Intro Flashcards
PharmacoDynamics?
Actions of drug on the body.
PharmacoDynamics: Drug –> body
Drug definition
Any substance acting on a biological system that can bring about a change in biological function through its chemical actions.
PharmacoKinetics?
Actions of the body on the drug.
PharmacoKinetics: Katawan –> drugs
Lightest drug in terms of molecular weight?
Lithium. MW 7 .
Used for bipolar disorders.
WOF nephrogenic diabetes insipidus
Heaviest drug?
Alteplase. MW 50,000.
Thrombolytic.
Anticoagulant of choice in pregnancy?
Heparin. It cannot cross the placenta because of its large size.
Vs warfarin that can cross placenta baby bleeds.
Heparin?
A hepe named PiTT with a large belly.
Heparin is large. i: intrinsic factor
MOA: increases antithrombin III. Monitored with PTT.
Antidote: protamine sulfate
Strongest bond
Covalent > ionic > hydrophobic
Organophosphate poisoning?
Cholinergic toxicity. DUMBELLS
Diarrhea, Urination, Miosis, Bronchocospasm,
Emesis, Lacrimation, Lethargy, Salivation
Antidote to organophosphate poisoning?
Pralidoxime but only for the first 6-8 hours. After that covalent bonds can no longer be broken by it.
Atropine may also be used.
Permeation?
Movement of drug molecules into and within biological environments.
Components of pharmocoKinetics?
ADME
Absorption, Distribution, Metabolism, Elimination
Vitamin B12 is bound to?
Intrinsic factor
Iron is bound to?
Transferrin for transport
Ferritin for storage
Fick’s law of diffusion?
Absorption is faster through thinner membranes and in areas with larger surface area.
Henderson hasselbalch dissociation of weak acids
Protonated acid more lipid soluble, crosses biological membranes easier, unprotonated acid more water soluble, better clearance.
Henderson hasselbalch dissociation of weak bases
Unprotonated base more lipid soluble, better at crossing biological membranes.
Protonated base more water soluble, better clearance
Excretion of a weak acid may be accelerated by?
Alkalinizing urine with bicarbonate
Excretion of weak base accelerated by?
Acidifying urine with ammonium chloride.
First pass effect?
Drug is metabolized in the gut wall, the liver, and the portal circulation before it reaches the bloodstream.
Which quadrant of the buttocks is safest for IM drug administration?
Superolateral is safest.
Inferomedial WOF sciatic nerve
Sublingual route:
Lingual vein –> IJV –> brachiocephalic (innominate) vein –> SVC –> RA
Rectal route with first pass
If superior rectal vein from IMV –> portal vein, thus first pass
Topical preparations:
Acute inflammation –> drying agents
Chronic inflammation –> lubricating agents
Absorption
Transfer from site of administration to blood stream
Distribution
Leaves blood stream to enter target organ
Drug binding
Acidic drugs –> albumin
Basic drugs –> orosomucoid
Termination of drug action
Excretion
Release of drug and metabolites through urine, stool etc
Excretion
Rate of elimination is proportionate to concentration. Decrease by 50% for every half life decrease. Exponential decrease. Most common type
First-order elimination
Rate of elimination is constant regardless of concentration. Decrease is linearly.
Zero order elimination
Drugs that follow zero order kinetics
WHAT PET
Warfarin, Heparin, Aspirin, Tolbutamide, Phenytoin
Ethanol, Theophylline
Kd, EC50, Emax
Kd concentration required to bind half of the receptors
Emax efficacy
EC50 potency
ED50, TD50, LD50
ED50 median effective dose
TD50 median toxic dose
LD50 median lethal dose
Maximal effect an agonist can produce if the dose is taken to very high levels
Efficacy
Amount of drug needed to produce a given effect.
Graded dose dose required to produce 50% of the maximal effect.
Quantal dose response ed50 ld50 td50
Potency
Capable of fully activating the receptor system when bound.
High concentrations result in all receptors being activated
Full agonist
Produces less than the full effect even when the agonist has saturated all of the receptors.
Acts as an inhibitor when mixed with full agonist.
Partial agonist
Blocks or dampens drug response in the presence of an agonist
Antagonist
Binds reversibly, does not activate the effector system.
Shifts curve to the right. Increases ed50 decreased potency.
Can be overcome by adding more agonist
Competitive or reversible antagonist
Causes downward shift if the curve. Decreased efficacy Emax, same potency.
Not overcome by adding more agonist
Non-competitive or irreversible antagonist
Binds to a different receptor
Produces an effect opposite to that produced by the drug it is antagonizing.
Physiologic antagonist
Interacts directly with the drug being antagonized to remove it or to prevent it from binding
Chemical antagonist
Terazosin vs. norepinephrine
Beta blockers
Competitive or reversible antagonist
Phenoxybenzamine for pheochromocytoma
Non competitive irreversible antagonist
Histamine and epinephrine
Propranolol and thyroid hormone
Physiologic antagonist
Dimercaprol for heavy metal/lead poisoning
Pralidoxime for organophosphate poisoning
Chemical antagonist
Tachyphylaxis responsiveness diminishes, frequent exposure results in short-term dimunition
MED Loves CNN in HD
Metoclopromide, Ephedrine, Dobutamine, LSD,
Calcitonin, Nitroglycerin, Nicotine, Hydralazine, Desmopressin
Reversed by depletion of missing substrates
Tolerance
Idiosyncratic drug responses
Chloramphenicol and aplastic anemia
Allopurinol and cataracts
Drug eliminated with first-order kinetics, clearance is constant
Ratio
Elimination is proportional to concentration
Drugs eliminated with zero order kinetics clearance is constant
Amount.
Bioavailability is fraction of administered dose reaching systemic circulation.
It is determined by computing the area under the plasma concentration curve.
Maintenance dose computation
The Vd or volume of distribution is not in voiced in calculating for maintenance dose
Loading dose computation
Does not include clearance
Phase 1 reactions convert the parent drug to a more water-soluble polar product.examples are
HORD of phase 1
Hydrolysis, Oxidation, Reduction, Deamination
75% of drugs are metabolized by
CYP3A4 and CYP2D6
Enzyme induction
Increased synthesis of cyp450 enzymes and heme. Higher amount of the drug needed due to increased metabolism, excretion.
Enzyme inducers
ETHYL Booba takes PHEN and RIFuses GRISy CARB Shakes
Ethanol, Barbiturates, PHENytoin, RIFampicin, GRISeofulvin, St. John’s Wort/Smoking
Most potent enzyme inducers
Carbamazepine phenobarbital phenytoin RIFampicin
Enzyme inhibition
Lower doses of a drug are needed, drug stays in the system longer, reduction in blood flow to metabolizing organ
Suicide inhibitor
Metabolized to products that irreversibly inhibit the metabolizing enzyme.
Suicide inhibitors
Ethinyl estradiol, spirinolactone, allopurinol, PTU
Enzyme inhibitors
Inhibitors Stop CIber KEds from Eating GRApefruit Q
Isoniazid, Sulfonamide, Cimitedine, Ketoconazole, Erythromycin, Grapefruit juice, Ritonavir, Amiodarone, Quinidine
Category A
Human studies display no risk to fetus.
Animal studies do not show risk, but no human studies have been conducted. Or risk in animal studies but none displayed in human studies
Category B
Category C
Animal studies have shown adverse effects, no human studies done. Potential benefit justifies risk to fetus
Category D
Evidence if human fetal risk, but potential benefits justifies risks
Category x
Fetal adverse effects demonstrated, risk of fetal effects outweighs any benefit of drug. Absolute contraindications.
DES
Vaginal clear cell adenoCA
Misoprostol as teratogenic
Möbius sequence
Thalidomide
Phocomelia
Tetracycline
Tooth discoloration
Lithium
Atrialization of right ventricle. Ebstein’s anomaly.
Standard in vitro test for mutagenicity
Ames test
Carcinogens
Coal tar, aflatoxin, nitrosamines, urethane, vinyl chloride, polycyclic aromatic hydrocarbons in cigarette
