Pharmacology Final
● FDA
● Drug schedules
○ Potential for abuse
■ Schedule I is highest potential for abuse (little medical use at this time)
■ Schedule V is lowest potential for abuse
○ Opioids, benzodiazepines, anabolic steroids, barbiturates
○ Controlled substances
■ Restricted prescribing procedures, ie schedule II
PHARMACOKINETICS
Pharmaceutics
● Oral drugs become liquid/ solution to cross plasma membrane and be absorbed
Disintegration: break down Dissolution: is smaller Rate of absorption:
of tablet into smaller particles particles dissolve in the GI Time until drug is available to
fluid the body after disintegration
and dissolution
● Enteric coated drugs resist disintegration in the gastric acid and wait to be absorbed in alkaline
environment-therefore do not crush
● Food can increase or decrease absorption
● Never crush coated capsules--go further into GI tract
Pharmacokinetics
● Movement of drug to achieve action of drug
● Obstacles: fewer with IV meds than PO
● PO meds: stomach acid break down drug molecules
○ Liver chemical changes make a drug less active
○ GI plasma membrane may prevent entrance into the bloodstream
○ Drugs go from GI tract to the liver
● Drugs need to cross plasma membranes to enter cells to produce effect
Diffusion Active transport
Passive, high to low concentration (blood to Carrier protein or enzyme
tissues) Proteins are specific for what they will carry
Small, nonionized and lipid soluble drugs (sodium potassium pumps)
will pass through most easily. Weak acidic Low concentration to high concentration
drugs are less ionized, so they pass through Needs energy
more quickly, easily
Large, ionized (no charge) water soluble
drugs cannot pass easily
● 4 phases: absorption, distribution, metabolism, excretion
Absorption
● Process of movement of drug particles to body fluids. Movement happens in small intestines
● Absorption doesn't happen for IV meds (already in blood stream)
● Determines onset action and intensity of drugs
● Absorption rate 0-100%. Higher rate= greater effect
,Passive absorption of drugs
Facilitated diffusion Active absorption Pinocytosis
Carrier protein moves drug from Need carrier protein against Cells carry drugs across
higher to lower concentration gradient membrane by engulfing drug
Factors of absorption
● Concentration: higher dose= faster and greater response
○ Greater concentration gradient for diffusion
● GI membrane composed of lipids and fats. Lipid soluble drugs pass through faster. Water soluble
drugs need carrier to pass membrane
● Blood flow, pain, stress (slow gastric emptying time)
● Exercise, hunger pH
● IM in areas of increased blood flow
● Subcutaneous: decreased blood flow than muscle
Drug Ionization
● Large particles can pass through mucus membrane if nonionized
● charged/ionized particles don’t pass through easily
● Charge depends on environment
● Acidic drugs are absorbed in acidic environments since they are nonionized
● basic/alkaline drugs are absorbed in bases/basic environments since they are nonionized
● Drugs are absorbed better in a matched environment
First pass effect, first pass mechanism, hepatic first pass
● Drugs metabolized in liver after GI absorption
○ Intestinal lumen to portal vein to liver
○ Becomes inactive and is then excreted
● Most drugs affected by first pass
● Decrease in liver function= decrease in metabolism=decrease breakdown= a need for a decrease
in pt dose
Bioavailability
● Percent of drug that reaches systemic circulation and causes effect
● Oral drugs are never 100% Iv are usually 100% (IV dose is lower than oral)
● Factors affecting bioavailability
○ Form of drug, route, food, other drugs
○ Liver status
○ Liver disorders cause less of drug to be available
Distribution
● Process of which drug become available to body fluids and tissues
● Influenced by blood flow, drugs affinity to tissues, and protein binding effect
● Areas with highest blood flow have highest exposure to absorbed drugs
○ Heart, kidney, and liver have high exposure
○ Skin, bones, and cells have low exposure
○ Damaged blood cells have lower distribution (necrotic areas or broken bones)
Solubility
● Lipid solubility- increased distribution since plasma membranes allow them, pass more easily
, ● Only unbound or free drugs can reach target cells
● Bound drugs do not have an affect
● Higher protein binding, the less the effect of the drug
Drug protein complexes
● Protein binding effect (albumin, AGP-alpha glycoprotein)
● Some drugs bind to proteins too big to distribute across capillary membranes
○ Bind with protein no longer available to tissues
○ Only unbound free drugs can make an effect
● Can compete for binding sites on proteins
○ Drug with higher protein binding effect binds first. The other drug is more free
○ Drug that is less protein bound has a greater effect
○ Watch for toxicity
○ Higher protein bound have less effect. Free drug causes an effect
Other factors of distribution
● Blood brain barrier- can prevent certain drugs from getting into the brain. Good or bad
● Capillaries packed tightly do not let substances in easily
○ Lipid soluble and glucose can pass through
○ Large, water soluble can’t pass through
● Harmful cannot get in/out of the brain
● Some meds cannot get into the brain
Metabolism
● Biotransformation = chemical change of the drug
● Occurs in liver mostly. Sometimes GI tract and kidneys
● Metabolic changes of drugs in the liver allow for it to be excreted
● Active metabolites have greater effect than original form of the drug
● Liver disease can impact metabolism
Liver hepatic first pass
● Drugs not absorbed in intestines go to the liver
● Some of the drug is metabolized in the liver, inactivated or excreted before effect of drug occurs
● Some drugs cannot be given orally b/c of the first pass, so it is destroyed and unable to use
Four processes within the pharmacokinetic stage
1. Absorption
● Process of movement of drug particles to body fluids, mostly in the small intestine.
● Determines the onset of action for the drug
● Determines the intensity of drug action
- 0-100% absorption (oral meds cannot be 100%)
- Higher absorption=greater effect
● Enteric coating: protects against acid in stomach, allows absorption in small intestine (no
absorption in stomach)
● Extended release formula: absorption over long period
● Absorption of drugs
- Diffusion
, - Facilitated diffusion
- Active absorption
- Pinocytosis
● Other effects on absorption
● Blood flow, pain, stress (slow gastric emptying time), Exercise (shunts blood flow to
muscles, decreased blood flow to GI tract), hunger, pH
2. Distribution
● Those areas with highest blood flow have the highest exposure to absorbed drugs
● Lipid solubility increases distribution; tissue storages decreases distribution with
increased affinity; drug protein complexes
Solubility
o Only unbound or free drugs, can reach target cells; bound drugs do not have an effect;
the higher the protein binding the less the effect of the drug
o Drugs can have different binding effects
- Highly protein bound: (>89% of drug is bound); 11% is causing an
effect
- Moderately protein bound:(30-60% of drug is bound)
- Low protein bound: (<30% is bound)
- The drug with the higher binding effect binds first, the other drug
is freer. The drug that is less protein bound has greater effect. Have
to watch for drug toxicity. Drug-drug interaction.
- Ex. high protein bound, and moderate protein bound, moderate is
free and can cause toxicity.
Blood brain barrier (BBB)
- Anatomic barrier that inhibits drugs from leaving bloodstream
- Packed tightly, don’t allow substances in easily
- Can be harmful and cannot get in/out of brain
- Some meds cannot get into brain, protects toxins from getting
in
3. Metabolism (biotransformation)
● Chemical change of the drug
● Therapeutic effects; greater toxicity
● Liver and disease dysfunction can impact metabolism
● Half-life: time it takes for half the drug to be eliminated
● Can affect dosing; can be short or long
● Affects how often we give the medication
4. Excretion
- Renal excretion
PHARMACODYNAMICS
● Drug concentration and its effect on the body and how the body responds to the drug
● FDA
● Drug schedules
○ Potential for abuse
■ Schedule I is highest potential for abuse (little medical use at this time)
■ Schedule V is lowest potential for abuse
○ Opioids, benzodiazepines, anabolic steroids, barbiturates
○ Controlled substances
■ Restricted prescribing procedures, ie schedule II
PHARMACOKINETICS
Pharmaceutics
● Oral drugs become liquid/ solution to cross plasma membrane and be absorbed
Disintegration: break down Dissolution: is smaller Rate of absorption:
of tablet into smaller particles particles dissolve in the GI Time until drug is available to
fluid the body after disintegration
and dissolution
● Enteric coated drugs resist disintegration in the gastric acid and wait to be absorbed in alkaline
environment-therefore do not crush
● Food can increase or decrease absorption
● Never crush coated capsules--go further into GI tract
Pharmacokinetics
● Movement of drug to achieve action of drug
● Obstacles: fewer with IV meds than PO
● PO meds: stomach acid break down drug molecules
○ Liver chemical changes make a drug less active
○ GI plasma membrane may prevent entrance into the bloodstream
○ Drugs go from GI tract to the liver
● Drugs need to cross plasma membranes to enter cells to produce effect
Diffusion Active transport
Passive, high to low concentration (blood to Carrier protein or enzyme
tissues) Proteins are specific for what they will carry
Small, nonionized and lipid soluble drugs (sodium potassium pumps)
will pass through most easily. Weak acidic Low concentration to high concentration
drugs are less ionized, so they pass through Needs energy
more quickly, easily
Large, ionized (no charge) water soluble
drugs cannot pass easily
● 4 phases: absorption, distribution, metabolism, excretion
Absorption
● Process of movement of drug particles to body fluids. Movement happens in small intestines
● Absorption doesn't happen for IV meds (already in blood stream)
● Determines onset action and intensity of drugs
● Absorption rate 0-100%. Higher rate= greater effect
,Passive absorption of drugs
Facilitated diffusion Active absorption Pinocytosis
Carrier protein moves drug from Need carrier protein against Cells carry drugs across
higher to lower concentration gradient membrane by engulfing drug
Factors of absorption
● Concentration: higher dose= faster and greater response
○ Greater concentration gradient for diffusion
● GI membrane composed of lipids and fats. Lipid soluble drugs pass through faster. Water soluble
drugs need carrier to pass membrane
● Blood flow, pain, stress (slow gastric emptying time)
● Exercise, hunger pH
● IM in areas of increased blood flow
● Subcutaneous: decreased blood flow than muscle
Drug Ionization
● Large particles can pass through mucus membrane if nonionized
● charged/ionized particles don’t pass through easily
● Charge depends on environment
● Acidic drugs are absorbed in acidic environments since they are nonionized
● basic/alkaline drugs are absorbed in bases/basic environments since they are nonionized
● Drugs are absorbed better in a matched environment
First pass effect, first pass mechanism, hepatic first pass
● Drugs metabolized in liver after GI absorption
○ Intestinal lumen to portal vein to liver
○ Becomes inactive and is then excreted
● Most drugs affected by first pass
● Decrease in liver function= decrease in metabolism=decrease breakdown= a need for a decrease
in pt dose
Bioavailability
● Percent of drug that reaches systemic circulation and causes effect
● Oral drugs are never 100% Iv are usually 100% (IV dose is lower than oral)
● Factors affecting bioavailability
○ Form of drug, route, food, other drugs
○ Liver status
○ Liver disorders cause less of drug to be available
Distribution
● Process of which drug become available to body fluids and tissues
● Influenced by blood flow, drugs affinity to tissues, and protein binding effect
● Areas with highest blood flow have highest exposure to absorbed drugs
○ Heart, kidney, and liver have high exposure
○ Skin, bones, and cells have low exposure
○ Damaged blood cells have lower distribution (necrotic areas or broken bones)
Solubility
● Lipid solubility- increased distribution since plasma membranes allow them, pass more easily
, ● Only unbound or free drugs can reach target cells
● Bound drugs do not have an affect
● Higher protein binding, the less the effect of the drug
Drug protein complexes
● Protein binding effect (albumin, AGP-alpha glycoprotein)
● Some drugs bind to proteins too big to distribute across capillary membranes
○ Bind with protein no longer available to tissues
○ Only unbound free drugs can make an effect
● Can compete for binding sites on proteins
○ Drug with higher protein binding effect binds first. The other drug is more free
○ Drug that is less protein bound has a greater effect
○ Watch for toxicity
○ Higher protein bound have less effect. Free drug causes an effect
Other factors of distribution
● Blood brain barrier- can prevent certain drugs from getting into the brain. Good or bad
● Capillaries packed tightly do not let substances in easily
○ Lipid soluble and glucose can pass through
○ Large, water soluble can’t pass through
● Harmful cannot get in/out of the brain
● Some meds cannot get into the brain
Metabolism
● Biotransformation = chemical change of the drug
● Occurs in liver mostly. Sometimes GI tract and kidneys
● Metabolic changes of drugs in the liver allow for it to be excreted
● Active metabolites have greater effect than original form of the drug
● Liver disease can impact metabolism
Liver hepatic first pass
● Drugs not absorbed in intestines go to the liver
● Some of the drug is metabolized in the liver, inactivated or excreted before effect of drug occurs
● Some drugs cannot be given orally b/c of the first pass, so it is destroyed and unable to use
Four processes within the pharmacokinetic stage
1. Absorption
● Process of movement of drug particles to body fluids, mostly in the small intestine.
● Determines the onset of action for the drug
● Determines the intensity of drug action
- 0-100% absorption (oral meds cannot be 100%)
- Higher absorption=greater effect
● Enteric coating: protects against acid in stomach, allows absorption in small intestine (no
absorption in stomach)
● Extended release formula: absorption over long period
● Absorption of drugs
- Diffusion
, - Facilitated diffusion
- Active absorption
- Pinocytosis
● Other effects on absorption
● Blood flow, pain, stress (slow gastric emptying time), Exercise (shunts blood flow to
muscles, decreased blood flow to GI tract), hunger, pH
2. Distribution
● Those areas with highest blood flow have the highest exposure to absorbed drugs
● Lipid solubility increases distribution; tissue storages decreases distribution with
increased affinity; drug protein complexes
Solubility
o Only unbound or free drugs, can reach target cells; bound drugs do not have an effect;
the higher the protein binding the less the effect of the drug
o Drugs can have different binding effects
- Highly protein bound: (>89% of drug is bound); 11% is causing an
effect
- Moderately protein bound:(30-60% of drug is bound)
- Low protein bound: (<30% is bound)
- The drug with the higher binding effect binds first, the other drug
is freer. The drug that is less protein bound has greater effect. Have
to watch for drug toxicity. Drug-drug interaction.
- Ex. high protein bound, and moderate protein bound, moderate is
free and can cause toxicity.
Blood brain barrier (BBB)
- Anatomic barrier that inhibits drugs from leaving bloodstream
- Packed tightly, don’t allow substances in easily
- Can be harmful and cannot get in/out of brain
- Some meds cannot get into brain, protects toxins from getting
in
3. Metabolism (biotransformation)
● Chemical change of the drug
● Therapeutic effects; greater toxicity
● Liver and disease dysfunction can impact metabolism
● Half-life: time it takes for half the drug to be eliminated
● Can affect dosing; can be short or long
● Affects how often we give the medication
4. Excretion
- Renal excretion
PHARMACODYNAMICS
● Drug concentration and its effect on the body and how the body responds to the drug
