Week 11 Drugs Flashcards
4 Common drug targets
- Enzymes - increase/inhibit activity
- Ion channels - enhance/inhibit movement of ions
- Receptors - mimic endogenous compounds
- Transporters - occupy binding site -> prevent transportation of endogenous compounds
What is true drug receptor?
- only known ligand is drug
- no endogenous ligand has been identified
What are orthosteric agonist and allosteric agonists?
- Orthosteric agonist: binds to orthosteric site of receptor -> produce ultimate response
- Allosteric agonist: binds to allosteric site of receptor -> alters affinity/efficacy of receptor to ligand
3 Parameters affecting magnitude of receptor response
- Occupancy of receptors
- Efficacy of receptor signal
- Number of receptors
2 Observable properties of drugs
- Potency - concentration required to elicit the same magnitude of response
- Efficacy - maximal response that can be achieved
2 Properties of antagonist and agonists
- Affinity - degree of attraction (for both agonist and antagonist)
- Efficacy - effect resulted from binding of receptor (for agonist ONLY as antagonist blocks activation of receptor)
4 Phases of pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Elimination
4 Mechanisms of drug movement from circulation to organ
- Simple diffusion (passive) - small, non-polar drugs
- Ion trapping - for weak electrolytes (weak acid can cross in acidic environment)
- Carrier-meditaed transport (facilitated diffusion and active transport) - larger drugs
- Pinocytosis - for macromolecules
What is bioavailability
Fractional extent to which a dose of drug reaches its site of action
3 steps of absorption of orally administered drugs
- Disintegration of dosage form - into granules
- Dissolution of drugs in fluids in absorption site (gastric fluid)
- Transfer of drug molecule across membrane lining the GI tract into systemic circulation
What is first-pass effect?
Main organ in which first-pass effect occurs for orally-administered drugs
Drug is metabolized between the site of absorption and site of sampling for measurement of drug concentration
Main organ: Liver
Where do drugs go after absorption into systemic circulation?
Distribution:
enter interstitial fluid -> intracellular fluid
What is drug displacement?
The two classes of drugs classified
Drug displacement:
competition between drugs for binding with plasma proteins
Class I: dose is less than protein binding capacity
Class II: dose is higher than protein binding capcity
What property does lipophillic drugs have in pharmacokinetics
Promote absorption and distribution
Hinder elimination and excretion
2 Types of drug metabolism
- Phase I: change functional group of parent chemical
2. Phase II: add a conjugate to the parent chemical
What is CYP450? What is its primary reaction?
Most well-known drug metabolic enzyme
Phase I reaction: change functional group of parent chemical (drug)
Major organ involved in drug excretion
Kidney
3 Common Phase II reaction of drug metabolism
- Glucuronidation - increases water solubility of parent drug
- Sulfation
- Acetylation
Routes of drug excretion
- By kidney as urine
- Biliary excretion (as bile)
- Fecal excretion
- Other routes: saliva, breast milk, tears, sweat
How are half-lives of zero-order, first-order and second-order drugs affected?
Zero-order: proportional to initial concentration (high conc -> stay in body for longer)
First-order: constant
Second-order: inversely proportional to initial concentration
6 Types of Adverse Drug reactions
- Type A - augmented (dose-related)
- Type B - bizarre
- Type C - chronic (long term, dose accumulation)
- Type D - delayed
- Type E - end-of-treatment
- Type F - failure of efficacy (no response)
4 types of patients due to metabolic phenotype
- Poor metabolizer
- Intermediate metabolizer
- Extensive metabolizer
- Ultrarapid metabolizer
Functions of 4 main types of adrenergic receptors
alpha-1: vasoconstriction, contraction of smooth muscles
alpha-2: suppress release of presynaptic noradrenaline
beta-1: increase heart contractility, increase heart rate
beta-2: vasodilation, relaxation of smooth muscle
2 broad types of drugs that affect sympathetic nervous sytem
- Sympathomimetics - direct (bind to adrenergic receptors) /indirect (increase release of noradrenaline)
- Sympatholytics - direct (block receptor activation) /indirect (inhibit synthesis of noradrenaline)
