1 - Intro to Pharm Flashcards
What are the 3 categories of therapeutic compounds?
- Small molecule drugs →Chemicals
→Can pass through cell membranes to reach intracellular targets
→Rapidly absorbed and metabolized.
→Ex. Ibuprofen - for headache - Biologics
→ Antibodies, proteins, or hormones are used to treat patients
→Typically administered via injection
→More specific in targeting diseases, reducing side effects compared to small molecules.
→ Lager molecules
→ Ex. Insulin - Natural health products
→ Vitamins, herbal preparations, traditional Chinese medicines, and probiotics
What are 3 Phases of Clinical Trial Phases ?
Phase 1: Safety
→Purpose: determine if the medication/treatment safe
→Are there side effects?
→How does it move through the body?
→Participants: Small groups (<100)
→Distinct Feature: Focused mainly on safety rather than effectiveness.
Phase 2: Efficacy
→Purpose: Assess if the medication/treatment effective in treating targeted condition?
→Does it relieve, reverse, or stop progression
→How safe is it?
→What is most effective dosage?
→Participants: 100-300 ppl w/ exact condition being studied
→Distinct Feature: Focuses on treatment effectiveness in addition to safety.
Phase 3: Confirmation
→Purpose: compares the medication/treatment to standard treatment for condition?
→More effective, less effective?
→Longer-term adverse effects?
→How might it be used with existing treatments?
→Participants: 300-3000
Exact condition being studied
→Distinct Feature: Large-scale testing to confirm efficacy and monitor side effects before approval.
Phase 4: Follow-Up
→Purpose: After the medication/treatment is approved, evaluates how does it work for other patients with the condition?
→Are there long-term benefits/risks?
→Participants: Several thousand who have been prescribed the medication
→Distinct Feature: Conducted after market approval to monitor ongoing safety and effectiveness.
Structure of Phospholipids
- Plasma membrane is a bilayer (has 2 layers of phospholipids):
- Phospholipids contain heads and fatty acid tails
→Heads are hydrophilic (love water) - positioned so they interact with water in cytoplasm inside the cell and with water found outside of cell
→ Fatty acid tails are lipophilic (fat loving) - point tails inward to avoid the water
→ The core (lipophilic fatty acid tail region) is what causes the membrane to be selectively permeable - Lipophilic drugs can cross membranes easily
Lipophilic Vs. Hydrophilic Drugs Crossing Membranes
- After an oral drug is ingested, it must be absorbed through the intestine, enter the bloodstream (capillaries), and travel to its target site of action
Absorption in Small Intestine
→Lipophilic drugs cross the membrane easily via simple diffusion (passive transport).
→Hydrophilic drugs require uptake transporters to be absorbed
Entry into Capillaries (Bloodstream)
- Once inside intestinal cells, drugs must enter capillaries to reach systemic circulation.
→Lipophilic drugs diffuse easily into the capillaries.
→Hydrophilic drugs may require transporters or pass through fenestrations (small pores) in the capillary walls.
Transport Through the Bloodstream
→Lipophilic drugs may bind to plasma proteins (like albumin) for transport.
→Hydrophilic drugs dissolve directly in the blood (since they are water-soluble)
Delivery to the Site of Action
→Lipophilic drugs cross cell membranes by simple diffusion and reach their site of action efficiently.
→Hydrophilic drugs often require specific transporters or channels to enter cells
How Drugs Cross the Plasma Membrane
1) Simple diffusion
→ Lipophilic (fat-soluble) drugs can dissolve through fatty acid tails of phospholipids - they cross membranes completely unassisted
→ Hydrophilic/polar drugs - can not cross membrane because they are soluble in water and do not dissolve in lipids
2)Ion channel
→ Ions are small and cross via ion channels
→ Ion channels are selective, based on the size and charge of the ion
→ Very few drugs use ion channels
3) Uptake drug transporter
→The protein undergoes shape change to move the drug across the membrane
→ The drug must be the correct shape and size to fit into the binding site and be transported
→Efflux transporters
- Can protect a cell from accumulating too much of a drug
- Can interfere with getting appropriate drug concentrations inside of a cells
Weak Acid VS. Weak Base
Weak Acid
→Not ionized (remains in neutral form)
→Easily crosses membranes (lipophilic in acidic environment)
→High absorption (remains uncharged and can pass through membranes)
→Ex. Aspirin (absorbed well in the stomach)
Weak Base
→Ionized (becomes charged)
→Difficult to cross membranes (hydrophilic in acidic environment)
→Poor absorption (ionized and cannot pass through membranes)
→Ex. Morphine (not well absorbed in the stomach)
What is pH trapping?
- changing the pH to be able to trap a weak acid and more can be excreted
- Important in drug overdose
Ex. Aspirin (weak acid)
→If someone takes too much aspirin - we want to make sure not too much is absorbed and enough stays in filtrate
→Patient can be given IV solution to raise pH of their filtrate causing aspirin molecules to become charged; they get trapped in filtrate and more of the drug gets excreted in urine and does not have effects on body
Continuous Capillaries
→Muscles, brain, lungs, heart
→Least permeable (tight junctions)
→Endothelial cells tightly connected; few intercellular clefts
→Limits paracellular transport; controls selective diffusion (e.g., in blood-brain barrier)
Brain
→Has continuous capillaries with almost no permeability bw endothelial cells = NO paracellular transport through intercellular clefts
→This is why most drugs can not cross the brain unless they are lipophilic enough to move by simple diffusion or a membrane transporter exists
Requires transcellular transport (lipophilic drugs or transporters
→No major role in drug excretion
Fenestrated Capillary
→Kidneys (glomerulus), intestines, endocrine glands
→Moderately permeable (small fenestrations)
→Has intercellular clefts and small fenestrations (pores)
→Allows rapid exchange of small molecules, ions, and drugs (e.g., kidney filtration)
→Drugs can easily move through intercellular clefts and fenestrations bc they are smaller molecule
→Proteins and cells will NOT fit through
→Kidney filters drugs into urine
Sinusoidal Capillary
→Liver, bone marrow, spleen
→Most permeable (large fenestrations & clefts)
→Has large fenestrations and wide intercellular clefts
→Allows passage of larger molecules like proteins and drugs (e.g., liver metabolism & bile excretion)
→Drugs pass easily through both fenestrations and clefts, allowing metabolism and excretion via bile
→Liver processes drugs for excretion via bile/feces
Narrow VS. Wide therapeutic range
Narrow Range
→A small difference between the effective dose and the toxic dose
→Requires close monitoring of blood levels to avoid toxicity
→Higher risk of overdose or adverse effects
→Ex. Warfarin, Digoxin, Lithium
→Small adjustments in dosage can lead to toxicity or ineffectiveness
Wide Range
→A large difference between the effective dose and the toxic dose
→Less frequent monitoring needed
→Lower risk, as fluctuations are less likely to cause harm
→Ex. Ibuprofen, Amoxicillin
→More flexibility in dosing without serious effects
What are Adverse drug Reaction
1) Genetics
→Affects how we metabolize drugs and influences drug transport - can prevent a drug from being eliminated properly
→If drugs are not eliminated properly = drug concentration in blood increases = harmful effects
→Males and females can also respond to drugs differently
2) Age
→Elderly and children are at risk of adverse drug rxns
3) Another disease/condition
→Ex. Someone with liver disease may not properly eliminate/metabolize drugs
4) Other drugs
→Other drugs can interfere - known as drug-drug interactions
5) Allergic Reaction
→People can be allergic to drugs and experience symptoms such as: hives, rash etc.
6) Act on another organ
→The drug can also act on another organ/tissue that is not intended to be treated, creating “off-target effects”
→Ex. Relieving opioid drugs (codeine, morphine) are intended to act on pain pathways, but can cause constipation bc they affect normal movement patterns of the intestines
→Side effects - aka off-target effects
