General Pharmacology

• - Do not resemble the substrate.
• - Can not be overcome by increasing substrate concentration
• - Do not bind the active site
• - Decrease Vmax
• - Do not change Km
• - Decrease efficacy

• - Resemble the substrate
• - Can be overcome by increasing substrate concentration
• - Bind the active site
• - Do not change Vmax
• - Increase Km
• - Decrease potency

affinity

enzyme concentration

• - amount of drug in the body to the plasma concentration
• - Vd of protein-bound drugs can be altered by liver and kidney disease

Vd = amount of drug in the body/plasma drug concentration (units L)

• Low Vd: distribute in blood
• Medium Vd: distribute in extracellular space or body water
• High Vd: distributes in tissues

• - relates the rate of elimination to the plasma concentration
• Cl = rate of elimination/plasma drug concentration
• = 0.7Vd / t_1/2

• - time required to change the amount of drug in the body by 1/2 during elimination
• t_1/2 = 0.7Vd/Cl (in hours)
• - 1 t_1/2: 50% concentration
• - 2 t_1/2: 75% concentration
• - 3 t_1/2: 87.5% concentration
• - 4 t_1/2: 94% concentration

• Loading Dose = CpVd/F
• Maintenance Dose = CpCl/F

• Cp = target plasma concentration
• F = bioavailability

• - in patients with impaired renal or hepatic function,
• loading dose remains the same
• maintenance dose decreases

• Zero Order - rate of elimination is constant, regardless of concentration
• - Cp decreases linearly with time
• - phenytoin, ethanol, aspirin

• First Order - rate of elimination is proportional to the concentration
• - Cp decreases exponentially with time

• Ionized Species Get Trapped
• Weak Acids
• - trapped in basic environments
• - treat overdose with bicarbonate
• - pH > pKa nonprotonated form (ionic)

• Weak Bases
• - trapped in acidic environments
• - treat overdose with ammonium chloride
• - pH<pKa protonated form (ionic)

• Phase I
• - reduction, oxidation, hydrolysis
• - slightly polar, water soluble metabolites
• - cytochrome P450

• Phase II
• - acetylation, glucuronidation, sulfation
• - usually yields very polar, inactive metabolites (renally excreted)
• - conjugation

Geriatric patients lose Phase I first

Efficacy - maximal effect a drug can produce (Vmax)

Potency - amount of drug needed for a given effect (Km)

• - acts on the same receptor system as the full agonist but has a lower maximal efficacy, regardless of the dose
• - potency is an independent factor; therefore, a partial agonist can have lower potency, equivalent potency, or higher potency

• TI = Ld50/Ed50
• - want a higher TI
• - TILE pneumonic

• Nicotinic ACh Receptors - ligand gated Na⁺/K⁺ channels
• - N_N - autonomic ganglia
• - N_M - neuromuscular junctions

• Muscarinic ACh Receptors - G-Protein coupled receptors
• - 5 subtypes: M1 - M5

• - Sympathetic
• - Gq protein class (IP3 increases Ca2+, DAG increases Protein Kinase C)
• - increase vascular smooth muscle contraction
• - mydriasis (pupillary dilator muscle contraction)
• - increase sphincter contraction

• - Sympathetic
• - Gi protein class (decreases cAMP and PKA)
• - decrease sympathetic outflow
• - decrease insulin release

• - Sympathetic
• - Gs protein class (increases cAMP and PKA)
• - increases heart rate
• - increases contractility
• - increases renin release
• - increases lipolysis

• - Sympathetic
• - Gs protein class (increases cAMP and PKA)
• - vasodilation
• - bronchodilation
• - increase heart rate
• - increase contractility
• - increase lipolysis
• - increase insulin release
• - decrease uterine tone

• - Parasympathetic
• - Gq protein class (IP3 increases Ca2+, DAG increases Protein Kinase C)
• - CNS
• - enteric nervous system

• - Parasympathetic
• - Gi (decrease cAMP and PKA)
• - decrease heart rate
• - decrease contractility of atria

• - Parasympathetic
• - Gq protein class (IP3 increases Ca2+, DAG increases Protein Kinase C)
• - increase exocrine gland secretions
• - increase gut peristalsis
• - increase bladder contraction
• - bronchoconstriction
• - miosis (pupillary sphincter muscle contraction)
• - accomodation (ciliary muscle contraction)

• - Dopamine
• - Gs protein class (increase cAMP and PKA)
• - relaxes renal vascular smooth muscle

• - Dopamine
• - Gi protein class (decrease cAMP and PKA)
• - modulates transmitter release (especially in the brain)

• - Histamine
• - Gq protein class (IP3 increases Ca2+, DAG increases Protein Kinase C)
• - increase nasal and bronchial mucus production
• - contraction of bronchioles
• - prutitis
• - pain

• - Histamine
• - Gs protein class (increase cAMP and PKA)
• - increase gastric acid secretion

• - Vasopresssin
• - Gq protein class (IP3 increases Ca2+, DAG increases Protein Kinase C)
• - increase vascular smooth muscle contraction

• - Vasopressin
• - Gs (increase cAMP and PKA)
• - increase water permeability and reabsorption in the collecting tubules of the kindney