M1: Introduction to Pharm

Question 1

What is Pharmacodynamics and Pharmacokinetics

Answer 1

Pharmacodynamics = The effects of the drug on the body

Pharmacokinetics = The effect of the body on the drug

Question 2

Mechanism of Drug Action

Answer 2

1. Mediated by Receptors:
   - modulate endogenous process
   - you can either stimulate or inhibit a receptor
2. Not mediated by Receptors:
   - non specific interactions

Question 3

Receptors

Answer 3

• protein molecules
• target of drug actions

Locations:
1. Extracellular:
- located on outer surface of cell membrane
- for water soluble drugs = cannot cross cell membrane

2. Intracellular
   - located on inner surface inside the cell
   - for fat soluble drugs = can cross cell membrane

Question 4

Form of Drug Receptors

Answer 4

1. Regulatory Proteins
   - best ones
   - activated by endogenous ligands (every receptor has its own specific ligand)
2. Transporters
   - transports endogenous substances across cell membranes
3. Enzymes
   - catalyze biological reaction
4. Structural Proteins
   - contribute to cell structure

Question 5

Agonsits/Antagonists

Answer 5

1. Agonists
   - boosts effect
   - partial agonists
2. Antagonists
   - reversible, irreversible, blocks effect
   - allosteric inhibitors = noncompetitive, blocks effect of allosteric site

Question 6

D-R Interactions

Answer 6

1. Intracellular Receptors = steroid receptors
2. Enzyme-linked Receptors = insulin receptors
3. Ion Channel Receptors = calcium channel blockers
4. G-Protein Coupled Receptors = adrenergic receptors
5. Chemical signal crosses membrane and acts on intracellular receptor
6. Signal binds to extraceullar domain of transmembrane protein and activates cytoplasmic domain
7. Signal binds to tyrosine kinase and activates it
8. Signal opens ion channel
9. Signal binds to cell surface receptor linked to G-protein

Question 7

Dose and Response

Answer 7

Dose = quantity of therapeutic agent to be taken

Dose-Response Relationship = the more drug. the greater response until a certain point

1. Many receptors = full response
2. Drug, not many receptors = weak response
3. No receptors or different receptors = no response

Question 8

Potency and Efficacy

Answer 8

Potency: dose of drug required to make a response of a certain magnitude

Efficacy: the max response a drug can produce

Question 9

Therapeutic Index

Answer 9

• safety of a drug
• TI = TD50/ED50
• higher the TI, safer the drug

Question 10

Therapeutic Range

Answer 10

Range between where drug is ineffective and where drug is toxic

Question 11

Pharmacokinetics - ADME

Answer 11

1. Administration = move drug from injection site to blood
2. Distribution = move drug from blood to tissues
3. Metabolism (Biotransformation) = convert drug into different chemical compound = occurs in LIVER (primary site)
4. Excretion = remove drug through the kidneys

Question 12

Bioavailabiltiy

Answer 12

The percentage of a drug that reachers systemic circulation

Question 13

Factors Affecting Absorption

Answer 13

Factors Affecting Absorption
1. Lipid soluble
2. pH
3. Transit time
4. Food
5. Enzymatic and chemical stability
6. Dosage form

IV = SKIPS ABSORPTION

Question 14

Weak Acids and Bases

Answer 14

1. WEAK ACIDS
   - low pH = lots of hydrogen
   - hydrogen = unionized = fat soluble = high absorption
2. BASES
   - basic = few hydrogen = unionized = fat soluble = high absorption

Question 15

Drug Absorption Through GI

Answer 15

1. Stomach = dissolves
2. Small Intestine = high permeability, large surface area
3. Large Intestine = low permeability, small surface area, poor site for drug absorption

Question 16

Phases of Drug Metabolism

Answer 16

Phase 1 Reactions = OXIDATION (add/lose O2)
- CYP 3A4 metabolizes 50% of drugs

Phase 2 Reactions = CONJUGATION
- add water soluble thing to phase 1
- Glucuronidation = UGT
- Sulfation = SULT
- Gluthathione Conjugation = GST
- Acetylation = NAT

Question 17

Drug Clearance

Answer 17

Removing a drug from the body by metabolism or excretion

CL = rate of drug elimination / drug concentration in the blood / ml/min

Question 18

Drug Half Life

Answer 18

Time required to remove 50% of drug from the body.

Formula = 0.7 x Vd/CL

Half Life INCREASES if: Vd = high, CL = low

Question 19

First vs. Zero Order Kinetics

Answer 19

Elimination =
Rate of Elimination =
Extent of Elimination =
Main Organ =
Curve =
t/12 =
Drugs =

Question 20

Plateu Principle

Answer 20

Repeated drug increases plasma concentration until the rate of input (administration) = rate of output (elimination)

Takes 5x t 1/2

Question 21

Types of ADR: PHARMACODYNAMIC & NON - PHARMACODYNAMIC

Answer 21

PHARMACODYNAMIC:
1. Extension of therapeutic effect = overdose

2. Effect in non target organs

NON-PHARMACODYNAMIC:
1. Unrelated to drug action
2. Drug idiosyncrasy = genetic drug reaction
3. Allergic Reactions
4. Adverse biotransformation reaction
5. Addiction, Physical Dependence, Tolerance
6. Teratogenesis

Question 22

Types of DDI

Answer 22

Addition: 1+1 =2
- drugs given together have an additive effect
- 2 benzodiazepine

Synergism: 1+1 = 3
- increases sedative effect when bound to different receptors
- barbiturate and alcohol

Antagonism: 1+1 = 0
- one inhibits the other = no effect
- naloxone inhibits opioid receptor

Potentiation = one will do the effect and the other one will help the first one do the effect
- e.g. clavulanic acid prevents antibiotic resistance by secreting beta lactamase that happens in most penicillin

Question 23

Enzyme INDUCERS AND INHIBITORS

Answer 23

Enzyme Inducers:
- barbiturates
- phenytoin
- carbamazepine
- rifampicin
- smoking

Enzyme Inhibitors:
- cimetidine
- ciprofloxacin
- erythromycin
- fluoxetine
- grapefruit