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Pharm week 2
| Question | Answer |
|---|---|
| What determines the intensity of the drug response | Determined by the concentration of drug at its site of action, there are individual variations Factors - administration, pharmacokinetics, pharmacodynamics |
| How does administration affect the intensity of drug response? | Too much, too little,patient adherence, wrong administration |
| Pharmacokinetics | How much of the administered dose will get to its site of action? Study of drug movement throughout the body The impact of the body on drugs Determined by: drug absorption, drug distribution, drug metabolism, and drug excretion |
| Parmacokinetics looks at: | How drugs enter body How drugs reach their site of action How drugs are removed from the body |
| How do drugs cross membranes | Channels and pores (dissolving in liquids), transport systems, direct penetration (lipophilic, polar molecules, ions) |
| Absorption | Movement of drug from its site of administration into the blood Two routes - enteral and parenteral |
| Enteral route of absorption | Through intestines/digestion |
| Parenteral route of absorption | IV or injections Through food (TPN) Really bad for BV because there's lots of sugar and sugar leads to infections |
| Factors affecting drug absorption | Rate of dissolution Surface area Blood flow Lipid solubility pH partitioning |
| How does rate of dissolution affect drug absorption | Has to do with the content of pill and environment you're putting it into Ex - stomach with high acid content or stomach with someone who takes lots of antacids |
| How does surface area affect drug absorption | The larger the surface area, the faster the absorption will be |
| How does blood flow affect drug absorption | CO = SV X HR More blood flow = more absorption |
| How does lipid solubility affect drug absorption | Lipid soluble gets absorbed faster |
| How does pH partitioning affect drug absorption | Basic drugs will accumulate in acidic areas (opposites attract) Acidic drugs accumulate in alkaline areas Opposite environments will let drug cross barrier and cause ionization of drug |
| Barriers to IV drug administration | Meds are immediately into blood stream and that could be bad if its wrong drug It can cause infections (systemic effects) |
| Advantages to IV drug administration | -Rapid onset -Controlling how much blood stream is getting -If no meds are lost through absorption, we aren't wasting parts of drug -Cost effective (can use smaller amount through IV) |
| Disadvantages to IV drug administration | -Sometimes its costly if there are special storage instructions -Patient has to be in hospital -Drug becomes irreversible -Requires lots of fluid along with it -Infections -Air embolisms |
| Disadvantages to IM/SubQ drug administration | -Patient's don't like it -Not directly into blood -Incontinences -Pain from tissue injury -Not good for people on blood thinners (keeps bleeding/bruising) |
| Advantages to IM/SubQ drug administrations | Good route for poorly soluble drugs |
| Absorption pattern of IM/SubQ drug adminsitration | Rate of absorption is more determined by drug (is it water or lipid soluble?, what is the blood flow pattern to area injected?) Give injections in high blood flow areas |
| PO drug absorption disadvantages | Highly variable - depends on person Nutritional status Co-administration with other drugs Requires patient to be conscious and cooperative N&V Drug-drug interactions |
| PO drug absorption advantages | Convenient Safer than injections |
| PO pros and cons vs Parenteral pros and cons | |
| Topical drug administration | Local therapy to skin Ex - eye drops, nasal spray, oragel, vaginal topically |
| Transdermal drug administration | Patches Need to be moved around and taken off before new one is put on |
| Drug distribution | Movement of drugs throughout the body |
| Drug distribution is affected by | Blood flow to tissues Exiting vascular system Entering cells |
| How does drug exit vascular system? | Blood brain barrier Placental drug transfer Protein binding |
| Blood brain barrier distribution | Lipophilic or transport system can get across blood brain barrier It isn't fully developed at birth so everything can get up to their brains |
| Placental drug transfer distribution | Placenta doesn't provide absolute barrier Lipid phillic can easily cross (caffiene, nicotine, alcohol, or any other lipophilic drug) |
| Protein binding drug distribution | Drugs form reversible bonds with proteins Plasma albumin Drug can either be bound or unbound to plasma albumin If it can't be bound it can't get out of vascular system |
| How can drugs enter cells? | Receptors Lipid soluble or have transport system |
| Drug metabolism | Enzymatic alteration of drug structure |
| Hepatic drug-metabolizing enzymes | sdf |
| Therapeutic consequences of metabolism | Accelerated renal drug excretion Increased therapeutic action Drug inactivation Increase or decrease in toxicity Activation of prodrugs |
| Drug metabolism special considerations | Age Induction of drug-metabolizing enzymes First pass effect Nutritional status Competition between drugs |
| Drug excretion | Removal of drugs from the body Types - renal and non-renal |
| Renal excretion of drugs | |
| Non-renal routes of drug excretion | Breast milk Bile (feces) Lungs Sweat |
| Time course of drug responses | Plasma drug levels (minimum effective concentration - the level at which the drug is below the therapeutic range) (toxic concentration - above therapeutic range) Therapeutic range - the range we want drug to be in, we want it to be a long time Goal |
| Time course of drug responses slide 24 on A | dfg |
| Half-life | The time required for the amount of the drug in the body to decrease by 50% Time required for 1/2 drug concentration to be eliminated Determines dosing frequency Takes 4-5 half lifes to reach steady state |
| Plateau | Steady level Amount of drug eliminated = amount administered Slide 26 |
| Pharmacodynamics | The study of what drugs do to the body and how they do it |
| Dose-response relationships | Graded response All or nothing response Maximal efficacy Relative potency |
| Graded response | |
| All or nothing response | |
| Maximal efficacy | Largest effect that a drug can produce |
| Relative potency | amount of drug we must give to elicit an effect |
| Drug-receptor interactions | Drugs modify existing functions, they do not create physiologic function Binding of drug to receptor is usually reversible D+R <> D-R Complex --> response |
| Primary receptor families | Cell membrane-embedded enzymes Ligand-Gated ion channels G protein-coupled receptors Transcription factors |
| Cell-membrane embedded enzymes | |
| Ligand-gated ion channels | |
| G protein-coupled receptors | |
| Transcription factors | |
| Theories of drug-receptor interaction | Single occupancy Modified occupancy (affinity and intrinsic activity) |
| Agonist | Affinity and intrinsic activity Partial vs. full |
| Antagonists | Affinity, but no intrinsic activity Competitive vs. noncompetitive |
| Receptorless drugs | Some drugs don't act through receptors Act via physical/chemical interaction -Ex - antacids, antiseptics, saline laxatives |
| Interpatient variability in drug responses | Evaluate patients individually ED50 (average effective dose) - dose that is required to produce a defined therapeutic response in 50% of population |
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