ASAP

the strength of drug–receptor binding

affinity

↑ kd =

↓ affinity

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receptor upregulation or supersensitivity → rebound effects if suddenly withdrawn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

increases metabolism/transport → lower plasma drug levels, reduced effect.

Induction

decreases metabolism/transport → higher plasma drug levels, increased effect/toxicity.

Inhibition

WOULD LOWER DOSE (inhibition or induction)

Inhibition

__ 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

Can phase I become phase II through metabolites?

Yes

Organic cation transporters (BASES)

OCT

Organic anion transport polypeptides

OATP

Organic anion transport (ACIDS)

OAT

Efflux transporter

P-glycoprotein

How to deal with low aqueous solubility

Phosphate ester

+ hydrophilic group that can be removed post administration

Phosphate ester

How to deal with breaking?

Amino Acid esters

↑ absorption

Amino Acid esters

How to deal with low membrane permeation

Alkyl ester

+ a masking group to shield

Alkyl ester

How to deal with short duration of action

Amide ester

+ add a group that is removed slowly in the body

Amide ester

cut off ester (back to normal drug)

Esterases

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

After starting a new treatment, pts should be followed up in

1-3 months

When asthma is well controlled and therapies are stable, pts can be followed up every

3-12 months

When asthma is ___ a minimum of 3 months, a step-down therapy can be considered

well controlled

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 heart

hypokalemia

B-2 on brain

Restlessness / anxiety

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

Combination therapy with inhaled corticosteroids (ICS) and beta2 agonists ___ airway tone control and reduces inflammation

Improves