Pharmacodynamics Flashcards
(17 cards)
What is pharmacodynamics?and examples
Study of effects of drug in body and their mechanism ie digoxin inhibits Na+/K+ ATPase increase cardiac contractility
Differentiate drug action vs drug effect
Action- initial molecular binding ie beta blockers binding to adrenergic receptors
Effect-physiological outcome decrease heart rate
State types of drug effect
Stimulation
Inhibit/ depression
Replacement
Cytotoxic
Action of drugs is attributed by
Receptor
Non receptor
By targeting specific genetic changes
List different pharmacological actions
- Receptor mediated mechanism
2.Chemical action or Physiochemical properties ie chelating agents
3.analogues of pyrimidines and purine bases serving as substrates for DNA /RNA synthesis ie certain cancer
What are 4 receptor families
- Ligand gated ion channels ie nicotinic
- G-protein couple ie muscarinic
3.Enzymatic ie insulin - Nuclear ie steroid hormone
Give and explain 3 types of antagonism
- Receptor - ie same receptor , 2 drugs (agonist + antagonist) compete
2.physiologic -occurs as result of activating receptors with opposite effects ie Ach-reduce heart rate , epinephrine increase heart rate
3.chemical -2/more molecules form chemical bonds ie Cu chelated to penicillamine
Compare agonist , antagonist and inverse agonist
- Agonist -eph: binds and activates
- Antagonist-propranolol:binds and block
- Inverse agonist-antihistamine: suppress signaling activity
What’s the difference between competitive vs non competitive antagonist
1.Competitive : reversible ie Naloxone vs opioids
2. Non competitive: irreversible ie phenoxybenzamine covalently binds to alpha 1 receptors
How do Guanylyl Cyclades protein kinase G work( nitric oxide)
1.nitric oxide passes through permeable membrane
2.cause soluble guanylyl Cyclase convert GTP to cGMP
3. Activate pKG
4.To cause 3 effects 1.myosin phosphate-smooth muscle relaxation
2.transcription factors -gene expression
3.VASP-platelet inhibition
Explain cystolic tyrosine kinase
- Ligand ie growth hormone bind receptor
- JAK kinases phosphorylates each other
3.JAks phosphorylates STAT proteins - STAT diners enter nucleus
5.Act as transcription factors to alter mRNA synthesis
Ie growth hormone-for muscle growth
Describe the mechanism of corticosteroid receptor activation
- Inactive receptor bound to HSPs in cytosol ( heat shock proteins )
2.hormones ie cortisol binds and HSP dissociate
3.Receptor dimerizes and move to nucleus - Bind to glucocorticoid response element (GRE) to either increase or decrease gene transcription
Ie prednisone anti inflammatory effects
G protein coupled receptor signaling mechanism
1 Agonist binds to GPCR cause conformational change
2. Galpha subunit exchanges GDP for GTP
3. Galpha -GTP separate to activates effectors :
Either adenylyl cylase to increase cAMP or phospholipase C increase IP3 / DAG
4. GTP hydrolysis- signal termination
Match G protein subtypes to their effector pathways
- Gs - increase AC , increase cAMP (B adrenergic, H, 5HT , glucagon )
2.Gi- increase AC , increase cAMP , open K+ (a2 adrenergic, Ach)
3.Gq -phospholipase C - IP3 cytoplasmic Ca+2. (Ach)
4.Go - neurotransmitter in brain
Generally describe intercellular receptor
1.Steroid hormone ie VitD bind receptors in cytosol
2.Thyroid hormone bind to receptors in nucleus
3. These activates receptor proteins form dimer and move to promoter region of the DNA
4 . Alteration of transcription process
What is therapeutic index
TI = LD50/ ED59 high TI = safer drug ie penicillin.
Lower TI= narrow safety margin ie digoxin
Drug selectivity definition
Targets specific receptors / species
Ie caprofen is COX -2 selective in dogs not horses
