Wiseflow exam 2 Flashcards
Describe the following terms:
a. Pharmacokinetics
b. Invers agonist
c. IC50 value
d. Type B side effects
Pharmacodynamic: What drugs does with the body
Pharmacokinetics: What the body does with the drug
Invers agonist which decrease receptor activity that is ligand dependant. At a concentration response graph it would go below 0.
IC50 is the concentration of a drug or inhibitor needed to inhibit a biological process or response by 50%.
Type B side effects are rare but dangerous
Which drug or drugs is/are most potent?
The one with the lowest E50
Which drug(s) can you characterize as partial agonist/s?
All drugs that can’t reach an emax
Which drug(s) can you characterize as a full agonist/s?
All drugs that can reach emax
Q3 The figure shows the result from an experiment where an antagonist B was
characterized.
Interpret the results. How would you characterize the antagonist? Motivate and explain
your answer.
Competetive antagonist, decreased E50 and potency but not decreased Emax so it moves in x axis to the right but now decreasing in y axis. It’s because at high enough concentration it can still compete out the endogenous ligand.
Non competetive is decreased in x axis with decreased e max but not decreased e50 it dosn’t move in x axis. It can either bind allostericly or irreverisbly.
Wiseflow exam 2
Quesiton 5a
Which (none to all) of the following statements are true regarding the plasma concentration vs
time curve shown below? (2p)
A. The plasma half-life of the drug is constant
B. The rate of elimination is constant
C. The fastest rate of elimination is achieved at the highest concentrations of the drug
D. Each hour, the plasma concentration of the drug decrease by 20 mg/mL
a) true
b) no
c)yes
d)no
Adrenergic and cholinergic signaling are important in the autonomic nervous system.
Explain, based on the structure of the autonomic nervous system, which division (or
divisions) of the autonomic nervous system that can be activated by a nicotinic agonist.
Nicotinic acetylcholine receptors are ionotropic receptors found on both sympathetic and parasympathetic ganglia, as well as in the neuromuscular junction. Therefore, a nicotinic agonist can activate both the sympathetic and parasympathetic divisions of the autonomic nervous system, as well as skeletal muscle.
When a nicotinic agonist binds to a nicotinic acetylcholine receptor in a ganglion, it leads to depolarization and subsequent release of neurotransmitters from the postganglionic neuron, which then act on target organs or tissues. In the sympathetic nervous system, this can result in increased heart rate, dilation of bronchioles, and increased blood pressure, among other effects. In the parasympathetic nervous system, nicotinic agonists can lead to decreased heart rate, constriction of bronchioles, and increased gastrointestinal motility, among other effects.
Explain, based on the structure of the autonomic nervous system, which division (or
divisions) of the autonomic nervous system that can be activated by an adrenergic
agonist.
Adrenergic agonists are drugs that activate adrenergic receptors, which are primarily found in the sympathetic nervous system. Therefore, adrenergic agonists can activate the sympathetic division of the autonomic nervous system.
When an adrenergic agonist binds to an adrenergic receptor, it can mimic the effects of the sympathetic nervous system, leading to increased heart rate, dilation of bronchioles, increased blood pressure, and other effects. This is because the sympathetic nervous system is responsible for the “fight or flight” response, which prepares the body for physical activity and stress.
Q6 Adenosine di-phosphate (ADP) and thromboxane A (TXA ) are both important for normal
hemostasis. Different clinically used drugs have been developed that specifically target the
functions of ADP and TXA .
a. Describe the mechanism of action of clinically used drugs that target the function of ADP and
explain why this affects hemostasis. (1.5p)
Clopidogrel, The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP- mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible.
b. Describe the mechanism of action of clinically used drugs that target the function of TXA
and explain why this affects hemostasis. (2p)
acetylsalicylic acid is a common pain killer and partially inhibit platelet activation by irreversibly inhibiting COX 1/2 as a non competetive antagonist.
Acetylsalicylic acid (ASA) partially inhibits collagen-induced platelet activation by blocking the activity of cyclooxygenase-1 (COX-1). COX-1 is an enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H2, which is a precursor for thromboxane A2. Thromboxane A2 is a potent vasoconstrictor and prothrombotic agent that stimulates platelet aggregation. By blocking the activity of COX-1, ASA prevents the formation of thromboxane A2, thus inhibiting platelet aggregation.
Additionally, ASA has been shown to inhibit other pathways involved in platelet activation, such as the glycoprotein IIb/IIIa receptor pathway and the phospholipase C pathway.
c. Thrombin (also called factor IIa) is an important drug target. Explain why inhibition of
thrombin results in inhibition of coagulation. (1.5p)
Thrombin turns fibrinogen to fibrin
Anti-inflammatory drugs can use several different cellular targets to induce the antiinflammatory effect
a. Describe the mechanism of action of NSAIDs and explain how this action will
result in reduced inflammation
NSAID (enzyme inhibitors), non-steroidal anti-inflammatory drugs. They are COX inhibitors. Irreversible Treo, reversible ipren.NSAIDs inhibit the activity of both COX-1 and COX-2 enzymes, but they are more selective for COX-2. By inhibiting COX-2 activity, NSAIDs reduce the production of prostaglandins that mediate inflammation and pain, leading to reduced inflammation and pain.
In addition to inhibiting COX activity, some NSAIDs also have other mechanisms of action that contribute to their anti-inflammatory effects. For example, some NSAIDs can inhibit the activation of white blood cells, which are involved in the immune response and the production of pro-inflammatory cytokines. Others may interfere with the production of free radicals or oxidative stress, which are associated with inflammation.
Name and describe the mechanism of action for another antiinflammatory
drug that not belongs to the NSAIDS
Glucocorticoids binds to intracellular receptors, receptor ligand complex migrate to nucleus, that affect transcription of genes either up or down regulating.
Budesonide works by binding to glucocorticoid receptors in the body. This binding causes a decrease in the production of inflammatory mediators such as cytokines and leukotrienes. This reduces inflammation and swelling in the affected area.
Budesonide also has an anti-proliferative effect, which means it can help prevent the growth of certain cells that can cause inflammation. It also has an immunosuppressive effect, which means it can reduce the activity of the immune system and reduce inflammation.
Statins belong to a class of drugs that can counteract a riskfactor for
cardiovascular disease. Explain the mechanism of action (MoA) of statins. For full
points the drugs MoA must be adressed at a cellular level and also the
consequences for the individual that has a riskfactor that requires treatment
with statins
For this lipid lowering drugs which are called statins, they block an enzyme that is involved in cholesterol production, HMG. These cells develop receptors to capture circulating low density cholesterol.
Statins are a class of drugs used to lower cholesterol levels and reduce the risk of cardiovascular disease. The mechanism of action of statins involves their ability to inhibit the enzyme HMG-CoA reductase, which is responsible for the synthesis of cholesterol in the liver.
At the cellular level, statins competitively inhibit the activity of HMG-CoA reductase, which leads to a reduction in the synthesis of cholesterol in the liver. As a result, the liver takes up more circulating LDL-cholesterol from the bloodstream, reducing its concentration in the bloodstream. The liver also increases the expression of LDL receptors on its surface, further increasing LDL uptake from the bloodstream.
The consequences for an individual with a risk factor for cardiovascular disease who requires treatment with statins are a reduction in their LDL-cholesterol levels, which is a major risk factor for developing cardiovascular disease. The use of statins has been shown to decrease the incidence of major cardiovascular events, such as heart attacks and strokes, in individuals with or without a prior history of cardiovascular disease.
In addition to their cholesterol-lowering effects, statins may also have other beneficial effects on the cardiovascular system. For example, they have been shown to reduce inflammation in blood vessels, improve endothelial function, and stabilize plaques in the arteries. These effects may contribute to the reduction in cardiovascular events seen with statin therapy.
Salbutamol is a drug used in the treatment of obstructive airway diseases.
a. Describe the mechanism of action and pharmacological effect of Salbutamol.
the mechanism of action of salbutamol involves binding to beta2-adrenergic receptors on airway smooth muscle cells, leading to activation of the cAMP-PKA pathway and inhibition of smooth muscle contraction. These effects contribute to the bronchodilatory and anti-inflammatory effects of salbutamol.
Activation of PKA by cAMP leads to a decrease in intracellular calcium levels, which is the main trigger for smooth muscle contraction. This occurs via two mechanisms:
Inhibition of myosin light chain kinase (MLCK): PKA phosphorylates and inhibits MLCK, which is the enzyme responsible for phosphorylating myosin light chains and initiating smooth muscle contraction. By inhibiting MLCK, salbutamol reduces the ability of smooth muscle cells to contract.
Activation of myosin light chain phosphatase (MLCP): PKA also activates MLCP, which is the enzyme responsible for dephosphorylating myosin light chains and promoting smooth muscle relaxation. By activating MLCP, salbutamol promotes smooth muscle relaxation.
