Paragraphs for diagrams Flashcards
(11 cards)
Antagonist:
An antagonist is a substance which interferes with or inhibits the physiological action of another.
An antagonist binds to a receptor without causing activation, this prevents the agonist from binding. A full antagonist has 0 efficacy.
There are 2 types.
Competitive (Naloxone) this binds to the same site as the agonist competing for occupancy. This can be overwritten by increasing the agonist concentration .
Non-competitive antagonists (Ketamine) binds to an alternative site on the receptor which results in a change that lowers the receptors ability to respond to the agonist.
Agonist:
Agonists are substrates which initiate a physiological response when combined together with a receptor.
Agonists can activate a true receptor (adrenaline).
There are 3 types of agonists:
Full agonists bind to the receptor and produces the maximum response- Heroin
Partial agonists binds the receptor but produces sub maximum response (Buprenorphine)
Inverse agonists binds to receptors and gives an opposite response to the endogenous ligand (Antihistamines)
Dose response curve:
The response of an agonist is often plotted as a done response curve.
These graphs depict the effects of a rise in blood pressure, activation of enzyme or the contraction/ relaxation of a strip of smooth muscle.
It allows for the estimation of the maximal response that a drug can produce the concentration or dose needed to produce 50% maximal response
Drug target receptor:
1)Ligands located outside the cell
2)Ligands connect to receptor proteins based on active site shape
3) Receptor releases signal once ligand has connected to receptor.
A receptor is a sensing element that is a part of the chemical communication system .They co-ordinate all cell function in response to chemical messages such as hormones and neurotransmitters.
Drug target ion channels:
Voltage gated :
At resting potential, voltage gated Na+ ions are closed. When the membrane is depolarised, confirmational changes open the channel
Ligand gated ion channels:
Ligand gated ion channels open when a chemical (agonists) binds to an attached receptor. Ligand gated can be interfered with by drug affecting receptor function. They are the fastest neurotransmitters
Drug target Enzymes
Enzymes act as catalysts for biochemical reactions, the drugs may act as substrate analogues or false substrates.
Some drugs are prodrugs that require enzymatic conversion to activate.
Type 1 activates in cells (Heroin –> Morphine).
Type 2 activates outside the cells (Aspirin –> blood)
Blood brain Barrier
The BBB is a specialised structure designed to protect the CNS from harmful substances whilst allowing selective entry of specific essential molecules.
The BBB is made up of tight junctions between the cells meaning it is not leaky.
There is an outer impermeable layer made of parenthetical cells. Due to the tight junctions, drugs cannot pass between the cells.
Instead, they either go through the cell or be carried. Only lipophilic drugs can cross the BBB (Levodopa) whereas large drugs cant.
Capillaries:
Capillaries are the smallest blood vessels in the body and are responsible for the exchange of substances between blood and tissues.
Their structure influences the drug distribution and bioavailability.
There are 2 types
Fenestrated capillaries: Present in the kidney, pituitary and endocrine glands. They contain large pores and are very leaky which is good as it allows for drugs and hormones to escape.
Continuous capillaries: The most common, can be found in the muscle, liver and heart. They are a bit leaky, but drugs can still get through
Henderson- Hasselbalch:
Drug trapping is the movement of a weak acid or weak base drugs across physiological membranes driven by pH differences between compartments.
Only unionised drugs can easily diffuse across lipid cell membranes.
Bases are trapped in acidic compartments and acids are trapped in basic compartments.
The extent of which a weak acid or base is ionised depends on the pH and the drugs pKa
Diffusion:
The movement of a molecule can occur in four main ways.
These mechanisms are crucial for drugs to get from blood to target tissue.
Diffusion directly through lipid membrane: The main way for drugs to cross membrane, its passive and molecules move from high conc to low conc, non-saturable.
Combination with a carrier protein: The transport proteins embedded into the membrane, 2 types active transport and facilitated diffusion.
Diffusion through aqueous pores. The channels are formed by proteins (Aquaporins). The pores are big enough to let small pores pass
Pinocytosis: Involves the cell membrane engulfing the drug molecule with a vesicle .
Blood-plasma concentration curve:
This curve can be obtained by measuring the drug concentration in plasma samples taken at various time intervals after the drug has been administered. It provides information on how the drug reacts in the body over time
