2 Pharm: Drug- Receptor Interactions

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receptor

Back 1

receptor:
- macromolecular component of body tissue with which a drug, chemical or compound interacts to initiate its effect
- protein, enzyme, nucleic acid, ionic channels, or complex cellular component

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activated receptor

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- bond: covalent (rare, long term), hydrogen or van der Waals
- activation of the receptor initiates a sequence of biochemical changes within the cell or tissue, resulting in the pharmacological or physiological response

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ACh

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- enzyme complex in the body tissue also plays and important role for receptor-drug interaction
- ACh stim GI, drops HR
* check this*
- increased AChE (acetylcholinesterase): accumulation of ACh, increased bad effects such as gut/ muscle cramps

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agonist

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agonist:
- compound or drug that posseses affinity for a particular receptor and causes a change in the receptor, resulting in an observable effect
- partial agonist: less than max result, even if all receptors full

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affinity

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affinity:
- tendency of a drug to combine with a particular kind of receptor

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efficacy

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- efficacy= intrinsic activity:
- maximal effect the drug can produce

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potency

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potency:
- dose that must be administered to produce a particular effect of given intensity
- varies inversely with dose: the lower the dose required to produce a stated effect, the more potent

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antagonist

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antagonist:
- drug that blocks the response produced by an agonist
- affinity for a receptor, but lacks intrinsic activity
1. competitive/non- competitive
2. reversible or non-reversible

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anatgonism

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antagonism:
1. receptor antagonism
2. physiological antagonism: opposite/ same fx as another receptor
3. chemical antagonism

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selective

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selective:
- produces only a single effect
- eg heparin : anticoagulant

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specificity

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1. specific: acts at only one type of receptor but may produce mutliple effects because of locations in multiple organs
- eg atropine
2. non specific: several mechanisms of action
- eg acepromazine: sedation, anti-emetic, hypotension, hypothermia

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Signal Transduction

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1. Ligand-gated ion channels
2. G protein.
3. Intracellular receptors.
4. Protein tyrosine kinases.

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Ligand-gated ion channels

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* part of signal transduction
Ligand - gated ion channels:
- Regulate the flow of ions through the cellular membrane. Response occurs in milliseconds.
e.g. such as synaptic transmitters that act via ionic channels, includes acetylcholine (at nicotinic receptors), gamma- aminobutyric acid (GABA), glycine, glutamine.

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G proteins

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- part of signal transduction
G proteins couple the binding of the ligand on the cell surface receptor with intracellular second messenger.
a. Agonist binds to a receptor, causing guanosine diphosphate (GDP) to be displaced from the G protein and replaced with guanosine triphosphate (GTP).
b. The G protein GTP complex regulates the activity of enzymes or ion channels to produce a response. Hydrolysis of the GTP to GDP halts the activity.
c. G protein may elicit either stimulatory or inhibitory response. Each cell may have more than one G protein.

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Intracellular receptors

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- part of signal transduction
Intracellular receptors:
- are activated by a group of hormones that are highly lipid soluble and thus, are able to cross the cellular member.
Glucocorticoid receptors are located in the cytoplasm. They combine with drug and then move to the nucleus. Receptors for T3, T4 and the estrogens are in the nucleus. Receptor-drug complex increases binding of RNA polymerase, leading to transcription of target genes.
Response time can range from minute to hours because new proteins must be synthesized. Even after the drug treatment is stopped. Effect my last for hours to days.

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Protein tyrosine kinases

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-part of signal transduction
Protein tyrosine kinases:
mediate the response of insulin, epidermal growth factor (EGF), platelet derived growth factor (PDGF) and other tropic hormones.
These receptors are proteins and found in cell membrane, consisting of an extracellular portion that binds the ligand, a transmembrane portion that transmits the signal through the cell membrane, and a cytoplasmic portion that terminates in the cytoplasm.
Which contains tyrosine kinase activity. The enzyme catalyzes the phosphorylation of substrate protein, which produces a biological response.

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Dose- response relationship

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Dose- Response Relationship:
1. The intensity elicited by a drug is a function of dose administered, can be shown on simple cure.
2. Dose response can also be on a logarithmic curve.
a. Potency
b. Slope
c. Variability
d. Maximum effect.

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Quantitative Response in the Patient

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Quantitative Response in the Patient:
That is a Quantal dose response relationships.
a. Normal and cumulative from of frequency distribution curve. That relates to variation in concentration (mg/ml)
b. Therapeutic index: is used to evaluate the safety of the drug. It’s a ratio.
TI = LD50 / ED50

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Standard safety margin

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Standard Safety Margin
= LD 1- ED 99/ ED 99
eg 100 mg- 10 mg/ 10 X 100 = 900%
That if 10 mg dose is effective in 99% of the population and if given 100 mg of this drug kills 1% of the population than safety margin is 900%. Very safe drug.
If the ration of LD/ED is low drug has low safety margin.