Pharm- Pharmacodynamics Flashcards
Pharmacodynamics
- Action of drug on body
- Influence of drug on magnitude of response (intended/ toxic)
- Most effects ( beneficial/ harmful) result of interactions between drug and receptor on or inside cell
*not all drugs works via receptors (antacids)
Signal Transduction
Ligand- drug or natural molecule that acts as signal
Receptor- acts as signal detector
-in Pharm- any biological molecule to which drug binds and produces measurable response
Receptor states: Active/ inactive
* different ligands cause different actions depending on receptor
Ligand-gated ion channels
-Response very rapid
G protein- coupled receptors
- Ligand binding activates G proteins causes dissociation and subsequent interaction with other intracellular molecules
- Molecules then activate second messengers causing cellular response
Enzyme- linked receptors
-Ligand binding activates/ inhibits cytosolic enzyme activity
Duration: minutes - hours
-Effect metabolism, growth, and differentiation
Intracellular receptors
- Ligand must be lipophilic (get thru membrane)
- Primary target= transcription factors
- Hours to months to outcome
Ex: hormones. corticosteroids
3 Adaptations of receptors/ Signal Transduction
- Signal amplification
- small input -> large response
- Important to receptos responding to hormones, neurotransmitters, peptides - Desensitization/ down-regulation of receptors
- receptor-endocytosis-recycled
- receptor degraded- reduces receptor amount
- dysregulation of receptors- bring disease (DMII) - Up regulation
- Occurs when receptor blocking drugs given over time in high dose
Agonists
Agonist binds to receptor-influences normal physiologic response
Two types:
- Full: activate receptor- reults in normal response of endogenous ligand
- Partial: partially activates receptor- result in response less than normal ( withdrawal)
Antagonists
Bind to receptors-block binding of endogenous ligand ( dont activate receptors)
Types:
- Competitive/ reversible
- Irreversible
- Functional/ chemical
Competative Antagonism
- Both antagonist and agonist can bind to receptor- they compete
- Drug affinity determines binding
- Competitive antagonist prevent agonist from binding- maintain receptor in inactive form unless competition too strong
Irreversible Antagonism
- Drug binds covalently (high affinity) to active site on receptor- prevent anything else from activating receptor
- Effects of irreversible antagonism only overcome by synthesis of new receptors
Functional/ Chemical Antagonism
Functional: physiologic response/interaction of different receptor sites result in opposing effects
-Ex: histamine at H1 receptor v epi at B2- adrenergic receptor in bronchial muscle
Chemical: chemical modifies agonist so its incapable of binding to activate receptor
Ex: protamine sulfate protein (+) binds to heparin (-)
Therapeutic index (window)
- Relation of toxic dose to clinically effective dose
- Want large TI
- Measure of drugs safety
Tolerance
- Loss of therapeutic effect over time
- Often dose dependent ( overcome by higher dose)
Tachyphylaxis
(fast- blunted response)
- Rapid tolerance ( decreased physiologic response)
- Note dose dependent
ADRs
(adverse drug rxns)
- Unintended/ harmful rxns to meds at therapeutic dose
- Among leading cause of death in many countries
- Most preventable
- No med without risk
Types of ADRs
Extension of therapeutic effect
- drug has desirable effect
- too much of good thing is not better
- predictable
Ex: low BP after antihypertensive, fungal overgrowth after antibiotics
Non- Therapeutic
- allergy- IgE mediated response
- idiosyncratic ( extreme sensitivity, prolonged drug effect, resistance)
Iatrogenic (medical error)
- caused by provider
- patient education is key
ADR: Prescriber responsibility
- Use minimally effective dose
- eval patient and fam hx
- eval possible interactions
- patient education
Pharmacogenomics
- How genetic makeup affects individual response to drug
- CYP450 gene
Poor metabolizer
- decreased expected serum conc. of metabolite
- increased expected parent drug serum conc.
Extensive (normal)
-expected serum conc. of parent drug/ metabolite
Ultrarapid
- increased expected serum conc. of metabolite
- decreased expected parent drug conc.
Drug Type
Prodrug- needs metabolism to work
Active drug- metabolized to inactive drug
