ASAP

the strength of drug–receptor binding

affinity

↑ kd =

↓ affinity

(equilibrium dissociation constant) is the concentration at which 50% of receptors are bound

Kd

receptor downregulation or desensitization → tolerance, reduced drug effect

Chronic agonist therapy

receptor upregulation or supersensitivity → rebound effects if suddenly withdrawn

Chronic antagonist therapy

concentration for 50% max effect (potency)

EC50

maximal effect (efficacy)

Emax

↑ concentration =

↓ potency

↓ concentration =

↑ potency

If a drug elimination requires C545, what would happen to the drugs ½ life if the enzyme was eliminated by another drug?

↑ ½ and ↓ Cl

If C545 was induced (more made) by another drug, what would then happen to a different drugs ½ life if it is eliminated by C545?

↓ ½ life and ↑ Vmax

__ introduce or express/reveal a polar functional group.

Phase I

_ attach a polar molecule to the drug or the drugs metabolite.

Phase II

Functionalization (oxidation, reduction, hydrolysis)

Phase I

Conjugation

Phase II

devoid of pharmacological activity

Inactive metabolite

Has pharmacological activity

Active metabolite

Can phase I become phase II through metabolites?

Yes

Organic cation transporters

OCT

Organic anion transport polypeptides

OATP

Organic anion transport

OAT

Efflux transporter

P-glycoprotein

How to deal with low aqueous solubility

+ hydrophilic group that can be removed post administration, usually a phosphate

How to deal with low membrane permeation

+ a masking group to shield

How to deal with short duration of action

+ add a group that is removed slowly in the body, usually a amino acid

Prodrug

inactive precursor → active molecular structure

Patient receives therapy for symptom relief and can be used before exercise/allergies

Reliever therapy

Patients with persistent need this to control symptoms and reduce risk

Maintenance (Controller) therapy

one inhaler is used as a Maintenance and Reliever therapy

MART

SABA

Reliever

SABA+IBS

Reliever

SAMA

Reliever

SABA+SAMA

Reliever

ICS

Maintenance

ICS+LABA

Maintenance

LAMA

Maintenance

ICS+LABA+LAMA

Maintenance

B-2 causes ___ of smooth muscle

relaxation

B-2 ___ inflammation, prostaglandins, leukotrienes/histamines

decreases

B-2 ___ mast cell activation

decreases

b-2 on skeletal system

tremors

B-2 on heart

tachycardia

B-2 on liver

hyperglycemia

B-2 on plasma

hypokalemia

Corticosteroids __ inflammatory gene transcription

decrease

Corticosteroids __ anti-inflammatory gene transcription

increase

Corticosteroids __ expression of B-2 receptors in respiratory tract

Increase

Corticosteroids __ B-receptor kinase and beta-arrestin

decrease

Corticosteroids __ B-2 coupling to G-protein

enhance (increase)

Activation of B-2 receptors increases the ability of GRs to ___ to the nucleus

translocate

Activation of B-2 receptors _____ the binding of GR to GRE

increases