1. Definition of drug. Pharmacodynamics: Structure-dependent and independent drug actions Flashcards
Give the definition of ‘pharmacology’
Investigating the function-altering effect of several (exogenic and endogenic) substances in living entities.
Define pharmaceutical substances
If a substance can be used for treatment
Give the etymology of “Drug”
“Drug” (“droog” → “dry”)
What are pharmacodynamics?
The process of the drug entering the body
What are pharmacokinetics?
The interaction of the body on the drug
Which mnemonic is used to represent the pathway of the drug (pharmacodynamics)
ADME
“Corpora non agunt nisi fixata”
“A drug will not work unless it is bound”
Most drugs achieve their therapeutic effects by…
Interacting selectively with target molecules
- These play roles in physiologic or pathologic functioning
The selectivity of the drug binding may determine…
Adverse effects of a drug
Drug receptors are…
Macromolecules that, upon binding to a drug, mediate those biochemical and physiologic changes
Drugs binding to intracellular receptors
Highly lipophilic drugs that can easily pass through plasma membrane & also special barriers
Extracellular receptors
Surface protein receptors with extracellular domains linked to intracellular effector molecules
Which receptor types do drugs interact with?
- Ligand-gated ion channels
- G-protein coupled receptors
- Receptor-activated tyrosine kinases
- Intracellular nuclear receptors
Ligand-gated ion channels
Nicotinic ACh (nACh) receptors composed of 5 subunits
Give the area of the physiological function of nACh channels
- Neuromuscular junction
- Autonomic ganglia
- CNS
Give the function of the nACh receptor
- ACh binds to both α-subunits
- Channels open
- Na+ passes down its conc. gradient into cell
Give the types of nACh receptors (ligand-gated ion channels) involved in pharmacology
- Nm
- N<span>G</span>
Nm receptor - Area of function
Motor endplate of neuromuscular junctions of somatic nerves & skeletal muscles
N<span>G</span> Receptor - Area of function
Autonomic ganglia in adrenal medulla & certail areas in the brain
GABAA receptor-gated chloride ion channel
- Orthosteric ⇔ Allosteric effect (propofol acts as both)
- PAM = Positive allosteric modulator = Allosteric agonist
G-protein coupled receptors
7-transmembrane receptors
Give the types of G-protein coupled receptors
- Gαs (Stimulatory)
- GαI (Inhibitory)
- Gq
Gαs receptors - Action of function
- GTP → GDP
- Interaction with adenylate cyclase
- Catalyses: ATP → cAMP
- cAMP activated PKA
- Phosphorylation & activation of effector proteins
- Drug effect is carried out
List some Gαs receptors
- H2
- β1 Adrenoceptors
- β2 Adrenoceptors
H2 (Histamine) receptor function
- ↑ gastric production
- Vasodilation
- Relaxes SM
β1 adrenoceptors
(Excitatory)
- ↑ Heart rate & contractility
- ↑ Fat cell lipolysis
β2 adrenoceptors
(Inhibitory)
- Vasodilation
- Intestinal SM relaxation
- Bronchial SM relaxation
- Uterine SM relaxation
Gαi receptors
- GDP→GTP
- Inhibition of Adenylate Cyclase
- ↓cAMP production
Give an example of a Gαi receptor
α2 adrenoreceptors
α2 adrenoreceptors - Function
Prejunctional inhibition of norepinephrine & other neurotransmitter release
Gq receptors - Function
- ↑ Phospholipase activity
- Cleaves: Membrane phospholipid → DAG + IP
- DAG activated Protein Kinase C
- Phosphorylation & activation of cellular proteins
- IP releases Ca2+ from ER → cytoplasm
- Cellular processes activated
List some Gq coupled receptors
- α1 adrenoreceptors
- H1 receptors
- Serotonin receptors
H1 receptor - function
- ↑ Awakeness
- ↑ Vasodilation
- ↑ Permiability
α1 adrenoreceptors - Function
- Vasoconstriction
- GI relaxation
- Mydriasis
Receptor-activated tyrosine kinases
- Many growth-related signals
- Liganded receptors autophosphorylate tyrosine
Give an example of a receptor-activated tyrosine kinases
Insulin receptor substrate (IRS) → Insulin receptor
JAK inhibitors - function
“Janus kinase inhibitors”
- Inhibits JAK-1
- Interleukins-4 /-13 /-31 (Allergy, inflammation, pruritus)
- Used in atopic dermatitis
Intracellular nuclear receptors (NR) - Function
- Lipophylic ligands
- Binding ligand → structural changes in receptor
- Dissociation of chaperones → Receptor enters the nucleus
- Hetero-/homodimerisation of receptors & interaction with DNA
Give examples of intracellular nuclear receptors
- Ligand (pl. cortisol)
- HSP90 (Heat shock protein)
- CoA (Coactivator)
- Pol II (RNA polymerase II)
Identify receptor 1
Ligand-gated ion channel
Identify receptor 2
Identify receptor 3
Receptor-activated tyrosine kinases
Identify receptor 4
Intracellular nuclear receptors
Activation of conductance
- G-protein activation
- Generation of second messenger
- Activation of cell signaling
- Phosphorylation of tyrosines on key signalling molecules
- Activation of cell signalling
- Transport to the nucleus
- Activation of transcription and translation
