Basic Principles of Pharmacology Flashcards
Pharmacokinetics
What the body does to the drugs
A-D-M-E
Pharmacokdnamics
What the drugs do to the body
ENTERAL includes
Oral (PO)
Sublingual (SL)
Buccal
Rectal (BP)
PARENTERAL includes
Inhalation
Injection: IV, IM, SQ
TOPICAL includes
Transdermal
Nasal spray
Ointment (gold standard)
Increase skin hydration increases absorption
Relationship between first pas effect and bioavailability
The greater the first-pass effect, the less drug is available in the circulation thus the lower the bioavailability –> lower therapeutic effect and lower risk of toxicity
Bioavailability
the fraction or % of a drug that reaches systemic circulation
Why do we need to increase an oral dose to provide the same effect as an inhaled dose?
Oral dose goes through the first-pass effect via liver (more so than lung) thus more systemic circulation –> more systemic bioavailability
Substrates
the drug that is being metabolized by other drugs/enzymes
Inhibitors
a drug/enzyme that SLOW DOWN the metabolism of a substrate – thus less of that drug/substrate is being excreted –> more remain in circulation –> greater therapeutic effect or toxicity d/t MORE systemic bioavailability
Ex - Cimitidine is an inhibitor to Metformin –> slow down metabolism of Metformin –> more serum metformin –> increase metformin’s effect –> risk of hypoglycemia
Common INHIBITORS
G-PACMAN
G = grapefruit P = Protease inhibitors A = Azole antifungals C = Cimetidine M = Macrolides (except Azithromycin) A = Amioadarone N = Non-DHP CCBS (Diltiazem, Verapamil)
Common INDUCERS
P-CRABS
P = Phenytoin C = Carbamazepine R = Rifampin A = Alcohol (chronic) Barbiturates S = St. John's Wort
Inducers
Speeds Up metabolism of a substrate/drug
–> generally decrease drug effects
Ex:
-Prednisone is an inducer to Carbamazepine –> reduces serum level of carbamazepine which would leave pts at a higher risk for unanticipated seizures
Narrow Therapeutic Index Drugs (NTI)
Examples
- Anticoagulants (warfarin, heparins)
- Aminoglycoside antibiotics (Gentamycin, Tobramycin)
- Digoxin
- Hypoglycemic agents
- Levothyroxine sodium
- Lithium
- Phenytoin
- Theophylline
- TCA
- Valproic acid
Onset of drug action
time between administration and first sign of drug effect
Peak of drug action
-Point at which amount of drug being absorbed and distributed is equal to amount being metabolized and excreted.
Duration of drug action
Continued entry of drug into body with levels above minimum effective concentration
Termination of drug action
when drugs stop”working”
Therapeutic Range
equals MTC - MEC
MTC
amount to cause toxicity
MEC
Lowest concentration needed for drugs to work
Drug Half-Life
Time required for the amount of drug in the body to decrease by 50%
-determine the dosing interval (drugs with short half-life, dosing interval must be correspondingly short. If a long dosing interval were used, drug levels would fall below MEC between doses, and therapeutic effects would be lost)
Ligand
a molecule that fit into the active site of receptors –> activate those receptors –> propagate signal pathways
Agonists
Molecules that ACTIVATE receptors
- Drugs that mimics native ligand and stimulate the typical physiological response at the body natural receptors
- These drugs have both affinity (allow agonist to bind to receptors) and high intrinsic activity (allows the bound agonist to activate the receptor function)
Antagonists
Produce pharmacologic effects by preventing the activation of receptors by agonists
-Its effect is determine by the amount of agonist that are present – If there is no agonist present, administration of an antagonist will have no observable effect
- Have virtually no effects of their own on receptor function
- These drugs have affinity for a receptor but no intrinsic activity
Potency of a drug
Strength of a drug at a particular dosage
- the affinity of a drug for a receptor
- the amount of drugs require to produce 50% of maximal effect that drug can effect
Efficacy
Maximum effect that can be achieve by a drug such that after this is reach, no higher dosage can produce any further effect
True/False: Two drugs can have the same efficacy but different potency
True
Pregnancy related Physiologic Changes:
CARDIOVASCULAR
Cardio
- increased BV and CO and
- decreased systemic vascular resistance
Pregnancy related Physiologic Changes:
GI
- Increased pH of intestinal secretion
- Delayed gastric emptying
- Decreased gastric acid secretions
- Decreased intestinal motility
Pregnancy related Physiologic Changes:
RENAL
- Increased renal blood flow
- Increase GFR
Pregnancy related Physiologic Changes:
GYN/GU
-Increase uterine blood flow
Pregnancy - ABSORPTION
GI:
- Drugs stay in guts longer → delayed gastric emptying = delayed absorption
- Reduced gastric acid secretion → decreased absorption of certain medications
- N/V pregnancy → decreased absorption
Lungs:
-increased absorption of inhaled medications d/t increased blood flow to the lungs
Transdermal:
- increased absorption d/t ↑ peripheral vasodilation and ↑ in total body water (TBW)
Pregnancy - DISTRIBUTION
1) Water soluble drugs:
- Increase in TBW of 8L during pregnancy = dilution effect → decreased drug concentrations
2) Decreased levels of albumin
- Drugs that are highly bound to albumin, in this case, they will have higher serum concentrations during pregnancy
Pregnancy - ELIMINATION
- Increased progesterone stimulates hepatic enzyme systems → increasing elimination of hepatically eliminated medications
- Increased GFR → increased elimination through the kidneys
Pregnancy
Drugs that are more likely to cross the placenta
- Lipids soluble drugs
- Low molecular weight drugs
- Free drug (not bound to protein) - not that in pregnancy, there is a lower albumin level
Most important determinant of teratogenicity is ____
Timing of the exposure , which can be during, before , or after pregnancy
Drugs to Avoid in First Trimester
Beta blockers Benzos Thiazides ACE-I/ARBs Anti-epileptics Estrogen Warfarin Topical retinoids Methotrexate Lithium Cytotoxic drugs
Pharmacokinetics & Aging: ABSORPTION
- Decreased in small-bowel surface area -
- Decreased in GI mobility
- Increased in pH
Pharmacokinetics & Aging: DISTRIBUTION
- Increased body fat –> prolonged action of fat soluble drugs
- Decreased total body water –> Higher concentration of water-soluble drugs
- Decreased albumin –> higher concentration of active drugs (unbound/free drugs)
Pharmacokinetics & Aging: METOLISM
-Decreased hepatic metabolism –> Higher serum concentration
Pharmacokinetics & Aging: ELIMINATION
-Decreased renal drug clearance, Decrease GFR (even without renal diseases)
