week 8 10/15 quiz 7 Ch.67: important drug interactions and their mechanisms

factor that can alter response to drugs

the concurrent administration of other drugs

drugs can interact

pharmacokinetically (ADME) or pharmacodynamic (additive, synergistic, antagonistic), or combined interactions

botanical interactions

can increase or decrease a drug's effects, potentially causing side effects or reducing effectiveness

Herbal medications (botanicals) can interact with:

Other herbal supplements, Prescription medications, or Over-the-counter medications

Patient factors

can include intrinsic drug clearance, genetics, gender, concurrent diseases, and diet

Drug-specific factors

include dose, route of administration, drug formulation, and the sequence of drug administration

5 ways drugs can affect absorption

Adsorption, Binding/Chelation, Changes in gastric pH, Changes in GI motility, Changes in transport proteins

Adsorption

One substance sticks to the surface of another, preventing absorption

Binding/Chelation

Two substances bind together, forming a complex that is poorly absorbed

Changes in gastric pH

drug changes stomach acidity, affecting another drug's dissolution or absorption

Changes in GI motility

A drug speeds up or slows down movement through the GI tract, affecting absorption

Changes in transport proteins

Drugs affect transporters like P-glycoprotein (P-gp), which can pump drugs back into the intestine

-Inhibiting intestinal P-gp can increase absorption of certain drugs

Absorption rate

How quickly a drug enters the bloodstream

Tmax, Cmax

Extent of absorption

How much of the drug reaches systemic circulation

AUC (and bioavailability, F)

Decreased absorption rate

Drug enters the bloodstream more slowly.

The total amount absorbed may remain unchanged

Decreased extent of absorption

Less drug reaches systemic circulation.

Can lead to subtherapeutic concentrations (not enough drug to work).

Increased extent of absorption

More drug reaches systemic circulation.

Can cause toxicity or adverse effects

3 ways drugs can affect distribution

Competition for plasma protein binding, Displacement from tissue binding sites, and Alterations in tissue barriers (P-glycoprotein)

Competition for plasma protein binding

Drugs can compete for the same plasma protein binding sites, causing one drug to displace another and temporarily increase its free (active) concentration and effects in the bloodstream

Displacement from tissue binding sites

One drug can displace another drug from tissue binding sites, causing the displaced drug to enter the bloodstream and temporarily increase its blood concentration

Alterations in tissue barriers (P-glycoprotein)

P-gp prevents drugs from entering brain, if drug inhibits P-gp at bbb, more P-gp substrate drug can enter the brain → increases the drug's effects/toxicity in the CNS

Plasma protein displacement summary

Temporarily increase free drug in plasma

Tissue binding displacement summary

Temporarily increase drug concentration in blood

P-gp inhibition at BBB summary

May increase drug entry into brain

protein binding displacement alone

rarely causes significant toxicity, although other simultaneous interactions can still be important

Drugs can either

induce (speed up) or inhibit (slow down) the enzymes responsible for metabolizing other drugs

Enzyme Induction (Speeds Up Metabolism)

Increases CYP450 activity, causing faster drug metabolism and usually ↓ drug concentration and effectiveness.

Takes 7–14 days for maximum effect and may persist after stopping

Enzyme Inhibition (Slows Down Metabolism)

Decreases CYP450 activity, causing slower drug metabolism and usually ↑ drug concentration and toxicity risk. Effects occur relatively quickly

Drug metabolism occurs

in the liver and the wall of the small intestine

Renal Excretion: Changes in Urinary pH

Some drugs change urine pH, affecting the ionization of weak acids and weak bases.

More ionized = Less reabsorption = More excretion.

Less ionized = More reabsorption = Less excretion

Inhibition of Renal Transporters

Inhibiting these transporters can decrease drug elimination which causes ↑ drug concentration and risk of toxicity

-P-gp, OAT, and OCT

Ionized drugs

are generally trapped in urine and eliminated more easily because they cannot readily cross cell membranes

Pharmacodynamic interactions factors

Additive Effect, Synergistic Effect, Antagonistic Effect

Additive Effect (1 + 1 = 2)

Two drugs with similar effects are taken together, their combined effect equals the sum of their individual effects

Synergistic Effect (1 + 1 = 3)

Two drugs work together to produce a greater effect than expected from adding their individual effects

Antagonistic Effect (1 + 1 < 2)

Two drugs have opposing effects, one drug reduces or blocks the effect of another

Pharmacokinetic interactions

Change drug concentrations through ADME

Pharmacodynamic interactions

Change drug effects through receptor activity or physiological pathways

Combined Toxicity

When two or more drugs are taken together, they can increase the risk of organ damage, even if each drug alone would not cause toxicity

Same organ toxicity and Enhanced toxicity

Same organ toxicity

Two drugs that harm the same organ can increase the risk of damage

Enhanced toxicity

One drug can increase another drug's toxicity, even if it doesn't harm that organ itself