Lecture 1: Basic Principles of Pharmacology I Flashcards
What is pharmacokinetics?
Time course of drug absorption, actions, and elimination. (What the body does to the drugs.)
What is pharmacodynamics?
Types of drug actions (What the drugs do to the body.)
- Physiochemical actions (simple chemical interactions)
- Receptor interactions
What do Drug - Receptor interactions cause?
Cause molecular events to occur in each cell - enough of the events cause a change in cell function –> ultimately resulting in a change in tissue function.
Name two types of drug - receptor bonds.
- Reversible: ionic, Van der Waals, Hydrogen
2. Irreversible: covalent
Explain Receptor Theory.
The structure of the drug determines how it will fit into the receptor. The better the fit, the better the stimulation. Subtle changes in structure amongst a class of drugs can greatly influence the drugs’ effects.
Explain how agonist drugs work.
They bind to the receptor and produce a pharmacologic effect. (Activate receptor after binding.)
Explain how different agonists work on the log dose response graph.
All achieve the same Emax (Vmax) at different doses.
What are the two ways of quantifying agonism?
- Efficacy
2. Potency
What is efficacy?
- The ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor.
- Depends upon the structure of the drug
(First Aid) What is the significance of efficacy?
- Equals to Vmax or Emax
2. Non-competitive inhibitors reduce efficacy (change y-axis)
What is potency?
- Relates to the amount of drug that is needed for an effect
- Depends on the
1) The biologic system
a. receptor density
b. efficiency of the stimulus-response mechanisms of the tissue
2) Interaction of the drug with the receptor
a. affinity
b. efficacy
(First Aid) What is the significance of potency?
- Associated with Km (low Km = high potency)
2. Competitive inhibitors will reduce the potency
(First Aid) Explain efficacy.
- Maximal effect a drug can produce
2. High-efficacy drug classes are analgesic (pain) medications, antibiotics, antihistamines, and decongestants.
(First Aid) Explain potency.
- The amount of drug needed for a given effect
- Increased potency means increased affinity for receptor.
- Highly potent drug classes include chemotherapeutic (cancer) drugs, antihypertensive (blood pressure) drugs, and antilipid (cholesterol) drugs.
How do antagonists work?
- Antagonists can block the binding of agonists and prevent the pharmacologic response.
- Many things are learned about the structure and function of receptors from the use of antagonist
What are some of the agents used as antagonists as therapeutic agents to slow the system down?
Paralytic agents
What is the characteristics of competitive antagonists.
Antagonist effect can be overcome by increasing the does of the agonist.
What is the characteristics of noncompetitive antagonists?
- Can’t be overcome by increasing doses of agonist
2. Receptors remain occupied by antagonist and not enough DR interactions occur to achieve Emax.
(FA) Explain Km, Vmax.
- Km reflects the affinity of the enzyme for its substrate.
- Vmax is directly proportional to the enzyme concentration.
- Lower the Km higher the affinity
(FA) What happens when you add a competitive antagonist on the dose respond curve?
- Shifts curve to right –> Reduce potency, No change in efficacy
(FA) What are some examples of adding competitive antagonists to an agonist?
Diazepam + flumazenil on GABA receptor
flumazenil is a competitive antagonist at GABA benzodiazepine receptor
(FA) What is the effect of noncompetitive antagonist on the dose respond curve?
Shifts curve down –> Reduced efficacy
(FA) What is an example of noncompetitive antagonist?
Norepinephrine + phenoxybenazmine on alpha receptor (phenoxybenzamine is a nonselective, irreversible alpha blocker)
(FA) What is the effect of partial agonist on the does respond curve?
- Acts at the same site as full agonist, but with reduced maximal effect –> reduced efficacy.
- Potency is a different variable and can be increase or decrease
(FA) What is an example of a partial agonist?
Morphine + buprenorphine at opioid u-receptor
(FA) What are the receptors for G-protein-linked 2nd messengers? (G-protein class)
- alpa1, alpha2, beta1, beta2 (q, i, s, s) –> sympathetic
- M1, M2, M3 (q, i, q) –> Para-sympathetic
- D1, D2 (s, i) –> Dopamine
- H1, H2 (q, s) –> Histamine
- V1, V2 (q, s) –> Vasopressin
(FA) Mnemonics for G-protein class?
Qiss (kiss) and qiq (kick) till you’re siq (sick) of sqs (sex).
(FA) H1, alpha 1, V1, M1, M3 (HAVe 1 M&M)
Gq –> Phospholipase C –> PIP2 –> DAG (Protein Kinase C) & IP3 (Increased intracellular Ca2+)
(FA) B1, B2, D1, H2, V2
Gs –> Adenylyl cyclase –> cAMP –> Protein kinase A –> Increased intracellular Ca2+ in the heart
(FA) M2, alpha2, D2 (MAD 2’s)
Gs –> Adenylyl cyclase –> cAMP –> Protein kinase A –> Increased intracellular Ca2+ in the heart
What is drug action?
Molecular action - invisible
What is selectivity?
property of drug to cause a specific effect, few drugs produce a single effect
Pharmacokinetic deals with
dosing and elimination of drugs
Pharmacodynamic deals with
effects of the drugs on the body
Increased cGMP and cAMP via intracellular signaling leads to muscle ( )
relaxation (NO via cGMP, B2 via cAMP)
How does Angiotensin II work?
Increase IP3 –> increase Ca2+ intracellular conc –> smooth muscle contraction
How does NE via adrenergic nerve work via intracellular signaling?
Alpha 1 receptor –> increase IP3 –> increase Ca2+ intracellular conc –> smooth muscle contraction
Explain how Gs coupled receptor work
once ligand is bound, ATP –> cAMP
Explain how Gq coupled receptor work
Phospholipase C –> PIP2 produces DAG and IP3
What is “Intrinsic Activity?”
- Ability to stimulate the receptor once bound.
2. Relates to structure and influences efficacy and potency.
Greater intrinsic activity means
greater efficacy
(Check with notes) Hypersensitivity can occur
with antagonist (example: sudden withdrawal of beta blocker
Desensitivity can occur
with agonist
Efficacy is depend on
the structure of the drug
Potency is depend on
- The biologic system
a. receptor density
b. efficiency of the stimulus-response mechanisms of the tissue - Interaction of the drug with the receptor
a. affinity
b. efficacy
