Pharmacodynamics Flashcards
(66 cards)
1
Q
Steps of the drug use process
A
- Assessment
- Select the the optimal regimen for the patient
- Dispense and counsel
- Administration of the drug
- Monitor and follow up the patient
2
Q
What is medication reconciliation?
A
- The process of comparing the patient’s medication orders all medications the patient has been taking
- Prescription, over-the-counter, and dietary supplements
3
Q
What is the purpose of medication reconciliation?
A
Avoid medication errors
4
Q
What is the cause of more than 40% of medication errors?
A
Inadequate medication reconciliation
5
Q
What is evidence-based pharmacotherapy?
A
An approach to decision-making that relies on appraisal of scientific evidence and its strength
6
Q
What is first level evidence-based pharmacotherapy?
A
Reviews of evidence-based practice guidelines or current textbooks with evidence links
7
Q
What is second level of evidence -based pharmacotherapy?
A
Consultation of electronic databases of systematic reviews and/or meta-analyses
8
Q
What is third level evidence-based pharmacotherapy?
A
Literature searches using electronic database
9
Q
What is a medication error (ME)?
A
Any mistake in the medication process regardless of outcome
10
Q
What is an adverse drug event (ADE)?
A
Harm resulting from the use of the medication
- Some ADEs are the result of MEs
- Some ADEs are not the result of MEs (not due to error)
11
Q
What is an adverse drug reaction (ADR)?
A
And ADE that is not preventable (not caused by error)
- ADRs represent reactions to a normal pharmacological intervention
- A side effect is not an ADR unless it causes harm
12
Q
Is the difference between an adverse drug event and an adverse drug reaction? ADE vs ADR
A
- ADE: Sometimes preventable, sometimes not
- ADR: Not preventable, normal reaction to medication
13
Q
What are some examples of electronic guidelines for pharmacotherapy?
A
- UpToDate
- National guideline clearing House
- Medscape
- BMJ clinical evidence
14
Q
What are some examples of textbooks/reviews available electronically with updates for pharmacotherapy?
A
- Goodman and Gilman’s pharmacological basis of therapy
- Scientific American medicine online
15
Q
What are some examples of regular textbooks for pharmacotherapy?
A
Pharmacotherapy: principles and practice (Chisolm-Burns)
16
Q
What are the two main operational concepts of pharmacology?
A
- Pharmacodynamics
2. Pharmacokinetics
17
Q
What is pharmacodynamics?
A
- Sites of action for drug at a molecular level
- Attributes of drugs at the sites
- Effects of drugs, through these sites, on normal and relevant pathologic states
“The effect of a drug on the body”
18
Q
What is pharmacokinetics?
A
- Absorption: How the body breaks the drug down
- Distribution: How the body brings the drug to different tissues
- Elimination: How the body processes and excretes the drug
“The fate of a drug following its administration”
19
Q
To what does the “intended” effect of a drug refer?
A
- “On-target” effects
- Therapeutic use of drug
20
Q
To what does the “adverse” effect of a drug refer?
A
- “On-“ or “off-target” effects
- Lifestyle use of a drug
- Either licit or illicit
- Licit: Caffeine to help stay awake
- Illicit: Opiates for a high instead instead of for pain
21
Q
What is an “on-target” effect of a drug?
A
- Effects caused by the drug acting on its intended receptor in the body
- i.e. Antihistamine acting on H1 receptor to reduce itching (intended) or sedation (adverse)
22
Q
Is an “off-target” effect of a drug?
A
- Effects caused by the drug acting on UNINTENDED receptor in the body
- i.e. Antihistamine acting on muscarinic receptor causing dehydration and drying (adverse)
23
Q
What are the 6 major targets of drug action in the body?
A
- G protein-coupled receptors (GPCRs)
- Ion channels
- Enzyme-linked receptors
- Nuclear receptors
- Transporters
- Enzymes
24
Q
Describe how G protein-coupled receptors work
A
- A ligand, or agonist, binds to the G protein-coupled receptor embedded in the cell surface membrane
- The receptor undergoes a conformational change
- GDP in the G protein is exchanged for GTP, causing the alpha subunit to disassociate from the beta-gamma dimer
- Both subunits can work on in effector
- Sometimes it’s an activation of the effector, sometimes its inhibition of the effector
25
What are the proximal targets for G proteins and what are their effects?
- Gs = increase in adenylyl cyclase (increase cAMP)
- Gi = decrease in adenylyl cyclase (decrease cAMP, stimulate potassium channels)
- Gq = increase in PLC-B (increase in calcium)
- G12 = increase in rho (contractility, shape, etc.)
26
How do prostaglandin's work on neurons to incite pain?
- Prostaglandins are released from damaged tissue
- Prostaglandins bind with prostanoid receptors to stimulate Gs proteins, or excitatory proteins, and increase cAMP, which is pro-excitatory in a neuron
- The neuron depolarizes and propagates a nerve stimulus along an axon
- This causes the release of neurotransmitters and causes pain
27
How do opiates work to reduce pain?
- Opiates find to opiate receptors, which in turn activate potassium channels
- Potassium reflux hyperpolarizes the neuron and inhibits transmission of pain stimuli
28
How do bradykinins work on on neurons to incite pain?
- Bradykinins are released from damaged tissue
- Bradykinins bind with B2 receptors to stimulate Gq proteins, or excitatory proteins, and increase calcium in the cell
- The neuron depolarizes and propagates a nerve stimulus along an axon
- This causes the release of neurotransmitters and causes pain
29
What are the roles of ion channels?
- Sit below the cell surface
| - Conduct ions from one side of the membrane to the other (i.e. sodium, potassium, calcium)
30
Describe membrane potential
- Voltage is the potential across any membrane
- How was it generated?There's a lot of potassium on the inside, and a lot of sodium, calcium, and chloride on the outside
- At rest, inside of cell is more negatively charged than outside of cell, causing a negative action potential
31
How does an action potential work?
- The resting membrane potential of a cell is a voltage of about -65
- Sodium potassium channels help keep the inside more negative and outside more positive (for every 2 Ks transported into the cell, 3 Nas are transported out)
- An outside stimulus will cause sodium ion channels to let sodium into the cell, decreasing the voltage of the membrane potential
- Once the voltage hits a certain threshold, around -35 or 40, voltage-gated sodium and calcium channels are activated, causing sodium and calcium to flood into the cell, depolarizing the membrane
- The signal is propagated along the axon by stimulating adjacent sodium channels to open. The refractory period helps move the stimulus forward.
- Potassium channels open, allowing the the potassium out of the cell to help re-polarize the membrane
- Sodium potassium channels help bring the membrane potential back to resting state
32
What are the two types of ligand-gated ion channels?
Excitatory and inhibitory
33
How do excitatory ligand gated channels work?
Use cations (sodium, potassium) to cause depolarization
34
What ligands do excitatory ligand gated ion channels recognize?
Glutamate, acetylcholine (nicotinic receptors), and purines
35
How do in inhibitory ligand gated channels work?
Use anion chlorine to cause hyperpolarization
36
What ligands do inhibitory ligand gated ion channels recognize?
Gamma-aminobutyric acid (GABA) and glycine
37
What is the relationship between ligand gated and the voltage gated ion channels?
Ligand gated channels can activate voltage gated channels
38
What are enzyme-linked receptors?
Receptors that, when activated by agonist, exhibit:
1. a capacity to phosphorylate other proteins, usually tyrosine residues either
- Intrinsically, i.e. they are protein kinases or
- Extrinsically, through association with protein kinases
2. and sometimes a scaffolding functionality -> signal transduction
3. Important for cell growth, how immunologically cells communicate with each other (cancer, inflammatory diseases)
39
How do enzyme-linked receptors work?
1. Ligand binds with receptor
2. Kinases used P on receptors to phsphorylate proteins
2. When phosphorylated, these proteins cause signal cascades
40
What are some common drug act on enzyme-liked preceptors?
Insulin, cancer treatment
41
In what types of cells are nuclear receptors found?
Genes
42
What is the purpose of nuclear receptors?
Regular transcription of genes and gene activity
43
What types of drugs commonly act on nuclear receptors?
- Steroids
| - Sex hormones
44
What types of drugs commonly act of voltage gated ion channels?
- Local anesthetics
- Antiepileptics
- Antidysrhythmics
- Antihypertensives
45
What types of drugs commonly act on ligand gated ion channels?
- Muscle relaxants
- Anesthetics
- Sedatives
46
Name the different types of transporters
1. Passive transport, facilitated diffusion: Ions moving down their concentration gradient, No energy required
2. Primary active transport: Uses hydrolysis of ATP to transport against a concentration gradient
3. Secondary active transport: Uses passive energy of an ion moving down its concentration gradient to bring another ion against its concentration gradient
- Symport: Moves in the same direction as the passive ion
- Antiport: Moves in the opposite direction as the passive ion
47
What types of drugs commonly act on transporters?
- Antidepressants
- Amphetamines
- PPIs
- Diuretics
- Cardiac glycosides
48
What are the two most common sites of drug action?
1. G protein coupled receptors
| 2. Enzymes
49
How do drug act on enzymes?
Drugs inhibit an enzymatic activity
50
What are the two types of the inhibition of enzymatic activity?
1. Reversible inhibition
| 2. Irreversible inhibition
51
Describe reversible inhibition of enzymatic activity
- It is usually competitive, i.e. Drug and substrate compete for the same site
- For example, statins, which have a much higher affinity for binding site, compete with HCG CoA enzyme to inhibit cholesterol production/distribution
52
Describe irreversible inhibition of enzymatic activity
- Always based on stable covalent linkage between the drug and enzyme
- Drug attaches to enzyme permanently
- For example, Aspirin inhibits COX1 and COX2 by permanently covalently bonding to the binding site
53
Define agonist
- A macromolecular entity, endogenous (natural) or synthetic, that activates the receptor to which it is directed
- Can be classified as full or partial agonists
- Partial agonist cannot activate all receptors or pathways, while full agonists can
- High enough levels of weak partial agonists can compete with substrates and act as antagonists, i.e. Chantix competes with nicotine to help stop smoking
- Binds reversibly, along with antagonists, at orthosteric site, main binding site
54
Define antagonist
- A macromolecular entity, almost always synthetic, that prevents the actions of another ligand (i.e. agonist) At the receptor to which it is directed
- Can be classified as neutral (or pure) antagonists or inverse agonists
- Neutral antagonists bind directly binding site, or orthsteric site, to stop activation
- Inverse agonists bind to active receptors to lower the activity of the receptors themselves (all receptors have some level of activity and can even activate alone sometimes)
- Binds reversibly, along with agonists, at orthosteric site, main binding site
55
What is the difference between occupation activation?
- Occupation is governed by infinity, or how tightly a drug binds to a receptor
- Activation is governed by efficacy
- Binding does not necessarily cost activation, binding may not cause a response because there is no efficacy even if there is high affinity
56
What is the relationship between occupation and concentration of drug?
- With few ligands, there is higher affinity because the receptors want to bind the ligands
- With high levels of ligand, there is no affinity because receptors have bound enough ligands
57
Describe the three phases of drug response
- Phase 1: Very little drug causes very little in terms of response
- Phase 2: More drug gives a great deal more response
- Phase 3: Emax - more drug will not create more response, max effect
58
What is the difference between potency efficacy?
1. Potency: Concentration or dose of drug required to achieve a certain effect
- Usually referenced to EC50 or ED50 (50% refers to drug's own Emax), or the dose of drug that gives us half maximum effect
- The lower the EC50 or ED50, the greater the potency (i.e. If we only need a small amount to get to 50% of Emax, very potent. If we need a boat load of drug to get to 50% of Emax, not very potent.
2. Efficacy: Magnitude of the drug action at the limit of its concentration or dose (Emax)
- The greater the Emax, the greater the efficacy
59
What is the relationship between dose therapeutic response and dose adverse response?
How an increased concentration of a drug is related to adverse effects
60
What is the minimal useful effect of a drug?
The smallest dose that actually works with the least amount of side effects
61
What is the maximum tolerated adverse effect of a drug?
The dose at which the patient cannot tolerate the adverse effect any longer, the problem of the adverse effect is too significant
62
What is the therapeutic window?
The difference between the therapeutic effect, or when the drug begins to work, and toxic effect
63
What is duration of action of a drug?
Begins when drug starts working and ends when drug stops working
64
Describe the quantal dose response curve
- Quantal is based on population
- ED50 is % of human population that needs a certain dose have therapeutic response
- LD50 is the percent of people dead at a certain dose
65
What is the therapeutic index?
Toxic dose of the drug for 50% of the population divided by an effective dose for 50% of the population
- Therapeutic index = TD50/ED50
- The higher the therapeutic index, safer the drug
- Low therapeutic index means we need to monitor the person more
66
How do drug-drug interactions play out at a pharmacodynamic level?
- Drugs may compete for the same binding site, i.e. albuterol and beta blockers for B2 receptors
- Drugs may affect membrane potentials that impact efficacy of the other drugs, i.e. diuretics and dig both depend on K levels, diuretics lower K and cause dig tox
- Drugs works synergistically to potentiate side effects, i.e. antihistamines and alcohol work together at H1 receptors to cause excessive sedation
