Interactions

What is pharmacokinetics and pharmacodynamics?

• Pharmacokinetics - processes that affect the drugs stay in the body. Everything that happens from administration to the target

• Pharmacodynamics - drug-target or drug-drug-target interactions. Effect of drug at the receptor/cell/tissue

What is the physiology to control processes?

What is the physiology of the medulla oblongata?

What do drugs interact with?

Endogenous proteins

• Changing their structure or function (ir)reversibly

What are key features of drugs to be effective?

• Selective

• Specific

• Affinity and potency

What is affinity and potency and which combo is agonistic or antagonistic?

• Affinity - the attraction between drug/receptor or enzyme

• Potency - if the interaction operates the receptor system

• Affinity and potency - agonist (mimics action)

• Affinity and no potency - antagonist (blocks action)

How do agonists work?

• Endogenous function: controlled by endogenous agent which stimulates/is a substrate of a receptor/enzyme.

  • Effect is proportional to the concentration of the agent.

• Agonist does the same thing, but may be more potent

• Drug conc is proportional to its pharmacological effect based on a certain affinity and maximal response

How do antagonists work?

• Endogenous agent which stimulates/is a substrate of a
  receptor/enzyme.

  • Effect is proportional to the concentration of the agent.

• Antagonist prevents the endogenous agent’s effect

• Antagonist has a similar affinity for the receptor/enzyme

  • It has no potency so prevents function

What are the 4 ways agonists and antagonists interact?

• Competitively - agonist/antagonist have similar affinities, bind at the receptor/enzyme active site

  • Tamiflu, azoles, Viagra

• Non-competitively - antagonist binds at a different site,
  prevents function.

  • Miraviroc (anti-HIV)

• Uncompetitively - inhibitor binds to receptor/enzyme/agonist complex

• Irreversibly - drug destroys enzyme or receptor

  • Fluoxetine

How can competitive inhibition be overcome?

Add enough agonist

• Lower affinity but max potency

Why is grapefruit juice not allowed with some medication?

• Blocking the enzyme CYP3A4 in the intestines, which normally breaks down medications

• More drug enters the bloodstream instead of being metabolised → overdose and SEs

What medications cannot be taken while drinking grapefruit juice?

• Statins - Atorvastatin and simvastatin.

• BP meds - Ca channel blockers, felodipine and nifedipine.

• Immunosuppressants - cyclosporine.

• Anti-Anxiety/Psychiatric Drugs - Valium (diazepam) and Zoloft (sertraline).

• Heart Rhythm Meds - Amiodarone.

• Antihistamines - Fexofenadine

What is the therapeutic index?

• Wide - toxic concs to be high and normal to be low

• Narrow - levels are close together. High risk of toxicity

What drugs have a wide or narrow therapeutic indexes?

• Wide TI drugs: SSRI’s like fluoxetine, sertraline, citalopram or penicillin

• Narrow TI drugs: Tricyclic antidepressants like amitriptyline or warfarin, digoxin, levothyroxine