Absorption: Passive diffusion

A

Most common mechanism of absorption.

Diffusion accross the concentration gradient by solubility in lipid bilayer.

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20
Q

Passive Transport types:

A

Paracellular Transport

Diffusion

Facilitated Diffusion: carrier mediated
With the chemical gradient

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21
Q

Active Transport types:

A

Primary: ABC Transporter
Na and K ATPase

secondary: SLC cotransporters
Against the gradient
Requires energy

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22
Q

What is P- glycoprotein?

ABcB1 or MDR1

A

It an active transporter that exports bulky neutral cationic compounds from cells.

Steroids and drugs

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23
Q

Paracellular Transport ( passive transport)

A

The passage of solutes throughout intracellular gaps

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24
Q

Passive diffusion factors

A

Concentration gradient
Small molecular weight
Lips soluble water soluble
pH- only non-ionized forms can cross membranes

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25
Q

What is the Bronsted Lowry Acid-Base theory?

A

Acids are Proton Donors
Bases are Proton acceptors

Acidic Drugs will be ionized at high pH
Basic drugs will be ironized at low pH

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26
Q

What is the Henderson Hasselbalch equation?

A

PKa= pH + log (protonated/unprotonated)

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27
Q

What is the Henderson Hasslebalch equation for acids?

A

PKa= pH + log (noionized/ionized)

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28
Q

What is the Henderson Hassaelbalch equation for bases?

A

PKa=pH + log (ionized/noionized)

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29
Q

What is the take home message for Henderson Hasselbalch?

A

If a pH gradient exists across a membrane, the drug will accumulate on the side of the membrane where the drug will be most ionized.

30
Q

Practice Henderson Hasselbalch

A

Practice Henderson Hasselbalch

31
Q

Why is the small intestine the main site of absorption for most drugs?

A

Large surface area

pH gradient along various segments

32
Q

What is first pass metabolism

A

When drugs are taken orally and absorbed in the small intestine they must first pass through the liver. This limits bioavailability.

33
Q

What is bioavailability?

A

The Amount if an orally administered drug that reaches systemic circulation.

34
Q

What formulations help maintain bioavailability?

A 
Enteric coating ( aspirin)
Sustain release: metirpolol
35
Q

What are prodrugs?

Give an example?

A

Inactive compounds that are converted into their activated form by metabolism.

Example: Ace inhibitors
Enalapril inactive until converted into enalaprilat by esterases.

36
Q

How are drugs distributed?

A

Blood flow to organs.

37
Q

Which organs receive the most drug?

A

Highly perfused organs

Heart brain lungs liver kidney

38
Q

What are two specialized barriers in drug distribution?

A

Blood Brain barrier
- capillaries have astrocytes
And Tight junctions

Placental Barrier: weak barrier

39
Q

What role does albumin play in drug distribution?

A

albumin: a major carrier for acidic drugs

Alpha1- acidic glycoprotein binds to basic drugs

Bound drug cannot be distributed or eliminated

One drug can displace another from binding sites.

40
Q

Define Volume of Distribution ( Vd)

A

Vd is the measure of how a drug is distributed in the body.
Not a true volume.

Refers to the volume in which a drug would have to be dissolved in order to account for all the drug at the concentration present in plasma.

If it is not in the plasma it must be in the tissues.

41
Q

What is the equation for Vd

A

Vd=Amount of Drug in the Body divides by the concentration of drug in plasma (Cpss)

Intravenous:

Vd=dose( amount injected)/concentration of plasma (Cpss)

42
Q

Recall and explain slides 64-66

A

64-66

43
Q

What is Drug Metabolism

A

Drugs are metabolized from non-polar, active compounds to more polar, less active compounds

Types of metabolic reactions:
Phase 1
Phase 2

44
Q

Explain phase 1 metabolism:

A

Introduction of a functional group via: Oxidation, Reduction, hydrolytic rxns

Oxidation: CYP450, Flavin Monioxygenases

Hydrolysis of Epoxides

45
Q

What is an example of Oxidation:

A

Phenobarbital to hydroxyphenobarbital

46
Q

What are cytochrome P450s

A

Super family of enzymes

Located in the Endoplasmic Reticulm

Metabolism of drugs and food

Synthesis of compounds like steroids and fatty acids.

High in liver

47
Q

What are the most active CYPs in drug metabolism:

A

CYP2C CYP2D CYP3A

CYP3A4 high in the liver

48
Q

Name inhibitors of CYP3A4

A

Ketoconazole: decrease metabolism and clearance of other drugs.

49
Q

What is a CYP inhibitor found in food?

A

Grapefruit juice inhibits CYP3A4 which inhibits it’s metabolism of the drug which increases bioavailability and toxicity.

50
Q

Name CYP that are highly polymorphic

A 
CYP2D6
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4
51
Q

Explain Phase 2 Metabolism:

A

The coupling of drugs or metabolites to small polar molecules.
Requires a functional group on the substrate.
Results in termination of drug activity
Increase solubility
Catalytic rate is faster than CYPs

52
Q

Name two conjugations reactions in phase two

A

Glucronidation
- acetaminophen, morphine
Sulfation: acetaminophen, steroids

53
Q

What is first order kinetics of drug metabolism?

A

The rate of metabolism depends on the concentration of the drug.

Percent of drug removed by metabolism is constant.

54
Q

What is zero order kinetics if drug metabolism:

A

Rate of metabolism does not depend on the concentration of the drug.

Constant amount of the drug is metabolized per unit of time.

55
Q

What factors affect drug metabolism?

A

Age

Disease

Nutrition

Genetic Factors

Other Drugs

Duration of treatment

56
Q

What induces drug metabolism?

A

Receptors regulate drug metabolizing enzymes

Xenobiotics induce expressions of genes encoding drug metabolism enzymes

Example: pregnane X receptor

57
Q

How does St. John’s Wort induce drug metabolism?

What effect does that have example?

A
  1. Hyperforin (st.Johns wort) activates PXR
  2. PXR induces CYP3A4
  3. CYP3A4 metabolized oral contraceptives breaking then down
  4. oral contraceptives ineffective and babies are born
58
Q

Excretions

A

Drugs can be eliminated from the body unchanged or as metabolites.

59
Q

What are the sites of elimination

A

Kidney- Primary

Feces- unabsorbed orally ingested
Drug metabolites excreted by bile

Lung: Anesthetic gases

Breast Milk

60
Q

Define glomerular filtration

A

The renal excretion of drugs

Low molecular weight drugs filtered out.

Alterations in glomerular filtration rate can effect excretion.

61
Q

Define active tubular secretion:

A

Renal excretion of drugs

active process

System of organic acids ( glucaronides)

System of organic bases ( hexamethonium)

62
Q

Define passive tubular reabsorption:

A

Occurs by passive distribution

Lipophilic drugs can be reabsorbed. Hydrophilic drugs and ionized drugs will be excreted.

63
Q

What is urinary pH range?

A

4.5-8.0

64
Q

What is the rule for excretion at different pH?

A

Acidic urine favors the excretion of basic drugs

Basic urine favors the excretion of acidic drugs

65
Q

Acidifying agents:

A

Ammonium chloride or ascorbic acid

66
Q

Alkalizing agents:

A

Sodium bicarbonate

Sodium Citrate

67
Q

What is the rate of renal decline in adults?

A

1% per year

68
Q

Define clearance:

A

Clp “: A concept of metabolism and excretion of drugs.

Clearance is the volume of plasma that is cleared of drug in a unit of time.

69
Q

What is the equation for clearance?

A

CLp= Rate of Elimination/ concentration of drug in plasma ( Cp)

70
Q

First order Elimination:

A

Rate of elimination depends on the concentration of the drug that is present.

Exponential

Fixed half-life

71
Q

Zero order kinetics:

A

Rate of metabolism is constant does not depend on concentration of drug.

Linear

No fixed half life

Pharmacology (4 decks)

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