M1: Introduction to Pharm Flashcards
What is Pharmacodynamics and Pharmacokinetics
Pharmacodynamics = The effects of the drug on the body
Pharmacokinetics = The effect of the body on the drug
Mechanism of Drug Action
- Mediated by Receptors:
- modulate endogenous process
- you can either stimulate or inhibit a receptor - Not mediated by Receptors:
- non specific interactions
Receptors
- protein molecules
- target of drug actions
Locations:
1. Extracellular:
- located on outer surface of cell membrane
- for water soluble drugs = cannot cross cell membrane
- Intracellular
- located on inner surface inside the cell
- for fat soluble drugs = can cross cell membrane
Form of Drug Receptors
- Regulatory Proteins
- best ones
- activated by endogenous ligands (every receptor has its own specific ligand) - Transporters
- transports endogenous substances across cell membranes - Enzymes
- catalyze biological reaction - Structural Proteins
- contribute to cell structure
Agonsits/Antagonists
- Agonists
- boosts effect
- partial agonists - Antagonists
- reversible, irreversible, blocks effect
- allosteric inhibitors = noncompetitive, blocks effect of allosteric site
D-R Interactions
- Intracellular Receptors = steroid receptors
- Enzyme-linked Receptors = insulin receptors
- Ion Channel Receptors = calcium channel blockers
- G-Protein Coupled Receptors = adrenergic receptors
- Chemical signal crosses membrane and acts on intracellular receptor
- Signal binds to extraceullar domain of transmembrane protein and activates cytoplasmic domain
- Signal binds to tyrosine kinase and activates it
- Signal opens ion channel
- Signal binds to cell surface receptor linked to G-protein
Dose and Response
Dose = quantity of therapeutic agent to be taken
Dose-Response Relationship = the more drug. the greater response until a certain point
- Many receptors = full response
- Drug, not many receptors = weak response
- No receptors or different receptors = no response
Potency and Efficacy
Potency: dose of drug required to make a response of a certain magnitude
Efficacy: the max response a drug can produce
Therapeutic Index
- safety of a drug
- TI = TD50/ED50
- higher the TI, safer the drug
Therapeutic Range
Range between where drug is ineffective and where drug is toxic
Pharmacokinetics - ADME
- Administration = move drug from injection site to blood
- Distribution = move drug from blood to tissues
- Metabolism (Biotransformation) = convert drug into different chemical compound = occurs in LIVER (primary site)
- Excretion = remove drug through the kidneys
Bioavailabiltiy
The percentage of a drug that reachers systemic circulation
Factors Affecting Absorption
Factors Affecting Absorption
1. Lipid soluble
2. pH
3. Transit time
4. Food
5. Enzymatic and chemical stability
6. Dosage form
IV = SKIPS ABSORPTION
Weak Acids and Bases
- WEAK ACIDS
- low pH = lots of hydrogen
- hydrogen = unionized = fat soluble = high absorption - BASES
- basic = few hydrogen = unionized = fat soluble = high absorption
Drug Absorption Through GI
- Stomach = dissolves
- Small Intestine = high permeability, large surface area
- Large Intestine = low permeability, small surface area, poor site for drug absorption
Phases of Drug Metabolism
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
Drug Clearance
Removing a drug from the body by metabolism or excretion
CL = rate of drug elimination / drug concentration in the blood / ml/min
Drug Half Life
Time required to remove 50% of drug from the body.
Formula = 0.7 x Vd/CL
Half Life INCREASES if: Vd = high, CL = low
First vs. Zero Order Kinetics
Elimination =
Rate of Elimination =
Extent of Elimination =
Main Organ =
Curve =
t/12 =
Drugs =
Plateu Principle
Repeated drug increases plasma concentration until the rate of input (administration) = rate of output (elimination)
Takes 5x t 1/2
Types of ADR: PHARMACODYNAMIC & NON - PHARMACODYNAMIC
PHARMACODYNAMIC:
1. Extension of therapeutic effect = overdose
- 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
Types of DDI
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
Enzyme INDUCERS AND INHIBITORS
Enzyme Inducers:
- barbiturates
- phenytoin
- carbamazepine
- rifampicin
- smoking
Enzyme Inhibitors:
- cimetidine
- ciprofloxacin
- erythromycin
- fluoxetine
- grapefruit
